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| | Ccl2 | C-C motif chemokine 2; Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (By similarity). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain. Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phospho [...] (148 aa) |
| | Fasl | Tumor necrosis factor ligand superfamily member 6, membrane form; Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development. Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses. TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance. Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (By similarit [...] (279 aa) |
| | Hck | Tyrosine-protein kinase HCK; Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic p [...] (524 aa) |
| | Dnase2a | Deoxyribonuclease-2-alpha; Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the degradation of nuclear DNA in cellular apoptosis during development. Necessary for proper fetal development and for definitive erythropoiesis in fetal liver, where it degrades nuclear DNA expelled from erythroid precursor cells. Belongs to the DNase II family. (353 aa) |
| | Ikbkg | NF-kappa-B essential modulator; Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. Also considered to be a mediator for TAX activation of NF- kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires [...] (430 aa) |
| | Cd44 | CD44 antigen; Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment. Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection. Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its c [...] (780 aa) |
| | Hmox1 | Heme oxygenase 1; Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Exhibits cytoprotective effects since excess of free heme sensitizes cells to undergo apoptosis. (289 aa) |
| | Il27ra | Interleukin-27 receptor subunit alpha; Receptor for IL27. Requires IL6ST/gp130 to mediate signal transduction in response to IL27. This signaling system acts through STAT3 and STAT1. Involved in the regulation of Th1-type immune responses. Also appears to be involved in innate defense mechanisms. (623 aa) |
| | Cav1 | Caveolin-1; May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae. Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependen [...] (178 aa) |
| | Cd209d | CD209 antigen-like protein D; Probable pathogen-recognition receptor. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. May recognize in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens. (237 aa) |
| | Tnfaip8l2 | Tumor necrosis factor alpha-induced protein 8-like protein 2; Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis. Negative regulator of Toll-like receptor and T-cell receptor function. Prevents hyperresponsiveness of the immune system and maintains immune homeostasis. Inhibits JUN/AP1 and NF-kappa-B activation. Promotes Fas-induced apoptosis. (184 aa) |
| | Mertk | Tyrosine-protein kinase Mer; Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation [...] (994 aa) |
| | Mapkapk2 | MAP kinase-activated protein kinase 2; Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT1 [...] (386 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 in [...] (178 aa) |
| | Tnfaip3 | Tumor necrosis factor alpha-induced protein 3; Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in [...] (775 aa) |
| | Ifngr1 | Interferon gamma receptor 1; Associates with IFNGR2 to form a receptor for the cytokine interferon gamma (IFNG). Ligand binding stimulates activation of the JAK/STAT signaling pathway (By similarity). (477 aa) |
| | Tbk1 | Serine/threonine-protein kinase TBK1; Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X (By similarity). This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB (By similarity). In order to establish such [...] (729 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 least [...] (1210 aa) |
| | Nfkbia | NF-kappa-B inhibitor alpha; Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription. (314 aa) |
| | Lgmn | Legumain; Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. Required for normal lysosomal protein degradation in renal proximal tubules. Required for normal degradation of internalized EGFR. Plays a role in the regulation of cell proliferation via its role in EGFR degradation. (435 aa) |
| | Fos | Proto-oncogene c-Fos; Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling (By similarity). Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and [...] (380 aa) |
| | Pcsk1 | Neuroendocrine convertase 1; Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP. (753 aa) |
| | Parg | Poly(ADP-ribose) glycohydrolase; Poly(ADP-ribose) glycohydrolase that degrades poly(ADP- ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP- ribose). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers. It is however unable to cleave the ester bond between the terminal ADP- ribose and ADP-ribosylated residues, leaving proteins that are mono- ADP-ribosylated. Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG. Required to prevent detrimental [...] (961 aa) |
