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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.

PA2G4 belongs to the peptidase M24C family and functions as an RNA-binding protein involved in cellular proliferation and differentiation processes. PA2G4 is a component of pre-ribosomal ribonucleoprotein complexes, participating in ribosome assembly and regulating the later steps of rRNA processing. Also, PA2G4 interacts with ErbB-3 and may function as a modulator of the ErbB-3 mediated signal transduction pathway by regulating the effects of Neuregulin-1. Furthermore, PA2G4 is a transcriptional co-repressor of androgen receptor-regulated genes and other cell cycle regulatory genes through its interactions with histone deacetylases. PA2G4 is implicated in growth inhibition and the induction of differentiation of human cancer cells. In addition, PA2G4 mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site). PA2G4 associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA.

ARPC5 is a 151 amino acid subunit of the Arp2/3 complex. ARPC5 is believed to have a role in maintaining the integrity of Arp2/3. ARPC5 is a substrate for MAPKAPK-2 which, via phosphorylation of ARPC5, may participate in Arp2/3 regulatory functions and remodeling of the Actin cytoskeleton.

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.

BID is a pro-apoptotic Bcl-2 protein having only the BH3 domain. In reaction to apoptotic signaling, BID interacts with another Bcl-2 family of cell death regulators, called Bax, they form a heterodimer resulting to the insertion of Bax into the outer mitochondrial membrane. Bax induces the opening of the mitochondrial voltage-dependent anion channel which lead to the release of cytochrome c and other pro-apoptotic factors from the mitochondria resulting in activation of caspases. BID is a mediator of mitochondrial damage induced by caspase-8 (CASP8). CASP8 cleaves BID, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. The major proteolytic product p15 BID releasea cytochrome c. Isoform 1, Isoform 2 and Isoform 4 induce ice-like proteases and apoptosis while Isoform 3 does not induce apoptosis.

Trafficking Protein Particle Complex 2-Like (TRAPPC2L) takes part in vesicular transport from endoplasmic reticulum to Golgi. TRAPPC2L is a part of the TRAPP small subunits family and is expressed in various organs like testis, liver, bladder, lung, spleen and brain.

TRAPPC3 is a part of the TRAPP complex that takes part in connection of transport vesicles to the cis-Golgi membrane. Additionally, TRAPPC3 is involved in vesicular transport from endoplasmic reticulum to Golgi.

Signal-transducing adaptor protein 1 (STAP1) acts as a docking protein which operates downstream of Tec tyrosine kinase in B cell antigen receptor signaling. The STAP1 protein is directly phosphorylated by Tec in vitro where it partakes in a positive feedback loop, increasing Tec activity.

Regulator of G-protein signaling 14 (RGS14) is a member of the regulator of G protein signaling family. RGS14 contains one RGS domain, 2 Raf-like Ras-binding domains (RBDs) and one GoLoco motif. RGS14 reduces the signaling activity of G-proteins by binding, via its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. RGS14 is a scaffolding protein which integrates G protein and H-Ras/ERK/MAP kinase signaling pathways, thus making it suitably positioned to repress plasticity in CA2 neurons. Since RGS14 is highly enriched in CA2 pyramidal neurons, it has a role in inhibition of both synaptic plasticity at these synapses and hippocampal-based learning and memory.

Fas and Fas Ligand (FasL) are members of the TNF superfamily and are type I and type II transmembrane proteins, respectively. Binding of FasL to Fas initiates apoptosis in Fas-bearing cells. The apoptosis mechanism involves the recruitment of pro-caspase 8 through an adaptor molecule named FADD followed by processing of the pro-enzyme to active forms. These active caspases subsequently cleave a variety of cellular substrates leading to the eventual cell death. sFasR is able to inhibit FasL-induced apoptosis by acting as a decoy receptor whicht serves as a sink for FasL. The full length Fas Receptor is a 319 a.a type I transmembrane protein, which contains a 157 a.a extracellular domain, a 17 a.a transmembrane domain, and 145 a.a cytoplasmic domain. The mature human Fas ECD shares 55%, 58%, a.a sequence identity with the mouse, rat, Fas, respectively.

TRAIL Receptor-1 (DR4) and TRAIL Receptor-2(DR5) are members of the TNFR superfamily of transmembrane proteins and contain a cytoplasmic "death domain", which is capable of activating the cell's apoptotic machinery. These receptors are activated by binding to either membrane anchored or soluble TRAIL/Apo2L.

GNG4 belongs to a multigene family and is involved in defining the specificity of receptor-G protein interaction. In mammals, G protein alpha, beta and gamma polypeptides are encoded by no less than 16, 4 and 7 genes, respectively. It is a well-known fact that different G protein complexes expressed in different tissues carry structurally distinct members of the alpha beta and gamma subunits and that privileged connotation between members of subunit families rise G protein functional diversity.

