Proteins are any complex organic compounds that consist of one or more chains of amino acids. Proteins are typically essential components of any living cell and indispensable to the proper functioning of all organisms.
For more information, please see the Freebase wiki page on protein.
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ATP synthase delta subunit is a subunit of bacterial and chloroplast ATPase, or OSCP (oligomycin sensitivity conferral protein) in mitochondrial ATPase (note that in mitochondria there is a different delta subunit, IPR001469).
The OSCP/delta subunit appears to be part of the peripheral stalk that holds the F1 complex alpha3beta3 catalytic core stationary against the torque of the rotating central stalk, and links subunit A of the F0 complex with the F1 complex. In mitochondria, the peripheral stalk consists of OSCP, as well as F0 components F6, B and D. In bacteria and chloroplasts the peripheral stalks have different subunit compositions: delta and two copies of F0 component B (bacteria), or delta and F0 components B and B (chloroplasts).
Human delta subunit of ATP synthase is coded by gene ATP5O.
Wilkens, S.; Rodgers, A.; Ogilvie, I.; Capaldi, R. A. (1997). "Structure and arrangement of the delta subunit in the E. Coli ATP synthase (ECF1F0)". Biophysical chemistry 68 (1–3): 95–102. PMID 9468613. edit
This article incorporates text from the public domain Pfam and InterPro IPR000711
Prostaglandin-H2 D-isomerase (PTGDS) is an enzyme that in humans is encoded by the PTGDS gene.
The protein encoded by this gene is a glutathione-independent prostaglandin D synthase that catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2). PGD2 functions as a neuromodulator as well as a trophic factor in the central nervous system. PGD2 is also involved in smooth muscle contraction/relaxation and is a potent inhibitor of platelet aggregation. This gene is preferentially expressed in brain. Studies with transgenic mice over-expressing this gene suggest that this gene may be also involved in the regulation of non-rapid eye movement sleep. Furthermore, PTGDS and its product PGD2 are elevated in the bald-scalp areas of men with male pattern baldness (androgenetic alopecia).
Prostaglandin D2 synthase is used clinically as a diagnostic marker for liquorrhea, that is, to check whether fluid leaking from the nose or ear contains cerebrospinal fluid. This is important in the assessment of head trauma severity. In a medical context, the older term "β-trace protein" is frequently used to refer to PTGDS.
Hematopoietic prostaglandin D synthase
The enzyme citrate synthase (E.C. 18.104.22.168 [previously 22.214.171.124]) exists in nearly all living cells and stands as a pace-making enzyme in the first step of the Citric Acid Cycle (or Krebs Cycle). Citrate synthase is localized within eukaryotic cells in the mitochondrial matrix, but is encoded by nuclear DNA rather than mitochondrial. It is synthesized using cytoplasmic ribosomes, then transported into the mitochondrial matrix. Citrate synthase is commonly used as a quantitative enzyme marker for the presence of intact mitochondria.
Citrate synthase catalyzes the condensation reaction of the two-carbon acetate residue from acetyl coenzyme A and a molecule of four-carbon oxaloacetate to form the six-carbon citrate. Oxaloacetate will be regenerated after the completion of one round of the Krebs Cycle.
acetyl-CoA + oxaloacetate + H2O → citrate + CoA-SH
Oxaloacetate is the first substrate to bind to the enzyme. This induces the enzyme to change its conformation, and creates a binding site for the acetyl-CoA. Only when this citroyl-CoA has formed will another conformational change cause thioester hydrolysis and release coenzyme A. This ensures that the energy released from the thioester
Poly(A)-binding protein (PAB or PABP) is a RNA-binding protein which binds to the poly(A) tail of mRNA. The poly(A) tail is located on the 3' end of mRNA. The nuclear isoforms selectively binds to around 50 nucleotides and stimulates the activity of Polyadenylate polymerase.
The expression of mammalian Poly(A)-binding protein is regulated at the translational level by a feed-back mechanism: the mRNA encoding PABP contains in its 5' UTR an A-rich sequence which binds Poly(A)-binding protein. This leads to repression of translation
The cytosolic isoform of eukaryotes Poly(A) binding protein binds to the initiation factor eIF-4G via its C-terminal domain. EIF-4G is bound to eIF-4E, another initiation factor bound to the 5' cap on the 5' end of mRNA. This binding forms the characteristic loop structure of eukaryotic protein synthesis. Poly(A)-binding protein interacting proteins in the cytosol compete for the eIF-4G binding sites. Poly(A)-binding protein has also been shown to interact with a termination factor (eRF3)
Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F. And NSP3A, by taking the place of PABP on eIF4GI, is
Cyclin-dependent kinase 4 is part of the cyclin-dependent kinase family.
The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported.
It is regulated by Cyclin D.
Cyclin-dependent kinase 4 has been shown to interact with SERTAD1, CDC37, CEBPA, PCNA, Cyclin D3, Cyclin D1, CDKN2C, MyoD, P16, CDKN2B, Drebrin-like and CDKN1B.
Ku is a protein that binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Ku is evolutionarily conserved from bacteria to human. The ancestral bacterial Ku is a homodimer (two copies of the same protein bound to each other). Eukaryotic Ku is a heterodimer of two polypeptides, Ku70 (XRCC6) and Ku80 (XRCC5), so named because the molecular weight of the human Ku proteins is around 70 kDa and 80 kDa. The two Ku subunits form a basket-shaped structure that threads onto the DNA end. Once bound, Ku can slide down the DNA strand, allowing more Ku molecules to thread onto the end. In higher eukaryotes, Ku forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK. Ku is thought to function as a molecular scaffold to which other proteins involved in NHEJ can bind.
Both subunits of Ku have been experimentally knocked out in mice. These mice exhibit chromosomal instability, indicating that NHEJ is important for genome maintenance.
In many organisms, Ku has additional functions at telomeres in addition to its role in DNA repair.
Abundance of Ku80 seems
Kv7.1 (KvLQT1) is a potassium channel protein coded for by the gene KCNQ1. Kv7.1 is a voltage-gated potassium channel present in the cell membranes of cardiac tissue and in inner ear neurons among other tissues. In the cardiac cells, Kv7.1 mediates the IKs (or slow delayed rectifying K) current that contributes to the repolarization of the cell, terminating the cardiac action potential and thereby the heart's contraction. Structurally, KvLQT1 is made of six membrane-spanning domains S1-S6, two intracellular domains, and a pore loop. The KvLQT1 channel is made of four KCNQ1 subunits, which form the actual ion channel.
Mutations in the gene can lead to a defective protein and several forms of inherited arrhythmias as Long QT syndrome which is a prolongation of the QT interval of heart repolarization, Short QT syndrome, and Familial Atrial Fibrillation. Currents arising from Kv7.1 in over-expression systems have never been recapitulated in native tissues - Kv7.1 is always found in native tissues with a modulatory subunit. In cardiac tissue, these subunits comprise KCNE1 and yotiao. Though physiologically irrelevant, homotetrameric Kv7.1 channels also display a unique form of C-type
DNA replication factor Cdt1 is a protein that in humans is encoded by the CDT1 gene.
The protein encoded by this gene is a key licensing factor which, along with the protein Cdc6, functions to license DNA by forming the pre-replication complex (pre-RC). Its activity during the cell cycle is tightly regulated by its association with the protein geminin, which both inhibits Cdt1 activity during S phase in order to prevent re-replication of DNA and prevents it from ubiquitination and subsequent proteolysis.
CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of orthlogs in other species include:
DNA replication factor CDT1 has been shown to interact with SKP2. Cdt1 is recruited by the origin recognition complex in origin licensing. Null-mutations for Cdt1 are lethal in yeast; the spores undergo mitosis without DNA replication. The overexpression of Cdt1 causes rereplication in H. sapiens, which activates the Chk1 pathway, preventing entry into mitosis.
Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis. Several of these targets, including p53, CHK2 and H2AX are tumor suppressors.
The protein is named for the disorder Ataxia telangiectasia caused by mutations of ATM.
Throughout the cell cycle the DNA is monitored for damage. Damages result from errors during replication, by-products of metabolism, general toxic drugs or ionizing radiation. The cell cycle has different DNA damage checkpoints, which inhibit or maintain the next cell cycle step. There are two main checkpoints, the G1/S and the G2/M, during the cell cycle, which preserve correct progression. ATM plays a role in cell cycle delay after DNA damage, especially after double-strand breaks (DSBs). ATM together with NBS1 act as primary DSB sensor proteins. Different mediators, such as Mre11 and MDC1, acquire post-translational modifications which are generated by the sensor proteins. These modified mediator proteins then amplify the DNA damage
The Bcl-2–associated X protein, or Bax is a protein of the Bcl-2 gene family. It promotes apoptosis by competing with Bcl-2 proper.
The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Orthologs of the BAX gene have been identified in most mammals for which complete genome data are available.
Bax is a pro-apoptotic Bcl-2 protein containing BH1, BH2 and BH3 domains. In healthy mammalian cells, the majority of BAX is found in the cytosol, but upon initiation of apoptotic signaling, Bax undergoes a conformation shift, and inserts into organelle membranes, primarily the outer mitochondrial membrane. Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence suggest that activated Bax and/or Bak form an oligomeric pore, MAC in the outer membrane. This
Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.
TGFB is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. TGFB acts synergistically with TGFA in inducing transformation. It also acts as a negative autocrine growth factor. Dysregulation of TGFB activation and signaling may result in apoptosis. Many cells synthesize TGFB and almost all of them have specific receptors for this peptide. TGFB1, TGFB2, and TGFB3 all function through the same receptor signaling systems.[supplied by OMIM]
TGF-β1 was first identified in human platelets as a protein with a molecular mass of 25 kilodaltons with a potential role in wound healing. It was later characterized as a large protein precursor (containing 390 amino acids) that was proteolytically processed to produce a mature peptide of 112 amino acids.
TGF-β1 plays an important role in controlling the
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long (a length to width ratio of more than 10 million to one in human DNA). For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 micrometers (0.09 mm) of chromatin, which, when duplicated and condensed during mitosis, result in about 120 micrometers of chromosomes.
Five major families of histones exist: H1/H5, H2A, H2B, H3, and H4. Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1 and H5 are known as the linker histones.
Two of each of the core histones assemble to form one octameric nucleosome core particle, and 147 base pairs of DNA wrap around this core particle 1.65 times in a left-handed super-helical turn. The linker histone H1 binds the nucleosome and the entry and exit sites of the DNA, thus locking the DNA into place and allowing the formation of higher
Thyroxine-binding globulin (TBG) binds thyroid hormone in circulation. It is one of three proteins (along with transthyretin and albumin) responsible for carrying the thyroid hormones thyroxine (T4) and 3,5,3’-triiodothyronine (T3) in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest concentration. Despite its low concentration, TBG carries the majority of T4 in the blood. Due to the very low concentration of T4 & T3 in the blood, TBG is rarely more than 25% saturated with its ligand. Unlike transthyretin and albumin, TBG has a single binding site for T4/T3. TBG is synthesized primarily in the liver as a 54 kDa protein. In terms of genomics, TBG is a serpin; however, it has no inhibitory function like many other members of this class of proteins.
TBG tests are sometimes used in finding the reason for elevated or diminished levels of thyroid hormone. This is done by measuring resin binding to labeled thyroid hormone, which happens only when the labeled thyroid hormone is free.
The patient's serum is mixed with the labeled thyroid hormone; then, the resin is added to the whole mixture to measure the amount of free
Lamina-associated polypeptide 2 (LAP2), isoforms beta/gamma is a protein that in humans is encoded by the TMPO gene. LAP2 is an inner nuclear membrane (INM) protein.
Thymopoietin is a protein involved in the induction of CD90 in the thymus. The thymopoetin (TMPO) gene encodes three alternatively spliced mRNAs encoding proteins of 75 kDa (alpha), 51 kDa (beta) and 39 kDa (gamma) which are ubiquitously expressed in all cells. The human TMPO gene maps to chromosome band 12q22 and consists of eight exons. TMPO alpha is present diffusely expressed with the cell nucleus while TMPO beta and gamma are localized to the nuclear membrane. TMPO beta is a human homolog of the murine protein LAP2. LAP2 plays a role in the regulation of nuclear architecture by binding lamin B1 and chromosomes. This interaction is regulated by phosphorylation during mitosis. Given the nuclear localization of the three TMPO isoforms, it is unlikely that these proteins play any role in CD90 induction.
Thymopoietin has been shown to interact with Barrier to autointegration factor 1, AKAP8L, LMNB1 and LMNA.
The enzyme cytochrome c oxidase or Complex IV, EC 126.96.36.199) is a large transmembrane protein complex found in bacteria and the mitochondrion.
It is the last enzyme in the respiratory electron transport chain of mitochondria (or bacteria) located in the mitochondrial (or bacterial) membrane. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. In the process, it binds four protons from the inner aqueous phase to make water, and in addition translocates four protons across the membrane, helping to establish a transmembrane difference of proton electrochemical potential that the ATP synthase then uses to synthesize ATP.
The complex is a large integral membrane protein composed of several metal prosthetic sites and 13 protein subunits in mammals. In mammals, ten subunits are nuclear in origin, and three are synthesized in the mitochondria. The complex contains two hemes, a cytochrome a and cytochrome a3, and two copper centers, the CuA and CuB centers. In fact, the cytochrome a3 and CuB form a binuclear center that is the site of oxygen reduction. Cytochrome c which is reduced
Ricin ( /ˈraɪsɪn/), from the castor oil plant Ricinus communis, is a highly toxic, naturally occurring protein. A dose as small as a few grains of salt can kill an adult human. The LD50 of ricin is around 22 micrograms per kilogram (1.76 mg for an average adult, around ⁄228 of a standard aspirin tablet/0.4 g gross) in humans if exposure is from injection or inhalation. Oral exposure to ricin is far less toxic and a lethal dose can be up to 20–30 milligrams per kilogram.
Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. It is resistant, but not impervious, to digestion by peptidases. By ingestion, the pathology of ricin is largely restricted to the gastrointestinal tract where it may cause mucosal injuries; with appropriate treatment, most patients will make a full recovery. Because the symptoms are caused by failure to make protein, they emerge only after a variable delay from a few hours to a full day after exposure. An antidote not yet tested on humans has been developed by the UK military, and a vaccine has been developed by the US military which has so far shown to be safe and effective when lab mice were injected
Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites. α-Antithrombin is the dominant form of antithrombin found in blood plasma and has an oligosaccharide occupying each of its four glycosylation sites. A single glycosylation site remains consistently un-occupied in the minor form of antithrombin, β-antithrombin. Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to factor II and factor X.
Antithrombin is also termed Antithrombin III (AT III). The designations Antithrombin I through to Antithrombin IV originate in early studies carried out in the 1950s by Seegers, Johnson and Fell.
Antithrombin I (AT I) refers to the absorption of thrombin onto fibrin after thrombin has activated fibrinogen. Antithrombin II (AT II) refers to a cofactor in plasma, which together with heparin interferes with the interaction of thrombin and fibrinogen. Antithrombin III (AT III) refers to a substance in plasma that
RoXaN (Rotavirus 'X'-associated non-structural protein) also known as ZC3H7B (zinc finger CCCH-type containing 7B), is a protein that in humans is encoded by the ZC3H7B gene. RoXaN is a protein that contains tetratricopeptide repeat and leucine-aspartate repeat as well as zinc finger domains. This protein also interacts with the rotavirus non-structural protein NSP3.
Rotavirus mRNAs are capped but not polyadenylated, and viral proteins are translated by the cellular translation machinery. This is accomplished through the action of the viral nonstructural protein NSP3 which specifically binds the 3' consensus sequence of viral mRNAs and interacts with the eukaryotic translation initiation factor eIF4G I.
RoXaN (rotavirus X protein associated with NSP3) is 110-kDa cellular protein that contains a minimum of three regions predicted to be involved in protein-protein or nucleic acid-protein interactions. A tetratricopeptide repeat region, a protein-protein interaction domain most often found in multiprotein complexes, is present in the amino-terminal region. In the carboxy terminus, at least five zinc finger motifs are observed, further suggesting the capacity of RoXaN to bind other
Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity and iron export. APP is best known as the precursor molecule whose proteolysis generates beta amyloid (Aβ), a 37 to 49 amino acid peptide whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.
In humans, the gene for APP is located on chromosome 21 and contains at least 18 exons in 240 kilobases. Several alternative splicing isoforms of APP have been observed in humans, ranging in length from 365 to 770 amino acids, with certain isoforms preferentially expressed in neurons; changes in the neuronal ratio of these isoforms have been associated with Alzheimer's disease. Homologous proteins have been identified in other organisms such as Drosophila (fruit flies), C. elegans (roundworms), and all mammals. The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APP's
Concanavalin A (ConA) is a lectin (carbohydrate-binding protein) originally extracted from the jack-bean, Canavalia ensiformis. It is a member of the legume lectin family. It binds specifically to certain structures found in various sugars, glycoproteins, and glycolipids, mainly internal and nonreducing terminal α-D-mannosyl and α-D-glucosyl groups. ConA is a plant mitogen, and is known for its ability to stimulate mouse T-cell subsets giving rise to four functionally distinct T cell populations, including precursors to suppressor T-cell; one subset of human suppressor T-cells as well is sensitive to ConA. ConA was the first lectin to be available on a commercial basis, and is widely used in biology and biochemistry to characterize glycoproteins and other sugar-containing entities on the surface of various cells. It is also used to purify glycosylated macromolecules in lectin affinity chromatography, as well as to study immune regulation by various immune cells.
Like most lectins, ConA is a homotetramer: each sub-unit (26.5KDa, 235 amino-acids, heavily glycated) binds a metallic atom (usually Mn and a Ca). Its tertiary structure has been elucidated, and the molecular basis of its
Mabinlins are sweet-tasting proteins extracted from the seed of Mabinlang (Capparis masaikai Levl.), a Chinese plant growing in Yunnan province. There are four homologues. Mabinlin-2 was first isolated in 1983 and characterised in 1993, and is the most extensively studied of the four. The other variants of mabinlin-1, -3 and -4 were discovered and characterised in 1994.
The 4 mabinlins are very similar in their amino acids sequences (see below).
M-1: EPLCRRQFQQ HQHLRACQRY IRRRAQRGGL VD
M-2: QLWRCQRQFL QHQRLRACQR FIHRRAQFGG QPD
M-3: EPLCRRQFQQ HQHLRACQRY LRRRAQRGGL AD
M-4: EPLCRRQFQQ HQHLRACQRY LRRRAQRG
M-1: EQRGPALRLC CNQLRQVNKP CVCPVLRQAA HQQLYQGQIE GPRQVRQLFR AARNLPNICK IPAVGRCQFT RW
M-2: QPRRPALRQC CNQLRQVDRP CVCPVLRQAA QQVLQRQIIQ GPQQLRRLFD AARNLPNICN IPNIGACPFR AW
M-3: EQRGPALRLC CNQLRQVNKP CVCPVLRQAA HQQLYQGQIE GPRQVRRLFR AARNLPNICK IPAVGRCQFT RW
M-4: EQRGPALRLC CNQLRQVNKP CVCPVLRQAA HQQLYQGQIE GPRQVRRLFR AARNLPNICK IPAVGRCQFT RW
Amino acid sequence of Mabinlins homologues are adapted from Swiss-Prot biological database of protein.
The molecular weights of Mabinlin-1, Mabinlin-3 and Mabinlin-4 are 12.3 kDa, 12.3 kDa and 11.9 kDa, respectively.
Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin or neuroendocrine basic polypeptide), a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease. It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer's disease. In humans, all cells with a nucleus (cell core containing the DNA) produce cystatin C as a chain of 120 amino acids. It is found in virtually all tissues and body fluids. It is a potent inhibitor of lysosomal proteinases (enzymes from a special subunit of the cell that break down proteins) and probably one of the most important extracellular inhibitors of cysteine proteases (it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes). Cystatin C belongs to the type 2 cystatin gene family.
Glomerular filtration rate (GFR), a marker of kidney health, is best measured by injecting compounds such as inulin, radioisotopes such as chromium-EDTA, I-iothalamate, Tc-DTPA or radiocontrast agents such as iohexol, but
ALA synthase (EC 188.8.131.52) catalyzes the synthesis of D-Aminolevulinic acid (ALA) the first common precursor in the biosynthesis of all tetrapyrroles. The enzyme is expressed in all non-plant eukaryotes and the α-class of proteobacteria. Other organisms produce ALA through a three enzyme pathway known as the Shemin pathway. ALA is synthesized through the condensation of glycine and succinyl-CoA. In humans, transcription of ALA synthase is tightly controlled by the presence of Fe-binding elements, to prevent accumulation of porphyrin intermediates in the absence of iron. There are two forms of ALA synthase in the body. One form is expressed in red blood cell precursor cells (ALAS2), whereas the other (ALAS1) is ubiquitously expressed throughout the body. The red blood cell form is coded by a gene on chromosome x, whereas the other form is coded by a gene on chromosome 3. The disease X-linked sideroblastic anemia is caused by mutations in the ALA synthase gene on chromosome X, whereas no diseases are known to be caused by mutations in the other gene. Gain of function mutations in the erythroid specific ALA synthase gene have been shown recently to cause a previously unknown form of
In enzymology, a cystathionine beta-synthase (EC 184.108.40.206) is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are L-serine and L-homocysteine, whereas its two products are L-cystathionine and H2O.
This enzyme belongs to the family of lyases, specifically the hydro-lyases, which cleave carbon-oxygen bonds. The systematic name of this enzyme class is L-serine hydro-lyase (adding homocysteine; L-cystathionine-forming). Other names in common use include serine sulfhydrase, beta-thionase, methylcysteine synthase, cysteine synthase, serine sulfhydrylase, and L-serine hydro-lyase (adding homocysteine). This enzyme participates in 4 metabolic pathways: glycine, serine and threonine metabolism, methionine metabolism, selenoamino acid metabolism, and huntington's disease. It employs one cofactor, pyridoxal phosphate.
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 1JBQ and 1M54.
Regulator of G protein signaling 4 or RGS4 is a protein which regulates G protein signaling. A number of studies associate the RGS4 gene with schizophrenia, while some fail to detect an association.
RGS4 is also of interest as one of the three main RGS proteins (along with RGS9 and RGS17) involved in terminating signalling by the mu opioid receptor, and may be important in the development of tolerance to opioid drugs.
Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulates signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm.
RGS4 has been shown to interact with ERBB3, GNAQ and COPB2.
STAT1 is a member of the Signal Transducers and Activators of Transcription family of transcription factors. STAT1 is involved in upregulating genes due to a signal by either type I, type II or type III interferons. In response to IFN-γ stimulation, STAT1 forms homodimers or heterodimers with STAT3 that bind to the GAS (Interferon-Gamma Activated Sequence) promoter element; in response to either IFN-α or IFN-β stimulation, STAT1 forms a heterodimer with STAT2 that can bind the ISRE (Interferon Stimulated Response Element) promoter element. In either case, binding of the promoter element leads to an increased expression of ISG (Interferon Stimulated Genes).
Expression of STAT1 can be induced with diallyl disulfide, a compound in garlic.
STAT1 has been shown to interact with Protein kinase R, Src, IRF1, STAT3, MCM5, STAT2, CD117, Fanconi anemia, complementation group C, CREB-binding protein, Interleukin 27 receptor, alpha subunit, PIAS1, BRCA1, Epidermal growth factor receptor, PTK2, Mammalian target of rapamycin, IFNAR2, PRKCD, TRADD, C-jun, Calcitriol receptor, ISGF3G and GNB2L1.
CAMP responsive element binding protein 1, also known as CREB-1, is a protein that in humans is encoded by the CREB1 gene. This protein binds the cAMP response element, a DNA nucleotide sequence present in many viral and cellular promoters. The binding of CREB1 stimulates transcription.
