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| | ATG16L1 | Autophagy-related protein 16-1; Plays an essential role in autophagy: interacts with ATG12- ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II. Thereby, controls the elongation of the nascent autophagosomal membrane. Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production. Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response. Instead, promotes with NOD2 an autophagy-dependent antibacterial pathway. Plays a r [...] (624 aa) |
| | IL10RA | Interleukin-10 receptor subunit alpha; Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Upon binding to IL10, induces a conformational change in IL10RB, allowing IL10RB to bind IL10 as well. In turn, the heterotetrameric assembly complex, composed of two subunits of IL10RA and IL10RB, activates the kinases JAK1 and TYK2 that are constitutively associated with IL10RA and IL10RB respectively. These kinases then phosphorylate specific tyrosine residues in the intracellul [...] (578 aa) |
| | IL23A | Interleukin-23 subunit alpha; Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tu [...] (189 aa) |
| | IFNG | Interferon 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, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons; Belongs to the type II (or gamma) interferon family. (166 aa) |
| | DHX58 | Probable ATP-dependent RNA helicase DHX58; Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: compet [...] (678 aa) |
| | TLR2 | Toll-like receptor 2; Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble [...] (784 aa) |
| | IRAK3 | Interleukin-1 receptor-associated kinase 3; Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex. (596 aa) |
| | SMAD7 | Mothers against decapentaplegic homolog 7; Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a [...] (426 aa) |
| | MAP3K8 | Mitogen-activated protein kinase kinase kinase 8; Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up- [...] (467 aa) |
| | IL1B | Interleukin-1 beta; Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B- cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T- helper 1 (Th1) cells. (269 aa) |
| | IL18RAP | Interleukin-18 receptor accessory protein; Within the IL18 receptor complex, does not mediate IL18- binding, but involved in IL18-dependent signal transduction, leading to NF-kappa-B and JNK activation. May play a role in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells (Probable). (599 aa) |
| | STAT3 | Signal transducer and activator of transcription 3; Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differenti [...] (770 aa) |
| | SLC9A3 | Sodium/hydrogen exchanger 3; Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. (834 aa) |
| | ERBB2 | Receptor tyrosine-protein kinase erbB-2; Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and [...] (1255 aa) |
| | REG3G | Regenerating islet-derived protein 3-gamma 16.5 kDa form; Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan. Restricts bacterial colonization of the intestinal epithelial surface and consequently limits activation of adaptive immune responses by the microbiota. The uncleaved form has bacteriostatic activity, whereas the cleaved form has bactericidal activity against L.monocytogenes and methicillin-resistant S.aureus. Regulates keratinocyte proliferation and [...] (175 aa) |
| | IL9 | Interleukin-9; Supports IL-2 independent and IL-4 independent growth of helper T-cells; Belongs to the IL-7/IL-9 family. (144 aa) |
| | EGFR | Epidermal growth factor receptor; Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin- binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at leas [...] (1210 aa) |
| | IL18 | Interleukin-18; A proinflammatory cytokine primarily involved in polarized T- helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable). Belongs to the IL-1 family. (193 aa) |
| | CCR2 | C-C chemokine receptor type 2; Key functional receptor for CCL2 but can also bind CCL7 and CCL12. Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (Probable). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B. Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation (By similarity). Facilitates the export of matur [...] (374 aa) |
| | RETNLB | Resistin-like beta; Probable hormone; Belongs to the resistin/FIZZ family. (111 aa) |
| | NOD2 | Nucleotide-binding oligomerization domain-containing protein 2; Involved in gastrointestinal immunity. Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macroph [...] (1040 aa) |
| | CLDN2 | Claudin-2; Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. (230 aa) |
| | AXL | Tyrosine-protein kinase receptor UFO; Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates [...] (894 aa) |
| | IL13 | Interleukin-13; Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses. Positively regulates IL31RA expression in macrophages (By similarity). (146 aa) |
| | CASP3 | Caspase-3 subunit p12; Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. (277 aa) |
| | PTPN2 | Tyrosine-protein phosphatase non-receptor type 2; Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the develop [...] (415 aa) |
| | TOLLIP | Toll-interacting protein; Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity. Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP- dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates. (274 aa) |
| | TNIP1 | TNFAIP3-interacting protein 1; Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B- dependent gene expression by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1- dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this f [...] (636 aa) |