Calcium-activated nucleotidase 1 (CANT1) is a member of the apyrase family. The CANT1 protein is calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is as follows: UDP > GDP > UTP > GTP. Moreover, CANT1 has a very low activity towards ADP and an even lower activity towards ATP. As well as it doesn’t hydrolyze AMP and GMP. CANT1’s specific function is yet unknown, nevertheless its substrates are involved in several key signaling functions, including Ca2+ release, through activation of pyrimidinergic signaling. Mutations in the CANT1 gene are linked with Desbuquois dysplasia with hand anomalies.

KLRC3 belongs to the NKG2 group that can be found mostly in natural killer (NK) cells and encodes a family of transmembrane proteins known for their C-type lectin domain and their type II membrane orientation (extracellular C terminus). The NKG2 gene family is situated inside the NK complex, a region which has quite a few C-type lectin genes mostly expressed on NK cells.

Suppressor of Cytokine Signaling 3, also known as SOCS3 belongs to the SOCS family; in addition SOCS3 is a member of the STAT-induced STAT inhibitor (SSI). The SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of SOCS3 is induced by different cytokines, including IL6 and IL10. SOCS3 can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. Studies of the mouse counterpart of SOCS3 have shown the roles of SOCS3 in the negative regulation of fetal liver hematopoiesis, and placental development.

SCGN is a secreted calcium-binding protein which is found in the cytoplasm. It is related to calbindin D-28K and calretinin. Secretagogin is involved in KCL-stimulated calcium flux and cell proliferation.
Secretagogin plays a role in human non-functional pituitary adenomas.

Signal-regulatory protein beta-1 isoform 1 or SIRPB1, is an immunoglobulin-like cell surface receptor which is a part of the SIRP superfamily. SIRPB1 is a cell membrane receptor that takes part in the negative regulation of tyrosine kinase-coupled signaling pathway. SIRPB1 is engaged in the activation of tyrosine kinase SYK, SIRP alpha molecules (activates SHP-1 and SHP-2 protein tyrosine phosphatases), etc.

Regulator of G-protein signaling 5 (RGS5) binds directly to activated G alpha subunits and act as GTPase-activating proteins (GAPs) in order to weaken and/or modulate hormone and neurotransmitter receptor-initiated signaling by both G alpha-GTP and G beta gamma. Vascular endothelial cells express the RGS protein RGS5, where it correlates with capillary morphogenesis, consequently rendering it a candidate gene involved in capillary growth, angiogenesis, and also possibly the pathophysiology of stroke.

HCST (Hematopoietic Cell Signal Transducer) is part of the DAP10 family. HCST is capable of being a part of an immunoreceptor complex. HCST takes a vital part in inducing cytotoxicity against MHC class I chain-associated MICA & target cells expressing cell surface ligands such as UL16-binding protein (ULBP) & MICB. HCST complex participates in proliferation as well as cell survival by activating T & NK cell responses.

Tumor necrosis factor receptor superfamily member 11A or TNFRSF11A or RANK, is a protein, part of the tumor necrosis factor receptor (TNFR) group of proteins. RANK acts as the receptor of RANK-Ligand and regulates osteoclast activation & differentiation. RANK protein has been linked to activation of NF-kappa B & c-jun N-terminal kinase, enhancement of T cell growth, bone remodeling and repair, dendritic cell function, lymph node development, immune cell function, mammary gland development & thermal regulation.

Endoglin is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex.The Endoglin protein consists of a homodimer of 180 kDA with disulfide links. Endoglin has been found on endothelial cells, activated macrophages, fibroblasts, and smooth muscle cells. Furthermore, Endoglin has been found to be part of the TGF-beta1 receptor complex. Endoglin thus may be involved in the binding of TGF-beta1, TGF-beta3, activin-A, BMP-2, and BMP-7. Beside TGF-beta signaling endoglin may have other functions. It has been postulated that endoglin is involved in the cytoskeletal organization affecting cell morphology and migration. Endoglin has a role in the development of the cardiovascular system and in vascular remodeling. Endoglin expression is regulated during heart development . Experimental mice without the endoglin gene die due to cardiovascular abnormalities.

Protein Tyrosine Phosphatase Receptor Type N (PTPRN) is a catalytically inactive protein and a major target of autoimmune response in diabetes mellitus. The long C-terminal intracellular tail covers the majority of autoantibody epitopes. PTPRN is expressed in neural, neuroendocrine and pancreatic islet cells.

Synaptotagmin-11 (SYT11) protein may be involved in Ca2+-dependent exocytosis of secretory vesicles through Ca2+ and phospholipid binding to the C2 domain or may function as Ca2+ sensors in the process of vesicular trafficking and exocytosis.

Ras-related GTP binding C (RRAGC) is a monomeric guanine nucleotide-binding protein, or G protein. As a result of binding GTP or GDP, small G proteins act as molecular regulators in various cell processes and signaling pathways. RRAGC regulates the organization of the actin cytoskeleton and has an intrinsic GTPase activity. RRAGC is possibly necessary for the amino acid-induced relocalization of mTORC1 to the lysosomes and its succeeding activation by the GTPase RHEB, which is key step in the activation of the TOR signaling cascade by amino acids.