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EPHA2 is a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors are implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The EPHA2 gene encodes a protein that binds ephrin-A ligands. Mutations in the EPHA2 gene are the origin of certain genetically-related cataract disorders.

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.

The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of fas-mediated apoptosis using similar mechanisms.

Tumor necrosis factor receptor superfamily member 21 or TNFRSF21, is a protein that located in the cell membrane from the TNF receptor superfamily. By activating the NF-kappaB pathway, TNFRSF21 promotes cell apoptosis. The degeneration of cells caused by activating caspase 3 and caspase 6, the TNFRSF21 binds to the N-terminal APP in neuronal cell bodies and axons which leads to apoptosis. TNFRSF21 takes part in signaling cascades activated by stimulation of T-cell receptor.

Signal-Regulatory Protein Alpha, SIRPA belongs to the signal-regulatory-protein (SIRP) family, as well as theimmunoglobulin super family. The members of the SIRP family are receptor-type transmembrane glycoproteins which areinvolved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. SIRPA can bephosphorylated by tyrosine kinases. The phospho-tyrosine residues of this PTP have been shown to recruit SH2domain containing tyrosine phosphatases (PTP), and perform as substrates of PTPs. SIRPA take part insignal transduction mediated by a variety of growth factor receptors. CD47 has been shown to be a ligand forSIRPA.

Collagen triple helix repeat-containing protein 1 or CTHRC1 acts as a negative regulator of collagen matrix deposition. The protein is secreted from a 28kDa protein which is glycosylated and very conserved from lower chordates to mammals. CTHRC1 is found qualitatively in plasma of healthy human subjects. CTHRC1 plasma levels are also significantly elevated during pregnancy, in diabetes, in inflammatory and infectious conditions, in subjects with acute myeloid leukemia but not in subjects with solid cancers.CTHRC1 is highly connected with calcified tissues and cartilaginous matrix, but not with endothelial cells.

FADD is an adaptor protein that cooperates with a variety of cell surface receptors and mediates cell apoptotic signals. Using its C-terminal death domain, FADD is recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and consequently it take parts in the death signaling initiated by these receptors. FADD interaction with the receptors reviels the N-terminal effector domain of, which allows it to recruit caspase-8, and thus initiate the cysteine protease cascade. Knockout studies in mice furthermore propose the significance of FADD in premature T cell development. FADD plays a role in survival/proliferation and cell cycle development. FADD also takes part in cellular sublocalization, protein phosphorylation, and inhibitory molecules.

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).

The IL1RL1 gene is a member of the IL-1 receptor family, encoding a transmembrane protein with a structure similar to IL-1R1. IL1RL1 is a receptor for interleukin-33, its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. IL1RL1 may possibly be involved in helper T-cell function. IL1RL1 is highly expressed in kidney, lung, placenta, stomach, skeletal muscle, colon and small intestine.A soluble form of the IL1RL1 is produced from the same gene by alternative splicing and was shown to be expressed in several cell types including fibroblasts and mast cells. Soluble IL1RL1 also acts as a negative regulator of Th2 cytokine production and high levels have been reported in several disease states and conditions including asthma, sepsis and myocardial infarction.Analysis of the similar gene in mouse suggested that the IL1RL1 receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells.

Interleukin-13 receptor subunit alpha-1 (IL13RA1) is a subunit of the interleukin 13 receptor. The IL13RA1 subunit forms a receptor complex with IL4 receptor alpha, which is a subunit shared by IL13 and IL4 receptors. IL13RA1 binds tyrosine kinase TYK2, and thus may mediate the signaling processes which leads to the activation of JAK1, STAT3 and STAT6 induced by IL13 and IL4. IL13RA1 is vital for allergen-induced airway hyperactivity and mucus hypersecretion.

IL2-Ra is one of the three constituent subunits of the IL2 receptor.
IL-2Ra is released into the serum after increased cellular expression such as increased activation of B and T cells. Clinical manifestations of IL2-Ra elevation include autoimmune conditions and some leukemias and lymphomas.

EPHB4 or Ephrin type-B receptor 4 is encoded by the EPHB4 gene in humans. The receptor and its ligands (the ephrins) take part in different developmental stages, mainly in the nervous system. EPHB4 and other Ephrin receptors are the biggest subgroup of the RTK receptors. EPHB4 binds to ephrin B2 and has a crucial part in the development of the vascular system.