This protein is a CREB transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of this gene results in two transcript variants encoding different isoforms.
CREB1 has been shown to interact with HTATIP , RPS6KA5 , CREB binding protein , FHL2 , FHL3 , P53 , CEBPB and FHL5 .
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
GRB2-associated-binding protein 2 is a protein that in humans is encoded by the GAB2 gene.
The protein encoded by this gene, GAB2 is an adaptor protein serving as principal activator of Phosphatidylinositol 3-kinase. 10 SNPs of GAB2 gene have been found in one study to associate with risk of Alzheimer's disease in the carriers of ApoE4 allele.
GAB2 has been shown to interact with PTPN11, PLCG2, RICS, Grb2, PIK3R1, CRKL, AKT1 and SHC1.
Hsp40 (heat shock protein 40 kD) also known as DnaJ is a family of heat shock proteins that are expressed in a wide variety of organisms from bacteria to humans.
Hsp40 is a family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of Hsp40 interacts with Hsp70 heat shock proteins. Hsp40 heat-shock proteins play a role in regulating the ATPase activity of Hsp70 heat-shock proteins.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Hsp90 (heat shock protein 90) is a molecular chaperone and is one of the most abundant proteins expressed in cells. It is a member of the heat shock protein family, which is upregulated in response to stress. Hsp90 is found in bacteria and all branches of eukarya, but it is apparently absent in archaea. Whereas cytoplasmic Hsp90 is essential for viability under all conditions in eukaryotes, the bacterial homologue HtpG is dispensable under non-heat stress conditions.
Heat shock proteins, as a class, are among the most highly expressed cellular proteins across all species. As their name implies, heat shock proteins protect cells when stressed by elevated temperatures. They account for 1–2% of total protein in unstressed cells. However, when cells are heated, the fraction of heat shock proteins increases to 4–6% of cellular proteins. Heat shock protein 90 (Hsp90) is one of the most common of the heat-related proteins. The "90" comes from the fact that it weighs roughly 90 kiloDaltons. A 90 kDa protein is considered fairly large for a non-fibrous protein.
The functions of Hsp90 include assisting in protein folding, stabilizing various proteins such as steroid receptors, and aiding in
Nuclear factor 1 X-type is a protein that in humans is encoded by the NFIX gene. NFI-X3, a splice variant of NFIX, regulates Glial fibrillary acidic protein and YKL-40 in astrocytes.
NFIX has been shown to interact with SKI protein and it is also known to interact with AP-1. NFI-X3 has been shown to interact with STAT3.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Lactalbumin, alpha-, also known as LALBA, is a protein that in humans is encoded by the LALBA gene.
α-Lactalbumin is an important whey protein in cow's milk (~1 g/l), and is also present in the milk of many other mammalian species. In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose.
α-Lactalbumin forms the regulatory subunit of the lactose synthase (LS) heterodimer and β-1,4-galactosyltransferase (beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce lactose by transferring galactose moieties to glucose. As a multimer, alpha-lactalbumin strongly binds calcium and zinc ions and may possess bactericidal or antitumor activity. A folding variant of human alpha-lactalbumin that may form in acidic environments such as the stomach, called HAMLET, probably induces apoptosis in tumor and immature cells.
Research by a Dr. Vincent Tuohy at the Cleveland Clinic is using α-Lactalbumin as the basis for a potential breast cancer vaccine. Breast cancer usually develops later in life, well after the typical child-bearing age. This protein is normally expressed only during late
Amyloid beta (Aβ or Abeta) is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While best known as a component of amyloid plaques in association with Alzheimer's disease, evidence has been found that Aβ is a highly multifunctional peptide with significant non-pathological activity. Aβ is the main component of deposits found in the brains of patients with Alzheimer's disease.
Several potential activities have been discovered for Aβ that are not associated with disease, including activation of kinase enzymes, protection against oxidative stress, regulation of cholesterol transport, functioning as a transcription factor, and anti-microbial activity (potentially associated with Aβ's pro-inflammatory activity).
Aβ is the main component of amyloid plaques (deposits found in the brains of patients with Alzheimer's disease). Similar plaques appear in some variants of Lewy body dementia and in inclusion body myositis (a muscle disease), while Aβ can also form the aggregates that coat cerebral blood vessels in cerebral amyloid angiopathy. The plaques are composed of a tangle of regularly ordered fibrillar aggregates called amyloid fibers, a protein fold
Botulinum toxin is a protein and neurotoxin produced by the bacterium Clostridium botulinum. Botulinum toxin can cause botulism, a serious and life-threatening illness in humans and animals. When introduced intravenously in monkeys, type A (Botox Cosmetic) of the toxin exhibits an LD50 of 40–56 ng, type C1 around 32 ng, type D 3200 ng, and type E 88 ng; these are some of the most potent neurotoxins known. Popularly known by one of its trade names, Botox, it is used for various cosmetic and medical procedures. Botulinum can be absorbed from eyes, mucous membranes, respiratory tract or non-intact skin.
Justinus Kerner described botulinum toxin as a "sausage poison" and "fatty poison", because the bacterium that produces the toxin often caused poisoning by growing in improperly handled or prepared meat products. It was Kerner, a physician, who first conceived a possible therapeutic use of botulinum toxin and coined the name botulism (from Latin botulus meaning "sausage"). In 1897, Emile van Ermengem found the producer of the botulin toxin was a bacterium, which he named Clostridium botulinum. In 1928, P. Tessmer Snipe and Hermann Sommer for the first time purified the toxin. In 1949,
The Hfq protein (also known as HF-I protein) encoded by the hfq gene was discovered in 1968 as an Escherichia. coli host factor that was essential for replication of the bacteriophage Qβ. It is now clear that Hfq is an abundant bacterial RNA binding protein which has many important physiological roles. Usually mediated by interacting with Hfq binding sRNA.
In E. coli, Hfq mutants show multiple stress response related phenotypes. The Hfq protein is now known to regulate the translation of two major stress transcription factors ( σS (RpoS) and σE (RpoE) ) in Enterobacteria. It also regulates sRNA in Vibrio cholerae, a specific example being MicX sRNA. In Salmonella typhimurium Hfq has been shown to be an essential virulence factor as its deletion attenuates the ability of S.typhimurium to invade epithelial cells, secrete virulence factors or survive in cultured macrophages. In Salmonella Hfq deletion mutants are also non motile and exhibit chronic activation of the sigma mediated envelope stress response.
Hfq mediates its plieotrophic effects through several mechanisms. It interacts with regulatory sRNA and facilitates their antisense interaction with their targets. Its also acts
Cartilage oligomeric matrix protein is a protein that in humans is encoded by the COMP gene.
The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfide bonds. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Mutations can cause the osteochondrodysplasias pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED).
COMP is a marker of cartilage turnover.
Profilin is an actin-binding protein involved in the dynamic turnover and restructuring of the actin cytoskeleton. It is found in all eukaryotic organisms in most cells. Profilin is important for spatially and temporally controlled growth of actin microfilaments, which is an essential process in cellular locomotion and cell shape changes. This restructuring of the actin cytoskeleton is essential for processes such as organ development, wound healing, and the hunting down of infectious intruders by cells of the immune system.
Profilin also binds sequences rich in the amino acid proline in diverse proteins. While most profilin in the cell is bound to actin, profilins have over 50 different binding partners. Many of those are related to actin regulation, but profilin also seems to be involved in activities in the nucleus such as mRNA splicing.
Profilin binds some variants of membrane phospholipids (Phosphatidylinositol (4,5)-bisphosphate and Inositol triphosphate). The function of this interaction is the sequestration of profilin in an "inactive" form, from where it can be released by action of the enzyme phospholipase C.
Profilin is the major allergen present in birch, grass, and
The acyl carrier protein (ACP) is an important component in both fatty acid and polyketide biosynthesis with the growing chain bound during synthesis as a thiol ester at the distal thiol of a 4'-phosphopantetheine moiety. The protein is expressed in the inactive apo form and the 4'-phosphopantetheine moiety must be post-translationally attached to a conserved serine residue on the ACP by the action of holo-acyl carrier protein synthase (ACPS), a phosphopantetheinyl transferase.
4'-Phosphopantetheine is an essential prosthetic group of several acyl carrier proteins involved in pathways of primary and secondary metabolism including the acyl carrier proteins (ACP) of fatty acid synthases, ACPs of polyketide synthases, and peptidyl carrier proteins (PCP) and aryl carrier proteins (ArCP) of nonribosomal peptide synthetases (NRPS). Phosphopantetheine fulfills two demands in these biosynthetic pathways. First, the intermediates remain covalently linked to the synthases (or synthetases) in an energy-rich linkage. Second, the flexibility and length of the phosphopantetheine chain (approximately 2 nm) allows the covalently tethered intermediates to have access to spatially distinct
Beta-catenin (or β-catenin) is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo. β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway.
When β-catenin was sequenced, it was found to be a member of the armadillo family of proteins. These proteins have multiple copies of the so-called armadillo repeat domain, which is specialized for protein-protein binding. When β-catenin is not associated with cadherins and alpha-catenin, it can interact with other proteins such as ICAT and APC.
β-Catenin is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. β-Catenin also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete.
Recent evidence suggests that β-catenin plays an important role in various aspects of liver biology including liver development (both embryonic and postnatal), liver
In molecular biology, Beta-ketoacyl-ACP synthase EC 220.127.116.11, is an enzyme involved in fatty acid synthesis. It results in the formation of acetoacetyl ACP.
It is the enzyme that catalyses the condensation of malonyl-ACP with the growing fatty acid chain. It is found as a component of a number of enzymatic systems, including fatty acid synthetase (FAS), which catalyses the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH; the multi-functional 6-methysalicylic acid synthase (MSAS) from Penicillium patulum, which is involved in the biosynthesis of a polyketide antibiotic; polyketide antibiotic synthase enzyme systems; Emericella nidulans multifunctional protein Wa, which is involved in the biosynthesis of conidial green pigment; Rhizobium nodulation protein nodE, which probably acts as a beta-ketoacyl synthase in the synthesis of the nodulation Nod factor fatty acyl chain; and yeast mitochondrial protein CEM1. The condensation reaction is a two step process, first the acyl component of an activated acyl primer is transferred to a cysteine residue of the enzyme and is then condensed with an activated malonyl donor with the concomitant release of carbon
Curculin is a sweet protein that was discovered and isolated in 1990 from the fruit of Curculigo latifolia (Hypoxidaceae), a plant from Malaysia. Like miraculin, curculin exhibits taste-modifying activity; however, unlike miraculin, it also exhibits a sweet taste by itself. After consumption of curculin, water and sour solutions taste sweet. The plant is referred to locally as 'Lumbah'.
The active form of curculin is a heterodimer consisting of two monomeric units connected through two disulfide bridges. The mature monomers each consist of a sequence of 114 amino acids, weighing 12.5 kDa (curculin 1) and 12.7 kDa (curculin 2), respectively. While each of the two isoforms is capable of forming a homodimer, these do not possess the sweet taste nor the taste-modifying activity of the heterodimeric form. To avoid confusion, the heterodimeric form is sometimes referred to as "neoculin".
Amino acid sequence of sweet protein curculin adapted from Swiss-Prot biological database of protein sequences.
Curculin is considered to be a high-intensity sweetener, with a reported relative sweetness of 430-2070 times sweeter than sucrose on a weight basis.
A sweet taste, equivalent to a 6.8% or 12%
Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions. Lactoferrin is also present in secondary granules of PMN and is secreted by some acinar cells. Lactoferrin can be purified from milk or produced recombinantly. Human colostrum ("first milk") has the highest concentration, followed by human milk, then cow milk (150 mg/L).
Lactoferrin is one of the components of the immune system of the body; it has antimicrobial activity (bacteriocide, fungicide) and is part of the innate defense, mainly at mucoses. In particular, lactoferrin provides antibacterial activity to human infants. Lactoferrin interacts with DNA and RNA, polysaccharides and heparin, and shows some of its biological functions in complexes with these ligands.
Occurrence of iron-containing red protein in bovine milk was reported as early as in 1939; however, the protein could not be properly characterized because it could not be extracted with sufficient purity. Its first detailed
Neurofibromin 1 also known as neurofibromatosis-related protein NF-1 is a protein that in humans is encoded by the NF1 gene. Mutations in the NF1 gene are associated with neurofibromatosis type I (also known as neurofibromatosis, von Recklinghausen disease, and Watson disease).
NF1 encodes the protein neurofibromin, which appears to be a negative regulator of the ras signal transduction pathway.
NF1 is found within the mammalian postsynapse, where it is known to bind to the NMDA receptor complex. It has been found to lead to deficits in learning, and it is suspected that this is a result of its regulation of the Ras pathway. It is known to regulate the GTPase HRAS, causing the hydrolyzation of GTP and thereby inactivating it. Within the synapse HRAS is known to activate Src, which itself phosphorylates GRIN2A, leading to its inclusion in the synaptic membrane.
NF1 is also known to interact with CASK through syndecan, a protein which is involved in the KIF17/ABPA1/CASK/LIN7A complex, which is involved in trafficking GRIN2B to the synapse. This suggests that NF1 has a role in the transportation of the NMDA receptor subunits to the synapse and its membrane. NF1 is also believed to be
Rab escort protein 1 also known as rab proteins geranylgeranyltransferase component A 1 is an enzyme that in humans is encoded by the CHM gene.
This gene encodes component A of the RAB geranylgeranyl transferase holoenzyme. In the dimeric holoenzyme, this subunit binds unprenylated Rab GTPases and then presents them to the catalytic Rab GGTase subunit for the geranylgeranyl transfer reaction. Rab GTPases need to be geranylgeranyled on either one or two cysteine residues in their C-terminus to localize to the correct intracellular membrane.
CHM (gene) has been shown to interact with RAB1A, RAB7A and RAB3A.
Mutations in this gene are a cause of choroideremia; also known as tapetochoroidal dystrophy (TCD). This X-linked disease is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina.
Aequorin is a photoprotein isolated from luminescent jellyfish (like various Aequorea species, e.g., Aequorea victoria) and a variety of other marine organisms. It was originally isolated from the coelenterate by Osamu Shimomura.
Aequorin is composed of two distinct units, the apoprotein apoaequorin, with an approximate molecular weight of 22 kDa, and the prosthetic group coelenterazine, a luciferin.
The two components of aequorin reconstitute spontaneously, forming the functional protein. The protein bears three EF hand motifs that function as binding sites for Ca ions. When Ca occupies such sites, the protein undergoes a conformational change and converts through oxidation its prosthetic group, coelenterazine, into excited coelenteramide and CO2. As the excited coelenteramide relaxes to the ground state, blue light (wavelength = 469 nm) is emitted.
Since the emitted light can be easily detected with a luminometer, aequorin has become a useful tool in molecular biology for the measurement of intracellular Ca levels. Cultured cells expressing the aequorin gene can effectively synthesize aequorin: however, recombinant expression yields only the apoprotein, therefore it is necessary
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe (S. pombe). It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdc2. It has homologues in many other organisms, including mammals.
The regulation of cell size is critical to ensure functionality of a cell. Besides environmental factors such as nutrients, growth factors and functional load, cell size is also controlled by a cellular cell size checkpoint.
Wee1 is a component of this checkpoint. It is a kinase determining the timepoint of entry into mitosis, thus influencing the size of the daughter cells. Loss of Wee1 function will produce smaller than normal daughter cell, because cell division occurs prematurely.
Its name is derived from the Scottish dialect word wee, meaning small - its discoverer Paul Nurse was working at the University of Edinburgh in Scotland at the time of discovery.
Wee1 inhibits Cdc2 by phosphorylating it on two different sites, Tyr15 and Thr14. Cdc2 is crucial for the cyclin-dependent passage of the various cell cycle
HIV-1 protease (HIV PR) is a retroviral aspartyl protease (retropepsin) that is essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV PR cleaves newly synthesized polyproteins at the appropriate places to create the mature protein components of an infectious HIV virion. Without effective HIV PR, HIV virions remain uninfectious. Thus, mutation of HIV PR’s active site or inhibition of its activity disrupts HIV’s ability to replicate and infect additional cells, making HIV PR inhibition the subject of much pharmaceutical research.
HIV PR's protein structure has been investigated using X-ray crystallography. It exists as a homodimer, with each subunit made up of 99 amino acids. The active site lies between the identical subunits and has the characteristic Asp-Thr-Gly (Asp25, Thr26 and Gly27) sequence common to aspartic proteases. The two Asp25 residues (one from each chain) act as the catalytic residues. According to the mechanism for HIV PR protein cleavage proposed by Jaskolski et al., water acts as a nucleophile, which acts in simultaneous conjunction with a well-placed aspartic acid to hydrolyze the scissile peptide bond. Additionally, HIV PR has two molecular
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle. Coat-proteins, like clathrin, are used to build small vesicles in order to safely transport molecules between cells. The endocytosis and exocytosis of vesicles allows cells to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. On occasion, this mechanism also provides a pathway for raiding pathogens or toxins.
The clathrin triskelion is composed of three clathrin heavy chains and three light chains interacting at their C-termini. The three heavy chains provide the structural backbone of the clathrin lattice, and the three light chains are thought to regulate the formation and disassembly of a clathrin lattice. Clathrin heavy chain is, in concept, broken down into multiple subdomains, starting with the N-terminal domain, followed by
Globulin in human biochemistry is one of the three types of serum proteins, the others being albumin and fibrinogen. Some globulins are produced in the liver, while others are made by the immune system. The term globulin encompasses a heterogeneous group of proteins with typical high molecular weight, and both solubility and electrophoretic migration rates lower than for albumin. The normal concentration in blood is 2.60 to 4.60 g/dl.
It is sometimes used synonymously with globular protein. However, albumin is also a globular protein, but not a globulin. All other serum globular proteins are globulins. Protein electrophoresis is used to categorize globulins into the following four categories:
Globulin exists in various sizes. The lightest being Alpha globulin of the order 92 Kilo Dalton to the heaviest being Gamma Globulin which are about 120 Kilo Dalton. Being the heaviest, the Gamma Globulin are among the slowest to segregate in Electrophoresis. Since they are immunologically active, they are also called as Immunoglobulin.
Non-human globulin proteins exist as well, such as cucurbitin from squashes and vicilin and legumin from legumes and peas, functioning as protein storage
In molecular biology, HMG-CoA synthase EC 18.104.22.168 is an enzyme which catalyzes the reaction in which Acetyl-CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). It is the second reaction in the mevalonate-dependent isoprenoid biosynthesis pathway. HMG-CoA is an intermediate in both cholesterol synthesis and ketogenesis. This reaction is over-activated in patients with diabetes mellitus type 1 if left untreated, due to prolonged insulin deficiency and the exhaustion of substrates for gluconeogenesis and the TCA cycle, notably oxaloacetate. This results in shunting of excess acetyl-CoA into the ketone synthesis pathway via HMG-CoA, leading to the development of diabetic ketoacidosis.
HMG-CoA synthase contains an important catalytic cysteine residue that acts as a nucleophile in the first step of the reaction: the acetylation of the enzyme by acetyl-CoA (its first substrate) to produce an acetyl-enzyme thioester, releasing the reduced coenzyme A. The subsequent nucleophilic attack on acetoacetyl-CoA (its second substrate) leads to the formation of HMG-CoA.
HMG-CoA synthase occurs in eukaryotes, archaea and certain bacteria.
In vertebrates, there are
S100 calcium binding protein B or S100B is a protein of the S-100 protein family.
S100 proteins are localized in the cytoplasm and nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 21q22.3.
S100B is glial-specific and is expressed primarily by astrocytes, but not all astrocytes express S100B. It has been shown that S100B is only expressed by a subtype of mature astrocytes that ensheath blood vessels and by NG2-expressing cells.
This protein may function in neurite extension, proliferation of melanoma cells, stimulation of Ca fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. In the developing CNS it acts as a neurotrophic factor and neuronal survival protein. In the adult organism it is usually elevated due to nervous system damage, which makes it a potential clinical marker. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological,
Gamma subunit of ATP synthase F1 complex forms the central shaft that connects the F0 rotary motor to the F1 catalytic core. F-ATP synthases (also known as F1F0-ATPase, or H(+)-transporting two-sector ATPase) (EC 22.214.171.124) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), nine in mitochondria (A-G, F6, F8).
The human ATP synthase gamma subunit is encoded by the gene ATP5C1.
Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the alpha(3)beta(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis. These ATPases can also work in reverse to hydrolyse ATP to create a proton gradient.
The ATPase F1 complex gamma subunit forms the central shaft that
The C3a receptor also known as complement component 3a receptor 1 (C3AR1) is a G protein-coupled receptor protein involved in the complement system.
Although its official name implies it only binds C3a, it also binds C4a.
Ciliary neurotrophic factor is a protein that in humans is encoded by the CNTF gene.
The protein encoded by this gene is a polypeptide hormone and nerve growth factor whose actions have mainly been studied in the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations including astrocytes. The protein is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. In addition to the predominant monocistronic transcript originating from this locus, the gene is also co-transcribed with the upstream ZFP91 gene. Co-transcription from the two loci results in a transcript that contains a complete coding region for the zinc finger protein but lacks a complete coding region for ciliary neurotrophic factor. CNTF has also been shown to be expressed by cells on the bone surface, and to reduce the activity of bone forming cells, osteoblasts.
In 2001, it was reported that in a human study
Acetylseryltyrosylseryliso...serine is the third chemical name for "Coat Protein, Tobacco mosaic virus, Dahlemense Strain". In its complete form, the chemical name contains 1185 letters and is one of the longest words in English.
The term was published in the American Chemical Society's Chemical Abstracts in 1972, and is considered by some to be the longest real word. It does hold the record for the longest word published in an English language publication in a serious context — that is, for some reason other than to publish a very long word — but there are bigger proteins which would generate larger words if written.
In its complete form, the 1185-letter word is:
The letter combination yl appears in the word 166 times.
While this term may seem daunting in its length, its construction is actually simple because it describes a relatively simple yet lengthy organic molecule. Single-chain organic molecules are constructed of numerous functional groups connected together. The name of any single-chain organic molecule is constructed by simply stringing all the names of the composite functional groups together in the order in which they are found in the molecule itself. All functional
RNA polymerase II (also called RNAP II and Pol II) is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to its promoters and begin transcription.
The eukaryotic core RNA polymerase II was first purified using transcription assays. The purified enzyme has typically 10-12 subunits (12 in humans and yeast) and is incapable of specific promoter recognition. Many subunit-subunit interactions are known.
RPB3 is involved in RNA polymerase II assembly. A subcomplex of RPB2 and RPB3 appears soon after subunit synthesis. This complex subsequently interacts with RPB1. RPB3, RPB5, and RPB7 interact with themselves to form homodimers, and RPB3 and RPB5 together are able to contact all of the other RPB subunits, except RPB9. Only RPB1 strongly binds to RPB5. The RPB1 subunit also contacts RPB7, RPB10, and more weakly but most efficiently with RPB8. Once RPB1 enters the complex, other subunits such as RPB5 and RPB7 can enter, where RPB5 binds to RPB6 and RPB8
Titin ( /ˈtaɪtɪn/), also known as connectin, is a protein that in humans is encoded by the TTN gene. Titin is a giant protein that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured peptide sequences. These domains unfold when the protein is stretched and refold when the tension is removed.
Titin is the largest known protein. Furthermore the gene for titin contains the largest number of exons (363) discovered in any single gene.
Titin is important in the contraction of striated muscle tissues. It connects the Z line to the M line in the sarcomere. The protein contributes to force transmission at the Z line and resting tension in the I band region. It limits the range of motion of the sarcomere in tension, thus contributing to the passive stiffness of muscle. Variations in the sequence of titin between different types of muscle (e.g., cardiac or skeletal) has been correlated with differences in the mechanical properties of these muscles.
