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Interleukin-2 Receptor Gamma (IL2RG) is a cytokine receptor sub-unit which is common to the receptor complexes for at least six different interleukin receptors. IL2RG is located on the surface of immature blood-forming cells in bone marrow. One end of the IL2RG protein resides outside of the cell where it binds to cytokines and the other end of the IL2RG protein resides in the interior of the cell where it transmits signals to the cell's nucleus. IL2RG teams up with other proteins to direct blood-forming cells to form lymphocytes. In addition, IL2RG directs the growth and maturation of lymphocyte subtypes, which kill viruses, make antibodies, and help regulate the entire immune system.

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.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

Energy Homeostasis Associated (ENHO) participates in glucose homeostasis maintenance and lipid metabolism. ENHO is expressed in the liver and the brain. The role of ENHO in obesity or diabetes is studied.

Obestatin is a hormone that is produced in the cells lining the stomach and small intestine of several mammals including humans; it drastically reduces appetite in mice and is expected to do the same in humans. Obestatin is a peptide hormone - a relatively small protein. It is encoded by the same gene that also encodes ghrelin, a peptide hormone that increases appetite. The protein produced by that gene breaks into two smaller peptides, ghrelin and obestatin. Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor and is involved in regulating growth hormone release. Ghrelin is derived from a preprohormone called preproghrelin, which also generates a second peptide called obestatin. Ghrelin is an endogenous ligand for the orphan G protein-coupled receptor GPR39 and is involved in satiety and decreased food intake.

Ciliary Neurotrophic Factor Receptor, also known as CNTFR is a member of the type I cytokine receptor family. CNTFR binds to CNTF. The alpha subunit provides the receptor specificity. Sole nucleotide polymorphisms in CNTFR has been associated with variations in muscle strength, in addition to early onset of eating disorders.

CAMP belongs to the antimicrobial peptide family, contains highly conserved N-terminal signal peptide, a cathelin domain and a structurally variable cationic antimicrobial peptide that produced by extracellular proteolysis from the C-terminus. CAMP has numerous functions besides the antimicrobial activity such as: cell chemotaxis, immune mediator induction and inflammatory response regulation.

Stratifin is part of the 14-3-3 family. The 14-3-3 family of proteins plays an important regulatory function in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are 7 isoforms, beta, gamma, epsilon, sigma, zeta, tau and eta that have been identified in mammals. Stratifin is an epithelial cell marker that functions as a tumor suppressor whose expression can be down regulated via methylation. Failure of Stratifin expression results in a defective G2/M phase checkpoint and results in epithelial and non-epithelial tumorigenesis.

TNFSF15 is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of TNFSF15 is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. TNFSF15 is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. An additional isoform encoded by an alternatively spliced transcript variant has been reported but the sequence of this transcript has not been determined.

ErbB3, also called Her3 (human epidermal growth factor receptor 3), is a type I membrane glycoprotein that is a member of the ErbB family of tyrosine kinase receptors. ErbB family members serve as receptors for the epidermal growth factor (EGF) family of growth factors. Among ErbB family members, ErbB3 is unique in that it contains a defective kinase domain. ErbB3 is expressed in keratinocytes, melanocytes, skeletal muscle cells, embryonic myoblasts and Schwann cells. Monomeric ErbB3 serves as a low affinity receptor for the heregulins (HRG). ErbB3 can induce specific antibody production in vivo, hence to inhibit tumor cell growth. ErbB-3 can be used to treat early, medium and advanced or post-operative breast cancer with over-expression of ErbB2. According to its mechanism of action, ErbB3 is classified as a therapeutic for cancer.

Ipamorelin is a peptide selective agonist of the ghrelin/growth hormone secretagogue receptor and a growth hormone secretagogue. Ipamorelin is a pentapeptide that was derived from GHRP1. Ipamorelin significantly increases plasma growth hormone levels in both animals and humans. Like pralmorelin and GHRP-6, ipamorelin does not affect prolactin, FSH, LH or TSH levels. However, unlike GHRP2 and GHRP6, but as growth hormone-releasing hormone (GHRH), ipamorelin does not stimulate the secretion of adrenocorticotropic hormone (ACTH) or cortisol, and is highly selective for inducing the secretion only of GH.

SERPINA1 is secreted and is a serine protease inhibitor which its targets include elastase, plasmin, collagenase, leucocytic proteases, trypsin, chymotrypsin, and plasminogen activator. Defects in SERPINA1 gene can cause emphysema or liver disease. SERPINA1 is an endogenous inhibitor of serine proteases and inhibits the catalytic domain of human recombinant matriptase in vitro. Rise in SERPINA1 occurs as an acute phase response to tissue necrosis and inflammation. mutations in SERPINA1 and SLC11A1 genes change the balance between elastase produced by leukocytes during phagocytosis.

MANF is a 20kDa protein which belongs to the ARMET family. MANF was originally known as an arginine-rich region protein which was extremely mutated in a large number of tumors. MANF Expression is induced during ER stress, signifying that MANF takes part in protein quality control during ER stress.

IFN-gamma produced by lymphocytes activated by specific antigens or mitogens.
IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions, it is a potent activator of macrophages, and has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I IFNs.

Uteroglobin (SCGB1A1) which belongs to the Secretoglobin (SCGBs) superfamily, is a multifunctional protein that exerts anti-inflammatory and anti-tumorigenic effects by binding small hydrophobic molecules such as phospholipids and prostaglandins. Uteroglobin is involved in numerous functions including anti-inflammation, inhibition of phospholipase A2 and the sequestering of hydrophobic ligands. SCGB1A1 is expressed by Clara cells, the non-ciliated, non-mucous secretory cells predominant in lung bronchioles, and by other epithelia which communicate with the external environment. On top of sequestering pro-inflammatory mediators and carcinogens, Uteroglobin is implicated in the inhibition of cell migration and invasion, platelet aggregation, and T cell differentiation. SCGB1A1 gene defects are associated with a susceptibility to asthma.