| | IL23R | Interleukin-23 receptor; Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-Stat signaling cascade. IL23 functions in innate and adaptive immunity and may participate in acute response to infection in peripheral tissues. IL23 may be responsible for autoimmune inflammatory diseases and be important for tumorigenesis. Belongs to the type I cytokine receptor family. Type 2 subfamily. (629 aa) |
| | RARB | Retinoic acid receptor beta; Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. The RXRA/RARB heterodimer can act as a repressor on the DR1 element [...] (448 aa) |
| | TNF | Tumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T- cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 [...] (233 aa) |
| | INAVA | Innate immunity activator protein; Expressed in peripheral macrophages and intestinal myeloid- derived cells, is required for optimal PRR (pattern recognition receptor)-induced signaling, cytokine secretion, and bacterial clearance. Upon stimulation of a broad range of PRRs (pattern recognition receptor) such as NOD2 or TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9, associates with YWHAQ/14-3-3T, which in turn leads to the recruitment and activation of MAP kinases and NF-kappa-B signaling complexes that amplifies PRR-induced downstream signals and cytokine secretion. In the intestine, regulate [...] (578 aa) |
| | LACC1 | Laccase domain-containing protein 1; Central regulator of the metabolic function and bioenergetic state of macrophages. In macrophages, promotes flux through de novo lipogenesis to concomitantly drive high levels of both fatty-acid oxidation and glycolysis. (430 aa) |
| | IL18R1 | Interleukin-18 receptor 1; Within the IL18 receptor complex, responsible for the binding of the proinflammatory cytokine IL18, but not IL1A nor IL1B. Involved in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells. Contributes to IL18-induced cytokine production, either independently of SLC12A3, or as a complex with SLC12A3 (By similarity). (541 aa) |
| | IL1R1 | Interleukin-1 receptor type 1, membrane form; Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1- dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling comp [...] (569 aa) |
| | IL6 | Interleukin-6; Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasm [...] (212 aa) |
| | MTMR3 | Myotubularin-related protein 3; Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3- phosphate and phosphatidylinositol 3,5-bisphosphate. May also dephosphorylate proteins phosphorylated on Ser, Thr, and Tyr residues. (1198 aa) |
| | AREG | Amphiregulin; Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts; Belongs to the amphiregulin family. (252 aa) |
| | TTC7A | Tetratricopeptide repeat protein 7A; Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and FAM126A, via direct interactions (By similarity). (882 aa) |
| | NFKB1 | Nuclear factor NF-kappa-B p105 subunit; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dime [...] (969 aa) |
| | JAK2 | Tyrosine-protein kinase JAK2; Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN- beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors [...] (1132 aa) |
| | IL33 | Interleukin-33 (109-270); Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells. Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines. Also involved in activation of mast cells, basophils, eosinophils and natural killer cells. Acts as a chemoattractant for Th2 cells, and may function as an 'alarmin', that amplifies immune responses during tissue injury. Belongs to the IL-1 family. Highly divergent. (270 aa) |
| | IRF4 | Interferon regulatory factor 4; Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA- 3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and [...] (451 aa) |
| | CYBB | Cytochrome b-245 heavy chain; Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc. (570 aa) |
| | RNF186 | E3 ubiquitin-protein ligase RNF186; E3 ubiquitin protein ligase that is part of an apoptotic signaling pathway activated by endoplasmic reticulum stress. In that process, stimulates the expression of proteins specific of the unfolded protein response (UPR), ubiquitinates BNIP1 and regulates its localization to the mitochondrion and induces calcium release from the endoplasmic reticulum that ultimately leads to cell apoptosis. (227 aa) |
| | TNFSF15 | Tumor necrosis factor ligand superfamily member 15, membrane form; Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis. Belongs to the tumor necrosis factor family. (251 aa) |
| | TLR4 | Toll-like receptor 4; Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non- conserved histidines and are, therefore, species-specific. Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression. In complex with [...] (839 aa) |
| | NOX1 | NADPH oxidase 1; NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain. (564 aa) |
| | IRAK1 | Interleukin-1 receptor-associated kinase 1; Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquit [...] (712 aa) |
| | PTGS2 | Prostaglandin G/H synthase 2; Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays imp [...] (604 aa) |
| | STAT1 | Signal transducer and activator of transcription 1-alpha/beta; Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF [...] (750 aa) |
| | TLR9 | Toll-like receptor 9; Key component of innate and adaptive immunity. TLRs (Toll- like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine- phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Controls lymphocyte response to Helicobacter infection (By similarity). Upon CpG stimulation, induces B-cell proliferation, activation, survival and [...] (1032 aa) |