| | Osmr | Oncostatin-M-specific receptor subunit beta; Associates with IL31RA to form the IL31 receptor. Binds IL31 to activate STAT3 and possibly STAT1 and STAT5 (By similarity). Capable of transducing OSM-specific signaling events (By similarity); Belongs to the type I cytokine receptor family. Type 2 subfamily. (971 aa) |
| | Mcpt1 | Mast cell protease 1; Has a chymotrypsin-like activity. (246 aa) |
| | Tbc1d23 | TBC1 domain family member 23; Putative Rab GTPase-activating protein which plays a role in vesicular trafficking. Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles. Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (By similarity). Plays a role in brain development, including in cortical neuron positioning. May also be important for neurite outgrowth, possibly t [...] (684 aa) |
| | Sod1 | Superoxide dismutase [Cu-Zn]; Destroys radicals which are normally produced within the cells and which are toxic to biological systems; Belongs to the Cu-Zn superoxide dismutase family. (154 aa) |
| | C3 | Complement C3c alpha' chain fragment 1; C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates. [C3-beta-c]: Acts as a chemoattractant for neutrophils in chronic inflammation. (1663 aa) |
| | Dusp1 | Dual specificity protein phosphatase 1; Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle; Belongs to the protein-tyrosine phosphatase family. Non- receptor class dual specificity subfamily. (367 aa) |
| | Brd2 | Bromodomain-containing protein 2; Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly (By similarity). May play a role in spermatogenesis or folliculogenesis. (798 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 (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces [...] (235 aa) |
| | Lta | Lymphotoxin-alpha; Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM (By similarity). In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo. (202 aa) |
| | Sirt3 | NAD-dependent protein deacetylase sirtuin-3; NAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, PDHA1, SOD2, LCAD, SDHA and the ATP synthase subunit ATP5PO. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels. In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription. Acts as a regulator of ceram [...] (257 aa) |
| | Mstn | Growth/differentiation factor 8; Acts specifically as a negative regulator of skeletal muscle growth. (376 aa) |
| | Parp1 | Poly [ADP-ribose] polymerase 1; Poly-ADP-ribosyltransferase that mediates poly-ADP- ribosylation of proteins and plays a key role in DNA repair. Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP- ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF an [...] (1014 aa) |
| | Siglec1 | Sialoadhesin; Acts as an endocytic receptor mediating clathrin dependent endocytosis. Macrophage-restricted adhesion molecule that mediates sialic-acid dependent binding to lymphocytes, including granulocytes, monocytes, natural killer cells, B-cells and CD8 T-cells (By similarity). Preferentially binds to alpha-2,3-linked sialic acid. Binds to SPN/CD43 on T-cells. May play a role in hematopoiesis. May act as a counter-receptor for CLEC10A in lymph node. (1701 aa) |
| | Il6ra | Interleukin-6 receptor subunit alpha; Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulation of the immune response, acute-phase reactions and hematopoiesis. (460 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 (By similarity). May also promote apoptosis in response to lipoproteins (By similarity). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface [...] (784 aa) |
| | F3 | Tissue factor; Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited proteolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. (294 aa) |
| | Tnfrsf1b | Tumor necrosis factor receptor superfamily member 1B; Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2 (By similarity). (474 aa) |
| | Smpdl3b | Acid sphingomyelinase-like phosphodiesterase 3b; Lipid-modulating phosphodiesterase. Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling. Has in vitro phosphodiesterase activity, but the physiological substrate is unknown. Lacks activity with phosphocholine-containing lipids, but can cleave CDP-choline, and can release phosphate from ATP and ADP (in vitro) ; Belongs to the acid sphingomyelinase family. (456 aa) |
| | Wasl | Neural Wiskott-Aldrich syndrome protein; Regulates actin polymerization by stimulating the actin- nucleating activity of the Arp2/3 complex. Involved in various processes, such as mitosis and cytokinesis, via its role in the regulation of actin polymerization. Together with CDC42, involved in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. In addition to its role in the cytoplasm, also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization (By similarity). Binds to HSF1/HS [...] (501 aa) |
