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IL2 is a secreted cytokine that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine is a heterotrimeric protein complex whose gamma chain is also shared by interleukin 4 (IL4) and interleukin 7 (IL7). The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli.

Rho Guanine Nucleotide Exchange Factor 39, also known as ARHGEF39, is a protein coding gene which owns one DH (DBL-homology) domain and one PH domain. ARHGEF39 encourages cell proliferation.

GTP Cyclohydrolase I Feedback Regulator, also known as GCHFR, is a Protein coding gene which includes a homodimer. GCHFR binds and mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase I. GCHFR also regulates phenylalanine metabolism in the liver and in the production of biogenic amine neurotransmitters and nitric oxide.

TNFR1 belongs to the TNF-receptor superfamily. TNFR1 is a receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.
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. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.
TNFR1 is capable of signaling both cell survival and apoptosis. TNFR1-induced apoptosis requires 2 sequential signaling complexes. TNFR1 is capable of activating NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNFR1 contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Human TNFR1 has a major region which controls cell surface expression. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women.
Germline mutations of the extracellular domains of TNFR1 are linked to the autosomal dominant periodic fever syndrome. The impaired receptor clearance is believed to be a mechanism of the disease. Familial hibernian fever (FHF) is caused by defects in TNFRSF1A gene.

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair. Oncostatin-A is a member of the CXC chemokine family. Human PF4 is used for the proof of heparin-induced thrombocytopenia. Furthermore it is used as an inhibitor in the angiogenesis during tumor therapy.

Non-homologous end-joining factor 1 (NHEJ1) is a member of the XLF family. NHEJ1 is a DNA repair factor vital for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. NHEJ1 gene mutations cause different kinds of severe combined immunodeficiency disorders. NHEJ1 was initially detected as the protein mutated in five patients with growth retardation, microcephaly, and immunodeficiency. In addition, patients with NHEJ1 mutations have immunodeficiency caused by a defect in V(D)J recombination, which employs NHEJ to promote immune system diversity.

EIF5A is the single protein identified to contain remarkable amino acid formed by the action of deoxyhypusine synthase and deoxyhypusine hydroxylase using spermidine as the substrate. EIF5A takes part in the first step of peptide bond formation in translation, nevertheless further experiments implicates it as a universally conserved translation elongation factor. Modulation of EIF5A is connected to proliferation and cancer. Expression of EIF-5A is upregulated in the PBMCs of HIV-1 patients. EIF5A coordinates significant cellular processes like cell viability and senescence during its effects on the stability of certain mRNAs. Heat stress-induced loss of EIF-5A in a human pancreatic cancer cell line. EIF5A stability takes part in determining the fate of the particular cell type after severe heat stress.

GH-releasing peptides (GHRPs) are synthetic peptides that like GHRH act directly on pituitary somatotrophs to stimulate GH release. GHRP-2, an investigational drug, is one of the most potent members of the GHRP family. It has been shown to be effective in adults via the oral and intranasal as well as the iv route of administration.

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8) is a receptor for TNFSF8/CD30L. TNFRSF8 has a role in the regulation of cellular growth and transformation of activated lymphoblasts. In addition, the TNFRSF8 protein regulates gene expression via activation of NF-kappa-B. TNFRSF8 being a regulator of apoptosis, induces cell death or proliferation, depending on the cell type.

GDNF Family Receptor Alpha 3 (GFRA3) belongs to the GDNF receptor family. GFRA3 creates a signaling receptor complex with RET tyrosine kinase receptor and binds the ligand, artemin (ARTN).

TNFRSF14, a member of the TNF receptor superfamily, is a type I transmembrane protein. TNFRSF14 is expressed in peripheral blood T cells, B cells, monocytes and in various tissues enriched in lymphoid cells. TNFRSF14 operates as a co-stimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. Additionally, TNFRSF14 encourages the proliferation of T cells, and triggers apoptosis of various tumor cells.

Neutrophil Cytosolic Factor 4 (NCF4) is a cytosolic regulatory factor of the superoxide-producing phagocyte NADPH-oxidase, which is a multicomponent enzyme system imperative for host defense. The NCF4 protein is preferentially expressed in cells of myeloid lineage. NCF4 interacts mainly with neutrophil cytosolic factor 2 (NCF2/p67-phox) to create a complex with neutrophil cytosolic factor (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex subsequently activates flavocytochrome b, the membrane-integratedcatalytic core of the enzyme system. The PX domain of the NCF4 protein can bind phospholipid products of the PI(3) kinase, suggesting its part in PI(3) kinase-mediated signaling events. The phosphorylation of the NCF4 protein negatively regulates the enzyme activity.

PMF1-BGLAP is a locus which represents naturally occurring read-through transcription between the neighboring polyamine-modulated factor 1 (PMF1) and bone gamma-carboxyglutamate Gla protein (BGLAP) genes on chromosome 1. There are multiple transcript variants encoding isoforms as a results of alternative splicing which share sequence identity with the upstream gene product, but they have a different C-termini because of frameshifts as opposed to the downstream gene coding sequence.

