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Neuregulin/Heregulin is a family of structurally related polypeptide growth factors which are stemmed from alternatively spliced genes (NRG1, NRG2, NRG3 and NRG4). Thus far, there are more than 14 soluble and transmembrane proteins derived from the NRG1 gene. Proteolytic processing of the extracellular domain of the transmembrane NRG1 isoforms release soluble growth factors. HRG1-b1 is comprised of an Ig domain and an EGF-like domain which is necessary for direct binding to receptor tyrosine kinases erb3 and erb4. This binding stimulates erb3 and erb4 heterodimerization with erb2, promoting intrinsic kinase activity, which results in tyrosine phosphorylation. Even though HRG1-b1 biological effects are still unclear, it has been discovered to advance motility and invasiveness of breast cancer cells which in addition might entail up-regulation of expression and function of the autocrine motility-promoting factor (AMF).

FGF-23 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF-23 inhibits renal tubular phosphate transport. This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets (ADHR), an inherited phosphate wasting disorder. Abnormally high level expression of FGF23 was found in oncogenic hypophosphatemic osteomalacia (OHO), a phenotypically similar disease caused by abnormal phosphate metabolism. Mutations FGF23 have also been shown to cause familial tumoral calcinosis with hyperphosphatemia.

The Recombinant Protein L is comprised of 5 kappa-binding domains. Protein L has the exceptional ability to bind through kappa light chain interactions without hindering with the antibody’s antigen-binding site. This gives Protein L the capacity to bind a broader range of Ig classes and subclasses than other antibody-binding proteins. The recombinant Protein L is perfect for purification of polyclonal or monoclonal IgG antibodies. Protein L binds to IgG from humans, mice, rats and pigs.

MTHSFD, also known as Methenyltetrahydrofolate Synthetase Domain Containing protein, is linked to Pancreas, Annular and Gastrointestinal Defects. It has also been associated with Immunodeficiency Syndrome. Some of the Gene Ontology annotations that are related to the MTHSFD gene are nucleic acid binding and nucleotide binding.

ERO1-like protein alpha (ERO1L) is an essential oxidoreductase, which oxidizes proteins and is necessary for the folding of immunoglobulins. ERO1L covalently binds with PDI (protein disulfide-isomerase) and jointly they generate disulfide bonds between proteins in the endoplasmic reticulum. ERO1L is stimulated by hypoxia, proposing that ERO1L is regulated through the HIF (hypoxia inducible transcrip-tion factor) pathway. At low levels ERO1L is ubiquitously expressed, however at high levels it is expressed in the upper digestive tract and esophagus. In addition, ERO1L is involved in the release of the unfolded cholera toxin from reduced P4HB/PDI in case of infection by V.cholerae, thus having a role in retrotranslocation of the toxin. Furthermore, ERO1L plays an important role in ER stress-induced, CHOP-dependent apoptosis by activating the inositol 1,4,5-trisphosphate receptor IP3R1.

RALY belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) gene family. RALY takes part in pre-mRNA splicing and also in embryonic development. Moreover, alternate splicing results in multiple transcript variants have been found for RALY.

Pancreatitis-associated protein (PAP) is a secretory protein not normally expressed in healthy pancreas but highly induced during acute pancreatitis. While PAP has been shown to be anti-bacterial and antiapoptotic in vitro, its definitive biological function in vivo is not clear. Using antisepse oligonucleotides, inhibition of PAP expression significantly worsened pancreatitis in a rat model. During pancreatitis, PAP released by the pancreas could mediate lung inflammation through induction of hepatic TNF- alpha expression and subsequent increase in circulating TNF-alpha.
PAP is activated in primary liver cancers. In normal liver, the protein is undetectable in normal mature hepatocytes and found only in some ductular cells, representing potential hepatic progenitor cells. PAP can be considered hepatic cytokine that combines mitogenic and anti-apoptotic functions regarding hepatocytes, and consequently acts as a growth factor in vivo to enhance liver regeneration. In pancreatic cancor, PAP was overexpressed in 79% (30 of 38) of pancreatic ductal adenocarcinoma, 19% (7 of 36) of chronic pancreatitis, and 29% (2 of 7) of mucinous cystadenoma. PAP was found in malignant ductular structures in pancreatic carcinomas as well as in benign proliferating ductules and acinar cells in chronic pancreatitis. Elevation of PAP in patients with pancreatic cancer is not merely explainable by concomitant pancreatitis, but seems to be due to increased PAP production by the cancer cells and is also correlated to tumour load as expressed by the UICC stages.
Epithelial expression of PAP was induced under intestinal mucosal inflammation initiated by exposure to commensal bacteria or DSS as well as inflamed IBD colon. Increased serum level of PAP diagnosed ileal location in active Crohn disease with a sensitivity of 60%, a specificity of 94%, a positive predictive value of 84% and a negative predictive value of 81%. Elevated serum PAP (> 50 ng/mL) is significantly associated with disease activity and ileal location of Crohn disease.