The gene is found on chromosome 2 and has 363 exons.
A number of titin isoforms are produced in different striated muscle
Growth Associated Protein 43 also known as GAP43 is a protein that in humans is encoded by the GAP43 gene.
GAP43 has been termed a 'growth' or 'plasticity' protein because it is expressed at high levels in neuronal growth cones during development, during axonal regeneration and is phosphorylated after long-term potentiation (LTP) and after learning. This protein is considered a crucial component of the axon and presynaptic terminal, its null mutation leading to death within days after birth due to axon pathfinding defects.
GAP43 is also referred to as:
GAP43, is a nervous tissue-specific cytoplasmic protein that can be attached to the membrane via a dual palmitoylation sequence on cysteines 3 and 4. This sequence targets GAP43 to lipid rafts. It is a major protein kinase C (PKC) substrate and is considered to play a key role in neurite formation, regeneration, and plasticity. The role of GAP-43 in CNS development is not limited to effects on axons: It is also a component of the centrosome, and differentiating neurons that do not express GAP-43 show mislocalization of the centrosome and mitotic spindles, particularly in neurogenic cell divisions. As a consequence, in the cerebellum,
Cortactin (from “cortical actin binding protein”) is a monomeric protein located in the cytoplasm of cells that can be activated by external stimuli to promote polymerization and rearrangement of the actin cytoskeleton, especially the actin cortex around the cellular periphery. It is present in all cell types. When activated, it will recruit Arp2/3 complex proteins to existing actin microfilaments, facilitating and stabilizing nucleation sites for actin branching. Cortactin is important in promoting lamellipodia formation, invadopodia formation, cell migration, and endocytosis.
In humans, cortactin is encoded by the CTTN gene on chromosome 11.
Cortactin is a thin, elongated monomer that consists of an amino-terminal acidic (NTA) region; 37-residue-long segments that are highly conserved among cortactin proteins of all species and repeated up to 6.5 times in tandem (“cortactin repeats”); a proline-rich region; and an SH3 domain. This basic structure is highly conserved among all species that express cortactin.
Cortactin is activated via phosphorylation, by tyrosine kinases or serine/threonine kinases, in response to extracellular signals like growth factors, adhesion sites, or
High-mobility group protein B1, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.
HMG-1 belongs to high mobility group.
Activated macrophages and monocytes secrete HMGB1 as a cytokine mediator of Inflammation. Antibodies that neutralize HMGB1 confer protection against damage and tissue injury during arthritis, colitis, ischemia, sepsis, endotoxemia, and systemic lupus erythematosis. The mechanism of inflammation and damage is binding to TLR4, which mediates HMGB1-dependent activation of macrophage cytokine release. This positions HMGB1 at the intersection of sterile and infectious inflammatory responses.
HMGB1 has been studied as a DNA vaccine adjuvant.
HMGB1 has to interact P53.
HMGB1 is an intracellular protein that can translocate to the nucleus where it binds DNA and regulates gene expression. It can also be released from cells, in which extracellular form it can bind the inflammatory receptor RAGE (Receptor for Advanced Glycan Endproducts]. Release from cells seems to involve two distinct processes: necrosis, in which case cell membranes are permeabilized and intracellular constituents may diffuse out
Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a noncollagenous protein found in bone and dentin. In humans, the osteocalcin is encoded by the BGLAP gene.
Osteocalcin is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation and is pro-osteoblastic, or bone-building, by nature. It is also implicated in bone mineralization and calcium ion homeostasis. Osteocalcin acts as a hormone in the body, causing beta cells in the pancreas to release more insulin, and at the same time directing fat cells to release the hormone adiponectin, which increases sensitivity to insulin.
Current data suggests a possible role of osteocalcin in male fertility. Research from Columbia University Medical Center proposes that osteocalcin may enhance the synthesis of testosterone, which is a hormone believed to regulate aspects of male fertility. Although these studies were initially performed by only a single laboratory, at least two other groups have independently confirmed the role of osteocalcin in insulin secretion.
As osteocalcin is produced by osteoblasts, it is often used as a marker for the bone formation process. It
Pilin refers to a class of fibrous proteins that are found in pilus structures in bacteria. Bacterial pili are used in the exchange of genetic material during bacterial conjugation, and a short pilus called a fimbrium is used as a cell adhesion mechanism. Although not all bacteria have pili or fimbriae, bacterial pathogens often use their fimbriae to attach to host cells. In gram-negative bacteria, where pili are more common, individual pilin molecules are linked by noncovalent protein-protein interactions, while gram-positive bacteria often have polymerized pilin.
Pilin proteins themselves are α+β proteins characterized by a very long N-terminal alpha helix. Many pilins are post-translationally modified by glycosylation or phosphorylation. The assembly of a complete pilus relies on interactions between the N-terminal helices of the individual monomers. The pilus structure sequesters the helices in the center of the fiber lining a central pore, while antiparallel beta sheets occupy the exterior of the fiber. The exact mechanism of pilus assembly from monomers is not known, although chaperone proteins have been identified for some types of pilin. and specific amino acids required
The drug aprotinin (Trasylol, Bayer), is the bovine version of the small protein basic pancreatic trypsin inhibitor, or BPTI, which inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use was to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; this was confirmed by follow-up studies. Trasylol sales were suspended in May 2008, except for very restricted research use. In February 2012 the European Medicines Agency (EMA) scientific committee reverted its previous standpoint regarding aprotinin, and has recommended that the suspension be lifted.
Aprotinin is a monomeric (single-chain) globular polypeptide derived from bovine lung tissue. It has a molecular
Barnase (a portmanteau of "BActerial" "RiboNucleASE") is a bacterial protein that consists of 110 amino acids and has ribonuclease activity. It is synthesized and secreted by the bacterium Bacillus amyloliquefaciens, but is lethal to the cell when expressed without its inhibitor barstar. The inhibitor binds to and occludes the ribonuclease active site, preventing barnase from damaging the cell's RNA after it has been synthesized but before it has been secreted. The barnase/barstar complex is noted for its extraordinarily tight protein-protein binding, with an on-rate of 10sM.
Barnase has no disulfide bonds, nor does it require divalent cations or non-peptide components to fold. This simplicity, in combination with its reversible folding transition, means that barnase has been extensively studied in order to understand how proteins fold. The folding of barnase has been extensively studied in the laboratory of Alan Fersht, who used it as the test case in developing a method of characterizing protein folding transition states known as phi value analysis.
Barnase catalyzes hydrolysis at diribonucleotide GpN sites. Cleavage occurs in two steps using a general acid-base mechanism: a
Ceruloplasmin (or caeruloplasmin) is a ferroxidase enzyme that in humans is encoded by the CP gene.
Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948. Another protein, hephaestin, is noted for its homology to ceruloplasmin, and also participates in iron and probably copper metabolism.
It is an enzyme (EC 126.96.36.199) synthesized in the liver containing 8 atoms of copper in its structure. Ceruloplasmin carries about 70% of the total copper in human plasma while albumin carries about 15%. The rest is accounted for by macroglobulins. Albumin may be confused at times to have a greater importance as a copper carrier because it binds copper less tightly than ceruloplasmin. Ceruloplasmin exhibits a copper-dependent oxidase activity, which is associated with possible oxidation of Fe (ferrous iron) into Fe (ferric iron), therefore assisting in its transport in the plasma in association with transferrin, which can carry iron only in the ferric state. The molecular weight of human ceruloplasmin is reported to be 151kDa.
Like any other plasma protein, levels drop in patients with hepatic disease due to
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.
The protein encoded by this gene binds receptors such as the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the sem-5 gene of Caenorhabditis elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.
Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types, and so it is not surprising that a targeted gene disruption of Grb2 in mouse is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases,
The M2 protein is a proton-selective ion channel protein, integral in the viral envelope of the influenza A virus. The channel itself is a homotetramer (consists of four identical M2 units), where the units are helices stabilized by two disulfide bonds. It is activated by low pH.
The M2 protein unit consists of three protein domains: (i) the 24 amino acids on the N-terminal end, exposed to the outside environment (the N-terminal methionine is removed from the peptide and the remaining 23 amino acid sequence is also known as the M2 ectodomain, or M2e); (ii) the 22 mostly hydrophobic amino acids in the transmembrane region; and (iii) the 52 amino acids on the C-terminal domain, exposed to the inside of the viral particle. Two different high-resolution structures of truncated forms of M2 have been reported: the structure of a mutated form of the M2 transmembrane region (residues 22-46), as well as a longer version of the protein (residues 18-60) containing the transmembrane region and a segment of the C-terminal domain. The two structures also suggest different binding sites for the adamantane class of anti-influenza drugs. Moreover, the structure of the longer version (residues
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and an inhibitor of p53 transcriptional activation.
The murine double minute (mdm2) oncogene, which codes for the Mdm2 protein, was originally cloned, along with two other genes (mdm1 and mdm3) from the transformed mouse cell line 3T3-DM. Mdm2 overexpression, in cooperation with oncogenic Ras, promotes transformation of primary rodent fibroblasts, and mdm2 expression led to tumor formation in nude mice. The human homologue of this protein was later identified and is sometimes called Hdm2. Further supporting the role of mdm2 as an oncogene, several human tumor types have been shown to have increased levels of Mdm2, including soft tissue sarcomas and osteosarcomas as well as breast tumors. An additional Mdm2 family member, Mdm4 (also called MdmX), has been discovered and is also an important negative regulator of p53.
The key target of Mdm2 is the p53 tumor suppressor. Mdm2 has been identified as a p53
Sic1, a protein, is a stoichiometric inhibitor of Cdk1-Clb (B-type cyclins) complexes in the budding yeast Saccharomyces cerevisiae. Because B-type cyclin-Cdk1 complexes are the drivers of S-phase initiation, Sic1 prevents premature S-phase entry. Multisite phosphorylation of Sic1 is thought to time Sic1 ubiquitination and destruction, and by extension, the timing of S-phase entry.
In the G1 phase of the cell cycle, Sic1 binds tightly to the Cdc28-Clb complex and inhibits it. Low Cdc28-Clb activity leads to the disassembly of the mitotic spindle, the assembly of the prereplicative complex and initiation of bud formation in yeast.
At the START point in the yeast cell cycle, the G1-cyclins Cln3, Cln1 and Cln 2 activate Cdc28. The activated complex will phosphorylate Sic1 at multiple sites which leads to its degradation by the SCF complex. When Sic1 is degraded, the Cdc28-Clb complex is no longer inhibited and the cell can enter the S/M-phase. Thus Sic1 inactivation is essential for transition into S phase (Fig.1).
Cdc28 in complex with B-type cyclin (Cdc28-Clb) phosphorylates Swi5, the transcription factor of Sic1. This promotes the export of Swi5 from the nucleus to the cytoplasm
Thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A), also known as TBXAS1, is an enzyme that, in humans, is encoded by the TBXAS1 gene.
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke. The gene expresses two transcript variants.
Thromboxane synthase inhibitors are used as antiplatelet drugs. Ifetroban is a potent and selective thromboxane receptor antagonist. Dipyridamole antagonizes this receptor too, but has various other mechanisms of antiplatelet activity as well. Picotamide has activity both as a thromboxane synthase inhibitor and as
Wilson disease protein (also called ATP7B, full name ATPase, Cu++ transporting, beta polypeptide) is an ATPase that transports copper.
This gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least two putative copper-binding sites. This protein functions as a monomer, exporting copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Mutations in this gene have been associated with Wilson's disease.
Wilson disease protein has been shown to interact with ATOX1 and GLRX.
Gankyrin is a recently discovered oncoprotein that is a component of the 19S regulatory cap of the proteasome. Structurally, it contains a 33-amino acid ankyrin repeat that forms a series of alpha helices. It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. It also binds closely to the E3 ubiquitin ligase MDM2, which is a regulator of the degradation of p53 and retinoblastoma protein, both transcription factors involved in tumor suppression and found mutated in many cancers. Gankyrin also has an anti-apoptotic effect and is overexpressed in certain types of tumor cells such as hepatocellular carcinoma.
Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to take up glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in adipocytes it is stored as triglycerides.
Insulin stops the use of fat as an energy source by inhibiting the release of glucagon. With the exception of the metabolic disorder diabetes mellitus and metabolic syndrome, insulin is provided within the body in a constant proportion to remove excess glucose from the blood, which otherwise would be toxic. When blood glucose levels fall below a certain level, the body begins to use stored sugar as an energy source through glycogenolysis, which breaks down the glycogen stored in the liver and muscles into glucose, which can then be utilized as an energy source. As a central metabolic control mechanism, its status is also used as a control signal to other body systems (such as amino acid uptake by body cells). In addition, it has several other anabolic effects throughout the body.
When control of insulin levels fails, diabetes
A prion ' in the Scrapie form (PrP) /ˈpriːɒn/ is an infectious agent composed of protein in a misfolded form. This is the central idea of the Prion Hypothesis, which remains debated. This would be in contrast to all other known infectious agents (virus/bacteria/fungus/parasite) which must contain nucleic acids (either DNA, RNA, or both). The word prion, coined in 1982 by Stanley B. Prusiner, is derived from the words protein and infection. Prions are responsible for the transmissible spongiform encephalopathies in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle and Creutzfeldt–Jakob disease (CJD) in humans. All known prion diseases affect the structure of the brain or other neural tissue and all are currently untreatable and universally fatal.
Prions propagate by transmitting a misfolded protein state. When a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the disease-associated, prion form; the prion acts as a template to guide the misfolding of more proteins into prion form. These newly formed prions can then go on to convert more proteins themselves; this triggers a
Tryptophan synthase or tryptophan synthetase is an enzyme that catalyzes the final two steps in the biosynthesis of tryptophan. It is commonly found in Eubacteria, Archaebacteria, Protista, Fungi, and Plantae. However, it is absent from animalia. It is typically found as an α2β2 tetramer. The α subunits catalyze the reversible formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The β subunits catalyze the irreversible condensation of indole and serine to form tryptophan in a pyridoxal phosphate (PLP) dependent reaction. Each α active site is connected to a β active site by a 25 angstrom long hydrophobic channel contained within the enzyme. This facilitates the diffusion of indole formed at α active sites directly to β active sites in a process known as substrate channeling. The active sites of tryptophan synthase are allosterically coupled.
Subunits: Tryptophan synthase typically exists as an α-ββ-α complex. The α and β subunits have molecular masses of 27 and 43 kDa respectively. The α subunit has a TIM barrel conformation. The β subunit has a fold type II conformation and a binding site adjacent to the active site for monovalent
The Huntington gene, also called HTT or HD (Huntington disease) gene, is the IT15 ("interesting transcript 15") gene which codes for a protein called the huntingtin protein. The gene and its product are under heavy investigation as part of Huntington's disease clinical research.
It is variable in its structure, as there are many polymorphisms of the gene that can lead to variable numbers of glutamine residues present in the protein. In its wild-type (normal) form, it contains 6-35 glutamine residues. However, in individuals affected by Huntington's Disease (an autosomal dominant genetic disorder), it contains greater than 36 glutamine residues (highest reported repeat length is about 250). Its commonly used name is derived from this disease, previously the IT15 label was commonly used.
The mass of huntingtin protein is dependent largely on the number of glutamine residues it has, the predicted mass is around 350 kDa. Normal huntingtin is generally accepted to be 3144 amino acids in size. The exact function of this protein is not known, but it plays an important role in nerve cells. Within cells, huntingtin may be involved in signaling, transporting materials, binding proteins and
MuSK (for Muscle-Specific Kinase) is a receptor tyrosine kinase required for the formation of the neuromuscular junction. It is activated by a nerve-derived proteoglycan called agrin.
During development, the growing end of motor neuron axons secrete a protein called agrin. This protein binds to several receptors on the surface of skeletal muscle. The receptor that seems to be required for formation of the neuromuscular junction (NMJ), which comprises the nerve-muscle synapse, is called MuSK (Muscle-specific kinase). MuSK is a receptor tyrosine kinase - meaning that it induces cellular signaling by causing the addition of phosphate molecules to particular tyrosines on itself, and on proteins that bind the cytoplasmic domain of the receptor.
The requirement for MuSK in the formation of the NMJ was demonstrated primarily by mouse ("knockout") studies. In mice that are deficient for either agrin or MuSK, the neuromuscular junction does not form. Many other proteins also comprise the NMJ, and are required to maintain its integrity. For example, MuSK also binds a protein called "downstream-of-tyrosine-kinase-7" (Dok-7). Dok-7's PTB domain binds phosphorylated MuSK, which acts to
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein. It is soluble and monomeric.
Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains osmotic pressure, among other functions.
Albumin is synthesized in the liver as preproalbumin, which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin.
The reference range for albumin concentrations in blood is 3.4 to 5.4 g/dL. It has a serum half-life of approximately 20 days. It has a molecular mass of 67 kDa.
The gene for albumin is located on chromosome 4 and mutations in this gene can result in anomalous proteins. The human albumin gene is 16,961 nucleotides long from the putative 'cap' site to the first poly(A) addition site. It is split into 15 exons that are symmetrically placed within the 3 domains thought to have arisen by triplication of a single primordial domain.
Plasma albumin is a component of liver function tests (LFTs), but may
The Actin assembly-inducing protein (ActA) is a protein encoded and used by Listeria monocytogenes to propel itself through a mammalian host cell. ActA is a bacterial surface protein comprising a membrane-spanning region. In a mammalian cell the bacterial ActA interacts with the Arp2/3 complex and actin monomers to induce actin polymerization on the bacterial surface generating an actin comet tail. The gene encoding ActA is named actA or prtB.
As soon as L. monocytogenes bacteria are ingested by humans, they get internalized into intestinal epithelium cells and rapidly try to escape their internalization vacuole. In the cytosol they start to polymerize actin on their surface by the help of the ActA protein. It has been shown that ActA is not only necessary but also sufficient to induce motility of bacteria in the absence of other bacterial factors.
ActA was discovered by analysing lecithinase-negative Tn917-lac Listeria mutants because of the phenotype that they were unable to spread from cell to cell. These mutant bacteria still escaped from the phagosomes as efficiently as wild-type bacteria and multiplied within the infected cells but they were not surrounded by actin like
Ataxin-1 is a protein that in humans is encoded by the ATXN1 gene.
The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. ADCAs include spinocerebellar ataxia type 1 (previously also known as olivopontocerebellar atrophy type 1). Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to
Calmodulin (CaM) (an abbreviation for CALcium-MODULated proteIN) is a calcium-binding messenger protein expressed in all eukaryotic cells. CaM is a multifunctional intermediate messenger protein that transduces calcium signals by binding calcium ions and then modifying its interactions with various target proteins.
CaM mediates many crucial processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. CaM is expressed in many cell types and can have different subcellular locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes. Many of the proteins that CaM binds are unable to bind calcium themselves, and use CaM as a calcium sensor and signal transducer. CaM can also make use of the calcium stores in the endoplasmic reticulum, and the sarcoplasmic reticulum. CaM can undergo post-translational modifications, such as phosphorylation, acetylation, methylation and proteolytic cleavage, each of which has potential to modulate its actions.
Calmodulin is a small, highly conserved protein approximately 148 amino acids long (16706
Chlorotoxin is a 36-amino acid peptide found in the venom of the deathstalker scorpion (Leiurus quinquestriatus) which blocks small-conductance chloride channels. The fact that chlorotoxin binds preferentially to glioma cells has allowed the development of new methods, that still are under investigation, for the treatment and diagnosis of several types of cancer.
Chlorotoxin can be purified from crude leiurus, which belongs to scorpion toxin super family.
Chlorotoxin is a small toxin and at pH 7 is highly positive charged. It is a peptide consisting of 30–35 amino acids and 4 disulfide bonds; eight cysteine amino acids among its total number of amino acids present in the structure of this peptide are connected with four disulfide bonds. Chlorotoxin has a considerable sequence homology to the class of small insectotoxins.
Chlorotoxin is the first reported high-affinity peptide ligand for Cl channels and it blocks small conductance chloride channels. Each chloride channel can be closed by only one ligand molecule.
Using a recombinant chlorotoxin it was demonstrated that chlorotoxin specifically and selectively interacts with MMP-2 isoforms which are specifically upregulated in
High-mobility group protein B2 also known as high-mobility group protein 2 (HMG-2) is a protein that in humans is encoded by the HMGB2 gene.
This gene encodes a member of the non-histone chromosomal high-mobility group protein family. The proteins of this family are chromatin-associated and ubiquitously distributed in the nucleus of higher eukaryotic cells. In vitro studies have demonstrated that this protein is able to efficiently bend DNA and form DNA circles. These studies suggest a role in facilitating cooperative interactions between cis-acting proteins by promoting DNA flexibility. This protein was also reported to be involved in the final ligation step in DNA end-joining processes of DNA double-strand breaks repair and V(D)J recombination.
3-hydroxy-3-methylglutaryl-coenzyme A reductase is an enzyme that in humans is encoded by the HMGCR gene.
HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor as well as oxidized species of cholesterol. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis.
Proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein), also known as PRG2, is a protein which in humans is encoded by the PRG2 gene.
The protein encoded by this gene is the predominant constituent of the crystalline core of the eosinophil granule. High levels of the proform of this protein are also present in placenta and pregnancy serum, where it exists as a complex with several other proteins including pregnancy-associated plasma protein A (PAPPA), angiotensinogen (AGT), and C3dg. This protein may be involved in antiparasitic defense mechanisms as a cytotoxin and helminthotoxin, and in immune hypersensitivity reactions. It is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases.
PRG2 is a 117-residue protein that predominates in eosinophil granules. It is a potent enzyme against helminths and is toxic towards bacteria and mammalian cells in vitro. The eosinophil major basic protein also causes the release of histamine from mast cells and basophils, activates neutrophils and alveolar macrophages, and is directly implicated in epithelial cell damage, exfoliation and bronchospasm in
The Nuclear receptor related 1 protein (NURR1) also known as NR4A2 (nuclear receptor subfamily 4, group A, member 2) is a protein that in humans is encoded by the NR4A2 gene. NURR1 is a member of the nuclear receptor family of intracellular transcription factors.
NURR1 plays a key role in the maintenance of the dopaminergic system of the brain. Mutations in this gene have been associated with disorders related to dopaminergic dysfunction, including Parkinson's disease, schizophrenia, and manic depression. Misregulation of this gene may be associated with rheumatoid arthritis. Four transcript variants encoding four distinct isoforms have been identified for this gene. Additional alternate splice variants may exist, but their full length nature has not been determined.
Research has been conducted on Nurr1’s role in inflammation, and may provide important information in treating disorders caused by dopaminergic neuron disease. Inflammation in the CNS can result from activated microglia (macrophage analogs for the central nervous system) and other pro-inflammatory factors, such as bacterial lipopolysaccharide (LPS). LPS binds to toll like receptors (TLR), which induces inflammatory
Thymidylate synthetase (EC 188.8.131.52) is the enzyme used to generate thymidine monophosphate (dTMP), which is subsequently phosphorylated to thymidine triphosphate for use in DNA synthesis and repair.
The following reaction catalyzed by thymidylate synthetase:
By means of reductive methylation, deoxyuridine monophosphate (dUMP) and N5,N10-methylene tetrahydrofolate are together used to form dTMP, yielding dihydrofolate as a secondary product.
This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer. The enzyme is essential for regulating the balanced supply of the 4 DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death. The enzyme is an important target for certain chemotherapeutic drugs. Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain. A cysteine residue is involved in the catalytic
Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.
This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun and stimulates CRE-dependent transcription. The protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. Additional transcript variants have been identified but their biological validity has not been determined.
The gene atf2 is located at human chromosome 2q32. The protein ATF-2 has 505 amino acids. Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton. ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and JNK. ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol ester has been demonstrated.