| | Tnfrsf1a | Tumor necrosis factor receptor superfamily member 1A; 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 (By similarity). (454 aa) |
| | Nfkbib | NF-kappa-B inhibitor beta; Inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. However, the unphosphorylated form resynthesized after cell stimulation is able to bind NF-kappa-B allowing its transport to the nucleus and protecting it to further NFKBIA-dependent inactivation. Association with inhibitor kappa B-interacting NKIRAS1 and NKIRAS2 prevent its phosphorylation rendering it more resistant to degradation, explaining its slower degradation. (359 aa) |
| | Ikbkb | Inhibitor of nuclear factor kappa-B kinase subunit beta; Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is transloca [...] (757 aa) |
| | N4bp1 | NEDD4-binding protein 1; Inhibitor of the E3 ubiquitin-protein ligase ITCH. Acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates. Belongs to the N4BP1 family. (893 aa) |
| | Tradd | Tumor necrosis factor receptor type 1-associated DEATH domain protein; Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B (By similarity). The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A. (310 aa) |
| | Psmb10 | Proteasome subunit beta type-10; The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Plays a role in determining the T-cell repertoire for an antiviral T-cell response; Belongs to the peptidase T1B family. (273 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 [...] (575 aa) |
| | Ldlr | Low-density lipoprotein receptor; Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits; Belongs to the LDLR family. (862 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. Isoform 2 is defective in its ability to induce IRAK phosphorylation and NF- kappa-B activation and can function as a negative regulator of activation by IL-1 or lipopolysaccharide (LPS). Activates IRF1 resulting in it [...] (296 aa) |
| | Zc3h12a | Endoribonuclease ZC3H12A; Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay. Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation. Prevents aberrant T-cell-mediated immune reaction by degradation of mul [...] (596 aa) |
| | Rnf146 | E3 ubiquitin-protein ligase RNF146; E3 ubiquitin-protein ligase that specifically binds poly-ADP- ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CA [...] (359 aa) |
| | Lyn | Tyrosine-protein kinase Lyn; Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-c [...] (512 aa) |
| | Flt3 | Receptor-type tyrosine-protein kinase FLT3; Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only m [...] (1000 aa) |
| | Map3k7 | Mitogen-activated protein kinase kinase kinase 7; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as a [...] (606 aa) |
| | Mif | Macrophage migration inhibitory factor; Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity (By simi [...] (115 aa) |
| | Clic4 | Chloride intracellular channel protein 4; Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Promotes cell-surface expression of HRH3 (By similarity). May play a role in angiogenesis. (253 aa) |
| | Itln1 | Intelectin-1a; Lectin that specifically recognizes microbial carbohydrate chains in a calcium-dependent manner. Binds to microbial glycans that contain a terminal acyclic 1,2-diol moiety, including beta-linked D-galactofuranose (beta-Galf), D-phosphoglycerol- modified glycans, D-glycero-D-talo-oct-2-ulosonic acid (KO) and 3- deoxy-D-manno-oct-2-ulosonic acid (KDO). Binds to glycans from Gram- positive and Gram-negative bacteria, including K.pneumoniae, S.pneumoniae, Y.pestis, P.mirabilis and P.vulgaris. Does not bind mammalian glycans. Probably plays a role in the defense system agains [...] (313 aa) |
| | Npy1r | Neuropeptide Y receptor type 1; Receptor for neuropeptide Y and peptide YY. (382 aa) |
| | Stx11 | Syntaxin-11; SNARE that acts to regulate protein transport between late endosomes and the trans-Golgi network. (287 aa) |
| | Senp1 | Sentrin-specific protease 1; Protease that catalyzes two essential functions in the SUMO pathway. The first is the hydrolysis of an alpha-linked peptide bond at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptides, SUMO1, SUMO2 and SUMO3 leading to the mature form of the proteins. The second is the deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins, by cleaving an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein. Deconjugates SUMO1 from HIPK2 (By similarity). Deconjug [...] (640 aa) |
| | Lat2 | Linker for activation of T-cells family member 2; Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2. (203 aa) |
| | Hectd3 | E3 ubiquitin-protein ligase HECTD3; E3 ubiquitin ligases accepts ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of TRIOBP and its subsequent proteasomal degradation, thus facilitating cell cycle progression by regulating the turn-over of TRIOBP (By similarity). Mediates also ubiquitination of STX8. (861 aa) |