Histidine triad nucleotide-binding protein 2 (HINT2) belongs to the triad proteins, which are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides. Hydrolase is most likely involved in steroid biosynthesis, furthermore it might play a role in apoptosis. HINT2 shows high expression in liver and pancreas. Expression is significantly down-regulated in hepatocellular carcinoma (HCC) patients.

MRPL28 is found in a variety of normal tissues such as spleen, testis, thymus, liver, kidney, brain, adrenal, lung and retinal tissue. 39S ribosomal protein L28, mitochondrial (MRPL28), is a part of the ribosomal protein L28P family. Mammalian mitochondrial ribosomal proteins encoded by nuclear genes and helps in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. MRPL28 is an important therapeutic reagent for HLA-A24 (A24) patients since this antigen is distinguished by tumor-infiltrating lymphocyte (TIL) 1290, which targets the A24 serotype.

Heterogeneous Nuclear Ribonucleoprotein A/B (HNRNPAB) is a member of the subfamily of ubiquitously expressed heterogeneous nuclearribonucleoproteins (hnRNPs). The hnRNPs are produced by RNA polymerase II and are components of theheterogeneous nuclear RNA (hnRNA) complexes. They are linked with pre-mRNAs in the nucleus and seem to influence pre-mRNA processing and further aspects of mRNA metabolism and transport. Whereas all of the hnRNPsare present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. HNRNPAB, which binds to one of the components of the multiproteineditosome complex, has two repeats of quasi-RRM (RNA recognition motif) domains that bind to RNAs. Among the diseases associated with HNRNPAB are wells syndrome, and cystic fibrosis.

Omentin is a recently recognized gene highly localized to the mental tissue (visceral adipose tissue). Omentin is present in the stromal vascular cells in the adipose tissue rather than in the adipocytes. Omentin is predominantly expressed in the visceral adipose tissue than the subcutaneous tissue, with the omentin mRNA being 150 times higher in the visceral adipose tissue. Omentin has also been detected in human blood using western blot analysis, and seems to increase insulin-stimulated glucose uptake in 3T3-L1 adipocytes in mice. Omentin seems to increase Akt phosphorylation irrespective of insulin presence. Its role in glucose metabolism and obesity remains to be described; an insulin-sensitizing action is possible.Differences in Omentin expression has been noted in adipose tissue from normals and patients with inflammatory bowel disease although its significance is unknown.

OTOR proteins is also known as fibrocyte-derived protein (Fdp) and Melanoma inhibitory activity-like (MIAL). Otoraplin is a member of the melanoma-inhibiting activity gene family. Otoraplin is a secreted 16 kDa globular protein that is expressed in the inner ear by periotic mesenchyme and developing and mature fibrocytes. OTOR is highly homologous to MIA/cartilage-derived retinoic acid-sensitive protein (CD-RAP), which is a cartilage-specific protein that is also expressed in malignant melanoma cells. The 111 amino acid mature human otoraplin contains 1 SH3 domain (46 – 107 amino acids) and a Tyr at position 50 that is reportedly sulfated. Otoraplin takes pasrt in the initiation of periotic mesenchyme chondrogenesis.
Otoraplin is secreted through the Golgi apparatus and plays a role in cartilage development and maintenance. A frequent polymorphism in the translation start codon of OTOR can abolish translation and may be associated with forms of deafness.

MRG-binding protein (MRGBP or C20ORF20) is a 204 amino acid protein which is a part of the NuA4 histone acetyltransferase (HAT) complex that functions to acetylate histone H2A and H4. The HAT complex may be essential for the activation of transcriptional programs linked with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. C20ORF20 also has a potential to interact with MORF4L1/MRG15 and MORF4L2/MRGX.