Several studies implicate
Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate S phase and mitosis. It is part of the pre-replicative complex (pre-RC) and is required for loading Mini Chromosome Maintenance (MCM) proteins onto the DNA, an essential step in the initiation of DNA synthesis. In addition, it’s a member of the family of AAA+ ATPases and highly associated to Orc1p.
Cdc6p is an ATP binding protein and a member of the pre-replicative complex (pre-RC) together with the origin recognition complex (ORC), Cdt1 and the MCM complex (containing MCM2-7p). Cdc6p assembles after ORC in an ATP dependent manner and is required for loading MCM proteins onto the DNA. Reconstruction of electron microscope images showed that the ORC-Cdc6p complex forms a ring-shaped structure with similar dimensions to those of ring-shaped MCM helicase. It is thought that the Cdc6p-Cdt1 complex uses ATP hydrolysis to thread DNA through the central hole of the MCM doughnut. Mutations in the
DNA-binding protein inhibitor ID-4 is a protein that in humans is encoded by the ID4 gene.
Transcription factors containing a basic helix-loop-helix (bHLH) motif regulate expression of tissue-specific genes in a number of mammalian and insect systems. DNA-binding activity of the bHLH proteins is dependent on formation of homo- and/or heterodimers. Dominant-negative HLH proteins encoded by Id-related genes, such as ID4, also contain the HLH-dimerization domain but lack the DNA-binding basic domain. Consequently, Id proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins (Pagliuca et al., 1995).[supplied by OMIM]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP gene.
MTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein. Protein disulfide isomerase (PDI) completes the heterodimeric microsomal triaglyceride transfer protein, which has been shown to play a central role in lipoprotein assembly. Mutations in MTP can cause abetalipoproteinemia.
Apoprotein B48 on chylomicra and Apoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.
Click on genes, proteins and metabolites below to link to respective articles.
The dopamine receptor D4 is a G protein-coupled receptor encoded by the DRD4 gene. As with other dopamine receptor subtypes, the D4 receptor is activated by the neurotransmitter dopamine. It is linked to many neurological and psychiatric conditions including schizophrenia, Parkinsons disease, bipolar disorder, addictive behaviors, and eating disorders such as anorexia nervosa, bulimia nervosa and binge eating.
It is also a target for drugs which treat schizophrenia and Parkinson disease. The D4 receptor is considered to be D2-like in which the activated receptor inhibits the enzyme adenylate cyclase, thereby reducing the intracellular concentration of the second messenger cyclic AMP.
The human protein is coded by the DRD4 on chromosome 11 located in 11p15.5.
There are slight variations (mutations/polymorphisms) in the human gene:
Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, schizophrenia, and the personality trait of novelty seeking.
The 48-base pair VNTR in exon 3 range from 2 to 11 repeats. The frequency of the alleles varies greatly between populations,
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related is a protein that in humans is encoded by the HMG20B gene.
HMG20B has been shown to interact with KIF4A, HDAC1, Histone deacetylase 2, PHF21A, RCOR1 and BRCA2.
Kv7.2 (KvLQT2) is a potassium channel protein coded for by the gene KCNQ2.
It is associated with benign familial neonatal epilepsy.
The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Nexin is a proteinous inter-doublet linkage that prevents microtubules in the outer layer of axonemes from movement with respect to each other. Otherwise vesicular transport proteins such as dynein would dissolve the whole structure.
Nitric oxide synthase, inducible is an enzyme that in humans is encoded by the NOS2 gene.
Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing of this gene results in two transcript variants encoding different isoforms.
Nitric oxide synthase 2A has been shown to interact with Caveolin 1 and Rac2.
Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In humans, protein S is encoded by the PROS1 gene. In 1979, researchers in Seattle, Washington first discovered protein S and arbitrarily named it after the city of its discovery.
The best characterized function of Protein S is its role in the anti coagulation pathway, where it functions as a cofactor to Protein C in the inactivation of Factors Va and VIIIa. Only the free form has cofactor activity.
Protein S can bind to negatively charged phospholipids via the carboxylated GLA domain. This property allows Protein S to function in the removal of cells which are undergoing apoptosis. Apoptosis is a form of cell death that is used by the body to remove unwanted or damaged cells from tissues. Cells which are apoptotic (i.e. in the process of apoptosis) no longer actively manage the distribution of phospholipids in their outer membrane and hence begin to display negatively charged phospholipids, such as phosphatidyl serine, on the cell surface. In healthy cells, an
Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene.
The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with this protein, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus.
STAT2 has been shown to interact with MED14, CREB-binding protein, SMARCA4, STAT1, IFNAR2, IFNAR1 and ISGF3G.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Troponin is a complex of three regulatory proteins (troponin C, troponin I and troponin T) that is integral to muscle contraction in skeletal and cardiac muscle, but not smooth muscle.
Discussions of troponin often pertain to its functional characteristics and/or to its usefulness as a diagnostic marker for various heart disorders.
Troponin is attached to the protein tropomyosin and lies within the groove between actin filaments in muscle tissue. In a relaxed muscle, tropomyosin blocks the attachment site for the myosin crossbridge, thus preventing contraction. When the muscle cell is stimulated to contract by an action potential, calcium channels open in the sarcoplasmic membrane and release calcium into the sarcoplasm. Some of this calcium attaches to troponin which causes it to change shape, exposing binding sites for myosin (active sites) on the actin filaments. Myosin binding to actin forms cross bridges and contraction (cross bridge cycling) of the muscle begins.
Troponin is found in both skeletal muscle and cardiac muscle, but the specific versions of troponin differ between types of muscle. The main difference is that the TnC subunit of troponin in skeletal muscle has four
Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein that in humans is encoded by the RARRES2 gene.
Retinoids exert biologic effects such as potent growth inhibitory and cell differentiation activities and are used in the treatment of hyperproliferative dermatological diseases. These effects are mediated by specific nuclear receptor proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. RARRES1, RARRES2 (this gene), and RARRES3 are genes whose expression is upregulated by the synthetic retinoid tazarotene. RARRES2 is thought to act as a cell surface receptor.
Chemerin is a chemoattractant protein that acts as a ligand for the G protein-coupled receptor CMKLR1 (also known as ChemR23). Chemerin is a 14 kDa protein secreted in an inactive form as prochemerin and is activated through cleavage of the C-terminus by inflammatory and coagulation serine proteases.
Chemerin was found to stimulate chemotaxis of dendritic cells and macrophages to the site of inflammation.
In humans, chemerin mRNA is highly expressed in white
Lanosterol synthase is an oxidosqualene cyclase (OSC) enzyme that converts (S)-2,3-oxidosqualene ((S)-2,3-epoxysqualene) to a protosterol cation and finally to lanosterol. Lanosterol is a key four-ringed intermediate in cholesterol biosynthesis. In humans, lanosterol synthase is encoded by the LSS gene.
In eukaryotes, lanosterol synthase is an integral monotopic protein associated with the cytosolic side of the endoplasmic reticulum. Some evidence suggests that the enzyme is a soluble (non-membrane bound) protein in the few prokaryotes that produce it.
Due to the enzyme’s role in cholesterol biosynthesis, there is interest in lanosterol synthase inhibitors as potential cholesterol reducing drugs, to complement existing statins.
Though some data on the mechanism has been obtained by the use of suicide inhibitors, mutagenesis studies, and homology modeling, it is still not fully understood how the enzyme catalyzes the formation of lanosterol.
Initial Epoxide Protonation and Ring Opening: Before the acquisition of the protein’s X-ray crystal structure, site-directed mutagenesis was used to determine residues key to the enzyme’s catalytic activity. It was determined that an aspartic
aP2 (adipocyte Protein 2) is a carrier protein for fatty acids that is primarily expressed in adipocytes and macrophages. aP2 is also called fatty acid binding protein 4 (FABP4). Blocking this protein either through genetic engineering or drugs has the possibility of treating heart disease, diabetes, asthma, obesity, and fatty liver disease.
CREB-binding protein, also known as CREBBP or CBP, is a protein that in humans is encoded by the CREBBP gene. The CREB protein carries out its function by activating transcription, where interaction with transcription factors is managed by one or more CREB domains: the nuclear receptor interaction domain (RID), the CREB and MYB interaction domain (KIX), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). The CREB protein domains, KIX, TAZ1 and TAZ2, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53.
This gene is ubiquitously expressed and is involved in the transcriptional coactivation of many different transcription factors. First isolated as a nuclear protein that binds to cAMP-response element-binding protein (CREB), this gene is now known to play critical roles in embryonic development, growth control, and homeostasis by coupling chromatin remodeling to transcription factor recognition. The protein encoded by this gene has intrinsic histone acetyltransferase activity and also acts as a scaffold to stabilize additional protein interactions with the transcription complex.
Fatty acid synthase (FAS) is an enzyme that in humans is encoded by the FASN gene.
Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis. It is not a single enzyme but a whole enzymatic system composed of two identical 272 kDa multifunctional polypeptides, in which substrates are handed from one functional domain to the next.
Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids.
Fatty acids are aliphatic acids fundamental to energy production and storage, cellular structure and as intermediates in the biosynthesis of hormones and other biologically important molecules. They are synthesized by a series of decarboxylative Claisen condensation reactions from acetyl-CoA and malonyl-CoA. Following each round of elongation the beta keto group is reduced to the fully saturated carbon chain by the sequential action of a ketoreductase (KR), dehydratase (DH), and enol reductase (ER). The growing fatty acid chain is carried between these active sites while attached covalently to the phosphopantetheine prosthetic group of an acyl carrier protein (ACP), and is
Human Herpes Virus (HHV) Infected Cell Polypeptide 0 (ICP0) is a protein, encoded by the DNA of herpes viruses. It is produced by herpes viruses during the earliest stage of infection, when the virus has recently entered the host cell; this stage is known as the immediate-early or α ("alpha") phase of viral gene expression. During these early stages of infection, ICP0 protein is synthesized and transported to the nucleus of the infected host cell. Here, ICP0 promotes transcription from viral genes, disrupts structures in the nucleus known as nuclear dots or promyelocytic leukemia (PML) nuclear bodies, and alters the expression of host and viral genes in combination with a neuron specific protein. At later stages of cellular infection, ICP0 relocates to the cell cytoplasm to be incorporated into new virion particles.
ICP0 was identified as an immediate-early polypeptide product of Herpes simplex virus-1 (HSV-1) infection in 1976. The gene, in HSV-1, from which ICP0 is produced is known as HSV-1 α0 ("alpha zero"), Immediate Early (IE) gene 1, or simply as the HSV-1 ICP0 gene. The HSV-1 ICP0 gene was characterized and sequenced in 1986. This sequence predicted a 775 amino acid
The proteolytic enzyme mucunain is a substance in the tissues of certain legumes of the genus Mucuna, especially velvet bean (M. pruriens). In these species the mucunain is found in stiff hairs, or trichomes, covering the seed pods.
When the hairs rub off and come in contact with skin they cause severe itching and irritation. The hairs are small enough to be carried airborne by the wind and are painful if they come in contact with the eyes. Walking shoeless on soil where hairy Mucuna grows can cause irritation in the feet.
The hairs have also been consumed as an herbal remedy for intestinal worms, sometimes mixed with honey for easier swallowing. The pod hairs also contain an amount of serotonin, which, when applied to the skin with mucunain, increases the pruritic qualities of the chemical.
Phorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the PMAIP1 gene, and is also known as Noxa.
Noxa (Latin for damage) is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members can form hetero- or homodimers, and they act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The expression of Noxa is regulated by the tumor suppressor p53, and Noxa has been shown to be involved in p53-mediated apoptosis.
Noxa has been shown to interact with MCL1, BCL2-like 1 and Bcl-2.
Polyketide synthases (PKSs) are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis.
The PKS genes for a certain polyketide are usually organized in one operon in bacteria and in gene clusters in eukaryotes.
PKSs can be classified into three groups:
Type I PKSs are further subdivided:
Iterative PKSs (IPKSs) can be still further subdivided:
Each type I polyketide-synthase module consists of several domains with defined functions, separated by short spacer regions. The order of modules and domains of a complete polyketide-synthase is as follows (in the order N-terminus to C-terminus):
The polyketide chain and the starter groups are bound with their carboxy functional group to the SH groups of the ACP and the KS domain through a thioester linkage: R-C(=O)OH + HS-protein R-C(=O)S-protein + H2O.
The growing chain is handed over from one thiol group to the next by trans-acylations and is released at the end by hydrolysis or by cyclization (alcoholysis or aminolysis).
The Tamm–Horsfall glycoprotein (THP) also known as uromodulin is a glycoprotein that in humans is encoded by the UMOD gene. Up to 150 mg/day of uromodulin may be excreted in the urine, making it the most abundant protein in normal urine.
The human UMOD gene is located on chromosome 16. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same isoform.
THP is a GPI-anchored glycoprotein. It is not derived from blood plasma but is produced by the thick ascending limb of the loop of Henle of the mammalian kidney. While the monomeric molecule has a MW of approximately 68 kDa, it is physiologically present in urine in large aggregates of up to several million Da. When this protein is concentrated at low pH, it forms a gel. Tamm–Horsfall protein is a high abundant protein in mammalian urine. A recent list of the most abundant proteins in urine has been published (table 1 of), where uromodulin represents the 16th most concentrated one (results based on MSMS determinations). It is the matrix of urinary casts derived from the secretion of renal tubular
Guanine monphosphate synthetase, (EC 184.108.40.206) also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.
In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP.
In enzymology, a GMP synthetase (glutamine-hydrolysing) (EC 220.127.116.11) is an enzyme that catalyzes the chemical reaction
The 4 substrates of this enzyme are ATP, xanthosine 5'-phosphate, L-glutamine, and H2O, whereas its 4 products are AMP, diphosphate, GMP, and L-glutamate.
This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds carbon-nitrogen ligases with glutamine as amido-N-donor. The systematic name of this enzyme class is xanthosine-5'-phosphate:L-glutamine amido-ligase (AMP-forming). Other names in common use include GMP synthetase (glutamine-hydrolysing), guanylate synthetase
Micrococcal Nuclease (S7 Nuclease or MNase) is an endo-exonuclease that preferentially digests single-stranded nucleic acids.The rate of cleavage is 30 times greater at the 5' side of A or T than at G or C and results in the production of mononucleotides and oligonucleotides with terminal 3'-phosphates. The enzyme is also active against double-stranded DNA and RNA and all sequences will be ultimately cleaved.
The enzyme has a molecular weight of 16.9kDa.
The pH optimum is reported as 9.2. The enzyme activity is strictly dependent on Ca and the pH optimum varies according to Ca concentration. The enzyme is therefore easily inacitvated by EGTA.
This enzyme is the extracellular nuclease of Staphylococcus aureus. Two strains, V8 and Foggi, yield almost identical enzymes. A common source is E.coli cells carrying a cloned nuc gene encoding Staphylococcus aureus extracellular nuclease (micrococcal nuclease).
The 3-dimensional structure of micrococcal nuclease (then called Staphyloccal nuclease) was solved very early in the history of protein crystallography, in 1969, deposited as now-obsolete Protein Data Bank file 1SNS. Higher-resolution, more recent crystal structures are available for
Mitochondrial trifunctional protein is a protein which catalyzes several reactions in beta oxidation. It has two subunits:
The three functions are long-chain 3-hydroxy acyl-coenzyme A dehydrogenase, 2-enoyl coenzyme A (CoA) hydratase, and long-chain 3-ketoacyl CoA thiolase.
Disorders are associated with:
p53 (also known as protein 53 or tumor protein 53), is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation.
The name p53 is in reference to its apparent molecular mass: It runs as a 53-kilodalton (kDa) protein on SDS-PAGE. But, based on calculations from its amino acid residues, p53's mass is actually only 43.7 kDa. This difference is due to the high number of proline residues in the protein, which slows its migration on SDS-PAGE, thus making it appear heavier than it actually is. This effect is observed with p53 from a variety of species, including humans, rodents, frogs, and fish.
p53 is also known as:
In humans, p53 is encoded by the TP53 gene located on the short arm of chromosome 17 (17p13.1). The gene spans 20 kb, with a non-coding exon 1 and a very long first intron of 10 kb.The coding sequence contains five regions showing a high degree of conservation in
Paxillin is a signal transduction adaptor protein discovered in 1990 in the laboratory of Keith Burridge. The C-terminal region of paxillin contains four LIM domains that target paxillin to focal adhesions, it is presumed through a direct association with the cytoplasmic tail of beta-integrin. The N-terminal region of paxillin is rich in protein–protein interaction sites. The proteins that bind to paxillin are diverse and include protein tyrosine kinases, such as Src and FAK, structural proteins, such as vinculin and actopaxin, and regulators of actin organization, such as COOL/PIX and PKL/GIT. Paxillin is tyrosine-phosphorylated by FAK and Src upon integrin engagement or growth factor stimulation, creating binding sites for the adapter protein Crk.
VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing.
Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the formation of the circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity is restricted mainly to cells of the vascular endothelium, although it does have effects on a limited number of other cell types (e.g. stimulation monocyte/macrophage migration). In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF also enhances microvascular permeability and is sometimes referred to as vascular permeability factor.
All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated through transphosphorylation. The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin-like domains, a single
ATPases (or ATP synthases) are membrane-bound enzyme complexes/ion transporters that combine ATP synthesis and/or hydrolysis with the transport of protons across a membrane. ATPases can harness the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.
Some ATPases work in reverse, using the energy from the hydrolysis of ATP to create a proton gradient.
There are different types of ATPases, which can differ in function (ATP synthesis and/or hydrolysis), structure (F-, V- and A-ATPases contain rotary motors) and in the type of ions they transport.
The alpha and beta (or A and B) subunits are found in the F1, V1, and A1 complexes of F-, V- and A-ATPases, respectively, as well as flagellar ATPase and the termination factor Rho. The F-ATPases (or F1F0-ATPases), V-ATPases (or V1V0-ATPases) and A-ATPases (or A1A0-ATPases) are composed of two linked complexes: the F1, V1 or A1 complex contains the catalytic core that synthesizes/hydrolyses ATP, and the F0, V0 or A0 complex that forms the membrane-spanning pore. The F-, V- and A-ATPases all contain rotary motors, one that drives proton translocation across the
Binding immunoglobulin protein (BiP) also known as 78 kDa glucose-regulated protein (GRP-78) or heat shock 70 kDa protein 5 (HSPA5) is a HSP70 molecular chaperone located in the lumen of the endoplasmic reticulum (ER) that binds newly-synthesized proteins as they are translocated into the ER, and maintains them in a state competent for subsequent folding and oligomerization. BiP is also an essential component of the translocation machinery, as well as playing a role in retrograde transport across the ER membrane of aberrant proteins destined for degradation by the proteasome. BiP is an abundant protein under all growth conditions, but its synthesis is markedly induced under conditions that lead to the accumulation of unfolded polypeptides in the ER. In humans, BiP is encoded by the HSPA5 gene.
When Chinese hamster K12 cells are starved of glucose, the synthesis of several proteins, called glucose-regulated proteins (GRPs), is markedly increased. Hendershot et al. pointed out that one of these, GRP78 (HSPA5), also referred to as 'immunoglobulin heavy chain-binding protein' (BiP), is a member of the heat-shock protein-70 (HSP70) family and is involved in the folding and assembly of
Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. Cyclin D protein is anywhere from 155 (in zebra mussel) to 477 (in Drosophila) amino acids in length.
Once the cells reach a critical cell size (and if no mating partner is present in yeast) and if growth factors and mitogens (for multicellular organism) or nutrients (for unicellular organism) are present, cells enter the cell cycle. In general, all stages of the cell cycle are chronologically separated in humans and are triggered by cyclin-Cdk complexes which are periodically expressed and partially redundant in function. Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The abundance of cyclins is generally regulated by protein synthesis and degradation through an APC/c dependent pathway.
Cyclin D is one of the major cyclins produced in terms of its functional importance. It interacts with four Cdks: Cdk2, 4, 5, and 6. In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle
Low density lipoprotein receptor-related protein associated protein 1 also known as LRPAP1 or RAP is a chaperone protein which in humans is encoded by the LRPAP1 gene.
LRPAP1 is involved with trafficking of certain members of the LDL receptor family including LRP1 and LRP2. It is a glycoprotein that binds to the alpha-2-macroglobulin receptor, as well as to other members of the low density lipoprotein receptor family. It acts to inhibit the binding of all know ligands for these receptors, and may prevent receptor aggregation and degradation in the endoplasmic reticulum, thereby acting as a molecular chaperone. It may be under the regulatory control of calmodulin, since it is able to bind calmodulin and be phosphorylated by calmodulin-dependent kinase II.
LDL-receptor-related protein associated protein has been shown to interact with LRP2.
This article incorporates text from the public domain Pfam and InterPro IPR010483
The retinoblastoma protein (abbreviated pRb, RB or RB1) is a tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases.
pRb belongs to the pocket protein family, whose members have a pocket for the functional binding of other proteins. Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomaviruses, bind and inactivate pRb, this can lead to cancer.
In humans, the protein is encoded by the RB1 gene located on 13q14.1-q14.2. If both alleles of this gene are mutated early in life, the protein is inactivated and results in development of retinoblastoma cancer, hence the name Rb. It is not known why an eye cancer results from a mutation in a gene that is important all over the body.
Two forms of retinoblastoma were noticed: a bilateral, familial form and a unilateral, sporadic form. Sufferers of the former were 6 times more likely to develop other types of cancer later in life. This highlighted the fact
Shq1p is a protein involved in the rRNA processing pathway. It was discovered by Pok Yang in the Chanfreau laboratory at UCLA. Depletion of Shq1p has led to decreased level of various H/ACA box snoRNAs (H/ACA box snoRNAs are responsible for pseuduridylation of pre-rRNA) and certain pre-rRNA intermediates.
During the synthesis of eukaryotic ribosomes, four mature ribosomal RNAs (the 5S, 5.8S, 18S, and 25S) must be synthesized. Three of these rRNAs (5.8S, 18S, and 25S) come from a single pre-rRNA known as the 35S. Although many of the intermediates in this rRNA processing pathway have been identified in the last thirty years, there are still a number of proteins involved in this process whose specific function is unknown.
Shq1, a protein thought to play a role in the stabilization and/or production of box H/ACA snoRNA, is still uncharacterized. It has been proposed that Shq1, along with Naf1p, is involved in the initial steps of the biogenesis of H/ACA box snoRNPs (box H/ACA snoRNAs form complexes with proteins, thereby forming snoRNPs) because of its association with certain snoRNP proteins during the snoRNP’s maturation, while showing very little association with the mature snoRNP
Glial fibrillary acidic protein (GFAP) is a protein that in humans is encoded by the GFAP gene.
Glial fibrillary acidic protein is an intermediate filament (IF) protein that is expressed by numerous cell types of the central nervous system (CNS) including astrocytes, and ependymal cells. GFAP has also been found to be expressed in glomeruli and peritubular fibroblasts taken from rat kidneys Leydig cells of the testis in both hamsters and humans, human keratinocytes, human osteocytes and chondrocytes and stellate cells of the pancreas and liver in rats. First described in 1971, GFAP is a type III IF protein that maps, in humans, to 17q21. It is closely related to its non-epithelial family members, vimentin, desmin, and peripherin, which are all involved in the structure and function of the cell’s cytoskeleton. GFAP is thought to help to maintain astrocyte mechanical strength, as well as the shape of cells but its exact function remains poorly understood, despite the number of studies using it as a cell marker. Glial fibrllary acidic protein was named and first isolated and characterized by Lawrence F. Eng in 1969. A review documenting its importance in neuropathology and
Nitric oxide synthases (EC 18.104.22.168) (NOSs) are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule, having a vital role in many biological processes. It is the intercellular signal that controls vascular tone (hence blood pressure), insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis (growth of new blood vessels) and in the development of nervous system. It is believed to function as a retrograde neurotransmitter and hence is likely to be important in learning. Nitric oxide signalling is mediated in mammals by the calcium/calmodulin controlled isoenzymes eNOS (endothelial NOS) and nNOS (neuronal NOS); the inducible isoform iNOS is involved in immune response, binds calmodulin at all physiologically relevant concentrations, and produces large amounts of NO as a defense mechanism. It is the proximate cause of septic shock and may play a role in many diseases with an autoimmune etiology.