| | Lrrc8e | Volume-regulated anion channel subunit LRRC8E; Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes. The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine. Mediates efflux of amino acids, such as aspartate, in response to osmotic stress. Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depen [...] (795 aa) |
| | Bbs12 | Bardet-Biedl syndrome 12 protein homolog; Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Involved in adipogenic differentiation. (708 aa) |
| | Ffar2 | Free fatty acid receptor 2; G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin- sensitive, G(i/o)-alpha f [...] (330 aa) |
| | Irak2 | Interleukin-1 receptor-associated kinase-like 2; Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization. (622 aa) |
| | Ticam1 | TIR domain-containing adapter molecule 1; Involved in innate immunity against invading pathogens. Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF- kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis. Ligand binding to these receptors results in TRIF recruitment through its TIR domain. Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively. Phosphorylation by TBK1 on the pLxIS motif [...] (732 aa) |
| | Foxo1 | Forkhead box protein O1; Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalc [...] (652 aa) |
| | Cd14 | Monocyte differentiation antigen CD14; Coreceptor for bacterial lipopolysaccharide. In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating 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. Acts as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell su [...] (366 aa) |
| | Zfp36 | mRNA decay activator protein ZFP36; Zinc-finger RNA-binding protein that destabilizes numerous cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis. Acts as an 3'- untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Recruits deadenylase CNOT7 (and probably the CCR4- NOT complex) via association with CNOT1, and hence promotes ARE- mediated mRNA deadenylation. Functions also by recruiting com [...] (319 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) |
| | March2 | E3 ubiquitin-protein ligase MARCHF2; E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May be involved in endosomal trafficking through interaction with STX6. (287 aa) |
| | Nfil3 | Nuclear factor interleukin-3-regulated protein; Acts as a transcriptional regulator that recognizes and binds to the sequence 5'-[GA]TTA[CT]GTAA[CT]-3', a sequence present in many cellular and viral promoters. Represses transcription from promoters with activating transcription factor (ATF) sites (By similarity). Represses promoter activity in osteoblasts. Represses transcriptional activity of PER1. Represses transcriptional activity of PER2 via the B- site on the promoter. Activates transcription from the interleukin-3 promoter in T-cells (By similarity). Competes for the same consens [...] (462 aa) |
| | Fam49b | Protein FAM49B. (324 aa) |
| | Lep | Leptin; Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways. In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones. In the periphery, increases basal met [...] (167 aa) |
| | Lif | Leukemia inhibitory factor; LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes; Belongs to the LIF/OSM family. (203 aa) |
| | Egr1 | Early growth response protein 1; Transcriptional regulator. Recognizes and binds to the DNA sequence 5'- GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes. Binds double-stranded target DNA, irrespective of the cytosine methylation status (By similarity). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor form [...] (533 aa) |
| | Cebpb | CCAAT/enhancer-binding protein beta; Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Plays also a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant functions with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipo [...] (296 aa) |
| | Irak4 | Interleukin-1 receptor-associated kinase 4; 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 to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquiti [...] (459 aa) |
| | Apc | Adenomatous polyposis coli protein; Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)- induced cell migration (By similarity). Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane a [...] (2842 aa) |
| | Hmgb1 | High mobility group protein B1; Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functio [...] (215 aa) |
| | Ncoa3 | Nuclear receptor coactivator 3; Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone- dependent fashion. Plays a central role in creating a multisubunit coactivator complex, probably via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interac [...] (1403 aa) |
| | Stat6 | Signal transducer and transcription activator 6; Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling; Belongs to the transcription factor STAT family. (837 aa) |
| | Dusp22 | Dual specificity protein phosphatase 22; Activates the Jnk signaling pathway. Dephosphorylates and deactivates p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). (205 aa) |
