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TRAF2 protein is related with transduce signals from members of the TNFR superfamily. TRAF2 is located in the cytoplasm binds to TRAF1, TRAF2, or TRAF3, thus inhibiting TRAF function by sequestering the TRAFs in a suppressed state in the cytoplasm. Overexpression of TANK inhibits TRAF2-mediated NF-Kappa-B activation signaled by CD40 and both TNF receptors and inhibits LMP1-mediated NF-kappa-B activation by blocking the association of TRAF2 with LMP1. TRAF2 is necessary for the cellular response to TNF-alpha by connecting upstream signalling molecules to the IKKs and p65.

Peroxisome proliferators are non-genotoxic carcinogens which are purported to exert their effect on cells through their interaction with members of the nuclear hormone receptor family termed peroxisome proliferators activated receptors (PPARs). Nuclear hormone receptors are ligand-dependent intracellular proteins that stimulate transcription of specific genes by binding to specific DNA sequences following activation by the appropriate ligand. Studies indicate that PPARs are activated by peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643, as well as by some fatty acids.

E-selectin which is also called Endothelial leukocyte adhesion molecule 1, ELAM1, ELAM belongs to a family of divalent cation-dependent carbohydrate-binding glycoproteins or adhesion molecules. Eselectin is expressed on the surface of endothelial cells and mediates the interaction of leukocytes and platelets with endothelial cells during an inflammatory response. E-selectin is present in single copy in the human genome and contains 14 exons spanning about 13 kb of DNA.

Discoidin Domain Receptor Tyrosine Kinase 1 (DDR1) is a transmembrane glycoprotein which is a part of the discoidin-like domain containing subfamily of receptor tyrosine kinases. DDR1 functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. DDR1 is expressed in epithelial cells, mainly in the kidney, lung, gastrointestinal tract, and brain and is significantly overexpressed in several human tumors.

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.

GH receptor, also known as GHR is part of the cytokine receptor family. GHR binds 2 receptor molecules and in this manner induces signal transduction through receptor dimerization. Furthermore, at high concentrations, GH performs as an antagonist since there is a large difference in affinities at the respective binding sites. The antagonist action can be enhanced further by reducing binding in the low affinity binding site.

VEGF-C, also known as Vascular Endothelial Growth Factor Related Protein (VRP), is a recently discovered VEGF growth factor family member that is most closely related to VEGF-D. Human VEGF-C cDNA encodes a pre-pro-protein of 416 amino acids residues. It is almost identical to the mouse VEGF-C protein. Similar to VEGF-D, VEGF-C has a VEGF homology domain spanning the middle third of the precursor molecule and long N- and C-terminal extensions. In adults, VEGF-C is highly expressed in heart, placenta, ovary and small intestine. Recombinant human VEGF-C, lacking the N- and C-terminal extensions and containing only the middle VEGF homology domain, forms primarily non-covalently linked dimers. This protein is a ligand for both VEGFR-2/KDR and VEGFR-3/FLT-4. Since VEGFR-3 is strongly expressed in lymphatic endothelial cells, it has been postulated that VEGF-C is involved in the regulation of the growth and/or differentiation of lymphatic endothelium. Although recombinant human VEGF-C is also a mitogen for vascular endothelial cells, it is much less potent than VEGF-A.

Erythropoietin or EPO is a hormone (glycoprotein), part of the type I cytokine group of proteins. EPO is found mainly in the kidney tissue, produced from fibroblast-like cortical interstitial cells near the proximal tubules. EPO is also present in the blood, where it acts as red cell production regulator, by the promotion of differentiation of erythroid and thereby starts hemoglobin synthesis. Furthermore, EPO has neuroprotective activity towards brain injuries & anti-apoptotic activity in different tissues.

VEGF-C152S is a point mutant generated by the replacement of the second conserved Cys residue of the recombinant processed VEGF-C by a Ser residue. VEGF-C 152S is analog to the human VEGF-C 156S mutant and only active toward VEGFR-3/FLT-4 but, unlike wild type VEGF-C, is unable to bind to and to activate signaling through VEGFR-2/KDR. VEGF-C152S was inactive in the vascular permeability assay and did not increase migration of the capillary endothelial cells, indicating that these VEGF-like effects of VEGF-C require VEGFR-2 binding. VEGF-C, also known as Vascular Endothelial Growth Factor Related Protein (VRP), is a recently discovered VEGF growth factor family member that is most closely related to VEGF-D. The rat VEGF-C cDNA encodes a pre-pro-protein of 416 amino acids residues. It is almost identical to the mouse VEGF-C protein. Similar to VEGF-D, VEGF-C has a VEGF homology domain spanning the middle third of the precursor molecule and long N- and C-terminal extensions. In adults, VEGF-C is highly expressed in heart, placenta, ovary and small intestine. Recombinant rat VEGF-C, lacking the N- and C-terminal extensions and containing only the middle VEGF homology domain, forms primarily non-covalently linked dimers. This protein is a ligand for both VEGFR-2/KDR and VEGFR-3/FLT -4. Since VEGFR-3 is strongly expressed in lymphatic endothelial cells, it has been postulated that VEGF-C is involved in the regulation of the growth and/or differentiation of lymphatic endothelium. Although recombinant rat VEGF-C is also a mitogen for vascular endothelial cells, it is much less potent than VEGF-A.

