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Dopachrome Tautomerase also known as DCT, belongs to the tyrosinase family. DCT takes a significant part in the synthesis of the melanin pigment including tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1). Which are highly involved in eumelanin synthesis. The change among the eumelanin and the pheomelanin pathways is assumed to depend on the presence of cysteine. Hence, in the lack of cysteine, dopaquinone, the product of tyrosinase action, is transformed to cyclodopa (leucodopachrome) and afterwards to dopachrome (and DOPA).

Myostatin (GDF-8), a member of the TGFbeta superfamily, is a potent and specific negative regulator of skeletal muscle mass. In serum, myostatin circulates as part of a latent complex containing myostatin propeptide and/or follistatin-related gene. The myostatin propeptide is known to bind and inhibit myostatin in vitro. This interaction is relevant in vivo, with a majority (>70%) of myostatin in serum bound to its propeptide. The myostatin propeptide is negative regulator of myostatin in vivo.

Developmentally-regulated GTP-binding protein 1 (DRG1) is a member of the GTP1/OBG family. DRG1 has a role in cell proliferation and differentiation, as well as in apoptosis, proposing a role in tumor formation and metastasis. Expression of the DRG1 was considerably reduced in breast tumor cells, particularly in patients with lymph node or bone metastasis as compared to those with localized breast cancer. The DRG1 protein is expressed at high levels in the heart, kidney and skeletal muscle and at lower levels in the brain, liver, placenta, lung, colon and spleen.

Dynein light chain roadblock-type (DYNLRB1) belongs to the roadblock dynein light chain family and encodes a cytoplasmic protein which is capable of binding intermediate chain proteins. Upregulation of the DYNLRB1 gene is linked with hepatocellular carcinomas, suggesting that DYNLRB1 may be involved in tumor progression.

NRP1 is a coreceptor bound on membranes to tyrosine kinase receptors for semaphorin family proteins and endothelial growth factors, it is a type one transmembrane protein. Neuropilin-1 takes part in cell survival, angiogenesis, invasion, migration, and axon guidance. the protein is a potential target for cancer therapies as it interacts with VEGF (co-receptor).

SRGN is identified as a hematopoietic cell granule proteoglycan. Proteoglycans stored in the secretory granules of various hematopoietic cells also hold a protease-resistant peptide core, and is vital for neutralizing hydrolytic enzymes. SRGN is related to the macromolecular complex of granzymes and perforin that acts as a intermediary of granule-mediated apoptosis.

BID is a pro-apoptotic Bcl-2 protein having only the BH3 domain. In reaction to apoptotic signaling, BID interacts with another Bcl-2 family of cell death regulators, called Bax, they form a heterodimer resulting to the insertion of Bax into the outer mitochondrial membrane. Bax induces the opening of the mitochondrial voltage-dependent anion channel which lead to the release of cytochrome c and other pro-apoptotic factors from the mitochondria resulting in activation of caspases. BID is a mediator of mitochondrial damage induced by caspase-8 (CASP8). CASP8 cleaves BID, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. The major proteolytic product p15 BID releasea cytochrome c. Isoform 1, Isoform 2 and Isoform 4 induce ice-like proteases and apoptosis while Isoform 3 does not induce apoptosis.

BIRC7 is a part of the inhibitor of apoptosis protein (IAP) family and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is necessary for inhibitory activity & cooperates with caspases, while the RING finger domain sometimes increases anti-apoptotic activity but doesn’t inhibit apoptosis by itself. 2 transcript variants encoding diverse isoforms have been found for this gene. The 2 isoforms have dissimilar antiapoptotic characteristics, with isoform a protecting cells from apoptosis induced by staurosporine and isoform b defending cells from apoptosis induced by etoposide.
BIRC7 has direct contact with several caspases together with caspase-3, caspase-7, & caspase –9. BIRC7 inhibits the activation of caspase-9 induced by Apaf-1, cytochrome c, and dATP.

IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.

BTC is a potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells. The effects of betacellulin are mediated by the EGF receptor and other related receptors.

Periostin is a disulfide linked 90 kDa, 811 amino acid protein originally isolated as a osteoblast-specific factor that functions as a cell adhesion molecule for preosteoblasts and is thought to be involved in osteoblast recruitment, attachment and spreading. Additionally, periostin expression has previously been shown to be significantly increased by both transforming growth factor beta-1(TGFbeta1) and bone morphogenetic protein (BMP-2). OSF-2 has a typical signal sequence, followed by a cysteine-rich domain, a fourfold repeated domain and a C-terminal domain. The fourfold repeated domain of OSF-2 shows homology with the insect protein fasciclin
Periostin mRNA is expressed in the developing mouse embryonic and fetal heart, and that it is localized to the endocardial cushions that ultimately divide the primitive heart tube into a four-chambered heart.

FGF8 is part of the fibroblast growth factor family. FGF family members have wide mitogenic and cell survival activities, and participate in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF8 supports androgen and anchorage independent growth of mammary tumor cells. FGF8 over expression increases tumor growth and angiogensis. The adult expression of FGF-8 gene is restricted to testes and ovaries. FGF8 functions as an embryonic epithelial factor. FGF8 takes part in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination.