| | PTPN22 | Tyrosine-protein phosphatase non-receptor type 22; Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2. Positively regulates toll-like receptor (TLR)-induced type 1 interferon production. Promotes host [...] (807 aa) |
| | CX3CR1 | CX3C chemokine receptor 1; Receptor for the CX3C chemokine fractalkine (CX3CL1); binds to CX3CL1 and mediates both its adhesive and migratory functions. Acts as coreceptor with CD4 for HIV- 1 virus envelope protein (in vitro). Isoform 2 and isoform 3 seem to be more potent HIV-1 coreceptors than isoform 1. (387 aa) |
| | OCLN | Occludin; May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions. (522 aa) |
| | TSLP | Thymic stromal lymphopoietin; [Isoform 1]: Cytokine that induces the release of T-cell- attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly activating mast cells. (159 aa) |
| | ICOSLG | Ig-like domain-containing protein; Inducible T cell costimulator ligand. (309 aa) |
| | CD4 | T-cell surface glycoprotein CD4; Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kina [...] (458 aa) |
| | TNFRSF1A | Tumor necrosis factor receptor superfamily member 1A, membrane form; Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. (455 aa) |
| | OSM | Oncostatin-M; Growth regulator. Inhibits the proliferation of a number of tumor cell lines. Stimulates proliferation of AIDS-KS cells. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells. Uses both type I OSM receptor (heterodimers composed of LIFR and IL6ST) and type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity). Belongs to the LIF/OSM family. (252 aa) |
| | XBP1 | X-box-binding protein 1, cytoplasmic form; Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland (By similarity). Involved in terminal differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regio [...] (261 aa) |
| | TGFB1 | Transforming growth factor beta-1 proprotein; Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively. Transforming growth factor beta-1: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form fo [...] (390 aa) |
| | ZNRF4 | E3 ubiquitin-protein ligase ZNRF4; E3 ubiquitin-protein ligase which specifically induces ubiquitination and proteasomal degradation of CANX within the endoplasmic reticulum. Could have a role in spermatogenesis (By similarity). (429 aa) |
| | MYD88 | Myeloid differentiation primary response protein MyD88; Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. MyD88-mediated signaling in intestinal epithelial cells is crucial for maintena [...] (317 aa) |
| | IL17A | Interleukin-17A; Ligand for IL17RA and IL17RC. The heterodimer formed by IL17A and IL17F is a ligand for the heterodimeric complex formed by IL17RA and IL17RC. Involved in inducing stromal cells to produce proinflammatory and hematopoietic cytokines ; Belongs to the IL-17 family. (155 aa) |
| | TLR5 | Toll-like receptor 5; Pattern recognition receptor (PRR) located on the cell surface that participates in the activation of innate immunity and inflammatory response. Recognizes small molecular motifs named pathogen-associated molecular pattern (PAMPs) expressed by pathogens and microbe-associated molecular patterns (MAMPs) usually expressed by resident microbiota. Upon ligand binding such as bacterial flagellins, recruits intracellular adapter proteins MYD88 and TRIF leading to NF- kappa-B activation, cytokine secretion and induction of the inflammatory response. Plays thereby an impo [...] (858 aa) |
| | MYH14 | Myosin-14; Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. (2036 aa) |
| | LOC102723996 | ICOS ligand; Ligand for the T-cell-specific cell surface receptor ICOS. Acts as a costimulatory signal for T-cell proliferation and cytokine secretion; induces also B-cell proliferation and differentiation into plasma cells. Could play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function (By similarity). (302 aa) |
| | IL22 | Interleukin-22; Cytokine that contributes to the inflammatory response in vivo. (179 aa) |
| | TRAF6 | TNF receptor-associated factor 6; E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seem [...] (522 aa) |
| | JAK3 | Tyrosine-protein kinase JAK3; Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails o [...] (1124 aa) |
| | TYK2 | Non-receptor tyrosine-protein kinase TYK2; Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain. (1187 aa) |
| | IRGM | Immunity-related GTPase family M protein; Putative GTPase which is required for clearance of acute protozoan and bacterial infections. Functions in innate immune response probably through regulation of autophagy. May regulate proinflammatory cytokine production and prevent endotoxemia upon infection. May also play a role in macrophages adhesion and motility (By similarity). Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. (181 aa) |
| | IRF5 | Interferon regulatory factor 5; Transcription factor involved in the induction of interferons IFNA and INFB and inflammatory cytokines upon virus infection. Activated by TLR7 or TLR8 signaling; Belongs to the IRF family. (514 aa) |
| | IL10 | Interleukin-10; Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro- inflammatory cytokines i [...] (178 aa) |
| | CISH | Cytokine-inducible SH2-containing protein; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasom [...] (275 aa) |
| | SIGIRR | Single Ig IL-1-related receptor; Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor- proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP. (410 aa) |