| | Il22 | Interleukin-22; Cytokine that contributes to the inflammatory response in vivo; Belongs to the IL-10 family. (179 aa) |
| | Prkce | Protein kinase C epsilon type; Calcium-independent, phospholipid- and diacylglycerol (DAG)- dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin- dependent signaling, by mediating angiotensin-2-induced activation of integrin beta- [...] (737 aa) |
| | Ramp1 | Receptor activity-modifying protein 1; Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL. Belongs to the RAMP family. (148 aa) |
| | Arid5a | AT-rich interactive domain-containing protein 5A; DNA-binding protein that may regulate transcription and act as a repressor by binding to AT-rich stretches in the promoter region of target genes (By similarity). May positively regulate chondrocyte- specific transcription such as of COL2A1 in collaboration with SOX9 and positively regulate histone H3 acetylation at chondrocyte-specific genes. May stimulate early-stage chondrocyte differentiation and inhibit later stage differention. Can repress ESR1- mediated transcriptional activation; proposed to act as corepressor for selective nucl [...] (619 aa) |
| | Plekhf1 | Pleckstrin homology domain-containing family F member 1; May induce apoptosis through the lysosomal-mitochondrial pathway. Translocates to the lysosome initiating the permeabilization of lysosomal membrane (LMP) and resulting in the release of CTSD and CTSL to the cytoplasm. Triggers the caspase-independent apoptosis by altering mitochondrial membrane permeabilization (MMP) resulting in the release of PDCD8 (By similarity). (279 aa) |
| | Elavl1 | ELAV-like protein 1; RNA-binding protein that binds to the 3'-UTR region of mRNAs and increases their stability. Involved in embryonic stem cells (ESCs) differentiation: preferentially binds mRNAs that are not methylated by N6-methyladenosine (m6A), stabilizing them, promoting ESCs differentiation. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs. Binds avidly to the AU- rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Binds [...] (326 aa) |
| | Thbd | Thrombomodulin; Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated. (577 aa) |
| | Nlrp3 | NACHT, LRR and PYD domains-containing protein 3; As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (or possibly CASP4/CASP11). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion. The active cytokines a [...] (1033 aa) |
| | Peli1 | E3 ubiquitin-protein ligase pellino homolog 1; E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (By similarity). Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation. Mediates 'Lys-48'-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3. [...] (418 aa) |
| | Adam17 | Disintegrin and metalloproteinase domain-containing protein 17; Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Plays a role in the proteolytic processing of ACE2 (By similarity). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of [...] (846 aa) |
| | Rhbdf2 | Inactive rhomboid protein 2; Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own. Belongs to the peptidase S54 family. (827 aa) |
| | Nfe2l2 | Nuclear factor erythroid 2-related factor 2; Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, hetero [...] (597 aa) |
| | Ifit2 | Interferon-induced protein with tetratricopeptide repeats 2; IFN-induced antiviral protein which inhibits expression of viral messenger RNAs lacking 2'-O-methylation of the 5' cap. The ribose 2'-O-methylation would provide a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism). Binds AU-rich viral RNAs, with or without 5' triphosphorylati [...] (470 aa) |
| | Itgal | Integrin alpha-L; Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is a receptor for F11R (By similarity). Integrin ITGAL/ITGB2 is a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-c [...] (1162 aa) |
| | Lrrc19 | Leucine-rich repeat-containing protein 19. (364 aa) |
| | Sarm1 | NAD(+) hydrolase SARM1; NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism. Acts as a negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway by promoting Wallerian degeneration, an injury-induced form of programmed subcellular death which involves degeneration of an axon distal to the injury site. Wallerian degeneration is triggered by NAD(+) depletion: in response to injury, SARM1 is activated and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD(+ [...] (764 aa) |
| | Foxn1 | Forkhead box protein N1; Transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs) both in the prenatal and postnatal thymus. Acts as a master regulator of the TECs lineage development and is required from the onset of differentiation in progenitor TECs in the developing fetus to the final differentiation steps through which TECs mature to acquire their full functionality. Regulates, either directly or indirectly the expression of a variety of genes that mediate diverse aspects of thymus development and function, includin [...] (648 aa) |