TES also called Testin is a tumor suppressor protein which is involved in cell adhesion, cell spreading and in the restructuring of the actin cytoskeleton. TES protein localizes to cell-cell contacts and actin stress fibres, and interacts with a diversity of cytoskeletal proteins such as Zyxin, Mena, VASP, Talin and Actin. The ability of TES to associate with alpha-actinin, paxillin and Zyxin is dependent on the conformational form of the protein.

Fibroblast Growth Factors (FGFs) comprise a family of at least eighteen structurally realted proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentation, angiogenesis, wound healing and tumorgenesis. The biological activities of the FGFs are mediated by a family if type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGFR-1to -4 are known. Multiple forms of FGFR-1 to -3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGFR-1 and -2 results in receptors containing all three Ig domains, referred to as the alpha isoform, or only IgII and IgIII, referred to as the ? isoform. Only the alpha isoform has been identified for FGFR-3 and FGFR-4. Additional splicing events for FGFR-1 to -3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. Mutations in FGFR-1 to -3 have been found in patients with birth defects involving craniosynostosis.

Prohibitin (PHB) is an evolutionarily conserved gene that is ubiquitously expressed and which Mutations have been linked to sporadic breast cancer. PHB is thought to be a negative regulator of cell proliferation and may be a tumor suppressor. Prohibitin is expressed as two transcripts with changeable lengths of 3' untranslated region. The longer transcript is present at higher levels in proliferating tissues and cells, proposing that this longer 3' untranslated region functions as a trans-acting regulatory RNA.

The La protein is a 47 kDa polypeptide that frequently acts as an autoantigen in systemic lupus erythematosus and Sjogren's syndrome patients. La is involved in various aspects of RNA metabolism, including binding and protecting 3-prime UUU(OH) elements of newly RNA polymerase III - transcribed RNA, processing 5-prime and 3-prime ends of pre-tRNA precursors, acting as an RNA chaperone, and binding viral RNAs linked to hepatitis C virus. It occurs in both the nucleus and the cytoplasm, where it assumes different roles. In the nucleus, La protein facilitates the production of tRNAs, acting as an RNA polymerase III (RNAP III) transcription factor by attaching to the U-rich 3'UTR of nascent transcripts, aiding in their folding and maturation. In the cytoplasm, La protein facilitates the translation of specific mRNAs, acting as a translation factor. As an RNA binding protein (RBP), La protein associates with subsets of mRNAs which contain a 5'-terminal oligopyrimidine (5'TOP) motif known to direct protein synthesis. The binding of La protein to particular classes of RNA molecules regulates their downstream processing, guards them from endonuclease digestion, and organizes their export from the nucleus. La/SS-B appears to be readily disposed to proteolysis, which results in many smaller (42kD, 320, and 270) nevertheless still immunoreactive polypeptides. La/SS-B antigen is strongly conserved across species. Anti-La/SS-B autoantibodies were originally found as precipitating autoantibodies in sera of Sjogren's Syndrome patients and referred to as SjT. Anti-La/SS-B precipitins are most frequently found in Sjogren's Syndrome, Systemic Lupus Erythematosus (SLE) and Subacute Cutaneous Lupus. Also, there seems to be a correlation between anti-La/SS-B and the absence of nephritis in SLE patients.

