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FHIT is a member of the histidine triad gene family. FHIT gene encodes a diadenosine 5',5'''-P1,P3-triphosphate hydrolase involved in purine metabolism. FHIT gene includes the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and abnormal transcripts of this gene. The FHIT protein is a tumor suppressor with reduced or no expression in numerous types of cancer. FHIT may also act as a tumor suppressor in normal cells. Alterations and deletions of the FHIT (Fragile Histidine Triad) gene are strongly linked to the genesis and establishment of human tumors of the lung, cervix, breast, colon, stomach, and pancreas. The expression of FHIT is more often lost in cancers of individuals with familial mutations causing deficiency in DNA repair genes such as BRCA1, BRCA2 and MSH2. In vitro FHIT functions as a hydrolase that cleaves diadenosine triphosphate (Ap3A) to ADP and AMP. The FHIT -Ap3A enzyme-substrate complex seems to be the tumor suppressor signal. The restoration of FHIT expression in FHIT -deficient cancer cells leads to apoptosis, involving the intrinsic caspase pathway, in cancer-derived cells and in tumor xenografts.

Interleukin 10 or IL-10 or human cytokine synthesis inhibitory factor, is a cytokine (anti-inflammatory). IL10 gene is coding for il-10 In humans. Interleukin 10 has a receptor complex that is built from a couple of IL-10 receptor-1 and a couple of IL-10 receptor-2 proteins. therfore, the whole receptor unit consists of four IL-10 receptor molecules. IL-10 binds the receptor and causes STAT3 signalling through the phosphorylation of the cytoplasmic ends of IL-10 receptor 1 and IL-10 receptor 2 through JAK1 and Tyk2.

SOS1, also known as Gingival Fibromatosis, is a Ras & Rac guanine nucleotide exchange factor. SOS1 is comprised of a number of significant domains. The REM and CDC25 domains provide the catalytic activity of SOS1 towards Ras and the histone fold DH/PH (Dbl homology & Pleckstrin homology) domains function, in tandem, to stimulate GTP/GDP exchange for Rac. Moreover, binding of GTP activates Ras proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be enhanced by GTPase-activating proteins.

Cardiotrophin-like cytokine (CLC/ NNT-1) belongs to the IL-6 family of cytokines. All family members share the receptor subunit gp130, which belongs to the type I cytokine receptor superfamily. NNT1 is a trophic factor for motor neurons, a stimulator of ACTH release from corticotrophs, and an inducer of IgE synthesis and B cell proliferation. Cells expressing NNT-1 include embryonic muscle, lung epithelium, and mesenchyme. NNT1 binds to and activates the ILST/gp130 receptor.

4-1BBR is a member of the TNF-receptor superfamily. 4-1BB receptor contributes to the clonal expansion, survival, and development of T cells.4-1BBRcan also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. The expression of this receptor is induced by lymphocyte activation. TRAF adaptor proteins have been shown to bind to this receptor and transduce the signals leading to activation of NF-kappaB.

Galectins are a family of animal lectins with an affinity for beta-galactosides. This family has at least 14 identified members. Galectins share similarities in the CRD (the carbohydrate recognition domain). Galectins are synthesized as cytosolic proteins. Though localized principally in the cytoplasm and lacking a classical signal peptide, galectins can also be stimulated to secretion by non-classical pathways or alternatively targeted to the nucleus. Galectins are involved in modulating cell-cell and cell-matrix interactions. Galectin-8 is a tandem-repeat-type member of the galectin family, consisting of 2 CRDs attached by a linker peptide. Galectin-8 is greatly expressed in lung carcinomas, a number of forms of prostate carcinomas, in addition to other tumor cells. Galectin-8 attaches to a subset of cell surface integrins to modulate ECM-integrin interactions. Once immobilized, Galectin-8 promotes cell adhesion by ligation and clustering of cell surface integrin receptors. On the other hand, as a soluble ligand, Galectin-8 can inhibit cell adhesion.

Neuregulin is a signaling protein for ErbB2/ErbB4 receptor heterodimers on the cardiac muscle cells, playing an important role in heart structure and function through inducing ErbB2/ErbB4 receptor phosphorylation and cardiomyocyte differentiation. Research on molecular level discovered that neuregulin recombinant could make disturbed myocardial cell structure into order and strengthen the connection between myocardial cells by intercalated discs re-organization. Pharmacodynamic experiments in animals showed that neuregulin (NRG1) recombinant can reduce the degree of damage on myocardial cells caused by ischemia, hypoxia and viral infection.

The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. Galectin-1 is an autocrine negative growth factor that regulates cell proliferation. Galectin-1 regulates cell apoptosis and cell differentiation. Galectin-1 binds CD45, CD3 and CD4 & inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of lyn kinase. Galectin-1 and its ligands are one of the master regulators of immune responses as T-cell homeostasis and survival, T-cell immune disorders, inflammation and allergies as well as host–pathogen interactions. Galectin-1 expression or overexpression in tumors and/or the tissue surrounding them must be considered as a sign of the malignant tumor progression that is often related to the long-range dissemination of tumoral cells (metastasis), to their dissemination into the surrounding normal tissue, and to tumor immune-escape. Galectin-1 in its oxidized form plays a number of important roles in the regeneration of the central nervous system after injury. The targeted overexpression (or delivery) of Galectin-1 should be considered as a method of choice for the treatment of some kinds of inflammation-related diseases, neurodegenerative pathologies and muscular dystrophies. In contrast, the targeted inhibition of Galectin-1 expression is what should be developed for therapeutic applications against cancer progression. Galectin-1 is thus a promising molecular target for the development of new and original therapeutic tools. There is 88% homology between the human and mouse galectin-1.

