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Connective Tissue Growth Factor belongs to the CCN family of proteins. The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). The CCN genes encode secreted proteins associated with the Extracellular Matrix (ECM) and cell membrane. CCN proteins are matricellular proteins which are involved in the regulation of various cellular functions including: proliferation, differentiation, survival, adhesion and migration. They are expressed in derivatives of the three embryonic sheets and are implicated in the development of kidney, nervous system, muscle, bone marrow, cartilage and bone. During adulthood, they are implicated in wound healing, bone fracture repair, and pathologies such as: fibrosis, vascular ailments and tumorigenesis.
Full length secreted CCN proteins can show an antiproliferative activity, whereas truncated isoforms are likely to stimulate proliferation and behave as oncogenes. The full length protein consists of four modulesModule I shares partial identity with the N-terminal part of the Insulin-like Growth Factor Binding Proteins (IGFBPs).
Module II includes a stretch of 70amino acid residues – which shares sequence identity with the Von Willebrand Factor Type C repeat (VWC).
Module III contains sequences sharing identity with the Thrombospondin type 1 repeat (TSP1) (WSXCSXXCG), which is thought to be implicated in the binding of sulfated glycoconjugates and to be important for cell adhesion. Module IV, also designated CT, is encoded by exon5. It is the leasts conserved one of the four domains at the level of nucleotide sequence, but it appears to be critical for several of the biological functions attributed to the CCN proteins. Module IV resembles the CT domain of several extracellular protein including, Von Willebrand's factor and mucins. Sequence similarities to heparin-binding motifs are also found within this domain.
Proteolysis of the secreted full-length CCN proteins that has been reported in the case of CCN2 and CCN3 might result in the production of CCN-derived peptides with high affinity for ligands that full-length CNN proteins bind only poorly. Amino-truncated CCN2 isoforms were biologically active whereas no specific biological activity has been attributed to the truncated CCN3. Although the molecular processes underlying the production of these secreted isoforms is presently unknown, it is important to note that proteolysis occur at the same amino acid residues in both CCN2 and CCN3. An elevated expression of CCN2 has also been detected by Northern blotting in human invasive mammary ductal carcinomas, dermatofibromas, pyogenic granuloma, endothelial cells of angiolipomas and angioleiomyomas, and in pancreatic tumors. A study performed with chondrosarcomas representative of various histological grades established that CCN2 expression was closely correlated with increasing levels of malignancy. In agreement with CCN2 playing a role in brain tumor angiogenesis, immunocytochemistry studies indicated that both glioblastoma tumor cells and proliferating endothelial cells stained positive for CCN2. In astrocytomas, CCN2 expression was particularly elevated in high grade tumors, with a marked effect of CCN2 on cell proliferation. Downregulation of CCN2 expression in these cells was associated with a growth arrest at the G1/S transition while over-expression of CCN2 induced a two-fold increase of the number of cells in the G1 phase. Gene profiling analysis allowed to identify a set of about 50 genes whose expression might account for the proliferative activity of CCN2 in these cells. CCN2 was seen in a higher proportion of mononuclear cells of patients with acute lymphoblastic leukemia.

Low affinity immunoglobulin gamma Fc region receptor III-A (FCGR3A) is a receptor for the Fc portion of immunoglobulin G, and is involved in the elimination of antigen-antibody complexes from the circulation, as well as other antibody-dependent responses. FCGR3A needs to associate with the gamma subunit of Fc epsilon. The FCGR3A receptor is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, while FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. In addition, FCGR3A is expressed on macrophages, subpopulation of T-cells, immature thymocytes and placental trophoblasts. FCGR3A mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis. FCGR3A gene mutations are linked with susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia.

LY86 is vital for effective CD180 cell surface expression and is vastly expressed in B-cells, tonsil and monocytes. LY86 collaborate with TLR4 and CD180 to facilitate the essential immune response to bacterial lipopolysaccharide (LPS) and cytokine production.

Sjogren syndrome/scleroderma autoantigen 1, SSSCA1 is involved in mitosis. SSSCA1 is a centromere-associated protein which can induce anti-centromere antibodies. In addition SSSCA1 is recognized by a subset of anti-centromere antibodies from patients with sclerodermaand Sjogren's syndrome.