The canonical reaction catalyzed by NOS is:
NOS isoforms catalyze many other leak and side reactions such as superoxide production at the expense of NADPH, so this stoichiometry is not
Odorant-binding proteins are abundant small soluble proteins secreted in the nasal mucus of many animal species and in the sensillar lymph of chemosensory sensilla of insects.
The olfactory receptors of terrestrial animals exist in an aqueous environment, yet detect odorants that are primarily hydrophobic. The aqueous solubility of hydrophobic odorants is greatly enhanced via odorant-binding proteins, which exist in the extracellular fluid surrounding the odorant receptors. This family is composed of pheromone binding proteins (PBP), which are male-specific and associate with pheromone-sensitive neurons and general-odorant-binding proteins (GOBP).
These proteins were initially identified on the basis of their ability to bind with moderate-affinity radioactively labeled odorants.
Sodium channel protein type 4 subunit alpha is a protein that in humans is encoded by the SCN4A gene.
The Nav1.4 voltage-gated sodium channel is encoded by the SCN4A gene. Mutations in the gene are associated with hypokalemic periodic paralysis, hyperkalemic periodic paralysis, paramyotonia congenita, and potassium-aggravated myotonia.
Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. It is expressed in skeletal muscle, and mutations in this gene have been linked to several myotonia and periodic paralysis disorders.
In hypokalemic periodic paralysis, arginine residues making up the voltage sensor of Nav1.4 are mutated. The voltage sensor comprises the S4 alpha helix of each of the four transmembrane domains (I-IV) of the protein, and contains basic residues that only allow entry of the positive sodium ions at appropriate membrane voltages by blocking or opening the channel pore. In
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.
Some such enzymes are integral membrane proteins (anchored within biological membranes), and move solutes across the membrane, typically against their concentration gradient. These are called transmembrane ATPases.
Transmembrane ATPases import many of the metabolites necessary for cell metabolism and export toxins, wastes, and solutes that can hinder cellular processes. An important example is the sodium-potassium exchanger (or Na/KATPase), which establishes the ionic concentration balance that maintains the cell potential. Another example is the hydrogen potassium ATPase (H/KATPase or gastric proton pump) that acidifies the contents of the stomach.
Besides exchangers, other categories of transmembrane ATPase include co-transporters and pumps (however, some exchangers are also pumps). Some of these, like the Na/KATPase,
Cell division protein kinase 6 is an enzyme that in humans is encoded by the CDK6 gene.
It is regulated by Cyclin D.
The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb.
Cyclin-dependent kinase 6 was shown to interact with CDKN2C, P16, PPM1B, Cyclin D3, Cyclin D1 and PPP2CA.
Cystathionine-β-synthase, also known as CBS, is an enzyme (EC 22.214.171.124) that in humans is encoded by the CBS gene. It catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine:
CBS uses the cofactor pyridoxal-phosphate (PLP) and can be allosterically regulated by effectors such as the ubiquitous cofactor S-adenosyl-L-methionine (adoMet). This enzyme belongs to the family of lyases, to be specific, the hydro-lyases, which cleave carbon-oxygen bonds.
CBS is a multidomain enzyme composed of an N-terminal enzymatic domain and two CBS domains. The CBS gene is the most common locus for mutations associated with homocystinuria.
The systematic name of this enzyme class is L-serine hydro-lyase (adding homocysteine; L-cystathionine-forming). Other names in common use include:
The human enzyme cystathionine β-synthase is a tetramer and comprises 551 amino acids with a subunit molecular weight of 63 kDa. It displays a modular organization of three modules with the N-terminal heme domain followed by a core that contains the PLP cofactor. The cofactor is deep in the heme domain and is linked by a Schiff base. A Schiff base is a functional group containing a C=N
The heat shock proteins hslV and hslU (also known as clpQ and clpY respectively) are expressed in many bacteria such as E. coli in response to cell stress. The hslV protein is a protease and the hslU protein is an ATPase; the two form a symmetric assembly of four stacked rings, consisting of an hslV dodecamer bound to an hslU hexamer, with a central pore in which the protease and ATPase active sites reside. The hslV protein degrades unneeded or damaged proteins only when in complex with the hslU protein in the ATP-bound state. The complex is thought to resemble the hypothetical ancestor of the proteasome, a large protein complex specialized for regulated degradation of unneeded proteins in eukaryotes, many archaea, and a few bacteria.
Both proteins are encoded on the same operon within the bacterial genome. Unlike many eukaryotic proteasomes, which have several different peptide substrate specificities, hslV has a specificity similar to that of chymotrypsin; hence it is inhibited by proteasome inhibitors that specifically target the chymotrypsin site in eukaryotic proteasomes. Although the HslVU complex is stable on its own, some evidence suggests that the complex is formed in vivo
Integrin-linked kinase (ILK) is a 59kDa protein originally identified while conducting a yeast-two hybrid screen with integrin β1 as the bait protein (Hannigan et al., 1996). Since its discovery, ILK has been associated with multiple cellular functions including cell migration, cell proliferation, cell-adhesions, and signal transduction.
Transduction of extracellular matrix signals through integrins influences intracellular and extracellular functions, and appears to require interaction of integrin cytoplasmic domains with cellular proteins. Integrin-linked kinase (ILK), interacts with the cytoplasmic domain of beta-1 integrin. This gene was initially described to encode a serine/threonine protein kinase with 4 ankyrin-like repeats, which associates with the cytoplasmic domain of beta integrins and acts as a proximal receptor kinase regulating integrin-mediated signal transduction. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.. Recent results showed that ILK contains 5 ankyrin-like repeats, and that the C-terminal kinase domain is actually a pseudo-kinase with adaptor function .
In 2008, ILK was found to localize to the
Rieske proteins are iron-sulfur protein (ISP) components of cytochrome bc1 complexes and cytochrome b6f complexes which were first discovered and isolated by John S. Rieske and co-workers in 1964. It is a unique [2Fe-2S] cluster in that one of the two Fe atoms is coordinated by two histidine residues rather than two cysteine residues. They have since been found in plants, animals, and bacteria with widely ranging electron reduction potentials from -150 to +400 mV.
Ubiquinol-cytochrome-c reductase (also known as bc1 complex or complex III) is an enzyme complex of bacterial and mitochondrial oxidative phosphorylation systems. It catalyses the oxidoreduction of the mobile redox components ubiquinol and cytochrome c, generating an electrochemical potential, which is linked to ATP synthesis.
The complex consists of three subunits in most bacteria, and nine in mitochondria: both bacterial and mitochondrial complexes contain cytochrome b and cytochrome c1 subunits, and an iron-sulphur 'Rieske' subunit, which contains a high potential 2Fe-2S cluster. The mitochondrial form also includes six other subunits that do not possess redox centres. Plastoquinone-plastocyanin reductase (b6f
Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and alpha-actinin.
Integrin receptors are involved in the attachment of adherent cells to the extracellular matrix and of lymphocytes to other cells. In these situations, talin codistributes with concentrations of integrins in the plasma membrane. Furthermore, in vitro binding studies suggest that integrins bind to talin, although with low affinity. Talin also binds with high affinity to vinculin, another cytoskeletal protein concentrated at points of cell adhesion. Finally, talin is a substrate for the calcium-ion activated protease, calpain II, which is also concentrated at points of cell–substratum contact.
Talin consists of a large C-terminal rod domain that contains bundles of alpha helices and an N-terminal FERM (band 4.1, ezrin, radixin, and moesin) domain with
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. This is the process by which T cells are attracted to specific tissue and organ targets. Many forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells. A few individuals carry a mutation known as CCR5-Δ32 in the CCR5 gene, protecting them against these strains of HIV.
In humans, the CCR5 gene that encodes the CCR5 protein is located on the short (p) arm at position 21 on chromosome 3. Certain populations have inherited the Delta 32 mutation resulting in the genetic deletion of a portion of the CCR5 gene. Homozygous carriers of this mutation are resistant to M-tropic strains of HIV-1 infection.
The CCR5 protein belongs to the beta chemokine receptors family of integral membrane proteins. It is a G protein-coupled receptor which functions as a chemokine receptor in the CC chemokine group.
The natural chemokine ligands that bind to this receptor are RANTES (a chemotactic cytokine protein also known as CCL5) and macrophage inflammatory protein (MIP) 1α and 1β (also
Fas-Associated protein with Death Domain (FADD) is an adaptor molecule that bridges the Fas-receptor, and other death receptors, to caspase-8 through its death domain to form the death-inducing signaling complex (DISC) during apoptosis.
The protein encoded by this gene is an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals. Through its C-terminal death domain, this protein can be recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and, thus, it participates in the death signaling initiated by these receptors. Interaction of this protein with the receptors unmasks the N-terminal effector domain(see structural image on the right side) of this protein, which allows it to recruit caspase-8, and thereby activate the cysteine protease cascade. Knockout studies in mice also suggest the importance of this protein in early T cell development.
FADD has been shown to interact with ABCA1, CFLAR, PEA15, NACA, Caspase 10, Caspase 8, Fas receptor, Fas ligand, DAP3, DEDD, TNFRSF1A, TRADD, TNFRSF10B and MBD4.
Heme oxygenase 2 is an enzyme that in humans is encoded by the HMOX2 gene.
Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 (this enzyme) belong to the heme oxygenase family.
CD207, langerin (Cluster of Differentiation 207) is a protein which in humans is encoded by the CD207 gene. Langerin is a type II transmembrane cell surface receptor produced by Langerhans cells.
The protein encoded by this gene is expressed in Langerhans cells which are immature dendritic cells of the epidermis and mucosa. It is also expressed in several other dendritic cell types including dermal CD103+ DCs and splenic CD8+ DCs. Langerin is localized in the Birbeck granules, organelles present in the cytoplasm of Langerhans cells and consisting of superimposed and zippered membranes. It is a C-type lectin with mannose binding specificity, and it has been proposed that mannose binding by this protein leads to internalization of antigen into Birbeck granules and providing access to a nonclassical antigen-processing pathway.
Langerin on mucosal Langerhans cells of the human genital epithelium binds to HIV-1 and subsequently internalizes it into Birbeck granules to be degraded.
Neuregulin 1 or NRG1 is a protein that in humans is encoded by the NRG1 gene. NRG1 is one of four proteins in the neuregulin family that act on the EGFR family of receptors. Neuregulin 1 is produced in numerous isoforms by alternative splicing, which allows it to perform a wide variety of functions. It is essential for the normal development of the nervous system and the heart.
Neuregulin 1 (NRG1) was originally identified as a 44-kD glycoprotein that interacts with the NEU/ERBB2 receptor tyrosine kinase to increase its phosphorylation on tyrosine residues. It is known that an extraordinary variety of different isoforms are produced from the NRG1 gene by alternative splicing. These isoforms include heregulins (HRGs), glial growth factors (GGFs) and sensory and motor neuron-derived factor (SMDF). They are tissue-specific and differ significantly in their structure. The HRG isoforms all contain immunoglobulin (Ig) and epidermal growth factor-like (EGF-like) domains. GGF and GGF2 isoforms contain a kringle-like sequence plus Ig and EGF-like domains; and the SMDF isoform shares only the EGF-like domain with other isoforms. The receptors for all NRG1 isoforms are the ERBB family of
Retinol binding protein 4, plasma, also known as RBP4, is protein that in humans is encoded by the RBP4 gene.
This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, which prevents its loss by filtration through the kidney glomeruli. A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells.
Retinol-binding protein 4 has recently been described as an adipokine that contributes to insulin resistance in the AG4KO mouse model. It is secreted by adipocytes, and can act as a signal to other cells, when there is a decrease in plasma glucose concentration.
Cystathionine-beta-synthase, also known as CBS, is a human gene.
The protein encoded by this gene is involved in the transsulfuration pathway. The first step of this pathway, from homocysteine to cystathionine, is catalyzed by this protein. CBS deficiency can cause homocystinuria which affects many organs and tissues, including the eyes and the skeletal, vascular and central nervous systems.
Glial cell-derived neurotrophic factor, also known as GDNF is a protein that, in humans, is encoded by the GDNF gene. GDNF is a small protein that potently promotes the survival of many types of neurons.
This gene encodes a highly conserved neurotrophic factor. The recombinant form of this protein was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. Mutations in this gene may be associated with Hirschsprung's disease.
The most prominent feature of GDNF is its ability to support the survival of dopaminergic and motorneurons.
These neuronal populations die in the course of Parkinson's disease and amyotrophic lateral sclerosis (ALS). GDNF also regulates kidney development and spermatogenesis,
The Nav1.5 is a sodium ion channel protein that in humans is encoded by the SCN5A gene. Mutations in the gene are associated with long QT syndrome type 3 (LQT3), Brugada syndrome, primary cardiac conduction disease and idiopathic ventricular fibrillation.
The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. The encoded protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene are a cause of long QT syndrome type 3 (LQT3), an autosomal dominant cardiac disease. Alternative splicing results in two transcript variants encoding separate isoforms which differ by a single amino acid. Mutation nomenclature has been assigned with respect to the longer isoform.
Nav1.5 has been shown to interact with Syntrophin, alpha 1.
Nav1.5 interacts with ankyrin-G through a nine-amino acid ankyrin-G binding sequence.
Villin is a 92.5 kDa tissue-specific actin-binding protein associated with the actin core bundle of the brush border. Villin contains multiple gelsolin-like domains capped by a small (8.5 kDa) "headpiece" at the C-terminus consisting of a fast and independently-folding three-helix bundle that is stabilized by hydrophobic interactions. The headpiece domain is a commonly studied protein in molecular dynamics due to its small size and fast folding kinetics and short primary sequence.
Villin is made up of seven domains, six homologous domains make up the N-terminal core and the remaining domain makes up the C-terminal cap. Villin contains three phosphatidylinositol 4,5-biphosphate (PIP2) binding sites, one of which is located at the head piece and the other two in the core. The core domain is approximately 150 amino acid residues grouped in six repeats. On this core is an 87 residue, hydrophobic, C-terminal headpiece The headpiece (HP67) is made up of a compact, 70 amino acid folded protein at the C-terminus. This headpiece contains an F-actin binding domain. Residues K38, E39, K65, 70-73:KKEK, G74, L75 and F76 surround a hydrophobic core and are believed to be involved in the binding
Kv7.3 (KvLQT3) is a potassium channel protein coded for by the gene KCNQ3.
It is associated with benign familial neonatal epilepsy.
The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and one of two related proteins encoded by the KCNQ2 and KCNQ5 genes, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2).
KvLQT3 has been shown to interact with KCNQ5.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Bacteriorhodopsin is a protein used by Archaea, the most notable one being Halobacteria. It acts as a proton pump; that is, it captures light energy and uses it to move protons across the membrane out of the cell. The resulting proton gradient is subsequently converted into chemical energy.
Bacteriorhodopsin is an integral membrane protein usually found in two-dimensional crystalline patches known as "purple membrane", which can occupy up to nearly 50% of the surface area of the archaeal cell. The repeating element of the hexagonal lattice is composed of three identical protein chains, each rotated by 120 degrees relative to the others. Each chain has seven transmembrane alpha helices and contains one molecule of retinal buried deep within, the typical structure for retinylidene proteins.
It is the retinal molecule that changes its conformation when absorbing a photon, resulting in a conformational change of the surrounding protein and the proton pumping action. It is covalently linked to Lys216 in the chromophore by Schiff base action. After photoisomerization of the retinal molecule, Asp85 becomes a proton acceptor of the donor proton from the retinal molecule. This releases a
Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion.
Disintegrins work by countering the blood clotting steps, inhibiting the clumping of platelets. They interact with the beta-1 and -3 families of integrins receptors. Integrins are cell receptors involved in cell–cell and cell–extracellular matrix interactions, serving as the final common pathway leading to aggregation via formation of platelet–platelet bridges, which are essential in thrombosis and haemostasis. Disintegrins contain an RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequence motif that binds specifically to integrin IIb-IIIa receptors on the platelet surface, thereby blocking the binding of fibrinogen to the receptor–glycoprotein complex of activated platelets. Disintegrins act as receptor antagonists, inhibiting aggregation induced by ADP, thrombin, platelet-activating factor and collagen. The role of disintegrin in preventing blood coagulation renders it of medical interest, particularly with regard to its use as an anti-coagulant.
Disintegrins from different snake species have been
Enterostatin is a pentapeptide derived from a proenzyme in the gastrointestinal tract called procolipase. It reduces food intake, in particular fat intake, when given peripherally or into the brain.
Enterostatin is created in the intestine by pancreatic procolipase, the other colipase serving as an obligatory cofactor for pancreatic lipase during fat digestion. Enterostatin can be created in the gastric mucosa and the mucosal epithelia in the small intestine. An increased high fat diets will cause the procolipase gene transcription and enterostatin to release into the gastrointestinal lumen. Enterostatin appears in the lymph and circulation after a meal. Enterostatin has been shown to selectively reduce fat intake during a normal meal. The testing has been successful with different species.
The signaling pathway of the peripheral mechanism uses afferent vagal to hypothalamic centers. The central responses are mediated through a pathway including serotonergic and opioidergic components. Inveterately, enterostatin cuts fat intake, bodyweight, and body fat. This reaction may involve multiple metabolic effects of enterostatin, which include a decrease of insulin secretion, a growth in
Transforming growth factor-beta 2 (TGF-β2) is a secreted protein known as a cytokine that performs many cellular functions and has a vital role during embryonic development (alternative names: Glioblastoma-derived T-cell suppressor factor, G-TSF, BSC-1 cell growth inhibitor, Polyergin, Cetermin). It is an extracellular glycosylated protein. It is known to suppress the effects of interleukin dependent T-cell tumors. There are two named isoforms of this protein, created by alternative splicing of the same gene.
TRAF-interacting protein is a protein that in humans is encoded by the TRAIP gene.
This gene encodes a protein that contains an N-terminal RING finger motif and a putative coiled-coil domain. A similar murine protein interacts with TNFR-associated factor 1 (TRAF1), TNFR-associated factor 2 (TRAF2), and cylindromatosis. The interaction with TRAF2 inhibits TRAF2-mediated nuclear factor kappa-B, subunit 1 activation that is required for cell activation and protection against apoptosis.
TRAF interacting protein has been shown to interact with FLII, TRAF1 and TRAF2.
Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the TRIM5 gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates species-specific, early block to retrovirus infection.
TRIM5α is composed of 493 amino acids that is found in the cells of most primates. TRIM5α is an intrinsic immune factor important in the innate immune defense against retroviruses, along with the APOBEC family of proteins, tetherin and TRIM22.
TRIM5α belongs to the TRIM protein family (TRIM stands for TRIpartite Motif); this family was first identified by Reddy in 1992 as the proteins that contain a RING finger zinc binding domain, a B-box zinc binding domain, followed by a coiled-coil region. TRIM5α bears the C-terminal PRY-SPRY or B30.2 domain in addition to the other domains.
When a retrovirus enters a host cell’s cytoplasm, it undergoes processes such as capsid uncoating and reverse transcription. TRIM5 present in the cytoplasm recognizes motifs within the capsid proteins and interferes with the uncoating process, therefore preventing successful reverse transcription and transport to the nucleus of
Ubiquitin is a small regulatory protein that has been found in almost all tissues (ubiquitously) of eukaryotic organisms. It directs proteins to compartments in the cell, including the proteasome which destroys and recycles proteins.
Ubiquitin can be attached to proteins and label them for destruction. This discovery won the Nobel Prize for chemistry in 2004.
Ubiquitin tags can also direct proteins to other locations in the cell, where they control other protein and cell mechanisms.
Ubiquitin (originally, ubiquitous immunopoietic polypeptide) was first identified in 1975 as an 8.5-kDa protein of unknown function expressed in all eukaryotic cells. The basic functions of ubiquitin and the components of the ubiquitination pathway were elucidated in the early 1980s at Fox Chase Cancer Center by Aaron Ciechanover, Avram Hershko, and Irwin Rose for which the Nobel Prize in Chemistry was awarded in 2004.
The ubiquitylation system was initially characterised as an ATP-dependent proteolytic system present in cellular extracts. A heat-stable polypeptide present in these extracts, ATP-dependent proteolysis factor 1 (APF-1), was found to become covalently attached to the model protein
Vitronectin also known as VTN is a protein that in humans is encoded by the VTN gene.
The protein encoded by this gene is a member of the pexin family. Vitronectin is an abundant glycoprotein found in serum and the extracellular matrix and promotes cell adhesion and spreading, inhibits the membrane-damaging effect of the terminal cytolytic complement pathway, and binds to several serpin serine protease inhibitors. It is a secreted protein and exists in either a single chain form or a clipped, two chain form held together by a disulfide bond. Vitronectin has been speculated to be involved in hemostasis and tumor malignancy.
Vitronectin is a 75 kDa glycoprotein, consisting of 459 amino acid residues. About one-third of the protein's molecular mass is composed of carbohydrates. On occasion, the protein is cleaved after arginine 379, to produce two-chain vitronectin, where the two parts are linked by a disulfide bond. No high resolution structure has been determined experimentally yet, except for the N-terminal domain.
The protein consists of three domains:
Several structures has been reported for the Somatomedin B domain. The protein was initially crystallized in complex with one of
ATP synthase (EC 126.96.36.199) is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate (ATP). ATP is the most commonly used "energy currency" of cells from most organisms. It is formed from adenosine diphosphate (ADP) and inorganic phosphate (Pi), and needs energy.
The overall reaction sequence is: ATP synthase + ADP + Pi → ATP Synthase + ATP
Energy is often released in the form of protium or H+, moving down an electrochemical gradient, such as from the lumen into the stroma of chloroplasts or from the inter-membrane space into the matrix in mitochondria.
Located within the mitochondria, ATP synthase consists of 2 regions
The nomenclature of the enzyme suffers from a long history. The F1 fraction derives its name from the term "Fraction 1" and FO (written as a subscript letter "o", not "zero") derives its name from being the oligomycin binding fraction. Oligomycin, an antibiotic, is able to inhibit the FO unit of ATP synthase.
These functional regions consist of different protein subunits - refer to tables.
The F1 particle is large and can be seen in the transmission electron microscope by negative staining. These are particles of
Hydramacin-1 is a type of antimicrobial protein. It was first isolated and reproduced in 2008 from cells of the freshwater hydroid Hydra. Only around 60 amino acids long, the protein is unique both in amino acid sequence and tertiary structure, prompting its classification in a new family of proteins, the macins. The protein's unusual structure is most likely a reason for the compound's potent antimicrobial qualities.
Antimicrobial tests determined that the protein has an antibacterial effect against both Gram-positive and Gram-negative bacteria. This potent antibacterial activity extended to known multi-resistant strains of pathogenic bacteria, such as those of Klebsiella oxytoca. Functionally, the protein causes bacterial cells to clump together and aggregate, changing the morphology of the bacterial aggregations it creates. This results in a disruption of the structure of the bacterial membrane.
Hydramacin-1 was first isolated from epithelial cells of the cnidarian Hydra, a small (almost-microscopic) freshwater animal related to corals, sea anemones and jellyfish. Like other members of the Phylum Cnidaria, Hydra possesses specialized defensive epithelial cells called cnidocytes
N-ethylmaleimide-sensitive factor, also known as NSF or N-ethylmaleimide sensitive fusion proteins, is an enzyme which in humans is encoded by the NSF gene.
