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Matrix Metalloproteinase-13 (MMP-13) is an enzyme that is a member of the MMP extracellular protease family. Extracellular protease enzymes, by virtue of their broad substrate specificities1, play a role in both normal and disease states of tissue proliferation. Among the targets of MMP-13 are collagen, gelatin, entactin, pro-TNF-a, and chemokine SDF-11-4.
MMP-13 is found in its latent form as a 52-56 kDa glycosylated proenzyme. Upon cleavage the 22-46 kDa5 MMP-1 becomes active in extracellular matrix remodeling.
Because of the prominent role that MMP-1 plays in cell migration and metastasis, it is an important target for inhibition screening.

S100G (calbindin D9K) is a vitamin D-dependent calcium-binding protein. S100G, which is a cytosolic protein, is a member of a family of calcium-binding proteins that includes calmodulin, parvalbumin, troponin C, and S100 protein. In the intestine, S100G is vitamin D-dependent and its expression correlates with calcium transport activity. S100G may increase Ca2+ absorption by buffering Ca2+ in the cytoplasm and increase ATP-dependent Ca2+ transport in duodenal basolateral membrane vesicles.

Fetuin is a liver-produced negative acute phase protein composed of two subunits, the A and B chains.
Fetuin homologs have been identified in several species including rat, sheep, pig, rabbit, guinea pig, cattle, mouse and human. Multiple physiological roles for these homologs have been suggested, including ability to bind to hydroxyapatite crystals and to specifically inhibit the tyrosine kinase (TK) activity of the receptor (IR).
Fetuin-A (alpha2-Heremans-Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response.
Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit CaxPO4 precipitation.
Fetuin may influence the resolution of inflammation by modulating the phagocytosis of apoptotic cells by macrophages.
ASHG blocks TGF-beta-dependent signaling in osteoblastic cells, and mice lacking ASHG display growth plate defects, increased bone formation with age, and enhanced cytokine-dependent osteogenesis.

Amine Oxidase Copper Containing 3 , also referred to AOC3, a copper amine oxidase with a topaquinone cofactor.
AOC3 is a cell adhesion protein which participates in recirculation & extravasation of lymphocyte by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin independent fashion.
Amine Oxidase Copper Containing 3 acts in adipogenesis.
The protein catalyzes the oxidative deamination of small primary amines such as methylamine, benzylamine & aminoacetone in a reaction that produces an aldehyde, ammonia and H2O2.

Hsp70-binding protein 1 (HSPBP1) is a member of a family of eukaryotic proteins identified as nucleotide exchange factors for HSP 70 that exhibit varying degrees of compartment and species specificity. HSPBP1 is localized mainly in cytoplasm and nucleus but is also found extracellularly. HSPBP1 is mostly expressed in heart and skeletal muscle .HSPBP1 binds to HSP 70, inhibits its activity and promotes dissociation of nucleotides from the HSP 70 ATPase domain. In addition, HSPBP1 inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and obstructing the ATP binding. HSPBP1 may also have a role in tumor (dys)regulation of chaperone proteins. Furthermore, HSPBP1 hinders ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR.

SLPI is a secreted inhibitor which guards epithelial tissues from serine proteases. SLPI is localized in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. SLPI inhibitory effect contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes. SLPI protein has broad-spectrum anti-biotic activity. SLPI is an acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. SLPI prevents elastase-mediated damage to oral and mucosal tissues.

NFKB inhibitor interacting Ras-like 2 (NKIRAS2) is an inhibitor of the transcription factor NF-kappaB. NKIRAS2 is similar to the Ras-like small GTPases which associate with IkappaB. The Ras-like proteins- NKIRAS1 and NKIRAS2, interact with the PEST domains of I?B? and I?B? and reduce their rate of degradation. NKIRAS2 is an atypical Ras-like protein which functions as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more impervious to degradation.

