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CD70 also known as TNFSF7 is a cytokine which binds to CD27. TNFSF7 takes part in T-cell activation as well as induces the proliferation of costimulated T-cells. Moreover, TNFSF7 enhances the generation of cytolytic T-cells. Among the diseases which are associated with TNFSF7: Include acute myocarditis & Myocarditis.

Hepatoma-derived growth factor, related protein 3 (HDGFRP3/HDGF2) is the original member of a family of polypeptides labeled HDGF related proteins (HRPs). The HDGF2 protein augments DNA synthesis and may play a part in cell proliferation. HDGF2 is expressed primarily in the testis and the brain, to an intermediate extent in the heart, and to a slight extent in the ovaries, kidneys, spleen, and liver in humans.

Paraoxonase-1 or PON1 is part of the paraoxonase group of proteins. PON1 is an enzyme, responsible to the toxic metabolites of a different of organophosphorus insecticides hydrolyzation. Furthermore, PON1 is a dominant anti-atherosclerotic part of HDL. The enzyme needs PPAR-gamma for activation, leading to synthesis and release of paraoxonase 1 from the liver tissue, resulting in atherosclerosis reduction. PON1 has many qualities for atheroprotective through inflammatory lipid peroxides metabolism. This enzyme can hydrolyze a large number of substrates, for example cyclic carbonates, lactones, nerve gases etc.

Proteasome assembly chaperone 2 (PSMG2) stimulates assembly of the 20S proteasome as part of a heterodimer with PSMG1. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits and promotes compilation of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization. PSMG2 is widely expressed with highest levels in the lung, brain and colon. It is moderately expressed in the muscle, stomach, spleen and heart, and weakly expressed in the small intestine, pancreas and liver. It is also highly expressed in hepatocellular carcinomas with low levels in surrounding liver tissue.

Muted homolog (MUTED) is a component of the BLOC-1 complex, a complex which is necessary for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. The BLOC-1 complex is needed to steer membrane protein cargos into vesicles assembled at cell bodies for release into neurites and nerve terminals. In addition, this complex, along with SNARE proteins, is suggested to be involved in neurite extension. MUTED also interacts with pallidin, dystrobrevin binding protein 1 and CNO/cappuccino. MUTED is ubiquitously expressed with higher levels in the brain, bone marrow, kidney, and liver and lower levels in the skeletal muscle.

PRDX1 is part of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. PRDX1 is an important protector of red blood cells against reactive oxygen species and in tumor prevention.
PRDX1 is antioxidant protective in cells, and contributes to the antiviral activity of CD8(+) T-cells. PRDX1 has a proliferative effect and is involved in cancer development or progression.
Peroxiredoxin-1 is plays a role in redox regulation of the cell. Peroxiredoxin decreases peroxides with reducing equivalents provided through the thioredoxin system but not from glutaredoxin. Peroxiredoxin is involved in eliminating peroxides generated during metabolism. Peroxiredoxin participates in the signaling cascades of growth factors and TNF-alpha by regulating the intracellular concentrations of h(2)o(2).

The FGFs are a family of more than 20 small (~17–26 kDa) secreted peptides. The initial characterization of these proteins focused on their ability to stimulate fibroblast proliferation. This mitogenic activity was mediated through FGF receptors (FGFRs) 1, 2, or 3. A fourth closely related tyrosine kinase receptor (FGFR4) was able to bind the FGFs but did not lead to a mitogenic response.
FGFs modulate cellular activity via at least 5 distinct subfamilies of high-affinity FGF receptors (FGFRs): FGFR-1, -2, -3, and -4, all with intrinsic tyrosine kinase activity and, except for FGFR-4, multiple splice isoforms, and FGFR-5, which lacks an intracellular kinase domain. There is growing evidence that FGFRs can be important for regulation of glucose and lipid homeostasis. The overexpression of a dominant negative form of FGFR-1 in ? cells leads to diabetes in mice, which thus implies that proper FGF signaling is required for normal ? cell function and glycemia maintenance. FGFR-2 appears to be a key molecule during pancreatic development. Moreover, FGFR-4 has been implicated in cholesterol metabolism and bile acid synthesis.
FGF-19, has been shown to cause resistance to diet-induced obesity and insulin desensitization and to improve insulin, glucose, and lipid profiles in diabetic rodents. Since these effects, at least in part, are mediated through the observed changes in metabolic rates, FGF-19 can be considered as a regulator of energy expenditure.
FGF-21 is preferentially expressed in liver, but an exact knowledge of FGF-21 bioactivity and its mode of action have been lacking to date. FGF-21 is a potent activator of glucose uptake on adipocytes, protects animals from diet-induced obesity when overexpressed in transgenic mice, and lowers blood glucose and triglyceride levels when therapeutically administered to diabetic rodents.