Synaptotagmin-4 (SYT4) is a part of the synaptotagmin proteins family. Synaptotagmins are a large gene family of synaptic vesicle type III integral membrane proteins that operate as regulators of both exocytosis and endocytosis and are involved in neurotransmitter secretion from small secretory vesicles. SYT4 is expressed in neuronal tissues, and has the highest mRNA levels in the hippocampus. The proximity of the SYT4 gene to markers of several psychiatric disorders implies an involvement of SYT4 in human disease such as pheochromocytoma, and parkinson's disease.

Tubulin folding cofactor C (TBCC) is a member of the TBCC family. TBCC has a role in the control of centrosome and Golgi apparatus positioning, with effects on cell shape and cell migration. Cofactor C is 1 of 4 proteins (cofactors A,D,E and C) engaged in the pathway leading to properly folded b-tubulin from folding intermediates. Cofactor E attaches to the cofactor D/beta-tubulin complex; their interaction with cofactor C subsequently causes the release of beta-tubulin polypeptides which are bound to the native state.

Coiled-Coil Domain Containing 69, also known as CCDC69 is a protein-coding gene. A significant paralog of CCDC69 is MTUS1.

Galactose-1-Phosphate Uridylyltransferase (GALT) catalyzes the 2nd step of the “Leloir pathway” of galactose metabolism, specifically the conversion of UDP-glucose + galactose-1-phosphate to glucose-1-phosphate + UDP-galactose. The deficiency of the GALT enzyme results in typical galactosemia in humans and may be fatal in the newborn stage if lactose is not eliminated from the diet. Galactosemia pathophysiology has not been clearly defined.

GCSF is a cytokine that controls the production, differentiation, and function of granulocytes. The active protein is found extracellularly. Three transcript variants encoding three different isoforms have been found for this gene.
Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This csf induces granulocytes.

Mesenchymal epithelial transition factor (c-MET) is a proto-oncogenic receptor tyrosine kinase. The endogenous ligand for c-MET is HGF (hepatocyte growth factor), which is a disulfide-linked heterodimeric molecule produced predominantly by mesenchymal cells. In the adult, c-MET protein expression is limited to stem and progenitor cells and is required for wound healing and hepatocyte regeneration. In the embryo, c-MET receptors are expressed on cells of epithelial origin, which are vital for invasive growth and mediate epithelial-mesenchymal transition (EMT). Abnormal activation of the HGF/MET pathway leads to a variety of cancers. c-MET mutation is linked with a poor prognosis since it can trigger tumor growth, angiogenesis and metastasis.

Endoglin is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex.
The protein consists of a homodimer of 180 kDA with disulfide links. It has been found on endothelial cells, activated macrophages, fibroblasts, and smooth muscle cells. Endoglin has been found to be part of the TGF-beta1 receptor complex. It thus may be involved in the binding of TGF-beta1, TGF-beta3, activin-A, BMP-2, and BMP-7. Beside TGF-beta signaling endoglin may have other functions. It has been postulated that endoglin is involved in the cytoskeletal organization affecting cell morphology and migration. Endoglin has a role in the development of the cardiovascular system and in vascular remodeling. Its expression is regulated during heart development . Experimental mice without the endoglin gene die due to cardiovascular abnormalities.

N-Acetylglucosamine Kinase (NAGK) is a part of the eukaryotic-type N-acetylglucosamine kinase family. NAGK transforms endogenous N-acetylglucosamine (GlcNAc), a main component of complex carbohydrates, from lysosomal degradation or nutritional sources into GlcNAc 6-phosphate. NAGK is a significant salvage enzyme of amino sugar metabolism in mammals which has ManNAc kinase activity.

NANS is a 359 amino acid protein that contains one AFP (antifreeze proteins)-like domain and functions in the biosynthesis of sialic acids. The ubiquitously expressed NANS enzymatically catalyzes the H2O-dependent formation of N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), both of which are sialic acids. NANS uses N-acetylmannosamine 6-phosphate as a substrate for Neu5Ac synthesis and mannose 6-phosphate as a substrate for KDN synthesis.

Myristate, a rare 14-carbon saturated fatty acid, is co-translationally attached by an amide linkage to the N-terminal glycine residue of cellular & viral proteins with various functions. N-Myristoyltransferase 1, also known as NMT1 catalyzes the transfer of myristate from CoA to proteins. NMT1 seems to be irreversible and is essential for full expression of the biologic activities of several N-myristoylated proteins, as well as the alpha subunit of the signal-transducing guanine nucleotide-binding protein, G protein.