NSF is a homohexameric AAA ATPase involved in membrane fusion. NSF is ubiquitously found in the cytoplasm of eukaryotic cells. It is a central component of the cellular machinery in the transfer of membrane vesicles from one membrane compartment to another. During this process, SNARE proteins on two joining membranes (usually a vesicle and a target membrane such as the plasma membrane) form a tight complex. This aids fusion of the vesicle with the target membrane. It has been proposed that the role of NSF is to undo these SNARE complexes once membrane fusion has occurred, using the hydrolysis of ATP as an energy source, allowing the dissociated SNAREs to be recycled for reuse in further rounds of membrane fusion. This proposal remains controversial, however. Recent work indicates that the ATPase function of NSF does not function in recycling of vesicles but rather functions in the act of fusing vesicles with the plasma membrane.
Because neuronal function depends on the release of neurotransmitters at a synapse — a process in
Neurotrophin-3 is a protein that in humans is encoded by the NTF3 gene.
The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 was the third neurotrophic factor to be characterized, after nerve growth factor (NGF) and BDNF (Brain Derived Neurotrophic Factor).
Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis.
NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB - see below).
Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.
RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:
The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues.
RasGAP contains one SH3 domain and two SH2 domains, a PH domain, and a GAP domain.
RAS p21 protein activator 1 has been shown to interact with SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor,
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.
Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular compartments and body tissues. It also acts as a plasma carrier by non-specifically binding several hydrophobic steroid hormones and as a transport protein for hemin and fatty acids. Too much serum albumin in the body can be harmful.
Major contributors to oncotic pressure (known also as colloid osmotic pressure) of plasma; carriers for various substances.
Albumin is a soluble, monomeric protein which comprises about one-half of the blood serum protein. Albumin functions primarily as a carrier protein for steroids, fatty acids, and thyroid hormones and plays a role in stabilizing extracellular fluid volume. Albumin is a globular un-glycosylated serum protein of molecular weight 65,000. Albumin is synthesized in the liver as preproalbumin which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in
Sonic hedgehog homolog (SHH) is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog (DHH) and Indian hedgehog (IHH). SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example of a morphogen as defined by Lewis Wolpert's French flag model—a molecule that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration. SHH remains important in the adult. It controls cell division of adult stem cells and has been implicated in development of some cancers.
The hedgehog gene (hh) was first identified in the classic Heidelberg screens of Christiane Nusslein-Volhard, as published in 1980. These screens, which led to her winning the Nobel Prize in 1995 along with developmental geneticist Edward B. Lewis, identified genes that control the segmentation pattern of Drosophila melanogaster (fruit fly) embryos. The hh loss of function mutant phenotype causes the embryos to be
Transformation/transcription domain-associated protein, also known asTRRAP, is a protein that in humans is encoded by the TRRAP gene. TRRAP belongs to the phosphatidylinositol 3-kinase-related kinase protein family.
TRRAP is an adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which in turn is responsible for epigenetic transcription activation. TRRAP a central role in MYC (c-Myc) transcription activation, and also participates in cell transformation by MYC. It is required for p53/TP53-, E2F1-, and E2F4-mediated transcription activation. It is also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes.
TRRAP is also required for the mitotic checkpoint and normal cell cycle progression. The MRN complex (composed of MRE11, RAD50, and NBS1) is involved in the detection and repair of DNA double-strand breaks (DSBs). TRRAP associates with the MRN complex and when TRRAP is removed, the complex shows reduced cDNA end-joining activity. Hence, TRRAP may function as a link between DSB repair and chromatin remodeling.
Model organisms have been
CD155 (cluster of differentiation 155) also known as the poliovirus receptor is a protein that in humans is encoded by the PVR gene.
CD155 is a Type I transmembrane glycoprotein in the immunoglobulin superfamily. Commonly known as Poliovirus Receptor (PVR) due to its involvement in the cellular poliovirus infection in primates, CD155's normal cellular function is in the establishment of intercellular adherens junctions between epithelial cells. The role of CD155 in the immune system is unclear, though it may be involved in intestinal humoral immune responses.
The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication.
CD155 is a transmembrane protein with 3 extracellular immunoglobulin-like domains, D1-D3, where D1 is recognized by the virus.
Low resolution structures of CD155 complexed with poliovirus have been obtained using electron microscopy while a high resolution structures of the ectodomain D1 and D2 of CD155 were
Cyclin B is a member of the cyclin family.
Cyclin B is a mitotic cyclin. The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle until mitosis, where they fall abruptly due to degradation of cyclin B (Cdk1 is constitutively present). The complex of Cdk and cyclin B is called maturation promoting factor or mitosis promoting factor (MPF).
Cyclin B is necessary for the progression of the cells into and out of M phase of the cell cycle.
At the end of S phase the phosphatase cdc25c dephosphorylates tyrosine15 and this activates the cyclin B/CDK1 complex. Upon activation the complex is shuttled to the nucleus where it serves to trigger for entry into mitosis. However, if DNA damage is detected alternative proteins are activated which results in the inhibitory phosphorylation of cdc25c and therefore cyclinB/CDK1 is not activated. In order for the cell to progress out of mitosis, the degradation of cyclin B is necessary.
The cyclin B/CDK1 complex also interacts with a variety of other key proteins and pathways which regulate cell growth and progression of mitosis. Cross-talk between many of these pathways links cyclin B levels
Disrupted in schizophrenia 1 is a protein that is encoded by the DISC1 gene in humans. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, clinical depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research.
In 1970, researchers performing cytogenetic research on a group of juvenile offenders in Scotland found an abnormal translocation in chromosome 1 of one of the boys, who also displayed characteristics of an affective psychological disorder. After this initial observation, the boy's family was studied and it was found that 34 out of 77 family members displayed the same translocation. According to the
Enaptin (UniProt name: SYNE1_HUMAN; accession number: Q8NF91) is a nuclear envelope protein found in human myocytes and synapses, which is made up of 8,797 amino acids. Post-translational amino acid modifications can be possible. Enaptin is involved in the maintenance of nuclear organization and structural integrity, tethering the cell nucleus to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. Enaptin has a remarkable structure with a coiled alpha-helical region and a large beta-sheet region in the upper part and at least four alpha-helices spliced together, indicating the similarity with collagen. The structural integrity of Enaptin can be shown by determining whether the protein forms a condensed supramolecule.
The molecular weight of the mature protein is approximately 1,011,041.95 Da, and it has a theoretical pI of 5.38 . The following results do not take into account any annotated post-translational modification. The protein's chemical formula is C44189H71252N12428O14007S321. It has a theoretical Instability Index (II) of 51.63, indicating that it would be unstable in a test tube. The protein's in vivo half-life, the time it takes
Fel d 1 is a protein that in cats is encoded by the CH1 (chain 1/Fel d 1-A) and CH2 (chain 2/Fel d 1-B) genes.
Fel d 1, produced largely in cat saliva and sebaceous glands, is the primary allergen present on cats and kittens. The protein is of an unknown function to the animal but causes an IgG or IgE reaction in sensitive humans (either as an allergic or asthmatic response). Removal of soft surfaces in the home (carpet, furniture), frequent washings of bed linens, HEPA filters and even washing cats has been proven to reduce the amounts of Fel d 1 present in the home.
Neutered males produce Fel d 1 in levels similar to females (both intact and spayed females produce Fel d 1 in similar levels). Even though females and neutered males produce Fel d 1 in lower levels, they still produce enough to cause allergic symptoms in sensitive individuals.
The complete quaternary structure of Fel d 1 has been determined. The allergen is a tetrameric glycoprotein consisting of two disulphide-linked heterodimers of [chains 1 and 2. Fel d 1 chains 1 and 2 share structural similarity with uteroglobin, a secretoglobin superfamily member; chain 2 is a glycoprotein with N-linked oligosaccharides. Both
Flagellin is a globular protein that arranges itself in a hollow cylinder to form the filament in bacterial flagellum. It has a mass of about 30,000 to 60,000 daltons. Flagellin is the principal substituent of bacterial flagellum, and is present in large amounts on nearly all flagellated bacteria.
The structure of flagellin is responsible for the helical shape of the flagellar filament, which is important for its proper function.
The N- and C-termini of flagellin form the inner core of the flagellin protein, and is responsible for flagellin's ability to polymerize into a filament. The central portion of the protein makes up the outer surface of the flagellar filament. While the termini of the protein is quite similar among all bacterial flagellins, the central portion is wildly variable.
Mammals often have acquired immune responses (T-cell and antibody responses) to flagellated bacterium, which occur frequently to flagellar antigens. Some bacteria are able to switch between multiple flagellin genes in order to evade this response.
The propensity of the immune response to flagellin may be explained by two facts:
In addition, a 22-amino acid sequence (flg22) of the conserved
Glycogen synthase (UDP-glucose-glycogen glucosyltransferase) is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers.
It is a glycosyltransferase enzyme (EC 188.8.131.52) that catalyses the reaction of UDP-glucose and (1,4-α-D-glucosyl)n to yield UDP and (1,4-α-D-glucosyl)n+1.
In other words, this enzyme converts excess glucose residues one by one into a polymeric chain for storage as glycogen. Its presence in the bloodstream is highest in the 30 to 60 minutes following intense exercise. It is a key enzyme in glycogenesis.
Much research has been done on glycogen degradation through studying the structure and function of glycogen phosphorylase, the key regulatory enzyme of glycogen degradation. On the other hand, much less is known about the structure of glycogen synthase, the key regulatory enzyme of glycogen synthesis. The crystal structure of glycogen synthase from Agrobacterium tumefaciens, however, has been determined at 2.3 A resolution. In its asymmetric form, glycogen synthase is found as a dimer, whose monomers are composed of two Rossmann-fold domains. This structural property, among others, is shared
Indian hedgehog homolog (Drosophila), also known as IHH, is a protein which in humans is encoded by the IHH gene.
The Indian Hedgehog protein is one of three proteins in the mammalian hedgehog family, the others being desert hedgehog (DHH) and Sonic hedgehog (SHH). It is involved in chondrocyte differentiation, proliferation and maturation especially during endochondral ossification. It regulates its effects by feedback control of parathyroid hormone-related peptide (PTHrP).
Parathyroid hormone/parathyroid hormone-related peptide receptor also known as parathyroid hormone 1 receptor (PTH1R) is a protein that in humans is encoded by the PTH1R gene. PTH1R functions as a receptor for parathyroid hormone (PTH) and for parathyroid hormone-related protein (PTHrP), also called parathyroid hormone-like hormone (PTHLH).
This "classical" PTH receptor is expressed in high levels in bone and kidney and regulates calcium ion homeostasis through activation of adenylate cyclase and phospholipase C. In bone, it is expressed on the surface of osteoblasts. When the receptor is activated through PTH binding, osteoblasts express RANKL (Receptor Activator of Nuclear Factor kB Ligand), which binds to RANK (Receptor Activator of Nuclear Factor kB) on osteoclasts. This turns on osteoclasts to ultimately increase the resorption rate.
It is a member of the secretin family of G protein-coupled receptors. The activity of this receptor is mediated by Gs G proteins which activate adenylyl cyclase. Besides, they also activate phosphatidylinositol-calcium second messenger system.
Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC),
Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase δ in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome. It is an example of a DNA clamp.
The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome.
PCNA was originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle. Part of the protein was sequenced and that sequence was used to allow isolation of a cDNA clone. PCNA helps hold DNA polymerase delta (Pol δ) to DNA. PCNA is clamped to DNA through the action of replication factor C (RFC), which is a heteropentameric member of the AAA+
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic (inactive) protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death, and maintaining the permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolytically inactivating proteins Factor Va and Factor VIIIa. APC is classified as a serine protease as it contains a residue of serine in its active site. In humans, protein C is encoded by the PROC gene, which is found on chromosome 2.
The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond. The protein C zymogen is activated when it binds to thrombin, another protein heavily involved in coagulation, and protein C's activation is greatly promoted by the presence of thrombomodulin and endothelial protein C receptors (EPCRs). Because of EPCR's role, activated protein C is found primarily near endothelial cells (i.e., those that make up the walls
Stathmin 1/oncoprotein 18, also known as STMN1, is a highly conserved 17 kDa protein. Its function as an important regulatory protein of microtubule dynamics has been well characterized. Eukaryotic microtubules are one of three major components of the cell’s cytoskeleton. They are highly dynamic structures that continuously alternate between assembly and disassembly. Stathmin performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cell’s needs. Microtubules are cylindrical polymers of α,β-tubulin. Their assembly is in part determined by the concentration of free tubulin in the cytoplasm.
At low concentrations of free tubulin, the growth rate at the microtubule ends is slowed and results in an increased rate of depolymerization (disassembly).
Stathmin interacts with two molecules of dimeric α,β-tubulin to form a tight ternary complex called the T2S complex. One mole of stathmin binds to two moles of tubulin dimers through the stathmin-like domain (SLD). When stathmin sequesters tubulin into the T2S complex, tubulin becomes non-polymerizable. Without tubulin polymerization, there is no microtubule assembly. Through this
Adipose differentiation-related protein, also known as ADFP or adipophilin, is a protein which in humans is encoded by the ADFP gene.
Adipocyte differentiation-related protein is associated with the globule surface membrane material. This protein is a major constituent of the globule surface. Increase in mRNA levels is one of the earliest indications of adipocyte differentiation
The Bcl-2-associated death promoter (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family , a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.
Bax/Bak are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows cytochrome c to escape into the cytoplasm and activate the pro-apoptotic caspase cascade. The anti-apoptotic Bcl-2 and Bcl-xL proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c.
Dephosphorylated BAD forms a heterodimer with Bcl-2 and Bcl-xL, inactivating them and thus allowing Bax/Bak-triggered apoptosis. When BAD is phosphorylated by Akt/protein kinase B (triggered by PIP3), it forms the BAD-(14-3-3)protein homodimer. This leaves Bcl-2 free to inhibit Bax-triggered apoptosis. BAD
In enzymology, a β-ketoacyl-[acyl-carrier-protein] synthase III (EC 184.108.40.206) is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are acetyl-CoA and malonyl-[acyl-carrier-protein], whereas its 3 products are acetoacetyl-[acyl-carrier-protein], CoA, and CO2. This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups.
This enzyme participates in fatty acid biosynthesis. β-ketoacyl-acyl-carrier-protein synthase III is involved in the dissociated (or type II) fatty-acid biosynthesis system that occurs in plants and bacteria. The role of FabH in fatty acid synthesis has been described in Streptomyces glaucescens, Streptococcus pneumoniae, and Streptomyces coelicolor.
The systematic name of this enzyme class is acetyl-CoA:malonyl-[acyl-carrier-protein] C-acyltransferase. Other names in common use include:
Mycobacterium tuberculosis, the cause of tuberculosis, evades effective immune clearance through encapsulation, especially with mycolic acids which are particularly resistant to the normal degradative processes of macrophages. Furthermore, this capsule inhibits entry of
Neuraminidase enzymes are glycoside hydrolase enzymes (EC 220.127.116.11) that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The best-known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread of influenza infection. The viral neuraminidases are frequently used as an antigenic determinants found on the surface of the Influenza virus. Some variants of the influenza neuraminidase confer more virulence to the virus than others. Other homologs are found in mammalian cells, which have a range of functions. At least four mammalian sialidase homologs have been described in the human genome (see NEU1, NEU2, NEU3, NEU4).
Neuraminidases, also called sialidases, catalyze the hydrolysis of terminal sialic acid residues from the newly formed virions and from the host cell receptors. Sialidase activities include assistance in the mobility of virus particles through the respiratory tract mucus and in the elution of virion progeny from the infected cell.
There are two major classes of Neuraminidase that cleave exo or endo poly-sialic acids:
Swiss-Prot lists 137 types of neuraminidase from
Pentraxins, also known as pentaxins, are an evolutionary conserved family of proteins characterised by containing a pentraxin protein domain. Proteins of the pentraxin family are involved in acute immunological responses. They are a class of pattern recognition receptors (PRRs).
Pentraxins are characterised by calcium dependent ligand binding and a distinctive flattened β-jellyroll structure similar to that of the legume lectins. The name "pentraxin" is derived from the Greek word for five (penta) and berries (ragos) relating to the radial symmetry of five monomers forming a ring approximately 95Å across and 35Å deep observed in the first members of this family to be identified. The "short" pentraxins include Serum Amyloid P component (SAP) and C reactive protein (CRP). The "long" pentraxins include PTX3 (a cytokine modulated molecule) and several neuronal pentraxins.
Three of the principal members of the pentraxin family are serum proteins: namely, C-reactive protein (CRP), serum amyloid P component protein (SAP), and female protein (FP). PTX3 (or TSG-14) protein is a cytokine-induced protein that is homologous to CRPs and SAPs, but its function has not yet been
cAMP receptor protein (CRP; also known as catabolite activator protein, CAP) is a regulatory protein in bacteria. CRP protein binds cAMP, which causes a conformational change that allows CRP to bind tightly to a specific DNA site in the promoters of the genes it controls CRP then activates transcription through direct protein-protein interactions with RNA polymerase.
The genes regulated by CRP are mostly involved in energy metabolism, such as galactose, citrate, or the PEP group translocation system. In Escherichia coli, cyclic AMP receptor protein (CRP) can regulate the transcription of more than 100 genes.
The signal to activate CRP is the binding of cyclic AMP. Binding of cAMP to CRP leads to a long-distance signal transduction from the N-terminal cAMP-binding domain to the C-terminal domain of the protein, which is responsible for interaction with specific sequences of DNA.""
At "Class I" CRP-dependent promoters, CRP binds to a DNA site located upstream of core promoter elements and activates transcription through protein-protein interactions between "activating region 1" of CRP and the C-terminal domain of RNA polymerase alpha subunit. At "Class II" CRP-dependent promoters,
DNA replication licensing factor MCM6 is a protein that in humans is encoded by the MCM6 gene. MCM6 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication.
The MCM complex consisting of MCM6 (this protein) and MCM2, 4 and 7 possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre-RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication. Mcm 6 has recently been shown to interact strongly Cdt1 at defined residues, by mutating these target residues Wei et al. observed lack of Cdt1 recruitment of Mcm2-7 to the pre-RC.
The MCM6 gene, MCM6, is expressed at very high level. MCM6 contains 18 introns. There are 2 non overlapping alternative last exons. The transcripts appear to differ by truncation of the 3' end, presence or absence of 2 cassette exons, common exons with
Probable transcription factor PML is a tumor suppressor protein that in humans is encoded by the PML gene.
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies (Nuclear dots) where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL). Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified.
Promyelocytic leukemia protein has been shown to interact with Retinoic acid receptor alpha, HDAC1, Nerve Growth factor IB, SKI protein, Zinc finger and BTB domain-containing protein 16, Cyclin T1, SIN3A, Retinoblastoma protein, Death associated protein 6, STAT3,
ATP synthase subunit alpha, mitochondrial is an enzyme that in humans is encoded by the ATP5A1 gene.
This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, using an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the alpha subunit of the catalytic core. Alternatively spliced transcript variants encoding the same protein have been identified. Pseudogenes of this gene are located on chromosomes 9, 2, and 16.
Model organisms have been used in the study of ATP5A1 function. A conditional knockout mouse line, called Atp5a1 was generated as part of the International Knockout Mouse Consortium program — a high-throughput
Follistatin also known as activin-binding protein is a protein that in humans is encoded by the FST gene. Follistatin is an autocrine glycoprotein that is expressed in nearly all tissues of higher animals.
Its primary function is the binding and bioneutralization of members of the TGF-β superfamily, with a particular focus on activin, a paracrine hormone.
An earlier name for the same protein was FSH-suppressing protein (FSP). At the time of its initial isolation from follicular fluid, it was found to inhibit the anterior pituitary's secretion of follicle-stimulating hormone (FSH).
Follistatin is part of the inhibin-activin-follistatin axis.
Currently there are three reported isoforms, FS-288, FS-300, and FS-315. Two, FS-288 and FS-315, are known to be created by alternative splicing of the primary mRNA transcript. FS-300 (porcine follistatin) is thought to be the product of posttranslational modification via truncation of the C-terminal domain from the primary amino-acid chain.
Although FS is ubiquitous its highest concentration has been found to be in the female ovary, followed by the skin.
The activin-binding protein follistatin is produced by folliculostellate (FS) cells of the
Beta globin (HBB, β-globinprotin), along with alpha globin (HBA), makes up the most common form of hemoglobin in adult humans. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains.
The gene is located in the β-globin locus. Expression of beta globin and the neighboring globins in the β-globin locus is controlled by single locus control region (LCR). The order of the genes in the beta-globin cluster is 5' - epsilon – gamma-G – gamma-A – delta – beta - 3'.
Mutant beta globin is responsible for the sickling of red blood cells seen in sickle cell anemia. Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia.
Human β-globin locus
HBB has been shown to interact with Hemoglobin, alpha 1.
The Ski protein is a nuclear protooncoprotein that is associated with tumors at high cellular concentrations. Ski has been shown to interfere with normal cellular functioning by both directly impeding expression of certain genes inside the nucleus of the cell as well as disrupting signaling proteins that activate genes.
Ski negatively regulates transforming growth factor-beta (TGF-beta) by directly interacting with Smads and repressing the transcription of TGF-beta responsive genes. This has been associated with cancer due to the large number of roles that peptide growth factors, of which TGF-beta are a subfamily, play in regulating cellular functions such as cell proliferation, apoptosis, specification, and developmental fate.
The name Ski comes from the Sloan-Kettering Institute where the protein was initially discovered.
The SKI proto-oncogene is located at a region close to the p73 tumor suppressor gene at the locus 1p36.3 locus of a gene, suggesting a similar function to the p73 gene.
The SKI protein has a 728 amino acid sequence, with multiple domains and is expressed both inside and outside of the nucleus. It is in the same family as the SnoN protein. The different domains
Carboxypeptidase A usually refers to the pancreatic exopeptidase which hydrolyzes peptide bonds of C-terminal residues with aromatic or aliphatic side chains. Most scientists in the field now refer to this enzyme as CPA1, and to a related pancreatic carboxypeptidase as CPA2.
In addition, there are 4 other mammalian enzymes named CPA-3 through CPA-6, and none of these are expressed in the pancreas. Instead, these other CPA-like enzymes have diverse functions.
CPA-1 and CPA-2 (and presumably all other CPAs) contain a zinc atom at the active site. Loss of the zinc leads to loss of activity, which can be replaced easily by zinc, and also by some other divalent metals (cobalt, nickel).
Caldesmon is a protein that in humans is encoded by the CALD1 gene.
Caldesmon is a calmodulin binding protein. Like calponin, caldesmon tonically inhibits the ATPase activity of myosin in smooth muscle.
This gene encodes a calmodulin- and actin-binding protein that plays an essential role in the regulation of smooth muscle and nonmuscle contraction. The conserved domain of this protein possesses the binding activities to Ca-calmodulin, actin, tropomyosin, myosin, and phospholipids. This protein is a potent inhibitor of the actin-tropomyosin activated myosin MgATPase, and serves as a mediating factor for Ca-dependent inhibition of smooth muscle contraction. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms.
CTP synthase (or CTP synthetase) is an enzyme involved in pyrimidine biosynthesis that interconverts UTP and CTP.
CTP synthase catalyzes the last committed step in pyrimidine nucleotide biosynthesis:
ATP + UTP + glutamine → ADP + Pi + CTP + glutamate
It is the rate-limiting enzyme for the synthesis of cytosine nucleotides from both the de novo and uridine salvage pathways.