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). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/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 and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

The cytokine Macrophage migration inhibitory factor (MIF) has been identified to be secreted by the pituitary gland and the monocyte/macrophage and to play an important role in endotoxic shock. MIF has the unique property of being released from macrophages and T cells in response to physiological concentrations of glucocorticoids. The secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentration.

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.

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). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/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 and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

Platelet-derived growth factor receptor beta (PDGFRB), belongs to the class III subfamily of receptor tyrosine kinases (RTK) which also consist of the receptors for Flt3-ligand, SCF and M-CSF. PDGFRB takes a vital part in blood vessel development by promoting growth, migration as well as recruitment of pericytes and smooth muscle cells to endothelial cells. PDGFRB helps in rearrangement of the actin cytoskeleton in addition the formation of membrane ruffles. PDGFRB phosphorylates, NCK1, PIK3R1, PTPN11, CBL, SHC1, RASA1/GAP and PLCG1.

Coagulation factor VIII participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder.

The term ‘PDGF’ refers to a family of disulphide bond-linked dimeric isoforms that act as autocrine and paracrine growth factors and are produced by a variety of cell types other than platelets.
They act as potent mitogens for almost all mesenchymally-derived cells. Aberrant expression is involved in certain cancers, fibroproliferative disorders and atherosclerosis. The protein also contributes to wound healing and neural regeneration. There are four members of the PDGF family – PDGF A, PDGF B, PDGF C and PDGF D. Two distinct types of PDGF-A exist – a short form that is soluble and a long form that is retained by the extracellular matrix.

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.

Hepatocyte Growth Factor (HGF) is a multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. HGF synergizes with Interleukin-3 and GM-CSF to stimulate colony formation of hematopoietic progenitor cells in vitro and may, therefore, also modulate hematopoiesis.

KGF-2 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-10 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. Studies of the mouse homolog of suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of lim bud formation. This gene is also implicated to be a primary factor in the process of wound healing.

A 88-kDa progranulin, also called proepithelin and PC cell-derived growth factor, is a single precursor protein of granulins which are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. Granulins are a variety of active, 6 kDa peptides and named granulin A (epithelin 1), granulin B (epithelin 2), granulin C, etc. Both the peptides and intact progranulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis.

PRDX2 is part of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. PRDX2 takes part as an antioxidant protective role in cells, and contributes to the antiviral activity of CD8(+) T-cells. PRDX2 has proliferative effect in cancer development or progression.
If PRDX2 protection is insufficient against peroxidases, the DNA damage results in neurological disease such as Alzheimer's or DNA damage leading to cancer.

Serine/threonine-protein kinase 16 (STK16) is a membrane-associated protein kinase which phosphorylates on serine and threonine residues. STK16 is involved in secretory vesicle trafficking or intracellular signaling. Furthermore, the STK16 protein may have a role in regulating stromal-epithelial interactions which occur during ductal morphogenesis in the mammary gland. STK16 can autophosphorylate on Tyr residue; it is however unclear whether STK16 has tyrosine-protein kinase toward other proteins. STK16 may also be involved in TGF-beta signaling.

Human Factor IX also called Christmas-Factor is a glycoprotein, which is synthesized in the liver and belongs to the serine proteases system and is part of the S1 peptidase family.
Lack of Factor-IX causes Hemophilia-B meaning Christmas Disease. Factor-IX has a N-terminus region which contains 12xGla residues which asist the calcium dpendant binding of Factor-IX to the phospholipid surface. Factor-IX is activated by either factor XIa or the factor VIIa/tissue factor/phospholipid complex. Cleavage yields the intermediate IXa, which is subsequently converted to the fully active form IXab.
Factor-IX binds initially to exosites on the factor XIa heavy chain, followed by interaction at the active site with subsequent bond cleavage. Coagulation factor IX is activated by interaction with the erythrocyte membrane, causing intrinsic coagulation. Chaperones & lectins act simultaniously to guarantee the proper folding of Factor-IX and the retention of mutant molecules. Human Factor IX, activated by either the Contact or Tissue Factor Pathway, is responsible for the activation of Factor X to Xa.

Transcription Factor B2, Mitochondrial (TFB2M) is an S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. In addition, TFB2M is essential for basal transcription of mitochondrial DNA, most likely via its interaction with POLRMT and TFAM. TFB2M promotes transcription independently of the methyltransferase activity. TFB2M like TFB1M, activates transcription of mitochondrial DNA more effectively, whilst having less methyltransferase activity.