Eukaryotic Translation Initiation Factor 3F, also known as EIF3F belongs to the eIF-3 subunit F family. EIF3F is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which isessential for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosomeand facilitates the recruitment of eIF-1, eIF-1A, eIF 2: GTP: methionyl-tRNAi and eIF-5 to form the 43S preinitiationcomplex (43S PIC). In addition, the eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA forAUG recognition. The eIF-3 complex is also necessary for disassembly and recycling of post termination ribosomalcomplexes and subsequently prevents premature union of the 40S and 60S ribosomal subunits prior to initiation. Among the diseases associated with EIF3F are intrahepatic cholangiocarcinoma, and cholangiocarcinoma.

Complement Factor B, also known as CFB, encodes complement factor B which is a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Once the alternative pathway is activated it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which connects with C3b to form the alternative pathway C3 convertase. Also, Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation.

LGALS2 is a soluble beta-galactoside binding lectin that controls cell-to-cell adhesion and cell-to-extracellular matrix interactions and takes part in tumor progression, pre-mRNA splicing and apoptosis. LGALS2 induces apoptosis in activated T cells and binds to the cytokine lymphotoxin-alpha (LTA) with threat of myocardial infarction.

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.

FLT3 ligand is a receptor for the fl cytokine has a tyrosine-protein kinase activity & a growth factor that regulates proliferation of early hematopoietic cells. Flt3-Ligand synergizes with other CSFs and interleukins to induce growth and differentiation.

FLT3 ligand is a receptor for the fl cytokine has a tyrosine-protein kinase activity & a growth factor that regulates proliferation of early hematopoietic cells. Flt3-Ligand synergizes with other CSFs and interleukins to induce growth and differentiation.

EIF1AY is comparable to eukaryotic translation initiation factor 1A (EIF1A). EIF1AY protein is essential for highest rate of protein biosynthesis. EIF1AY increases ribosome dissociation into subunits and is obligatory for the binding of the 43S complex (a 40S subunit, eIF2/GTP/Met-tRNAi and eIF3) to the 5' end of capped RNA.

TNFR2 belongs to the TNF-receptor superfamily. TNFR2 is receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. TNFR2 mediates the majority of the metabolic effects of TNF-alpha. In addition, knockout studies in mice propose a role for TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways. TNFR2 expression might have a significant role in the angiogenesis, tumor cell proliferation and metastasis of Invasive micropapillary carcinoma of the breast.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women. TNFR2 and TNFR1 form a heterocomplex which mediates the recruitment of 2 anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. IAPs’ function in TNF-receptor signaling is unknown; nevertheless, c-IAP1 is believed to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.

Osteopontin is a glycoprotein that was first identified in osteoblasts and is involved in bone remodeling, immune functions in fibroblasts, macrophages, and lymphocytes during inflammation and wound healing. SPP1 binds tightly to hydroxyapatite. SPP1 forms an integral part of the mineralized matrix. SPP1 is vital to cell-matrix interaction.
Secreted Phosphoprotein-1 protects against cardiac ischemia-reperfusion injury via late preconditioning. Expression of both Ostepontin and CD44 in hepatocellular carcinoma is linked with advanced tumor stage and contributes to prognosis information. SPP1 is the most over-expressed gene in intrahepatic cholangiocarcinoma. Secreted Phosphoprotein-1 overexpression is related with interstitial lung diseases.

EEF1A1 is an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible forthe enzymatic release of aminoacyl tRNAs to the ribosome. EEF1A1 is expressed in brain, placenta, lung, liver, kidney, and pancreas, and the other isoform (alpha 2) is expressed in brain, heart and skeletal muscle. EEF1A1 is recognized as an autoantigen in 66% of patients with Felty syndrome. EEF1A1 has multiple copies on numerous chromosomes, part of them, if not all, symbolize different pseudogenes. Among the diseases associated with EEF1A1 are tinea nigra and andcervical cancer.

Human TNFRSF10A is a type 1 transmembrane protein in the TNF R superfamily. TNFRSF10A is not expressed in rodents. The trimeric ligand Trail binds TNFRSF10A and induces apoptosis, and recombinant, soluble forms of the receptor inhibit Trail-induced apoptosis. TNFRSF10A is expressed generally in damaged, infected, and malignant cells. TNFRSF10A functions in immune surveillance, inducing apoptosis in cancer cells but not normal cells.

CDNF is a member of the ARMET family and acts as a trophic factor for dopamine neurons. CDNF inhibits the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons. When CDNF controlled after 6-OHDA-lesioning, it reestablishes the dopaminergic function and inhibits the degeneration of dopaminergic neurons in substantia nigra. CDNF is universally expressed in neuronal and non-neuronal tissues. The highest levels in the brain are found in the optic nerve and corpus callosum.

GHBP is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. A common alternate allele of this gene, called GHRd3, lacks exon three and has been well-characterized. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature. Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized.

NFKBIA belongs to the I-kappa-B family of proteins which is separated into four groups (IkB-a, IkB-b, IkB-g, IkB-e). NFKBIA inhibits the NFkB complex by binding and impounding it in the cytoplasm. When stimulated, NFKBIA is phosphorylated on serine residues targeting it for degradation by the ubiquitin pathway.

Chemokine (C-X-C motif) ligand (CXCL7) is a small cytokine belonging to the CXC chemokine family. It is a protein that is released in large amounts from platelets following their activation. It stimulates various processes including mitogenesis, synthesis of extracellular matrix, glucose metabolism and synthesis of plasminogen activator.