Heat-stable enterotoxins (STa) are small, cysteine-rich peptides secreted by Escherichia coli that are able to induce diarrhea through the stimulation of an intestine-specific receptor-guanylyl cyclase known as STaR. Binding of STa to STaR induces a dramatic increase in the cGMP content of the cell; the increase, in turn, inhibits salt absorption and stimulates chloride secretion. This imbalance of ions is accompanied by a massive accumulation of water in the gut that gives rise to the diarrhea and dehydration characteristic of enterotoxin activity. The identification of a receptor for STa on intestinal brush border membranes suggested the existence of an endogenous activator, described guanylin, a 15-amino acid peptide purified from rat small intestine, as a potential ligand for the STaR. This peptide shares sequence similarity with STa; see also uroguanylin. The molecular cloning of the human and mouse cDNAs encoding guanylin was reported. The sequences demonstrated that guanylin is present at the C-terminal end of a larger precursor protein. Expression in mammalian cells indicated that the 94- amino acid proguanylin is inactive. The biologically active guanylin can be released by either chemical or enzymatic treatment of proguanylin. By Northern blot analysis and in situ hybridization, showed that expression of guanylin mRNA is restricted to cells of the intestinal epithelium, specifically the Paneth cells at the base of the small intestinal crypts. These results demonstrate that guanylin is an endogenous activator of STaR isolated a cDNA encoding an apparent precursor of guanylin from a human intestinal cDNA library. The mRNA was expressed at high levels in human ileum and colon. In the mouse, interspecific backcross analysis used to map the Guca2 gene to the distal half of mouse chromosome 4 in a region of homology with human chromosome 1p. By fluorescence in situ hybridization mapped the GUCA2 gene to human 1p35-p34 Guanylin is thought to modulate intestinal water/electrolyte transport in a paracrine mode reported the nucleotide sequence of the gene, the characteristics of its circulating molecular form, and its localization in enterochromaffin cells of the gut. The gene, approximately 2.6 kb in size, consists of 3 exons interrupted by 2 introns. The hormonal form of guanylin is a 94-amino acid peptide with a molecular mass of 10.3 kDa. Guanylin is synthesized by gut enterochromaffin cells as a prohormone of 115 amino acids and is processed to the molecular form of 94 amino acids circulating in the blood.

UGDH is part of the UDP-glucose/GDP-mannose dehydrogenase family and is a widely expressed enzyme localized in the liver. UGDH transfers UDP-glucose to UDP-glucuronate and thus takes part in the biosynthesis of glycosaminoglycans such as hyaluronan, chondroitin sulfate, and heparan sulfate. These glycosylated products are ordinary molecules of the extracellular matrix and participate in signal transduction, cell migration, and cancer growth and metastasis.

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. The expression of this receptor is induced by lymphocyte activation. TRAF adaptor proteins have been shown to bind to this receptor and transduce the signals leading to activation of NF-kappaB.

Osteostat is the cytokine that binds to TNFRSF18/AITR/GITR and is important for interactions between activated T-lymphocytes and endothelial cells and may modulate T-lymphocyte survival in peripheral tissues. Osteostat is expressed at high levels in the small intestine, ovary, testis, kidney and endothelial cells after stimulation by lipopolysaccharides.
Osteostat protein is detectable in human microvascular EC and is highly up-regulated by IFN-alpha and IFN-beta. Osteostat inhibit differentiation of osteoclasts from monocytic precursor cells. Osteostat suppresses the early stage of osteoclastogenesis via inhibition of macrophage colony-stimulating factorinduced receptor activator of NF-kappaB (RANK) expression in the osteoclast precursor cells. Osteostat does not inhibit lipopolysaccharide-induced RANK expression in monocytes and dendritic cells, or activation-induced RANK expression in T cells. Osteostat is a novel regulator of osteoclast generation and substantiate the major role played by the endothelium in bone physiology.

Dimethylarginine dimethylaminohydrolase 1, is a part of the Dimethylarginine Dimethylaminohydrolase gene family. DDAH1 participates in nitric oxide generation by regulating cellular concentrations of methylarginines, that in turn inhibit nitric oxide synthase activity. Deficiency of DDAH1 results in ADMA (asymmetric dimethylarginine) increase and a decrease in cGMP generation.

Heterogeneous Nuclear Ribonucleoprotein K, also known as HNRNPK, is a part of the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). HNRNPK takes part in p53/TP53 reaction to DNA damage, acting at the level of both transcription activation and repression. HNRNPK is located in the nucleoplasm and has 3 repeats of KH domains which bind to RNAs.

Hematopoietic Prostaglandin D Synthase (HPGDS) belongs to the sigma class glutathione-S-transferase family. The HPGDS enzyme catalyzes the conversion of PGH2 to PGD2 and has a role in the production of prostanoids in the immune system and mast cells. The presence of the HPGDS enzyme can be utilized to identify the differentiation stage of human megakaryocytes. Furthermore, HPGDS is a prostaglandin involved in smooth muscle contraction/relaxation and an effective inhibitor of platelet aggregation, and the conjugation of glutathione with a extensive range of aryl halides and organic isothiocyanates. In addition, HPGDS displays low glutathione-peroxidase activity towards cumene hydroperoxide. HPGDS is expressed in a number of megakaryocytic cell lines but not in platelets. HPGDS is highly expressed in the adipose tissue, macrophages and placenta; however it is expressed at lower levels in the lung, heart, lymph nodes, appendix, bone marrow and fetal liver.