| | Arrb2 | Beta-arrestin-2; Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta- arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin- associated sorting proteins) and re [...] (421 aa) |
| | Trp53 | Cellular tumor antigen p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its intera [...] (390 aa) |
| | Fitm2 | Fat storage-inducing transmembrane protein 2; Plays an important role in lipid droplet accumulation. Plays a role in the regulation of cell morphology and cytoskeletal organization. (262 aa) |
| | Mavs | Mitochondrial antiviral-signaling protein; Required for innate immune defense against viruses. Acts downstream of DHX33, DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF- kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state (By similarity). Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of def [...] (503 aa) |
| | Pilrb1 | Paired immunoglobulin-like type 2 receptor beta; Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRB is thought to act as a cellular signaling activating receptor that associates with ITAM-bearing adapter molecules on the cell surface. Seems to associate with DAP12 and is a receptor for CD99. May be involved in target cell recognition by natural killer cells and in activation of dendritic cells. (224 aa) |
| | Ifi204 | Interferon-activable protein 204; Inhibits the transcription of ribosomal RNA. May inhibit DNA binding by UBTF. Inhibits cell growth via p53/TP53 and RB1-dependent and independent pathways. Acts as a coactivator of RUNX2 during osteogenesis. May be involved in macrophage differentiation. Enables skeletal muscle and cardiac myocyte differentiation by sequestring Id proteins in the cytosol and promoting their ubiquitination and subsequent degradation. Belongs to the HIN-200 family. (619 aa) |
| | Tlr7 | Toll-like receptor 7; 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. TLR7 is a nucleotide-sensing TLR which is activated by single-stranded RNA. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. (1050 aa) |
| | Trem2 | Triggering receptor expressed on myeloid cells 2; Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding. Acts as a receptor for amyloid-beta protein 42, a cleavage product of the amyloid-beta precursor protein APP, and mediates its uptake and degradation by microglia. Binding to amyloid-beta 42 mediates microglial activation, proliferation, migration, apoptosis and expression of pro- inflammatory cytokines, such as IL6R and CCL3, and the anti- inflammatory cytokine ARG1. Acts as a receptor for lipoprotein particles such as [...] (249 aa) |
| | Traf2 | TNF receptor-associated factor 2; Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels [...] (508 aa) |
| | Tmem173 | Stimulator of interferon genes protein; Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double- stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol. Upon binding of [...] (378 aa) |
| | Foxp3 | Forkhead box protein P3, C-terminally processed; Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The s [...] (429 aa) |
| | Sh3bp2 | SH3 domain-binding protein 2; Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism (By similarity). (615 aa) |
| | S100a9 | Protein S100-A9; S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid [...] (113 aa) |
| | Stk38 | Serine/threonine-protein kinase 38; Negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2 (By similarity). (465 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 [...] (1013 aa) |
| | Snrk | SNF-related serine/threonine-protein kinase; May play a role in hematopoietic cell proliferation or differentiation. Potential mediator of neuronal apoptosis (By similarity). (748 aa) |
| | Rpl13a | 60S ribosomal protein L13a; Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the ribosome and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as cerupla [...] (203 aa) |
| | Sgms1 | Phosphatidylcholine:ceramide cholinephosphotransferase 1; Sphingomyelin synthases synthesize the sphingolipid, sphingomyelin, through transfer of the phosphatidyl head group, phosphatidylcholine, on to the primary hydroxyl of ceramide. The reaction is bidirectional depending on the respective levels of the sphingolipid and ceramide. Golgi apparatus SMS1 directly and specifically recognizes the choline head group on the substrate, requiring two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. Major form in macrophages. Required for cell [...] (419 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 (By similarity). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (By similarity). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Binds to the interleukin-6 (IL-6)- responsive elements identified in the promoters of various acute-phase protein genes (By similarity). Activated by IL31 through IL31RA (By s [...] (770 aa) |