Nogginwhich is encoded by the NOG gene, binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signaling proteins, such as bone morphogenetic protein-4 (BMP4). By diffusing through extracellular matrices more efficiently than members of the TGF-beta superfamily, noggin may play and important role in creating morphogenic gradients. Noggin appears to have pleiotropic effect, both early in development as well as in later stages. Noggin was originally isolated from Xenopus based on its ability to restore normal dorsal-ventral body axis in embryos that had been artificially ventralized by UV treatment. The results of the mouse knockout of noggin suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation. There are several dominant human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1). All NOG mutations altered evolutionarily conserved amino acid residues. The amino acid sequence of human noggin is highly homologous to that of Xenopus, rat and mouse.

EFNB1 is a member of the Eph family. The cell-surface proteins Ephrins split into two groups, ephrin-A and ephrin-B, based on their structure and function and perform as ligands for Eph receptors. The transmembrane EFNB1 proteins have conserved cytoplasmic tyrosine residues that are phosphorylated upon interaction with an EphB receptor. In addition, EFNB1 transduces outside-in signals by C-terminal protein interfaces which influence integrin-mediated cell attachment and migration.

BAFF binds to tnfrsf13b/taci and tnfrsf17/bcma. Tnfsf13/april binds to the same 2 receptors, together, they form a 2 ligands -2 receptors pathway involved in the stimulation of b- and t-cell function and the regulation of humoral immunity. A third b-cell specific baff-receptor (baffr/br3) promotes the survival of mature b-cells and the b-cell response.
B Lymphocyte Stimulator functions as a potent B-cell growth factor in costimulation assays.
Administration of BAFF Human recombinant to mice disrupts splenic B-cell and T-cell zones and results in elevated levels of serum immunoglobulin.

SOX2 is a transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206. SOX4 is important for early embryogenesis and for embryonic stem cell pluripotency.

BAG3 Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. BAG3 has anti-apoptotic activity. BAG proteins participate with Hip for their binding to Hsc70/Hsp70 ATPase domain and encourage substrate release. BAG proteins have about 45 amino acid BAG domain close to the C terminus however they differ noticeably in their N-terminal regions. BAG3 includes a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact particularly with the Hsc70 ATPase domain in vitro and in mammalian cells. They bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. BAG3 plays a role as a protein-refolding cochaperone of the bcl2 binding protein BAG family and as upregulated in response to persistent stress of cellular calcium balance dysregulation. BAG3 has been shown to diminish stress-induced apoptosis.

SPINT2 is a transmembrane protein acts as an inhibitor of HGF activator. SPINT2 inhibits plasmin, plasma and tissue kallikrein, and factor XIa. SPINT2 has two extracellular Kunitz domains that inhibit few serine proteases. SPINT2 is assumed tumor suppressor, mutations in SPINT2 leads to a congenital sodium diarrhea.

Betaine-Homocysteine Methyltransferase 2 (BHMT2) is involved in the regulation of homocysteine metabolism. Homocysteine is a sulfur-containing amino acid which has a key role in methylation reactions. Transfer of the methyl group from betaine to homocysteine generates methionine, which donates the methyl group to methylate DNA, proteins, lipids, and other intracellular metabolites. BHMT2 is one of two methyl transferases which can catalyze the transfer of the methyl group from betaine to homocysteine. BHMT2 converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor. Homocysteine metabolism anomalies are implicated in disorders varying from vascular disease to neural tube birth defects such as spina bifida.

F-Box Protein 2 (FBXO2) is a part of the F-box protein family. The F-box proteins are one of the 4 subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which takes part in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes. FBXO2 belongs to the Fbxs class which contains either different protein-protein interaction modules or no recognizable motifs. FBXO2 is extremely similar to the rat neural F Box 42 kDa protein which is enriched in the nervous system and plays a role in maintaining neurons in a postmitotic state.