The reaction proceeds by the ATP-dependent phosphorylation of UTP on the 4-oxygen atom, making the 4-carbon electrophilic and vulnerable to reaction with ammonia. The source of the amino group in CTP is glutamine, which is hydrolysed in a glutamine amidotransferase domain to produce ammonia. This is then channeled through the interior of the enzyme to the synthase domain. Here, ammonia reacts with the intermediate 4-phosphoryl UTP.
Two isozymes with CTP synthase activity exist in humans, encoded by the following genes:
Active CTP synthase exists as a homeotetrameric enzyme. At low enzyme concentrations and in the absence of ATP and UTP, CTP synthase exists as inactive monomer. As enzyme concentration increases, it polymerizes first to a dimer (such as the form shown to the left) and, in the presence of ATP and
Hop, occasionally written HOP, is an abbreviation for Hsp70-Hsp90 Organizing Protein. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90.
Hop belongs to the large group of co-chaperones, which regulate and assist the major chaperones (mainly heat shock proteins). It is one of the best studied co-chaperones of the Hsp70/Hsp90-complex. It was first discovered in yeast and homologues were identified in human, mouse, rat, insects, plants, parasites, and virus. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop).
The gene for human Hop is located on chromosome 11q13.1 and consists of 14 exons.
STI proteins are characterized by some structural features: All homologues have nine tetratricopeptide repeat (TPR) motifs, that are clustered into domains of three TPRs. The TPR motif is a very common structural feature used by many proteins and provides the ability of directing protein-protein interactions. Crystallographic structural information is available for the N-terminal TPR1 and the central TPR2A domains in complex with Hsp90 resp. Hsp70 ligand
Isopenicillin N synthase (IPNS) is a non-heme iron-dependent enzyme belonging to the oxidoreductase family. This enzyme catalyzes the formation of isopenicillin N from δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV).
This reaction is a key step in the biosynthesis of penicillin and cephalosporin antibiotics.
The active sites of most isopenicillin N synthases contain an iron ion.
This enzyme is also called isopenicillin N synthetase.
A Fe(II) metal ion in the active site of the enzyme is coordinated by at least two histidine residues, an aspartate residue, a glutamine residue, and two water molecules in the absence of a bound substrate. Just two histidine residues and one aspartic acid residue are entirely conserved. Therefore, it is highly significant that these two histidine residues, His214 and His270, and one aspartic acid residue, Asp216, are precisely the ones essential for activity. When ACV binds the active site, Gln330 and one water molecule are replaced by the ACV thiolate.
The linear tripeptide δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV) must first be assembled from its component amino acids by N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase (ACV
The legume lectins are a family of sugar binding proteins or lectins found in the seeds and, in smaller amounts, in the roots, stems, leaves and bark of plants belonging to the Fabaceae family. The exact function of the legume lectins in vivo is unknown but they are probably involved in the defense of plants against predators. Related proteins in other plant families and in animals have also been found. They have been used for decades as a model system for the study of protein-carbohydrate interactions, because they show an amazing variety of binding specificities and are easy to obtain and purify. Over the years, a quite impressive amount of structural data has been gathered. Well-studied members of this protein family include phytohemagglutinin and concanavalin A.
The legume lectins use an ingenious framework for binding specific sugars. This framework consists of a conserved monosaccharide binding site in which four conserved residues from four separate regions in the protein confer affinity (see figure), a variable loop that confers monosaccharide specificity and a number of subsites around the monosaccharide binding site that harbour additional sugar residues or hydrophobic
Prostaglandin-I synthase (EC 18.104.22.168) also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGIS gene. This enzyme belongs to the family of cytochrome P450 isomerases.
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A2 contribute to the development of myocardial infarction, stroke, and atherosclerosis.
Unlike most P450 enzymes, PGIS does not require molecular oxygen (O2). Instead it uses its heme cofactor to catalyze the isomerization of prostaglandin H2 to prostacyclin. Prostaglandin H2 is
Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprise the cytoskeleton. All IF proteins are expressed in a highly developmentally-regulated fashion; vimentin is the major cytoskeletal component of mesenchymal cells. Because of this, vimentin is often used as a marker of mesenchymally-derived cells or cells undergoing an epithelial-to-mesenchymal transition (EMT) during both normal development and metastatic progression.
A vimentin monomer, like all other intermediate filaments, has a central α-helical domain, capped on each end by non-helical amino (head) and carboxyl (tail) domains. Two monomers are likely co-translationally expressed in a way that facilitates their formation of a coiled-coil dimer, which is the basic subunit of vimentin assembly.
The α-helical sequences contain a pattern of hydrophobic amino acids that contribute to forming a "hydrophobic seal" on the surface of the helix. In addition, there is a periodic distribution of acidic and basic amino acids that seems to play an
Aldosterone synthase (or 18-hydroxylase) is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone.
The CYP11B2 gene provides instructions for making aldosterone synthase. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. This protein is primarily expressed in the zona glomerulosa of the adrenal cortex. Within the cell, it localizes to the inner membrane of the mitochondria. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency.
It converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone:
Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene.
Geminin is a nuclear protein that is present in most eukaryotics and highly conserved across species. Numerous functions have been elucidated for Geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation.
Geminin was originally identified as an inhibitor of DNA replication and substrate of the anaphase promoting complex (APC). Coincidentally, Geminin was also shown to expand the neural plate in the developing Xenopus embryo.
Geminin is a nuclear protein made up of about 200 amino acids, with a molecular weight of approximately 25 kDa. It contains an atypical leucine-zipper coiled-coil domain. It has no known enzymatic activity nor DNA binding motifs.
Geminin is absent during G1 phase and accumulates through S, G2 phase and M phases of the cell cycle. Geminin levels drop at the metaphase / anaphase transition of mitosis when it is degraded by the Anaphase Promoting Complex (APC/C).
During S phase, geminin is a negative regulator of DNA replication. In many cancer cell lines, inhibition of geminin by RNAi results in
Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-density (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a homoexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride.
The CETP gene is located on the sixteenth chromosome (16q21).
Rare mutations leading to increased function of CETP have been linked to accelerated atherosclerosis. In contrast, a polymorphism (I405V) of the CETP gene leading to lower serum levels has also been linked to exceptional longevity and to metabolic response to nutritional intervention. However, this mutation also increases the prevalence of coronary heart disease in patients with hypertriglyceridemia. The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.
Elaidic acid, a major component of trans fat, increases CETP activity.
As HDL can alleviate
The E6 protein is one of the key cancer-causing proteins expressed by the Human papillomavirus (HPV). Among the strains of HPV known to cause physical changes associated with cancer and pre-cancerous lesions, three oncoproteins are recognized: E5, E6 and E7. Although low-risk HPV strains also produce these proteins, the four major high-risk strains—HPV-16, HPV-18, HPV-31, and HPV-45—all exhibit E6 and E7 proteins. E6's activity in the high-risk strains can be oncogenic, or cancer-promoting. Therefore, it is the strains which exhibit these proteins which are associated with cervical cancer and pre-cancerous lesion development in women.
E6 is a 151 amino-acid peptide that incorporates a type 1 motif with a consensus sequence –(T/S)-(X)-(V/I)-COOH. It also has two zinc finger motifs.
E6 is of particular interest because it appears to have multiple roles in the cell and to interact with many other proteins. E6 primarily causes cancer by associating with and thereby inactivating P53 or Rb proteins, which act as tumor suppressors. When tumor suppressor proteins are inactivated tumor growth proceeds unchecked. E6's interaction with p53 and Rb marks these proteins for degradation by
Perforin-1 is a protein that in humans is encoded by the PRF1 gene.
Perforin is a cytolytic protein found in the granules of Cytotoxic T lymphocytes (CTLs) and NK cells. Upon degranulation, perforin inserts itself into the target cell's plasma membrane, forming a pore. The lytic membrane-inserting part of perforin is the MACPF domain. This region shares homology with cholesterol-dependent cytolysins from Gram-positive bacteria.
Perforin has structural and functional similarities to complement component 9 (C9). Like C9, this protein creates transmembrane tubules and is capable of lysing non-specifically a variety of target cells. This protein is one of the main cytolytic proteins of cytolytic granules, and it is known to be a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis.
Defects in this gene cause familial hemophagocytic lymphohistiocytosis type 2 (HPLH2), a rare and lethal autosomal recessive disorder of early childhood.
Perforin has been shown to interact with Calreticulin.
Perforin at NLM Genetics Home Reference
Transitional endoplasmic reticulum ATPase (TER ATPase) also known as valosin-containing protein (VCP) is an enzyme that in humans is encoded by the VCP gene.
Valosin-containing protein (VCP) is a member of a family that includes putative ATP-binding proteins involved in vesicle transport and fusion, 26S proteasome function, and assembly of peroxisomes. VCP, as a structural protein, is associated with clathrin, and heat-shock protein Hsc70, to form a complex. VCP has been implicated in a number of cellular events that are regulated during mitosis, including homotypic membrane fusion, spindle pole body function, and ubiquitin-dependent protein degradation.
Valosin-containing protein has been shown to interact with AMFR, SELS, BRCA1, NSFL1C, IκBα and Ataxin 3.
Mutations in VCP have been linked to inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia (IBMPFD). They may also be linked to familial amyotrophic lateral sclerosis.
Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 (ERp60) is a protein that in humans is encoded by the CALR gene.
Calreticulin is a multifunctional protein that binds Ca ions (a second messenger in signal transduction), rendering it inactive. The Ca is bound with low affinity, but high capacity, and can be released on a signal (see inositol triphosphate). Calreticulin is located in storage compartments associated with the endoplasmic reticulum.
The term "Mobilferrin" is considered to be the same as calreticulin by some sources.
Calreticulin binds to misfolded proteins and prevents them from being exported from the Endoplasmic reticulum to the Golgi apparatus.
A similar quality-control chaperone, calnexin, performs the same service for soluble proteins as does calreticulin. Both proteins, Calnexin and calreticulin, have the function of binding to oligosaccharides containing terminal glucose residues, thereby targeting them for degradation. In normal cellular function, trimming of glucose residues off the core oligosaccharide added during N-linked glycosylation is a part of protein processing. If "overseer"
Erbb2 interacting protein (ERBB2IP) also known as Erbin is a protein which in humans is encoded by the ERBB2IP gene. Discovered in 1997, Erbin is a 200kDa protein containing a PDZ domain.
This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternate transcriptional splice variants encoding different isoforms have been found for this gene, but only two of them have been characterized to date.
Erbin's C-terminal PDZ domain is able to bind to ErbB2, a protein tyrosine kinase which is often associated with poor prognosis in epidermal oncogenesis. Erbin's N-terminal region has been shown to disrupt Ras to Raf binding and may be, through this action, a tumor suppressing protein.
Erbin (protein) has been shown to interact with HER2/neu, Dystonin, PKP4, Mothers against decapentaplegic homolog 3 and ITGB4.
Sphingosine kinase 1 is an enzyme that in humans is encoded by the SPHK1 gene.
Sphingosine kinase 1 phosphorylates sphingosine to sphingosine-1-phosphate (S1P) SK1 is normally a cytosolic protein but is recruited to membranes rich in phosphatidate (PA), a product of Phospholipase D (PLD)
Sphingosine-1-phosphate (SPP) is a novel lipid messenger with both intracellular and extracellular functions. Intracellularly, it regulates proliferation and survival, and extracellularly, it is a ligand for EDG1. Various stimuli increase cellular levels of SPP by activation of sphingosine kinase (SPHK), the enzyme that catalyzes the phosphorylation of sphingosine. Competitive inhibitors of SPHK block formation of SPP and selectively inhibit cellular proliferation induced by a variety of factors, including platelet-derived growth factor and serum.
SPHK1 has been shown to interact with TRAF2.
Chromogranin A or parathyroid secretory protein 1 (gene name CHGA) is a member of the granin family of neuroendocrine secretory proteins, i.e. it is located in secretory vesicles of neurons and endocrine cells. In humans, chromogranin A protein is encoded by the CHGA gene.
Examples of cells producing chromogranin A are chromaffin cells of the adrenal medulla, paraganglia, enterochromaffin-like cells and beta cells of the pancreas.
Chromogranin A is the precursor to several functional peptides including vasostatin, pancreastatin, catestatin and parastatin. These peptides negatively modulate the neuroendocrine function of the releasing cell (autocrine) or nearby cells (paracrine). Other peptides derived from chromogranin A with uncertain function include chromostatin, WE-14 and GE-25.
Chromogranin A might promote the generation of secretory granules.
Chromogranin A is elevated in pheochromocytomas.
It is used as an indicator for pancreas and prostate cancer and in carcinoid syndrome. It might play a role in early neoplasic progression. It is also elevated in diabetes. Chromogranin A is cleaved by an endogenous prohormone convertase to produce several peptide fragments. See
Bifunctional purine biosynthesis protein PURH is a protein that in humans is encoded by the ATIC gene.
ATIC encodes an enzyme which generates inosine monophosphate from aminoimidazole carboxamide ribonucleotide.
It has two functions:
Lipopolysaccharide-binding protein is a protein that in humans is encoded by the LBP gene.
LBP is a soluble acute-phase protein that binds to bacterial lipopolysaccharide (or LPS) to elicit immune responses by presenting the LPS to important cell surface pattern recognition receptors called CD14 and TLR4.
The protein encoded by this gene is involved in the acute-phase immunologic response to gram-negative bacterial infections. Gram-negative bacteria contain a glycolipid, lipopolysaccharide (LPS), on their outer cell wall. Together with bactericidal permeability-increasing protein (BPI), the encoded protein binds LPS and interacts with the CD14 receptor, probably playing a role in regulating LPS-dependent monocyte responses. Studies in mice suggest that the encoded protein is necessary for the rapid acute-phase response to LPS but not for the clearance of LPS from circulation. This protein is part of a family of structurally and functionally related proteins, including BPI, plasma cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). Finally, this gene is found on chromosome 20, immediately downstream of the BPI gene.
Nicastrin, also known as NCSTN, is a protein that in humans is encoded by the NCSTN gene.
Nicastrin (abbreviated NCT) is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in processing amyloid precursor protein (APP) to the short Alzheimer's disease-associated peptide amyloid beta. The other proteins in the complex are presenilin, which is the catalytically active component of the complex, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin enhancer 2). Nicastrin itself is not catalytically active, but instead promotes the maturation and proper trafficking of the other proteins in the complex, all of which undergo significant post-translational modification before becoming active in the cell. Nicastrin has also been identified as a regulator of neprilysin, an enzyme involved in the degradation of amyloid beta fragment.
The protein was named after the Italian village Nicastro, reflecting the fact that Alzheimer's disease was described in 1963 after studying descendants of an extended family originating in the village of Nicastro that had Familial Alzheimer's Disease (FAD).
Nicastrin has been shown to interact with PSEN1 and
Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein which in humans is encoded by the ADIPOQ gene. It is involved in regulating glucose levels as well as fatty acid breakdown.
Adiponectin is a 244-amino-acid-long polypeptide. There are four distinct regions of adiponectin. The first is a short signal sequence that targets the hormone for secretion outside the cell; next is a short region that varies between species; the third is a 65-amino acid region with similarity to collagenous proteins; the last is a globular domain. Overall this gene shows similarity to the complement 1Q factors (C1Q). However, when the 3-dimensional structure of the globular region was determined, a striking similarity to TNFα was observed, despite unrelated protein sequences.
Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism. Adiponectin is exclusively secreted from adipose tissue (and also from the placenta in pregnancy) into the bloodstream and is very abundant in plasma relative to many hormones. Levels of the hormone are inversely correlated with body fat percentage in adults, while the
CDC45 is a protein that in humans is encoded by the CDC45L gene.
The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6/Cdc18, the minichromosome maintenance proteins (MCMs) and DNA polymerase, which is important for early steps of DNA replication in eukaryotes. This protein has been shown to interact with MCM7 and DNA polymerase alpha. Studies of the similar gene in Xenopus suggested that this protein play a pivotal role in the loading of DNA polymerase alpha onto chromatin. Multiple polyadenlyation sites of this gene are reported.
CDC45-related protein has been shown to interact with ORC1L, MCM6, MCM7, MCM3 and ORC6L.
Coronin is an actin binding protein which also interacts with microtubules and in some cell types is associated with phagocytosis. Coronin proteins are expressed in a large number of eukaryotic organisms from yeast to man.
Eugenio L. de Hostos et al. (1991) isolated a 55 kDa protein from actinomyosin complex of Dictyostelium discoideum, which was later shown to bind actin in vitro. This actin binding protein was named coronin after its strong immunolocalisation in the actin rich crown like extension of the cell cortex in D. discoidium. Initially this protein was admitted into club of actin binding proteins with least enthusiasm, as the primary structure did not match any other ABPs. But later on, the protein was identified in many eukaryotic cells and Dictyostelium discoideum was found to be impaired in cytokinesis, and many actin mediated processes like endocytosis, cell motility etc.
Coronin belongs to WD-repeat containing proteins which form a beta propeller tertiary structure. The crystal structure of Coronin 1A (see figure to the right) containing major part of the protein was solved in 2006.
The WD-repeat is a structural motif comprising approximately 40 amino acids usually
In enzymology, an ent-copalyl diphosphate synthase (EC 22.214.171.124) is an enzyme that catalyzes the chemical reaction:
Hence, this enzyme has one substrate, geranylgeranyl pyrophosphate, and one product, ent-copalyl pyrophosphate. This enzyme participates in gibberellin biosynthesis.
This enzyme belongs to the family of isomerases, specifically the class of intramolecular lyases. The systematic name of this enzyme class is ent-copalyl-diphosphate lyase (decyclizing). Other names in common use include ent-kaurene synthase A, and ent-kaurene synthetase A.
ent-Copalyl diphosphate synthases from fungi and mosses also have a distinct ent-kaurene synthase activity associated with the same protein molecule. The reaction catalyzed by ent-kaurene synthase is the next step in the biosynthetic pathway to gibberellins. The two types of enzymic activity are distinct, and site-directed mutagenesis to suppress the ent-kaurene synthase activity of the protein leads to build up of ent-copalyl pyrophosphate. Inhibition of ent-kaurene synthase activity, by replacing Mg in the growth medium with Ni, has the same effect.
Higher plants typically have separate proteins for ent-copalyl diphosphate synthase
A list of human ATPase genes is included along with their likely functions and interrelationships. The total quantity of adenosine triphosphate (ATP) in the human body is about 0.1 mole (about 6 x 10 molecules). This ATP is constantly being broken down into adenosine diphosphate (ADP) to provide energy for activity, and then converted back into ATP. At any given time, the total amount of ATP + ADP remains fairly constant. The energy used by our cells requires the hydrolysis of 100 to 150 moles (6 to 9 x 10 molecules) of ATP daily, which is around 50 to 75 kg. Typically, we will use up our body weight of ATP over the course of the day. This means that each ATP molecule is recycled 1000 to 1500 times daily, or about once every minute.
The Nomenclature Committee of the International Union of Biochemistry and Molecular Biology has a classification that is used to assigned an Enzyme Commission number (EC number) to an enzyme. Every EC number is associated with a recommended name for the respective enzyme. EC numbers do not specify enzymes, but enzyme-catalyzed reactions. If different enzymes (for instance from different organisms) catalyze the same reaction, then they receive the same
Integrin alpha M (ITGAM) is one protein subunit that forms the heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3 (CR3). ITGAM is also known as CR3A, and cluster of differentiation molecule 11B (CD11B). The second chain of αMβ2 is the common integrin β2 subunit known as CD18, and integrin αMβ2 thus belongs to the β2 subfamily (or leukocyte) integrins.
αMβ2 is expressed on the surface of many leukocytes involved in the innate immune system, including monocytes, granulocytes, macrophages, and natural killer cells. It mediates inflammation by regulating leukocyte adhesion and migration and has been implicated in several immune processes such as phagocytosis, cell-mediated cytotoxicity, chemotaxis and cellular activation. It is involved in the complement system due to its capacity to bind inactivated complement component 3b (iC3b). The ITGAM (alpha) subunit of integrin αMβ2 is directly involved in causing the adhesion and spreading of cells but cannot mediate cellular migration without the presence of the β2 (CD18) subunit.
In genomewide association studies, single nucleotide polymorphisms in ITGAM had the
Histone-lysine N-methyltransferase HRX is an enzyme that in humans is encoded by the MLL (ALL1) gene. MLL stands for Myeloid/Lymphoid, or Mixed-Lineage, Leukemia.
MLL is a histone methyltransferase deemed a positive global regulator of gene transcription. This protein belongs to the group of histone-modifying enzymes comprising transactivation domain 9aaTAD and is involved in the epigenetic maintenance of transcriptional memory.
Rearrangements of the MLL gene are associated with aggressive acute leukemias (ALL). It also may participate in the process of GAD67 downregulation in schizophrenia.
MLL (gene) has been shown to interact with HDAC1, PPP1R15A, Host cell factor C1, MEN1, RBBP5, ASH2L, CREB binding protein, WDR5, CTBP1 and PPIE.
Riboflavin synthase is an enzyme that catalyzes the final reaction of riboflavin biosynthesis:
(2) 6,7-dimethyl-8-ribityllumazine → riboflavin + 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
The Riboflavin synthase monomer is 23kDa. Each monomer contains two beta-barrels and one α-helix at the C-terminus (residues 186-206.) The monomer folds into pseudo two-fold symmetry, predicted by sequence similarity between the N-terminus barrels (residues 4-86) and the C-terminus barrel (residues 101-184). The enzyme from different species adopts different quaternary structures, from monomeric to 60 subunits
Two 6,7-dimethyl-8-ribityllumazine (Lumazine synthase) molecules are hydrogen bound to each monomer as the two domains are topologically similar. The active site is located in the interface of the substrates between monomer pairs and modeled structures of the active site dimer have been created. Only one of the active sites of the enzyme catalyze riboflavin formation at a time as the other two sites face outward and are exposed to solvent. The amino acid residues involved in hydrogen bonding to the ligand are pictured, participating residues may include Thr148, Met160, Ile162, Thr165,
Gli1 is a protein originally isolated in human glioblastoma.
The Gli proteins are the effectors of Hedgehog (Hh) signaling and have been shown to be involved in cell fate determination, proliferation and patterning in many cell types and most organs during embryo development. The Gli transcription factors activate/inhibit transcription by binding to Gli responsive genes and by interacting with the transcription complex. The Gli transcription factors have DNA binding zinc finger domains which bind to consensus sequences on their target genes to initiate or suppress transcription. Yoon showed that mutating the Gli zinc finger domain inhibited the proteins effect proving its role as a transcription factor. Gli proteins have an 18-amino acid region highly similar to the α-helical herpes simplex viral protein 16 activation domain. This domain contains a consensus recognition element for the human TFIID TATA box-binding protein associated factor TAFII31. Other proteins such as Missing in Metastasis (MIM/BEG4) have been shown to potentiate the effects of the Gli transcription factors on target gene transcription. Gli and MIM have been shown to act synergistically to induce epidermal
Antigen KI-67 also known as Ki-67 or MKI67 is a protein that in humans is encoded by the MKI67 gene (antigen identified by monoclonal antibody Ki-67).
Antigen KI-67 is a nuclear protein that is associated with and may be necessary for cellular proliferation. Furthermore it is associated with ribosomal RNA transcription. Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis.
The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0).
Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. The best-studied examples in this context are carcinomas of the prostate, brain and the breast. For these types of tumors, the prognostic value
Alpha 1-antichymotrypsin is an alpha globulin glycoprotein that is a member of the serpin superfamily.
It inhibits the activity of certain enzymes called proteases, such as cathepsin G that is found in neutrophils, and chymases found in mast cells, by cleaving them into a different shape or conformation. This activity protects some tissues, such as the lower respiratory tract, from damage caused by proteolytic enzymes.
This protein is produced in the liver, and is an acute phase protein that is induced during inflammation. Deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease.