NFATC2, also known as nuclear factor of activated T-cells 2, belongs to the nuclear factor of activated T cells family. NFATC2 takes a significant part in the course of T helper cell differentiation, activation, and effector function. Even though KO of an individual NFAT isoform in T cells directs to rather minor effects, T cells lacking for NFATC1 and 2 totally fail to produce T helper cell effector cytokines, for instance the interleukins IL-4 and IL-2. Moreover, NFATC2 is highly phosphorylated and kept in the cytoplasm. Next T cell receptor stimulation, dephosphorylation via calcium-activated calcineurin induces a conformational modification of NFATC2 which reveals a few nuclear localization sequences.

Osteostat is the cytokine that binds to TNFRSF18/AITR/GITR and is important for interactions between activated T-lymphocytes and endothelial cells and may modulate T-lymphocyte survival in peripheral tissues. Osteostat is expressed at high levels in the small intestine, ovary, testis, kidney and endothelial cells after stimulation by lipopolysaccharides.
Osteostat protein is detectable in human microvascular EC and is highly up-regulated by IFN-alpha and IFN-beta. Osteostat inhibit differentiation of osteoclasts from monocytic precursor cells. Osteostat suppresses the early stage of osteoclastogenesis via inhibition of macrophage colony-stimulating factorinduced receptor activator of NF-kappaB (RANK) expression in the osteoclast precursor cells. Osteostat does not inhibit lipopolysaccharide-induced RANK expression in monocytes and dendritic cells, or activation-induced RANK expression in T cells. Osteostat is a novel regulator of osteoclast generation and substantiate the major role played by the endothelium in bone physiology.

GH-releasing peptides (GHRPs) are synthetic peptides that like GHRH effect on pituitary somatotrophs to stimulate GH release. The GHRP1 is one of several synthetic met-enkephalin analogs that owns unnatural D-amino acids. They were developed for their growth hormone (GH) releasing activity and called GH secretatogues. They lack opioid activity but are potent stimulators of GH release. These secretatogues are distinct from the growth hormone releasing hormone (GHRH or GHRF) as they share no sequence relation and derive their function through action at a completely different receptor, the ghrelin receptor.

ARL11 (ADP-ribosylation factor-like protein 11) belongs to the ARF family of the Ras superfamily of small GTPases which are known to be involved in multiple regulatory pathways altered in human carcinogenesis. ARFs are highly conserved guanine nucleotide binding proteins which enhance the ADP-ribosyltransferase activity of choleratoxin. ARFs are important in eukaryotic vesicular trafficking pathways and they have a vital role in the activation of phospholipase D (PC-PLD). ARL11 is assumed to act as a tumor suppressor which may have a role in the regulation of apoptosis.

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.

WHSC2 (NELF-A) is a protein factor required for DRB-sensitive transcription. WHSC2 is one of the 5 components of the multisubunit NELF complex which cooperates with DSIF to repress RNA polymerase II elongation. The Wolf-Hirschhorn syndrome is a multiple malformation syndrome characterized by mental and developmental defects resulting from a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3).

Growth-hormone-releasing hormone (GHRH), also known as growth-hormone-releasing factor (GRF or GHRF) or somatocrinin, is a 44-amino acidpeptide hormoneproduced in the arcuate nucleusof the hypothalamus.
GHRH is released from neurosecretory nerve terminals of these arcuate neurons, and is carried by the hypothalamo-hypophysial portal circulation to the anterior pituitary glandwhere it stimulates growth hormone(GH) secretion. GHRH also stimulates the production of GH. GHRH is released in a pulsatile manner, stimulating similar pulsatile release of GH. In addition, GHRH also promotes slow-wave sleepdirectly.

RANGRF is a protein which acts as a guanine nucleotide release factor in mouse and regulates the expression and function of the Nav1.5 cardiac sodium channel in human. RANGRF also controls the intracellular trafficking of RAN. In cardiac cells, the RANGRF appears to regulate the cell surface localization of SCN5A.

Human AIF1 protein shares 98% homology/identity with that of rat. AIF1 is expressed in macrophages and neutrophils. The expression of AIF1 transcripts is upregulated by IFN-g in rat macrophages. AIF1 is expressed selectively in human macrophage-like cell lines, and in a subset of CD68(+) macrophages in the interstitial and perivascular spaces of human heart allografts. In quiescent cultured human vascular smooth muscle cells synthesis of AIF1 is induced by IFN-g, IL1b, and conditioned medium of T-cells. Overexpression of AIF1 in human VSMCs results in enhanced growth of these cells. AIF1 is expressed during apoptosis rat mammary gland and ventral prostate tissues. Allograft Inflammatory Factor 1 is expressed by several tumor-associated activated macrophages and microglial cells in rat and human gliomas. There is an evident relationship of AIF1-expressing activated macrophages and microglial cells with tumor malignancy in humans.

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, Neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MSGA-a). It is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis. CXCL1 is expressed by macrophages, neutrophilsand epithelial cells, and has neutrophil chemoattractant activity. CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors and is involved in the processes of angiogenesis, inflammation, wound healing, and tumorigenesis. This chemokine elicits its effects by signaling through the chemokine receptor CXCR2. The gene for CXCL1 is located on human chromosome 4 amongst genes for other CXC chemokines.