PDXP is the active form of vitamin B6 that functions as a coenzyme in preserving biochemical homeostasis. The desired degradation route from PLP to 4-pyridoxic acid involves the dephosphorylation of PLP by PDXP. PDXP shows activity to pyridoxal 5''-phosphate (PLP), pyridoxine 5''-phosphate (PMP) and Pyridoxine 5''-phosphate (PNP), with a highest activity with PLP followed by PNP.

Cerebral Cavernous Malformation 2, also known as CCM2 is a piece of the CCM signaling pathway which is a vital regulator of heart and vessel formation as well as integrity. CCM2 performs through the stabilization of endothelial cell junctions. In addition, CCM2 functions as a scaffold protein for MAP2K3-MAP3K3 signaling. CCM2 plays a key role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock. Mutations in CCM2 result in cerebral cavernous malformations. Multiple transcript variants encoding dissimilar isoforms have been discovered for CCM2.

Toll-interleukin1 receptor (TIR) domain containing adaptor protein (TIRAP) contains 1 TIR domain. TIRAP is an adapter molecule linked with toll-like receptors. TIRAP is required in TLR2 and TLR4 signaling pathways in the innate immune response. TIRAP activates NF-kappa-B, MAPK1, MAPK3 and JNK, which subsequently results in cytokine secretion and the inflammatory response. TIRAP is highly expressed in the liver, kidney, spleen, skeletal muscle and heart. TIRAP is also found in peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon and brain.

Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. The single FST gene encodes two isoforms, FST317 and FST344 containing 317 and 344 amino acids respectively, resulting from alternative splicing of the precursor mRNA. In a study in which 37 candidate genes were tested for linkage and association with polycystic ovary syndrome (PCOS) or hyperandrogenemia in 150 families, evidence was found for linkage between PCOS and follistatin. Follistatin binds directly to activin and functions as an activin antagonist. specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (fsh).

Tropomyosin alpha-3 chain (TPM3) belongs to the tropomyosin family of actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosins are dimers of coiled-coil proteins which polymerize end-to-end along the major groove in most actin filaments. Tropomyosins give stability to the filaments and regulate access of other actin-binding proteins. In muscle cells, tropomyosins regulate muscle contraction by controlling the binding of myosin heads to the actin filament. Mutations in the TPM3 gene cause autosomal dominant nemaline myopathy, and oncogenes formed by chromosomal translocations involving this locus are linked with cancer.

Procalcitonin is a peptide hormone mainly produced by the C cells of the thyroid and certain endocrine cells of the lung. Under normal expression conditions, procalcitonin is immediately cleaved into three specific fragments, an N terminal residue, calcitonin and katacalcin. Levels of unprocessed procalcitonin rise significantly after bacterial infection, trauma or shock.

Prosaposin (PSAP) is a precursor of 4 lysosomal saposin proteins (saposin A, B, C and D). Saposins are heat-stable glycoproteins which facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. PSAP stimulates neurite outgrowth and increases choline acetyltransferase activity. Prosaposin exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. The secreted prosaposin is assumed to have additional functions in human milk, cerebrospinal fluid and seminal plasma. PSAP gene mutations are linked with Gaucher disease, Tay-Sachs disease, and metachromatic leukodystrophy.

Mannose-6-Phosphate Receptor (M6PR) belongs to the P-type lectin family. P-type lectins play a vital role in lysosome function through the specific transport of mannose-6-phosphate-containing acid hydrolases from the Golgi complex to lysosomes. The M6PR protein functions as a homodimer and needs divalent cations for ligand binding. Lysosomal enzymes carrying phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the ensuing receptor-ligand complex is transferred to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex.

Hyaluronan And Proteoglycan Link Protein 1, which is also known as HAPLN1 is a part of the HAPLN family.HAPLN1 contains one Ig-like V-type domain and two Link domains. In the extracellular cartilage matrix, HAPLN1 stabilizes the aggregates of proteoglycan monomers by means of hyaluronic acid .