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.

EBAG9 is a type III transmembrane protein that is primarily located in the Golgi. EBAG9 is a tumor-associated antigen that is expressed at high frequency in a variety of cancers, such as advanced breast and prostate cancers. while the EBAG9 acts to inhibit the growth of receptor-binding cells and induced apoptosis of immune cells, cancer cells may evade immune surveillance. Thus immunodetection of EBAG9 expression can be a negative prognostic indicator. EBAG9 promotes progression of bladder cancer. In rheumatoid arthritis, the deficiency of EBAG9 induces CTL infiltration through failure to evade immune attack, therefore leading to apoptosis of the synovial lining cells. EBAG9 is involved in controlling exocytosis processes. EBAG9 expression plays a role in the progression of oral squamous cell carcinoma. EBAG9 plays a specific role in premature stages of breast carcinogenesis.

CD21 is expressed strongly on mature B cells, follicular dentritic cells and weakly on immature thymocytes and T lymphocytes. In B-cell ontogeny, CD21 appears after the pre-B-stage, is maintained during peripheral B-cell development and is lost upon terminal differentiation into plasma cells. CD21 expression is also gradually lost after stimulation of B cells in vitro. CD21 functions as receptor for C3d, C3dg and iC3b Complement components, for EBV and for IFNalpha. CD21 binds to CD23 and associates with CD19, CD81 and Leu13 to form a large signal-transduction complex involved in B cell activation.

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.

TNF Ligand Receptor Superfamily Member 25 (TNFRSF25) belongs to the TNF receptor superfamily that binds to the TNF-like protein TL1A. TNFRSF25 interacts directly with the adapter TRADD and regulates lymphocyte homeostasis. TNFRSF25 is also mediates activation of NF-kappa-B and induces apoptosis. TNFRSF25 signals are vital to exert T helper cell 2 effector activity in Th2-polarized CD4 cells and co-stimulate interleukin-13 production by glycosphingolipid-activated NKT cells.

Interleukin-23 receptor (IL23R) is a member of the type I cytokine receptor family, Type 2 subfamily. IL23R contains two fibronectin type-III domains and is expressed by monocytes, Th1, Th0, NK and dendritic cells. IL23R protein pairs with the receptor molecule IL12RB1/IL12Rbeta1, and both are necessary for IL23A signaling. IL23R protein associates constitutively with JAK2 (Janus kinase 2), and it also binds to transcription activator STAT3 in a ligand-dependent manner. IL23R binds IL23 and mediates T-cells, NK cells and perhaps certain macrophage/myeloid cells stimulation most likely by way of activation of the Jak-Stat signaling cascade. IL23R might be responsible for autoimmune inflammatory diseases and be vital for tumorigenesis.

Neuropilin 1 (Nrp1) is a transmembrane glycoprotein which functions as a co-receptor for several extracellular ligands including class III/IV semaphorins, some isoforms of vascular endothelial growth factor and transforming growth factor beta. Nrp1 binds vascular endothelial growth factor (VEGF)-A and is believed to serve as a coreceptor for kinase insert domain-containing receptor (KDR) by connecting with KDR and enhancing VEGF signaling. Nrp1 is a marker of regulatory T cells.

Interleukin 10 receptor, alpha subunit or CDW210A, is a part of the IL-10 receptor. This protein is encoded by the IL10RA gene in humans. IL10RA is a receptor for IL-10 (interleukin 10), it is part of the interferon receptors family. This protein is responsible for the inhibition of interferon receptors synthesis by taking part in the immunosuppressive signal of interleukin 10. Among its other roles are the insulin receptor substrate-2/PI 3-kinase/AKT pathway and phosphorylation of JAK1 and TYK2 kinases.

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.

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.

Thyroid Hormone Receptor Interactor 10 (TRIP10) is a part of the F-BAR family of proteins which is expressed in a variety of tissues, including kidney, brain, liver, lung, heart and pancreas. The F-BAR family of proteins contains an N-terminal, alpha-helical, region which is hydrophobic and related to the Bin Amphiphysin Rvs (BAR) protein family. TRIP10 is vital for the coordination of membrane tubulation with Actin cytoskeletal reorganization during endocytosis.