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ICOS (inducible T-cell costimulatory) belongs to the CD28 family of immune-assisted stimulatory receptors. ICOS forms homodimers and takes a significant part in immune responses, cell-cell signaling, as well as regulation of cell proliferation. The interaction of B7-H2 / ICOS takes a vital role in T-cell differentiation, T-B cell interaction in addition to humoral immune response is essential for the formation of reproductive centers as well as the production of cytokine IL-4. Moreover, ICOS is more effective in inducing IL-10 production, a cytokine which is important for the inhibitory function of T regulatory cells. The ICOS-B7RP-1 and B7-1 / B7-2-CD28 / CTLA-4 pathways offer a significant second signal which can regulate the inhibition, activation and fine regulation of T-lymphocyte responses. ICOS stimulates the production of Th1 and Th2 cytokines, however it can also participate in the generation of Th2 cells.

PDCL3 belongs to the phosducin-like protein family which its members are known to bind to the beta-gamma subunits of G proteins. PDCL3 is a potential regulator of heterotrimeric G proteins and has a large amino acid sequence homology with phosducin.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling.

IFN-alpha is produced by macrophages, IFN-alpha has antiviral activities and stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.

Cytotoxicity Triggering Receptor 3 also known as NCR3 is a natural cytotoxicity receptor (NCR) which assists NK cells in the lysis of tumor cells. Moreover, NCR3 interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of NCR3 has been related with mild malaria suceptibility. Three transcript variants encoding various isoforms have been found for this gene.

GH is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature.

TSLP protein is a hemopoietic cytokine which signals throughout a heterodimeric receptor complex composed of the thymic stromal lymphopoietin receptor & the Interleukin-7 receptor alpha chain. TSLP impacts myeloid cells thus induces the discharge of T cell-attracting chemokines from monocytes & increases the growth of CD11c(+) dendritic cells. TSLP is mainly expressed in the heart, liver and prostate. TSLP is related in its biological activities with IL-7 and binds with the heterodimeric receptor complex consisting of the Interleukin-7 receptor alpha chain & the TSLPR. Similar to IL-7, TSLP enhances phosphorylation of STAT3 and STAT5, though uses kinases excluding JAKs for its activation. TSLP induces the release of T cell-attracting chemokines such asTARC & MDC from monocytes & triggers CD11c(+) dendritic cells. TSLP activated dendritic cells primes naive T cells to manufacture pro-allergic cytokines such as Iinterleukin-4, Interleukin-5, Interleukin-13 and TNF-alpha whereas down-regulating Interleukin-10 and IFN-gamma play a role in the initiation of allergic inflammation.

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.

Major Histocompatibility Complex Class I C (HLA-C) belongs to the HLA class I heavy chain paralogues. The HLA-C (class I molecule) is a heterodimer comprised of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules have a key role in the immune system by presenting peptides derived from endoplasmic reticulum lumen. Class I molecules are expressed in virtually all cells.

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

Isocitrate Dehydrogenase is an enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and NADH. It occurs in cell mitochondria. The enzyme requires Mg2+, Mn2+; it is activated by ADP, citrate, and Ca2+, and inhibited by NADH, NADPH, and ATP. The reaction is the key rate-limiting step of the citric acid (tricarboxylic) cycle.

Il-6 is a cytokine with a wide variety of biological functions: it plays an essential role in the final differentiation of b-cells into ig-secreting cells, it induces myeloma and plasmacytoma growth, it induces nerve cells differentiation, in hepatocytes it induces acute phase reactants.

Glutamate-cysteine ligase (GCLM) is the first rate limiting enzyme of glutathione synthesis. The GCLM enzyme is comprised of 2 subunits, a heavy catalytic subunit and a light regulatory subunit. GCLM deficiency is associated with some forms of hemolytic anemia.

Vimentin expression in human malignant glioma cells depends on cellular density, algorithms of drug delivery and chemo/radio treatment. Vimentin and detyrosinated microtubules provide structural support for the extensive microtentacles observed in detached tumor cells and a mechanism to promote successful metastatic spread. Primary colorectal carcinomas display aberrant expression of vimentin, and have activated Notch and TGFbeta signaling pathways. Vimentin is a strong arterial substrate for transglutaminases. Transglutaminase-mediated vimentin dimerization results in a novel unifying pathway by which vasodilatory and remodeling responses may be regulated. Ablation of vimentin expression inhibits migration and invasion of colon and breast cancer cell lines. Vimentin is the main intermediate filament protein in mesenchymal cells and is therefore of value in the differential diagnosis of undifferentiated neoplasms.

IL-18 is a proinflammatory cytokine. This cytokine can induce the IFN-gamma production of T cells. The combination of this cytokine and IL12 has been shown to inhibit IL4 dependent IgE and IgG1 production, and enhance IgG2a production of B cells. IL-18 binding protein (IL18BP) can specifically interact with this cytokine, and thus negatively regulate its biological activity.

CD40 belongs to the TNF-receptor super family. CD40 has been found to be vital in mediating a wide range of immune and inflammatory responses including T cell-dependent immunoglobulin classswitching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA isaccounted to coordinately regulate the expression of CD40 and its ligand, which is significant forhomotypic cell interactions. Adaptor protein TNFR2 interacts with CD40 and functions as a mediator of thesignal transduction. The interaction of CD40 and its ligand is found to be essential for amyloid-beta-inducedmicroglial activation, and therefore is considered to be an early event in Alzheimer disease pathogenesis.

CD23 is a 45kDa glycoprotein, which is present on a subpopulation of freshly isolated peripheral blood and tonsil B cells and strongly expressed on EBV-transformed B lymphoblasts. The CD23 molecule is identical to the low affinity IgE receptor found on B cells. Expression of CD23 has been detected in neoplastic cells from cases of B cell chronic lymphocyctic leukaemia and some cases of centroblastic/centrocytic lymphoma.

Ornithine aminotransferase is a key enzyme in the pathway that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Ornithine aminotransferase (OAT) is a 49kDa nucleus-encoded protein imported into mitochondria to give the mature 48kDa OAT polypeptide. It is found in humans, animals, insects, plants and microorganisms. The OAT has a sex-differential expression in the mouse kidney. OAT plays central physiological roles in amino acid metabolism. OAT shows a large structural and mechanistic similarity to other enzymes from the subgroup III of aminotransferases that transfer an amino group from a carbon atom which doesn’t carry a carboxyl function. OAT is vital for nitrogen recycling from arginine but not for the stress-induced proline accumulation. OAT enzyme deficiency causes the autosomal recessive eye disease Gyrate Atrophy.

TPMT, thiopurine S-methyltransferase, is a cytosolic enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. TPMT activity exhibits autosomal codominant genetic polymorphism, and patients inheriting TPMT-deficiency are at high risk of potentially fatal hematopoietic toxicity.

Pyruvate Dehydrogenase Complex, Component X, also known as PDHX, encodes the E3 binding protein subunit of the PDH complex which contains 3 catalytic subunits. PDHX tethers E3 dimers to the E2 core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is critical for a functional PDH complex.