| | Unc93b1 | Protein unc-93 homolog B1; Plays an important role in innate and adaptive immunity by regulating nucleotide-sensing Toll-like receptor (TLR) signaling. Required for the transport of a subset of TLRs (including TLR3, TLR7 and TLR9) from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides and activate signaling cascades. May play a role in autoreactive B-cells removal. (619 aa) |
| | Rc3h1 | Roquin-1; Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs. Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and [...] (1130 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 (By similarity). (497 aa) |
| | Enpp2 | Ectonucleotide pyrophosphatase/phosphodiesterase family member 2; Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubul [...] (914 aa) |
| | Gba | Lysosomal acid glucosylceramidase; Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramide/GlcCer into free ceramide and glucose. Thereby, plays a central role in the degradation of complex lipids and the turnover of cellular membranes. Through the production of ceramides, participates to the PKC-activated salvage pathway of ceramide formation (By similarity). Also plays a role in cholesterol metabolism. May either catalyze the glucosylation of cholesterol, through a transglucosylation reaction that transfers glucose from glucosylceramide [...] (515 aa) |
| | Wwp2 | NEDD4-like E3 ubiquitin-protein ligase WWP2; E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; regulates POU5F1 protein level during differentiation of embryonal carcinoma cells (ECCs) but not in undifferentiated ECCs and embryonic stem cells (ESCs). Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits acti [...] (870 aa) |
| | Hnrnpd | Heterogeneous nuclear ribonucleoprotein D0; Binds with high affinity to RNA molecules that contain AU- rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-st [...] (355 aa) |
| | Sra1 | Steroid receptor RNA activator 1; Functional RNA which acts as a transcriptional coactivator that selectively enhances steroid receptor-mediated transactivation ligand-independently through a mechanism involving the modulating N- terminal domain (AF-1) of steroid receptors. Also mediates transcriptional coactivation of steroid receptors ligand-dependently through the steroid-binding domain (AF-2). Enhances cellular proliferation and differentiation and promotes apoptosis in vivo. May play a role in tumorigenesis (By similarity). Belongs to the SRA1 family. (232 aa) |
| | Nlrc3 | Protein NLRC3; Negative regulator of the innate immune response. Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating 'Lys-63'-linked ubiquitination and leaving unchanged the degradative 'Lys-48'-linked ubiquitination. Inhibits the PI3K-AKT-mTOR [...] (1102 aa) |
| | Rab27a | Ras-related protein Rab-27A; Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion. Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. (221 aa) |
| | Ash1l | Histone-lysine N-methyltransferase ASH1L; Histone methyltransferase specifically trimethylating 'Lys- 36' of histone H3 forming H3K36me3 (By similarity). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. The physiological significance of the H3K9me1 activity is unclear (Probable). (2958 aa) |
| | Slamf6 | SLAM family member 6; Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natur [...] (351 aa) |
| | Cd19 | B-lymphocyte antigen CD19; Functions as coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes. Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (By similarity). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores. Is not required for early steps during B cell differentiation in the blood marrow. Required for normal differentiation of B-1 cells. Required for normal B cell differentiation and proliferation in [...] (547 aa) |
| | Zdhhc1 | Probable palmitoyltransferase ZDHHC1; Belongs to the DHHC palmitoyltransferase family. (484 aa) |
| | Il18 | Interleukin-18; A proinflammatory cytokine primarily involved in polarized T- helper 1 (Th1) cell and natural killer (NK) cell immune responses. 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. Belongs to the IL-1 family. (192 aa) |
| | Prf1 | Perforin-1; Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes. (554 aa) |
| | Apba3 | Amyloid-beta A4 precursor protein-binding family A member 3; May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. May enhance the activity of HIF1A in macrophages by inhibiting the activity of HIF1AN (By similarity). (571 aa) |
| | Mbl1 | Mannose-binding protein A; Calcium-dependent lectin. Plays a role in the innate immune response by binding mannose, fucose and N-acetylglucosamine moieties on different microorganisms and mediating activation of the lectin complement pathway (By similarity). Binds to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells, facilitating their uptake by macrophages (By similarity). (239 aa) |
| | Trim38 | Tripartite motif-containing 38. (471 aa) |