γ-synuclein (Originally known as a breast cancer specific gene product, BCSG1) is an acidic neuronal protein of 127 amino acids. Gamma-Synuclein is a member of the Synuclein protein family, which is believed to be involved in the pathogenesis of neurodegenerative diseases. High levels of Gamma-Synuclein have been found in advanced breast carcinomas suggesting a correlation between overexpression of SNCG and breast tumor development. Synuclein-Gamma is found mostly in the peripheral nervous system (in primary sensory neurons, sympathetic neurons, and motor neurons) and retina. SNCG is also identified in the brain, ovarian tumors, and in the olfactory epithelium. SNCG expression in breast tumors is a marker for tumor progression. A modification in the expression of gamma-synuclein has been detected in the retina of Alzheimer''s patients.

The epidermal growth factor receptor (EGF R) subfamily of receptor tyrosine kinases comprises four members: EGF R (also known as HER1, ErbB1 or ErbB), ErbB2 (Neu, HER-2), ErbB3 (HER-3), and ErbB4 (HER-4). All family members are type I transmembrane glycoprotein that has an extracellular domain which contains two cysteine-rich domains separated by a spacer region that is involved in ligand-binding, and a cytoplasmic domain which has a membrane-proximal tyrosine kinase domain and a C-terminal tail with multiple tyrosine autophosphorylation sites. The human EGF R gene encodes a 1210 amino acid (aa) residue precursor with a 24 aa putative signal peptide, a 621 aa extracellular domain, a 23 aa transmembrane domain, and a 542 aa cytoplasmic domain. EGF R has been shown to bind a subset of the EGF family ligands, including EGF, amphiregulin, TGF-a , betacellulin, epiregulin, heparin-binding EGF and neuregulin-2 in the absence of a co-receptor. Ligand binding induces EGF R homodimerization as well as heterdimerization with ErbB2, resulting in kinase activation, tyrosine phosphorylation and cell signaling. EGF R can also be recruited to form heterodimers with the ligand-activated ErbB3 or ErbB4. EGF R signaling has been shown to regulate multiple biological functions including cell proliferation, differentiation, motility and apoptosis. In addition, EGF R signaling has also been shown to play a role in carcinogenesis.

Human norovirus is classified into two groups, group 1& group 2. Norwalk virus is the species which belongs to group 1 and was discovered in 1968 at Ohio. Norovirus is a familiar virus which causes human gastroenteritis with the following symptoms vomiting, diarrhea and sickness. CDC report revealed that there are 19-21 million Americans infected by Nororvirus annually with 800 deaths, 1 in 15 people with infection. Around the world, this virus affects about 267 million people and causes over 200,000 deaths each year; these losses are mostly in less developed countries and in the very young, elderly and immuno-suppressed population, though, most cases are self-limited with a full recovery within just a few days. Norovirus is extremely contagious and can spread from human to human through infected food, water or contaminated surfaces. The outbreaks usually occur from November-April, while the peak is in January. Norovirus is a positive sense RNA virus with 7.5 kb nucleotides, encoding a major structural protein VP1 with 50-55kDa. The full length of VP1 capsid comprises the internal N-terminal, Hinge, shell (S) and protruding (P) domains. P domain from 225 to 520 forms P1- P2-P1 structure. Moreover, P domain has a receptor binding region which recognizes human histo-blood group antigens (HBGAs). P domain expressed in bacteria can spontaneously form a P dime as well as a P particle aggregated by 12 P dimmers. P particle displays an increased binding activity to HBGAs higher than virus-like particle (VLP) formed by the full-length capsid. For norovirus vaccine development, we consider P domain as a good candidate.

Von Willebrand Factor A Domain Containing 2 (VWA2) is an extracellular matrix protein containing vWA-like domains. VWA2 contains a signal peptide sequence, an N-terminal VWA domain connected to 2 additional tandem vWA domains by a cysteine-rich sequence and an EGF-like domain. Also, another EGF-like domain is located at the C-terminus. Expression of VWA2 is induced in stage II, III and IV colon cancers and colon adenomas and is considered a novel serum marker for the diagnosis of early-stage colon cancer.

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

NEDD8 is part of the ubiquitin family. Human NEDD8 shares 60% amino acid sequence homology to ubiquitin. The NEDD8 system is essential for the regulation of protein degradation pathways involved in cell cycle progression, morphogenesis and tumorigenesis. NEDD8 is involved in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E-1 complex UbE1c- appbp1 and linkage to the E-2 enzyme UbE2m. Attachment of NEDD8 to cullins activates their associated E-3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.

Leucine Rich Repeat And Ig Domain Containing 1, also known as Lingo1 is primarily expressed in neuronal tissue, and most abundantly in the cortex. In addition, Lingo 1 is involved in the inhibition of axon regeneration all the way through a ternary complex formed with NgR1 (ligand-binding subunit) and p75 (signal transducing subunit). The inhibitory action is accomplished through RhoA-GTP upregulation in response to the presence of MOG, MAG or Nogo-66 in the central nervous system. Furthermore, LINGO-1 inhibits oligodendrocyte precursor differentiation as well as myelination, by a mechanism which also involves activation of RhoA, however it appears that it does not require 75 or NgR1.