ILK1 (Integrin-linked kinase) is a serine/threonine protein kinase, containing 4 ankyrin-like repeats. ILK1 regulates a number of biological properties which include: anchorage-independent cell cycle progression, tumor cell invasion and apoptosis. ILK1 can also be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Furthermore, ILK1 phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B.
ILK1 interacts with the cytoplasmic domains of integrin ?1 and ?3 subunits in addition to several adaptors and signaling proteins, it also acts as a proximal receptor kinase regulating integrin-mediated signal transduction. ILK1 is a focal adhesion protein part of the complex ILK-PINCH. This complex is deemed to be one of the convergence points of integrin- and growth factor-signaling pathway. ILK1 is stimulated rapidly but briefly by both cell fibronectin interactions in a PI3-K-dependent manner, probably through the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK.
ILK1 over-expression has been documented in a wide variety of human malignancies.

Peptidase Inhibitor 3, also referred to PI3, is neutrophil and pancreatic elastase-specific inhibitor of skin. The protein may prevent elastase mediated tissue proteolysis. PI3 has shown inhibition of alpha-4-beta-2/CHRNA2-CHRNB2 nicotinic acetylcholine receptor, a weak inhibition on Kv11.1/KCNH2/ERG1 and on the transient receptor potential cation channel subfamily V member 1.

Inositol Hexakisphosphate Kinase 2 (IP6K2) which is a part of the inositol IPK family converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate. IP6K2 also converts 1, 3, 4, 5, 6-pentakisphosphate (InsP5) to PP-InsP4. IP6K2 is a protein coding gene which suppresses the growth and affects the apoptotic activities of IFN-beta in several ovarian cancers.

Phosphatidylinositol-5-Phosphate 4-Kinase, Type II, Beta (PIP4K2B) belongs to the phosphatidylinositol-4-phosphate 5-kinase family.PIP4K2B catalyzes the phosphorylation of phosphatidylinositol-4-phosphate on the 5th hydroxyl of the myo-inositol ring to form phosphatidylinositol-4,5-bisphosphate. PIP4K2B amino acid sequence does not show resemblance to another kinases although PIP4K2B presents kinase activity.PIP4K2B also interacts with p55 TNF receptor.

KIAA0101 is a PCNA-binding protein which performs as a regulator of DNA repair all through DNA replication. Subsequent to DNA mutilation, the collaboration with PCNA is interrupted, enabling the interaction between monoubiquitinated PCNA and the translesion DNA synthesis DNA polymerase eta (POLH) at stalled replisomes, assisting the bypass of replication-fork-blocking lesions. Additionally, KIAA0101 performs as a controller of centrosome number.

Grancalcin is calcium-binding protein which is particularly abundant in human neutrophils. GCA is a member of the penta EF-hand (PEF) subfamily of EF-hand proteins, who also comprises calpain, sorcin, peflin, and ALG-2. GCA undergoes essential conformational changes upon binding of calcium, which subsequently exposes hydrophobic amino acid residues, that direct the protein to hydrophobic surfaces. GCA cooperates with L-plastin, a protein known to have actin bundling activity, which suggests that GCA has a part in the regulation of neutrophils adhesion.

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 the GCSF 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.

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.

Clusterin also known as Apolipoprotein J (APO-J) is a 75-80 kD disulfide-linked heterodimeric protein containing about 30% of N-linked carbohydrate rich in sialic acid but truncated forms targeted to the nucleus have also been identified.
The precursor polypeptide chain is cleaved proteolytically to remove the 22-mer secretory signal peptide and subsequently between residues 227/228 to generate the a and b chains. These are assembled in anti-parallel to give a heterodimeric molecule in which the cysteine-rich centers are linked by 5 disulfide bridges and are flanked by 2 predicted coiled-coil a-helices and 3 predicted amphipathic a-helices.
Across a broad range of species clusterin shows a high degree of sequence homology ranging from 70% -80%. It is nearly ubiquitously expressed in most mammalian tissues and can be found in plasma, milk, urine, cerebrospinal fluid and semen.
It is able to bind and form complexes with numerous partners such as immunoglobulins, lipids, heparin, bacteria, complement components, paraoxonase, beta amyloid, leptin and others. Clusterin has been ascribed a plethora of functions such as phagocyte recruitment, aggregation induction, complement attack prevention, apoptosis inhibition, membrane remodeling, lipid transport, hormone transport and/or scavenging, matrix metalloproteinase inhibition.
Clusterin is up/down regulated on the mRNA or protein level in many pathological and clinically relevant situations including cancer, organ regeneration, infection, Alzheimer disease, retinitis pigmentosa, myocardial infarction, renal tubular damage, autoimmunity and others.

Glutathione S-transferase omega 2 (GSTO2) is a member of the GST superfamily. GSTO2 is involved in catalyzing the reaction of glutathione with a broad range of organic compounds to form thioethers, a process which is vital for the metabolism and detoxification of a variety of xenobiotics and carcinogens. GSTO2 displays glutathione-dependent thiol transferase activity. GSTO2 has a high dehydroascorbate reductase activity and may be a factor in the recycling of ascorbic acid. GSTO2 also participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA). GSTO2 is expressed in an array of tissues, including the liver, kidney, skeletal muscle and prostate, while the strongest expression is seen in the testis.

CNDP Dipeptidase 1, also known as CNDP1 is a member of the peptidase M20A family. CNDP1 Mannheim which is the shortest allelic form has been more common in the absence of nephropathy in addition to being associated with lower serum carnosinase levels. Furthermore, Carnosine inhibited the increased production of fibronectin as well as collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells. Diabetic patients with the CNDP1 Mannheim variant are less at risk for nephropathy. In addition, on renal cells carnosine protects against the adverse effects of high glucose levels.