PAIP2 has a role as a repressor in the regulation of translation initiation of poly(A)-containing mRNAs. PAIP2 inhibitory activity on translation is mediated through its action on PABPC1. PAIP2 displaces the interaction of PABPC1 with poly(A) RNA and competes with PAIP1 for binding to PABPC1. PAIP2 association with PABPC1 results in disruption of the cytoplasmic poly(A) RNP structure organization.

FKBP6 is part of the immunophilin protein family, and is involved in immunoregulation and basic cellular functions involving protein folding and trafficking. FKBP6 is widely expressed in all tissues, FKBP6 is present at utmost levels in testis, liver, kidney, skeletal muscle and heart. Deletion of FKBP6 contributes to hypercalcemia and growth delay in Williams-Beuren syndrome.

Adiponectin is a recently discovered 244 amino acid protein, the product of the apM1 gene, which is physiologically active and specifically and highly expressed in adipose cells (Adipokine). The protein belongs to the soluble defense collagen super family; it has a collagen-like domain structurally homologous with collagen VIII and X and complement factor C1q-like globular domain. APM-1 forms homotrimers, which are the building blocks for higher order complexes found circulating in serum.

MMP-1 (interstitial collagenase) can break down a wide range of substrates including types I, II, III, VII, VIII, and X collagens as well as L-Selectin, pro-TNF, IGFBP-3, IGFBP-5, casein, gelatin, myelin basic protein, pro-MMP2 and pro-MMP9. A significant function of MMP-1 is the degradation of fibrillar collagens in extracellular matrix remodeling. MMP-1 is expressed in fibroblasts, keratinocytes, endothelial cells, monocytes and macrophages. MMP1 can be divided into a number of distinct domains: a prodomain which is cleaved on activation, a catalytic domain containing the zinc binding site and a short hinge region with a carboxyl terminal domain. MMP1 is part of a cluster of MMP genes which localize to chromosome 11q22.3.

Antigen 85A is a member of the antigen 85 complex (Antigen 85A, B, C). The enzymes of the antigen 85 complex have mycolyltransferase activity and catalyze the synthesis of the very rich glycolipid of the mycobacterial cell wall, the cord factor (trehalose 6,6'-dimycolate, TDM). The cord factor is vital for the integrity of the mycobacterial cell wall and pathogenesis of the bacillus. TDM is synthesized from two molecules of trehalose-6'-monomycolate (TMM) by Antigen 85A.

SDCBP2 has two class II PDZ domains. PDZ domains assist protein-protein interactions by attaching to the cytoplasmic C-terminus of transmembrane proteins, and PDZ-containing proteins mediate cell signaling and the organization of protein complexes. SDCBP2 attaches to phosphatidylinositol 4, 5-bisphosphate (PIP2) and take part in nuclear PIP2 arrangement and cell division.

CD166 antigen isoform 2 (ALCAM) is a type 1 membrane glycoprotein and belongs to the immunoglobulin superfamily. ALCAM is expressed on thymic epithelium, microvascular endothelium, activated lymphocytes and monocytes, and monocyte-derived dendritic cells. CD166 and CD6 interaction plays a role in T cell development and T cell regulation, as well as in the binding of T cells and B cells to activated leukocytes.

Selenoprotein W 1, also known as SEPW1 is a selenoprotein, which has a selenocysteine (Sec) residue at its active site. The selenocysteine is encoded through the UGA codon which normally signals translation termination. The 3' UTR of selenoprotein genes share a common stem-loop structure, the sec insertion sequence (SECIS), which is essential for the recognition of UGA as a Sec codon instead of as a stop signal. SEPW1 shows highest expression in skeletal muscle and heart, and also involved in oxidation-reduction reactions.

Olfactomedin 1 (OLFM1), also known as noelin, shares expansive sequence similarity with the rat neuronal olfactomedin-related ER localized protein. OLFM1 plays a vital role in regulating the production of neural crest cells by the neural tube.

Exosome component 8 and transcription factor 4 (EXOSC8) is a part of the exosome complex. In the cytoplasm, the RNA exosome complex is engaged in general mRNA turnover and specifically degrades naturally unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA inspection pathways, preventing translation of aberrant mRNAs. EXOSC8 appears to be involved in degradation of histone mRNA. EXOSC8 attaches to ARE-containing RNAs. The EXOSC8 gene encodes a 3'-5' exoribonuclease, which specifically interacts with mRNAs containing AU-rich elements. The EXOSC8 protein is part of the exosome complex, which is significant for the degradation of many RNA species.