Alpha 1-antichymotrypsin is also associated with the pathogenesis of Alzheimer's disease as it enhances the formation of amyloid-fibrils in this disease.
Alpha 1-antichymotrypsin has been shown to interact with DNAJC1.
Alpha 1-Antitrypsin or α1-antitrypsin (A1AT) is a protease inhibitor belonging to the serpin superfamily. It is generally known as serum trypsin inhibitor. Alpha 1-antitrypsin is also referred to as alpha-1 proteinase inhibitor (A1PI) because it inhibits a wide variety of proteases. It protects tissues from enzymes of inflammatory cells, especially neutrophil elastase, and has a reference range in blood of 1.5 - 3.5 gram/liter (in US the reference range is generally expressed as mg/dL or micromoles), but the concentration can rise manyfold upon acute inflammation. In its absence, neutrophil elastase is free to break down elastin, which contributes to the elasticity of the lungs, resulting in respiratory complications such as emphysema, or COPD (chronic obstructive pulmonary disease) in adults and cirrhosis in adults or children.
A1AT is a 52-kDa serpin and, in medicine, it is considered the most prominent serpin; the terms α1-antitrypsin and protease inhibitor (Pi) are often used interchangeably.
Most serpins inactivate enzymes by binding to them covalently, requiring very high levels to perform their function. In the acute phase reaction, a further elevation is required to "limit"
Barstar is a small protein synthesized by the bacterium Bacillus amyloliquefaciens. Its function is to inhibit the ribonuclease activity of its binding partner barnase, with which it forms an extraordinarily tightly bound complex within the cell until barnase is secreted. Expression of barstar is necessary to counter the lethal effect of expressed active barnase. The structure of the barnase-barstar complex is known.
This article incorporates text from the public domain Pfam and InterPro IPR000468
A carboxypeptidase (EC number 3.4.16 - 3.4.18) is a protease enzyme that hydrolyzes (cleaves) the peptide bond of an amino acid residue at the carboxy-terminal (C-terminal) end. (Contrast with an aminopeptidase, which cleaves peptide bonds at the other end of the residue.) Humans, animals, and plants contain several types of carboxypeptidases that have diverse functions ranging from catabolism to protein maturation.
The first carboxypeptidases studied were those involved in the digestion of food (pancreatic carboxypeptidases A1, A2, and B). However, most of the known carboxypeptidases are not involved in catabolism; they help to mature proteins (e.g., Post-translational modification) or regulate biological processes. For example, the biosynthesis of neuroendocrine peptides such as insulin requires a carboxypeptidase. Carboxypeptidases also function in blood clotting, growth factor production, wound healing, reproduction, and many other processes.
Carboxypeptidases are usually classified into one of several families based on their active site mechanism.
These names do not refer to the selectivity of the amino acid that is cleaved.
Another classification system for carboxypeptidases
Catabolite Activator Protein (CAP; also known as cAMP receptor protein, CRP) is a transcriptional activator that exists as a homodimer in solution, with each subunit comprising a ligand-binding domain at the N-terminus (CAP, residues 1-138), which is also responsible for the dimerization of the protein, and a DNA-binding domain at the C-terminus (DBD, residues 139-209). Two cAMP (cyclic AMP) molecules bind dimeric CAP with negative cooperativity and function as allosteric effectors by increasing the protein's affinity for DNA. Cytosolic cAMP levels rise when the amount of glucose transported into the cell is low, but lactose is readily available.
CAP has a characteristic helix-turn-helix structure that allows it to bind to successive major grooves on DNA. The two helices are reinforcing each, causing a 43° turn in the structure, so overall causing a 94° degree turn in the DNA.
This opens the DNA molecule up, allowing RNA polymerase to bind and transcribe the genes involved in lactose catabolism. Thus, CAP enhances the expression of the lac operon when lactose is present, but not glucose.
This requirement reflects the greater simplicity with which glucose may be metabolized in
CD36 (Cluster of Differentiation 36) is an integral membrane protein found on the surface of many cell types in vertebrate animals and is also known as FAT, SCARB3, GP88, glycoprotein IV (gpIV) and glycoprotein IIIb (gpIIIb). CD36 is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids.
Recent work using genetically modified rodents have identified a clear role for CD36 in fatty acid and glucose metabolism, heart disease, taste, and dietary fat processing in the intestine. It may be involved in glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy and Alzheimer's disease.
In humans, rats and mice, CD36 consists of 472 amino acids with a predicted molecular weight of approximately 53,000 Da. However, CD36 is extensively glycosylated and has an apparent molecular weight of 88,000 Da as determined by SDS polyacrylamide gel electrophoresis.
Using Kyte-Doolittle analysis, the amino acid sequence of CD36 predicts a
Dysferlin also known as dystrophy-associated fer-1-like protein is a protein that in humans is encoded by the DYSF gene.
Dysferlin is linked with skeletal muscle repair. A defect in the DYSF gene, located on chromosome 2p12-14, results in either of two types of muscular dystrophy; Miyoshi myopathy (MM) and Limb-girdle muscular dystrophy type 2B (LGMD2B). A reduction or absence of dysferlin usually becomes apparent in the third or fourth decade of life and is characterised by weakness and wasting of various voluntary skeletal muscles.
Dysferlin has been shown to interact with Caveolin 3.
GNAS complex locus, also known as GNAS, is a protein which in humans is encoded by the GNAS gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit (Gs-α), a key component of many signal transduction pathways.
This gene locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contains a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript exists, and this antisense transcript and one of the transcripts are paternally expressed, produce noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein.
The GNAS locus is imprinted and encodes 5 main transcripts:
Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit (Gs-α), a key element of the classical signal transduction pathway linking
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.
This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication, heterochromation organization, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells.
HMGA1 proteins are quite small (~10-12 kDa) and basic molecules and comprise of three AT-hooks with the RGRP (Arg-Gly-Arg-Pro) core motif, a novel cross-linking domain located between the second and third AT-hook and a C-terminal acidic tail characteristic for the HMG family comprising HMGA, HMGB and HMGN proteins.
HMGA1-GFP fusion proteins are highly dynamic in vivo (determined using FRAP analysis), but in contrast also show nanomolar affinity to AT-rich DNA in vitro (determined biochemically) which might be explained due to the extensive post-transcriptional modifications in vivo. HMGA1 preferentially binds to the minor groove of AT-rich regions in double-stranded DNA using its AT-hooks. It has little secondary structure in solution but assumes distinct conformations when bound to substrates such as DNA or
Arp2/3 complex is a seven-subunit protein that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most in actin cytoskeleton-containing eukaryotic cells. Two of its subunits, the Actin-Related Proteins ARP2 and ARP3 closely resemble the structure of monomeric actin and serve as nucleation sites for new actin filaments. The complex binds to the sides of existing ("mother") filaments and initiates growth of a new ("daughter") filament at a distinctive 70 degree angle from the mother. Branched actin networks are created as a result of this nucleation of new filaments. The regulation of rearrangements of the actin cytoskeleton is important for processes like cell locomotion, phagocytosis, and intracellular motility of lipid vesicles.
The Arp2/3 complex was named after it was identified by affinity chromatography from Acanthamoeba castellanii, though it had been previously isolated in 1989 in a search for proteins that bind to actin filaments in Drosophila melanogaster embryos . It is found in most eukaryotic organisms, but absent from a number of Chromalveolates and plants.
Many actin-related molecules
ATPase, subunit C of F0/V0 complex is the main transmembrane subunit of V-type, A-type and F-type ATP synthases.
ATPases (or ATP synthases) are membrane-bound enzyme complexes/ion transporters that combine ATP synthesis and/or hydrolysis with the transport of protons across a membrane. ATPases can harness the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. Some ATPases work in reverse, using the energy from the hydrolysis of ATP to create a proton gradient. There are different types of ATPases, which can differ in function (ATP synthesis and/or hydrolysis), structure (F-, V- and A-ATPases contain rotary motors) and in the type of ions they transport.
The F-ATPases (or F1F0-ATPases) and V-ATPases (or V1V0-ATPases) are each composed of two linked complexes: the F1 or V1 complex contains the catalytic core that synthesizes/hydrolyses ATP, and the F0 or V0 complex that forms the membrane-spanning pore. The F- and V-ATPases all contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis.
Subunit C (also called subunit 9, or proteolipid
Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the BAK1 gene. BAK1 orthologs have been identified in most mammals for which complete genome data are available.
The BAK protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. Dysregulation of the BAK gene has been implicated in human gastrointestinal cancers, indicating that the gene plays a part in the pathogenesis of some cancers.
The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress.
Recently, one study of the role of genetics in abdominal aortic aneurism (AAA) showed that different BAK1 variants can exist in both diseased and nondiseased AA tissues
β-Lactoglobulin is the major whey protein of cow and sheep's milk (~3 g/l), and is also present in many other mammalian species; a notable exception being humans. Its structure, properties and biological role have been reviewed many times .
Unlike the other main whey protein, α-lactalbumin, no clear function has been identified for β-lactoglobulin, although it binds to several hydrophobic molecules, suggesting its role in their transport. The strong suggestion is that the molecule exists primarily as a food source. Several genetic variants have been identified, the main ones in the cow being labelled A and B. Because of its abundance and ease of purification, it has been subjected to a wide range of biophysical studies. Its structure has been determined several times by X-ray crystallography and NMR. One such structure is shown on the right (from http://www.pdb.org entry 3BLG). β-lactoglobulin is of direct interest to the food industry since its properties can variously be advantageous or disadvantageous in dairy products and processing .
Bovine β-lactoglobulin is a relatively small protein of 162 residues, with an 18.4 kDa molecular weight (1 dalton being defined as 1 unified
Desmoplakin is a protein associated with desmosomes.
Desmoplakin is a protein that in humans is encoded by the DSP gene.
Desmosomes are intercellular junctions that tightly link adjacent cells. Desmoplakin is an obligate component of functional desmosomes that anchors intermediate filaments to desmosomal plaques. The N-terminus of desmoplakin is required for localization to the desmosome and interacts with the N-terminal region of plakophilin 1 and plakoglobin. This is further sub divided into a region called the "Plakin domain" made up of repetitive domains called Spectrin repeats. A crystal structure of part of the plakin domain has been resolved, while the entire plakin domain has been elucidated using Small angle X-ray scattering which revealed a non-linear structure, an unexpected result considering spectrin repeats are observed in linear orientations. The C-terminus of desmoplakin binds with intermediate filaments. These are further sub divided to three homologous Plakin repeat domains (see PDBs below). In the mid-region of desmoplakin, a coiled-coiled rod domain is responsible for homodimerization. Mutations in this gene are the cause of several cardiomyopathies and
Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a protein that in humans is encoded by the DCX gene.
Doublecortin (DCX) is a microtubule-associated protein expressed by neuronal precursor cells and immature neurons in embryonic and adult cortical structures. Neuronal precursor cells begin to express DCX while actively dividing, and their neuronal daughter cells continue to express DCX for 2–3 weeks as the cells mature into neurons. Downregulation of DCX begins after 2 weeks, and occurs at the same time that these cells begin to express, NeuN, a marker for mature neurons.
Due to the nearly exclusive expression of DCX in developing neurons, this protein has been used increasingly as a marker for neurogenesis. Indeed, the levels of DCX expression increase in response to exercise, which occurs in parallel with increased BrdU labelling, currently a "gold standard" in measuring neurogenesis.
Doublecortin was found to bind to the microtubule cytoskeleton. In vivo and in vitro assays show that Doublecortin stabilises microtubules and causes bundling. Doublecortin is a basic protein with an iso-electric point of 10, typical of microtubule-binding
Frataxin is a protein that in humans is encoded by the FXN gene.
Frataxin is localized to the mitochondrion. The function of frataxin is not entirely clear, but it seems to be involved in assembly of iron-sulfur clusters. It has been proposed to act as either an iron chaperone or an iron storage protein.
Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat).
Reduced expression of frataxin is the cause of Friedreich's ataxia (FRDA), a lethal neurodegenerative disease. The reduction in frataxin gene expression may be attributable from either the silencing of transcription of the frataxin gene because of epigenetic modifciations in the chromosomal entity or from the
Growth factor receptor-bound protein 7, also known as GRB7, is a protein which in humans is encoded by the GRB7 gene.
The product of this gene belongs to a small family of adaptor proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with epidermal growth factor receptor (EGFR) and ephrin receptors. The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). Alternative splicing results in multiple transcript variants encoding different isoforms, although the full-length natures of only two of the variants have been determined to date.
GRB7 is an SH2-domain adaptor protein that binds to receptor tyrosine kinases and provides the intra-cellular direct link to the Ras proto-oncogene. Human GRB7 is located on the long arm of chromosome 17, next to the ERBB2 (alias HER2/neu) proto-oncogene.
These two genes are commonly co-amplified (present in excess copies) in breast cancers. GRB7 thought to be involved in migration, is well known to be over-expressed in testicular germ cell tumors, esophageal
K-Casein (or Kappa-casein, k casein, kappa casein) is a mammalian milk protein involved in a number of important physiological processes. In the gut, the ingested protein is split into an insoluble peptide (para kappa-casein) and a soluble hydrophilic glycopeptide (caseinomacropeptide). Caseinomacropeptide is responsible for increased efficiency of digestion, prevention of neonate hypersensitivity to ingested proteins, and inhibition of gastric pathogens.
Caseins are a family of phosphoproteins (αS1, αS2, β, κ) that account for nearly 80% of bovine milk proteins (Lucey et al., 2003) and that form soluble aggregates because of the κ-casein molecules that stabilize the micellar structure. There are several models that account for the special conformation of casein in the micelles (Dalgleish, 1998). One of them proposes that the micellar nucleus is formed by several submicelles, the periphery consisting of microvellosities of κ-casein (Walstra, 1979; Lucey, 2002). Another model suggests that the nucleus is formed by casein-interlinked fibrils (Holt, 1992). Finally, the most recent model (Horne, 1998) proposes a double link among the caseins for gelling to take place. All 3 models
Keyhole limpet hemocyanin (KLH) is a large, multisubunit, oxygen-carrying, metalloprotein found in the hemolymph of the giant keyhole limpet, Megathura crenulata, that lives off the coast of California from Monterey Bay to Isla Asuncion off Baja California.
Keyhole limpet hemocyanin is an extremely large, heterogeneous glycosylated protein consisting of subunits with a molecular weight of 350,000 and 390,000 in aggregates with molecular weights of 4,500,000-13,000,000. Each domain of a KLH subunit contains two copper atoms that together bind a single oxygen molecule (O2). When oxygen is bound to hemocyanin, the molecule takes on a distinctive transparent, opalescent blue color. The KLH protein is potently immunogenic yet safe in humans and is therefore highly prized as a vaccine carrier protein. The large and highly glycosylated KLH protein cannot be reproduced synthetically. It is available only as a purified biological product from the Keyhole Limpet Megathura crenulata.
KLH is purified from the hemolymph of Megathura crenulata by a series of steps that typically includes ammonium sulfate precipitation and dialysis, and may involve chromatographic purification to obtain the
Lectins are sugar-binding proteins (not to be confused with glycoproteins, which are proteins containing sugar chains or residues) that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection. Lectins may be disabled by specific mono- and oligosaccharides, which bind to them and prevent their attachment to cell membranes.
The name "lectin" is derived from the Latin word legere, meaning, among other things, "to select".(lek'tin)
Although they were first discovered more than 100 years ago in plants, they are now known to be present throughout nature. It is generally believed that the earliest description of a lectin was given by Peter Hermann Stillmark in his doctoral thesis presented in 1888 to the University of Dorpat. Stillmark isolated ricin, an extremely toxic hemagglutinin, from seeds of the castor plant (Ricinus communis) The first lectin to be purified on a large scale and available on a commercial basis was concanavalin A, which is now the most-used lectin for characterization and purification
In biology, LSm proteins are a family of RNA-binding proteins found in virtually every cellular organism. LSm is a contraction of 'like Sm', because the first identified members of the LSm protein family were the Sm proteins. LSm proteins are defined by a characteristic three dimensional structure and their assembly into rings of six or seven individual LSm protein molecules.
The Sm proteins were first discovered as antigens targeted by so called Anti-Sm antibodies in a patient with a form of systemic lupus erythematosus (SLE), a debilitating autoimmune disease. They were named Sm proteins in honor of this patient, Stephanie Smith. Other proteins with very similar structures were subsequently discovered and named LSm proteins. New members of the LSm protein family continue to be identified and reported.
Proteins with similar structures are grouped into a hierarchy of protein families, superfamilies, and folds. The LSm protein structure is an example of a small beta sheet folded into a short barrel. Individual LSm proteins assemble into a six or seven member doughnut ring (more properly termed a torus), which usually binds to a small RNA molecule to form a ribonucleoprotein complex.
Major vault protein is a protein that in humans is encoded by the MVP gene.
This gene encodes the major vault protein which is a lung infection resistance-related protein. Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport. This protein mediates drug resistance, perhaps via a transport process. It is widely distributed in normal tissues, and overexpressed in multidrug-resistant cancer cells. The protein overexpression is a potentially useful marker of clinical drug resistance. This gene produces two transcripts by using two alternative exon 2 sequences; however, the open reading frames are the same in both transcripts.
Major vault protein has been shown to interact with Estrogen receptor alpha, PTEN and PARP4.
Midkine (MK or MDK) also known as neurite growth-promoting factor 2 (NEGF2) is a protein that in humans is encoded by the MDK gene.
Midkine is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin (NEGF1, 46% homologous with MK). It is a nonglycosylated protein, composed of two domains held by disulfide bridges. It is a developmentally important retinoic acid-responsive gene product strongly induced during mid-gestation, hence the name midkine . Restricted mainly to certain tissues in the normal adult, it is strongly induced during oncogenesis, inflammation and tissue repair.
MK is pleiotropic, capable of exerting activities such as cell proliferation, cell migration, angiogenesis and fibrinolysis. A molecular complex containing receptor-type tyrosine phosphatase zeta (PTPζ), low density lipoprotein receptor-related protein (LRP1), anaplastic leukemia kinase (ALK) and syndecans is considered to be its receptor.
MK appears to enhance the angiogenic and proliferative activities of cancer cells. The expression of MK (mRNA and protein expression) has been found to be elevated in multiple cancer types, such as neuroblastoma, glioblastoma,
Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the central nervous system (CNS). The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction.. MBP maintain the correct structure of myelin, interacting with the lipids in the myelin membrane .
MBP was initially sequenced in 1971 after isolation from myelin membranes. Since that time, knockout mice deficient in MBP that showed decreased amounts of CNS myelination and a progressive disorder characterized by tremors, seizures, and early death have been developed. The human gene for MBP is on chromosome 18; the protein localizes to the CNS and to various cells of the hematopoietic system.
The pool of MBP in the central nervous system is very diverse, with several splice variants being expressed and a large number of post-translational modifications on the protein, which include phosphorylation, methylation, deamidation, and citrullination. These forms differ by the presence or the absence of short (10 to 20 residues) peptides in various internal locations in the
NK2 homeobox 1 (NKX2-1), also known as thyroid transcription factor 1 (TTF-1), is a protein which in humans is encoded by the NKX2-1 gene.
Thyroid transcription factor-1 (TTF-1) is a protein that regulates transcription of genes specific for the thyroid, lung, and diencephalon. It is also known as thyroid specific enhancer binding protein. It is used in anatomic pathology as a marker to determine if a tumor arises from the lung or thyroid.
TTF-1 positive cells are found in the lung as type II pneumocytes and Clara cells. In the thyroid, follicular and parafollicular cells are also positive for TTF-1.
For lung cancers, adenocarcinomas are usually positive, while squamous cell carcinomas and large cell carcinomas are rarely positive. Small cell carcinomas (of any primary site) are usually positive. TTF1 is more than merely a clinical marker of lung adenocarcinoma. It plays an active role in sustaining lung cancer cells in view of the experimental observation that it is mutated in lung cancer.
However others have found that TTF-1 staining is often positive in pulmonary adenocarcinomas, large cell carcinomas, small-cell lung carcinomas, neuroendocrine tumors other than small-cell lung
p73 is a protein related to the p53 tumor protein. Because of its structural resemblance to p53, it has also been considered a tumor suppressor. It is involved in cell cycle regulation, and induction of apoptosis. Like p53, p73 is characterized by the presence of different isoforms of the protein. This is explained by splice variants, and an alternative promoter in the DNA sequence.
p73, also known as tumor protein 73 (TP73), protein was the first identified homologue of the tumor suppressor gene, p53. Like p53, p73 has several variants. It is expressed as distinct forms differing at either at the C- or the N-terminus. Currently, six different C-terminus splicing variants have been found in normal cells. The p73 gene encodes a protein with a significant sequence homology and a functional similarity with the tumor suppressor p53. The over-expression of p73 in cultured cells promotes a growth arrest and/or apoptosis similarly to p53.
The p73 gene has been mapped to a chromosome region (1p36. 2-3) a locus commonly deleted in various tumor entities and human cancers. Similar to p53 the protein product of p73 induces cell cycle arrest or apoptosis, hence its classification as a tumor
Phytohaemagglutinin (PHA, or phytohemagglutinin) is a lectin found in plants, especially legumes. PHA actually consists of two closely related proteins, called leucoagglutinin (PHA-L) and PHA-E. The letters E and L indicate these proteins agglutinate Erythrocytes and Leukocytes. Phytohaemagglutinin has carbohydrate-binding specificity for a complex oligosaccharide containing galactose, N-acetylglucosamine, and mannose.
It is found in the highest concentrations in uncooked red kidney beans and white kidney beans (also known as cannellini), and it is also found in lower quantities in many other types of green beans and other common beans (Phaseolus vulgaris), as well as broad beans (Vicia faba) such as fava beans. It has a number of physiological effects and is used in medical research. In high doses, it is a toxin.
The lectin has a number of effects on cell metabolism; it induces mitosis, and affects the cell membrane in regard to transport and permeability to proteins. It agglutinates most mammalian red blood cell types.
As a toxin, it can cause poisoning in monogastric animals, such as humans, through the consumption of raw or improperly prepared kidney beans. Measured in
SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12).
Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the intercrine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The intercrines are characterized by the presence of 4 conserved cysteines that form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, which includes beta chemokine, the cysteine residues are adjacent to each other. In the CXC subfamily, which includes alpha chemokine, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group.
SDF-1 is produced in two forms, SDF-1α/CXCL12a and SDF-1β/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid.
CXCL12 is strongly chemotactic for lymphocytes. During
Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.
The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by receptor-associated kinases and then form homo- or heterodimers that translocate to the cell nucleus, where they act as transcription activators. This protein is activated through phosphorylation of tyrosine 705, in response to various cytokines and growth factors including interferons, epidermal growth factor, Interleukin 5, Interleukin-6, hepatocyte growth factor, leukemia inhibitory factor (LIF), bone morphogenetic protein 2 and also the hormone leptin. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. Three alternatively spliced transcript variants encoding distinct isoforms have been described.
The binding of Interleukin
The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 30 base pairs upstream of the transcription start site in some eukaryotic gene promoters. TBP, along with a variety of TBP-associated factors, make up the TFIID, a general transcription factor that in turn makes up part of the RNA polymerase II preinitiation complex. As one of the few proteins in the preinitiation complex that binds DNA in a sequence-specific manner, it helps position RNA polymerase II over the transcription start site of the gene. However, it is estimated that only 10-20% of human promoters have TATA boxes. Therefore, TBP is probably not the only protein involved in positioning RNA polymerase II.
TBP is involved in DNA melting (double strand separation) by bending the DNA by 80° (the AT-rich sequence to which it binds facilitates easy melting). The TBP is an unusual protein in that it binds the minor groove using a β sheet.
Another distinctive feature of TBP is a long string of glutamines in the N-terminus of the protein. This region modulates the DNA binding activity of the C-terminus, and modulation of