CD200R1, also known as cell surface glycoprotein CD200 receptor 1, is an isoform of CD200 receptors which is expressed on cells of the myeloid lineage. CD200R1 inhibitory signaling pathway has been involved in taking a prominent role in limiting inflammation in a broad range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, in addition to inducible nitric oxide synthase in response to selected stimuli.

CRCP is a ubiquitous coupling protein for the calcitonin gene-related peptide and adrenomedullin receptors. CRCP controls ligand sensitivity in several tissues and has DNA-directed RNA polymerase activity, catalytic activity and calcitonin receptor activity.

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.

ELAV Like Neuron-Specific RNA Binding Protein 2, also known as ELAVL2 is a neural-specific RNA-binding protein which is recognized with his ability to bind to several 3' UTRs, as well as its own and in addition those of FOS and ID. ELAVL2 identify a GAAA motif in the RNA. One of the diseases associated with ELAVL2 is contagious pustular dermatitis.

Glutaredoxin-2 (GrxB) is amember of the glutaredoxin family. Glutaredoxins are small redox enzymes of approximately 100 amino-acid residues which use glutathione as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. GrxB is involved in reducing some disulfides in a coupled system with glutathione reductase. GrxB doesn’t act as hydrogen donor for ribonucleotide reductase.

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.

Eukaryotic translation initiation factor 4H (EIF4H) is a 248 amino acid protein which localizes to the perinuclear region of the cytoplasm and is expressed as 2 isoforms, termed short and long. EIF4H functions to stimulate the initiation of protein synthesis at the level of mRNA employment. EIF4H stimulates the RNA-dependent ATP hydrolysis catalyzed by EIF4A and EIF4B. EIF4H gene defects linked to Williams- Beuren syndrome (WBS), a rare developmental disorder characterized by cardiovascular and musculo-skeletal abnormalities and caused by the deletion of contiguous genes at 7q11.23.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Elongation factor 1-beta (EEF1B2) is a translation elongation factor. EEF1B2 is a guanine nucleotide exchange factor which is involved in the transfer of aminoacylated tRNAs to the ribosome. Both EEF1B2 and EEF1D stimulate the exchange of GDP bound to EEF1A to GTP.

Eukaryotic translation initiation factor 3 subunit J (EIF3J) is a member of the EIF-3 subunit J family. EIF3 has a crucial role in binding of initiator methionyl-tRNA and mRNA to the 40S ribosomal subunit to produce the 40S initiation complex. EIF3J binds to the aminoacyl (A) site and mRNA access channel of the 40S subunit, setting EIF3J directly in the ribosomal decoding center. In addition, EIF3J interacts with eIF1A and reduces 40S subunit affinity for mRNA. An elevated affinity for mRNA is restored upon enlistment of initiator tRNA, despite the fact EIF3J remains in the mRNA-binding cleft in the presence of tRNA.

RARRES2 is a secreted chemotactic protein that initiates chemotaxis through the ChemR23 G protein-coupled seven-transmembrane domain ligand. RARRES2 is upregulated by the synthetic retinoid tazarotene and found in a vast variety of tissues. RARRES2 acts as an adipokine, and is truncated on both termini from the proprotein. RARRES2 is structurally related to the cathelicidin precursors, cystatin C and kininogens. RARRES2 promotes calcium mobilization and chemotaxis of immature dendritic cells and macrophages. RARRES2 is secreted as a precursor of little biological activity, which requires proteolytic cleavage of its COOH-terminal domain to be exchangeed into a potent and highly specific agonist of ChemR23. RARRES2 signals via its receptor, ChemR23 (CMKLR1), as a positive regulator of adipocyte differentiation and metabolic function. The Chemerin receptor acts as a coreceptor for SIV and some primary HIV-1 strains. The Chemerin receptor has another ligand, called tazarotene-induced 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. CSF-1 induces cells of the monocyte/macrophage lineage. It plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.

Low affinity immunoglobulin gamma Fc region receptor III-A (FCGR3A) is a receptor for the Fc portion of immunoglobulin G, and is involved in the elimination of antigen-antibody complexes from the circulation, as well as other antibody-dependent responses. FCGR3A needs to associate with the gamma subunit of Fc epsilon. The FCGR3A receptor is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, while FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. In addition, FCGR3A is expressed on macrophages, subpopulation of T-cells, immature thymocytes and placental trophoblasts. FCGR3A mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis. FCGR3A gene mutations are linked with susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia.