STRINGSTRING
ADAM17 ADAM17 CYLD CYLD PTPN6 PTPN6 ADIPOQ ADIPOQ CASP4 CASP4 OAS1 OAS1 CXCR4 CXCR4 IL1R1 IL1R1 IL6 IL6 SHARPIN SHARPIN GSTP1 GSTP1 IRF7 IRF7 PAFAH1B1 PAFAH1B1 GPS2 GPS2 AGPAT1 AGPAT1 IL6ST IL6ST RABGEF1 RABGEF1 TAF9 TAF9 TRIM6 TRIM6 DDX58 DDX58 EDN1 EDN1 CCDC3 CCDC3 SYK SYK CARD16 CARD16 HSPA1A HSPA1A HSPA1B HSPA1B PADI2 PADI2 KLF4 KLF4 TLR4 TLR4 TREM2 TREM2 AGPAT2 AGPAT2 PTPN1 PTPN1 RNF113A RNF113A XIAP XIAP ZBP1 ZBP1 IRAK1 IRAK1 ECM1 ECM1 ADAR ADAR DHX9 DHX9 PRKN PRKN CNOT7 CNOT7 PARP9 PARP9 ZNF675 ZNF675 CASP8 CASP8 ARG1 ARG1 SH2B3 SH2B3 PALM3 PALM3 TSLP TSLP CAV1 CAV1 SLIT3 SLIT3 GAS6 GAS6 IL1R2 IL1R2 TBK1 TBK1 TRAIP TRAIP CSF1 CSF1 RFFL RFFL PELI3 PELI3 TRIM41 TRIM41 RNF185 RNF185 CPNE1 CPNE1 STAT2 STAT2 SPHK1 SPHK1 PTPN2 PTPN2 MAPK7 MAPK7 NKIRAS1 NKIRAS1 NLRP6 NLRP6 TRIM56 TRIM56 PYDC1 PYDC1 NKIRAS2 NKIRAS2 C1QTNF4 C1QTNF4 FADD FADD AXL AXL MED1 MED1 TRIM44 TRIM44 METTL3 METTL3 F2RL1 F2RL1 OTOP1 OTOP1 DCST1 DCST1 MMP12 MMP12 NOL3 NOL3 NLRP2B NLRP2B PTPN11 PTPN11 PYDC2 PYDC2 IL1RN IL1RN IRAK2 IRAK2 USP29 USP29 PXDN PXDN TRAF2 TRAF2 PYCARD PYCARD APOA1 APOA1 OAS3 OAS3 CDC37 CDC37 TLE5 TLE5 PPP2CB PPP2CB RIPK2 RIPK2 BIRC7 BIRC7 TTLL12 TTLL12 USP18 USP18 MAP2K5 MAP2K5 TNFRSF1A TNFRSF1A CD74 CD74 GFI1 GFI1 LAPTM5 LAPTM5 PPARG PPARG OTULIN OTULIN HPX HPX STAP1 STAP1 WNT5A WNT5A TXK TXK MUL1 MUL1 IL7 IL7 PIAS4 PIAS4 NLRC5 NLRC5 DNAJA3 DNAJA3 SPPL2A SPPL2A UBE2K UBE2K IRAK3 IRAK3 TLR2 TLR2 RIPK1 RIPK1 IL36RN IL36RN CARD8 CARD8 NR1H2 NR1H2 STING1 STING1 IFIH1 IFIH1 ISG15 ISG15 SOCS1 SOCS1 SAMHD1 SAMHD1 CD300LF CD300LF IKBKE IKBKE IRF3 IRF3 CCL5 CCL5 H2BC11 H2BC11 NR1H3 NR1H3 SPPL2B SPPL2B YTHDF3 YTHDF3 TNFAIP3 TNFAIP3 CD24 CD24 USP27X USP27X TREX1 TREX1 NR1H4 NR1H4 LSM14A LSM14A NLRP2 NLRP2 YTHDF2 YTHDF2 HIF1A HIF1A CASP1 CASP1 IKBKB IKBKB NAIP NAIP ANGPT1 ANGPT1 IRGM IRGM SLIT2 SLIT2 ROBO1 ROBO1 PARP14 PARP14 SPATA2 SPATA2 TICAM2 TICAM2 CACTIN CACTIN PTPRC PTPRC OTUD4 OTUD4 TRIM32 TRIM32 VRK2 VRK2 HIPK1 HIPK1 SIGIRR SIGIRR MAVS MAVS LRRC70 LRRC70
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ADAM17Disintegrin 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. 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 Notch pathway by mediating cleavage of Notch, generating the membra [...] (824 aa)
CYLDUbiquitin carboxyl-terminal hydrolase CYLD; Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis. Plays an important role in the regulation of pathways leading to NF-kappa-B activation. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF- kappa-B activation. Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules. Plays a role in the regu [...] (956 aa)
PTPN6Tyrosine-protein phosphatase non-receptor type 6; Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis. (624 aa)
ADIPOQAdiponectin; Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis [...] (244 aa)
CASP4Caspase-4 subunit 1; Inflammatory caspase. Essential effector of NLRP3 inflammasome-dependent CASP1 activation and IL1B and IL18 secretion in response to non- canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS. Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators. Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection. In later stages of th [...] (377 aa)
OAS12'-5'-oligoadenylate synthase 1; Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition [...] (414 aa)
CXCR4C-X-C chemokine receptor type 4; Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade. Plays a role in regulation of cell migration, e.g. during wound healing. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Involved in hematopoiesis and in car [...] (356 aa)
IL1R1Interleukin-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)
IL6Interleukin-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)
SHARPINSharpin; Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BI [...] (387 aa)
GSTP1Glutathione S-transferase P; Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. (210 aa)
IRF7Interferon regulatory factor 7; Key transcriptional regulator of type I interferon (IFN)- dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN- stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependen [...] (516 aa)
PAFAH1B1Platelet-activating factor acetylhydrolase IB subunit alpha; Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule slidi [...] (410 aa)
GPS2G protein pathway suppressor 2; Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'- linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context. Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and [...] (327 aa)
AGPAT11-acyl-sn-glycerol-3-phosphate acyltransferase alpha; Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. (283 aa)
IL6STInterleukin-6 receptor subunit beta; Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates Janus kinases. That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3. Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Does not bind IL6 [...] (918 aa)
RABGEF1Rab5 GDP/GTP exchange factor; Rab effector protein acting as linker between gamma-adaptin, RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates nucleotide exchange on RAB5A. Can act as a ubiquitin ligase (By similarity). (505 aa)
TAF9Transcription initiation factor TFIID subunit 9; Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription. (264 aa)
TRIM6Tripartite motif-containing protein 6; E3 ubiquitin-protein ligase which ubiquitinates MYC and inhibits its transcription activation activity, maintaining the pluripotency of embryonic stem cells (By similarity). Involved in the synthesis of unanchored K48-linked polyubiquitin chains which interact with and activate the serine/threonine kinase IKBKE, leading to phosphorylation of STAT1 and stimulation of an antiviral response ; Belongs to the TRIM/RBCC family. (516 aa)
DDX58Antiviral innate immune response receptor RIG-I; Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and proinflammatory cytokines. Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments. The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms. Up [...] (925 aa)
EDN1Big endothelin-1; Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells. Belongs to the endothelin/sarafotoxin family. (212 aa)
CCDC3Coiled-coil domain-containing protein 3; Negatively regulates TNF-alpha-induced pro-inflammatory response in endothelial cells (ECs) via inhibition of TNF-alpha-induced NF-kappaB activation in ECs. Positively regulates lipid accumulation in adipose cells (By similarity). (270 aa)
SYKTyrosine-protein kinase SYK; Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can a [...] (635 aa)
CARD16Caspase recruitment domain-containing protein 16; Caspase inhibitor. Acts as a regulator of procaspase-1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation. Inhibits the release of IL1B in response to LPS in monocytes. Also induces NF-kappa-B activation during the pro-inflammatory cytokine response. Also able to inhibit CASP1-mediated neuronal cell death, TNF- alpha, hypoxia-, UV-, and staurosporine-mediated cell death but not ER stress-mediated cell death. Acts by preventing activation of cas [...] (197 aa)
HSPA1AHeat shock protein family A member 1A. (641 aa)
HSPA1BHeat shock 70 kDa protein 1A; Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and AD [...] (641 aa)
PADI2Protein-arginine deiminase type-2; Catalyzes the deimination of arginine residues of proteins. (665 aa)
KLF4Krueppel-like factor 4; Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also fu [...] (479 aa)
TLR4Toll-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)
TREM2Triggering 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 (By similarity). Acts as a receptor for lipoprotein pa [...] (230 aa)
AGPAT21-acyl-sn-glycerol-3-phosphate acyltransferase beta; Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. (278 aa)
PTPN1Tyrosine-protein phosphatase non-receptor type 1; Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c- src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. Belongs to the protein-tyrosi [...] (435 aa)
RNF113AE3 ubiquitin-protein ligase RNF113A; Required for pre-mRNA splicing as component of the spliceosome. E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin onto target proteins. Catalyzes polyubiquitination of SNRNP200/BRR2 with non-canonical 'Lys-63'-linked polyubiquitin chains. Plays a role in DNA repair via its role in the synthesis of 'Lys-63'-linked polyubiquitin chains that recruit ALKBH3 and the ASCC complex to sites of DNA damage by alkylating agents. Ubiquitinates CXCR4, leading to its degradation, and thereby contributes to the termination of CXCR4 signaling. (343 aa)
XIAPE3 ubiquitin-protein ligase XIAP; Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligas [...] (497 aa)
ZBP1Z-DNA-binding protein 1; Participates in the detection by the host's innate immune system of DNA from viral, bacterial or even host origin. Plays a role in host defense against tumors and pathogens. Acts as a cytoplasmic DNA sensor which, when activated, induces the recruitment of TBK1 and IRF3 to its C-terminal region and activates the downstream interferon regulatory factor (IRF) and NF-kappa B transcription factors, leading to type-I interferon production. ZBP1-induced NF-kappaB activation probably involves the recruitment of the RHIM containing kinases RIPK1 and RIPK3 (By similarity). (429 aa)
IRAK1Interleukin-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)
ECM1Extracellular matrix protein 1; Involved in endochondral bone formation as negative regulator of bone mineralization. Stimulates the proliferation of endothelial cells and promotes angiogenesis. Inhibits MMP9 proteolytic activity. (567 aa)
ADARDouble-stranded RNA-specific adenosine deaminase; Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structur [...] (1226 aa)
DHX9ATP-dependent RNA helicase A; Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing. Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo- nucleotide triphosphates (NTPs). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA [...] (1270 aa)
PRKNE3 ubiquitin-protein ligase parkin; Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'- linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of m [...] (465 aa)
CNOT7CCR4-NOT transcription complex subunit 7; Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Its function seems to be partially redundant with that of CNOT8. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translationa [...] (285 aa)
PARP9Protein mono-ADP-ribosyltransferase PARP9; ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses. Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose). In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones. During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to [...] (854 aa)
ZNF675Zinc finger protein 675; May be involved in transcriptional regulation. May play a role during osteoclast differentiation by modulating TRAF6 signaling activity. (568 aa)
CASP8Caspase-8 subunit p10; Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CA [...] (538 aa)
ARG1Arginase-1; Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys. Belongs to the arginase family. (330 aa)
SH2B3SH2B adapter protein 3; Links T-cell receptor activation signal to phospholipase C- gamma-1, GRB2 and phosphatidylinositol 3-kinase. (575 aa)
PALM3Paralemmin-3; ATP-binding protein, which may act as a adapter in the Toll- like receptor (TLR) signaling. (673 aa)
TSLPThymic 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)
CAV1Caveolin-1; May act as a scaffolding protein within caveolar membranes. 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-dependent manner. Recrui [...] (178 aa)
SLIT3Slit homolog 3 protein; May act as molecular guidance cue in cellular migration, and function may be mediated by interaction with roundabout homolog receptors. (1530 aa)
GAS6Growth arrest-specific protein 6; Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. (678 aa)
IL1R2Interleukin-1 receptor type 2, membrane form; Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competetive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors. (398 aa)
TBK1Serine/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. 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. In order to establish such an antiviral state, TBK1 form s [...] (729 aa)
TRAIPE3 ubiquitin-protein ligase TRAIP; E3 ubiquitin ligase acting as a negative regulator of innate immune signaling. Inhibits activation of NF-kappa-B mediated by TNF. Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation (By similarity). Involved in response to genotoxic lesions during genome replication. Promotes H2AX and RPA2 phosphorylation after replication-associated DNA damage and assists fork progression at UV-indu [...] (469 aa)
CSF1Processed macrophage colony-stimulating factor 1; Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male a [...] (554 aa)
RFFLE3 ubiquitin-protein ligase rififylin; E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor ne [...] (363 aa)
PELI3E3 ubiquitin-protein ligase pellino homolog 3; E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. 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. Can activate AP1/JUN and ELK1. Not required for NF-kappa-B activation; Belongs to the pellino family. (469 aa)
TRIM41E3 ubiquitin-protein ligase TRIM41; Functions as an E3 ligase that catalyzes the ubiquitin- mediated degradation of protein kinase C. Belongs to the TRIM/RBCC family. (630 aa)
RNF185E3 ubiquitin-protein ligase RNF185; E3 ubiquitin-protein ligase that regulates selective mitochondrial autophagy by mediating 'Lys-63'-linked polyubiquitination of BNIP1. Acts in the endoplasmic reticulum (ER)- associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis. Responsible for the cotranslational ubiquitination and degradation of CFTR in the ERAD pathway. Preferentially associates with the E2 enzymes U [...] (192 aa)
CPNE1Copine-1; Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Involved in the TNF-alpha receptor signaling pathway in a calcium- dependent manner. Exhibits calcium-dependent phospholipid binding properties. Plays a role in neuronal progenitor cell differentiation; induces neurite outgrowth via a AKT-dependent signaling cascade and calcium- independent manner. May recruit target proteins to the cell membrane in a calcium-dependent manner. May function in membrane trafficking. Involved in TNF-alpha-induced NF-kappa-B transcription [...] (542 aa)
STAT2Signal transducer and activator of transcription 2; Signal transducer and activator of transcription that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive [...] (851 aa)
SPHK1Sphingosine kinase 1; Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo- dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis. Involved in the regulation of inflammatory response and neuroinflammation. Via [...] (470 aa)
PTPN2Tyrosine-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)
MAPK7Mitogen-activated protein kinase 7; Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ER [...] (816 aa)
NKIRAS1NF-kappa-B inhibitor-interacting Ras-like protein 1; Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation. May act by blocking phosphorylation of NFKBIB and mediating cytoplasmic retention of p65/RELA NF-kappa-B subunit. It is unclear whether it acts as a GTPase. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB. (192 aa)
NLRP6NACHT, LRR and PYD domains-containing protein 6; As the sensor component of the NLRP6 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 NLRP6, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. The precise NLRP6 activation stimulus has not been identified yet (By similarity). Essent [...] (892 aa)
TRIM56E3 ubiquitin-protein ligase TRIM56; E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity. In response to pathogen- and host-derived double-stranded DNA (dsDNA), targets STING1 to 'Lys-63'- linked ubiquitination, thereby promoting its homodimerization, a step required for the production of type I interferon IFN-beta (By similarity). Independently of its E3 ubiquitin ligase activity, positive regulator of TLR3 signaling. Potentiates extracellular double stranded RNA (dsRNA)-induced expression of IFNB1 and interferon- stimulated genes ISG15, IFIT1/ISG56, CXCL10, [...] (755 aa)
PYDC1Pyrin domain-containing protein 1; Associates with PYCARD/ASC and modulates its ability to collaborate with MEFV/pyrin and NLRP3/cryopyrin in NF-kappa-B and pro- caspase-1 activation. Suppresses kinase activity of NF-kappa-B inhibitor kinase (IKK) complex, expression of NF-kappa-B inducible genes and inhibits NF-kappa-B activation by cytokines and LPS. (89 aa)
NKIRAS2NF-kappa-B inhibitor-interacting Ras-like protein 2; Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation. May act by blocking phosphorylation of NFKBIB and nuclear localization of p65/RELA NF-kappa-B subunit. It is unclear whether it acts as a GTPase. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB (By similarity); Belongs to the small GTPase superfamily. Ras family. KappaB-Ras subfamily. (191 aa)
C1QTNF4Complement C1q tumor necrosis factor-related protein 4; May be involved in the regulation of the inflammatory network. Its role as pro- or anti-inflammatory seems to be context dependent. Seems to have some role in regulating food intake and energy balance when administered in the brain. This effect is sustained over a two-day period, and it is accompanied by decreased expression of orexigenic neuropeptides in the hypothalamus 3 h post-injection (By similarity). (329 aa)
FADDFAS-associated death domain protein; Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling. (208 aa)
AXLTyrosine-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)
MED1Mediator of RNA polymerase II transcription subunit 1; Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene- specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Acts as a coactivator for [...] (1581 aa)
TRIM44Tripartite motif-containing protein 44; May play a role in the process of differentiation and maturation of neuronal cells (By similarity). May regulate the activity of TRIM17. Is a negative regulator of PAX6 expression. (344 aa)
METTL3N6-adenosine-methyltransferase catalytic subunit; The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing. In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core. N6- methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays [...] (580 aa)
F2RL1Proteinase-activated receptor 2, alternate cleaved 1; Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can [...] (397 aa)
OTOP1Proton channel OTOP1; Proton-selective channel that specifically transports protons into cells. Proton channel activity is only weakly- sensitive to voltage (By similarity). Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes. In the vestibular system of the inner ear, required for the formation and function of otoconia, which are calcium carbonate crystals that sense gravity and acceleration (By similarity). Probably acts by maintaining the pH appropriate for [...] (612 aa)
DCST1E3 ubiquitin-protein ligase DCST1; E3 ubiquitin-protein ligase which mediates 'Lys-48'-linked ubiquitination of STAT2 and induces its proteosomal degradation thereby negatively regulating type-I-interferon signaling. (706 aa)
MMP12Macrophage metalloelastase; May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3; Belongs to the peptidase M10A family. (470 aa)
NOL3Nucleolar protein 3; [Isoform 1]: May be involved in RNA splicing. (270 aa)
NLRP2BNLR family pyrin domain-containing protein 2B; May function as a negative regulator of NF-kappa-B by preventing RELA/p65 phosphorylation at 'Ser-536', thereby inhibiting its transcriptional activity. Through NF-kappa-B regulation may control cytokine release upon Toll-like receptors activation and therefore play a role in modulation of innate immunity. May also play a role in cell cycle progression and apoptotic process. (45 aa)
PTPN11Tyrosine-protein phosphatase non-receptor type 11; Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73. (597 aa)
PYDC2Pyrin domain-containing protein 2; May play a role in innate immunity by disrupting the interaction between PYCARD and NLRP3, thereby regulating the NLRP3 inflammasome. May also inhibit NF- kappa-B signaling distally by affecting the nuclear accumulation of RELA. (97 aa)
IL1RNInterleukin-1 receptor antagonist protein; Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure. (180 aa)
IRAK2Interleukin-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. (625 aa)
USP29Ubiquitin specific peptidase 29. (922 aa)
PXDNPeroxidasin homolog; Displays low peroxidase activity and is likely to participate in H(2)O(2) metabolism and peroxidative reactions in the cardiovascular system. Plays a role in extracellular matrix formation. (1479 aa)
TRAF2TNF 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 [...] (501 aa)
PYCARDApoptosis-associated speck-like protein containing a CARD; Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8- dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase- 9, -2 and -3. Involved in macrophage pyroptosis, a cas [...] (195 aa)
APOA1Truncated apolipoprotein A-I; Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility. (267 aa)
OAS32'-5'-oligoadenylate synthase 3; Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibi [...] (1087 aa)
CDC37Hsp90 co-chaperone Cdc37, N-terminally processed; Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity. Inhibits HSP90AA1 ATPase activity. (378 aa)
TLE5TLE family member 5; Transcriptional corepressor. Acts as dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Essential for the transcriptional repressor activity of SIX3 during retina and lens development. Belongs to the WD repeat Groucho/TLE family. (264 aa)
PPP2CBSerine/threonine-protein phosphatase 2A catalytic subunit beta isoform; PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Belongs to the PPP phosphatase family. PP-1 subfamily. (309 aa)
RIPK2Receptor-interacting serine/threonine-protein kinase 2; Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3 [...] (540 aa)
BIRC7Baculoviral IAP repeat-containing protein 7 30kDa subunit; Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibit [...] (298 aa)
TTLL12Tubulin--tyrosine ligase-like protein 12; Negatively regulates post-translational modifications of tubulin, including detyrosination of the C-terminus and polyglutamylation of glutamate residues. Also, indirectly promotes histone H4 trimethylation at 'Lys-20' (H4K20me3). Probably by controlling tubulin and/or histone H4 post-translational modifications, plays a role in mitosis and in maintaining chromosome number stability. During RNA virus-mediated infection, acts as a negative regulator of the DDX58/RIG-I pathway by preventing MAVS binding to TBK1 and IKBKE. (644 aa)
USP18Ubl carboxyl-terminal hydrolase 18; Involved in the regulation of inflammatory response to interferon type 1. Can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds. Necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms. Belongs to the peptidase C19 family. (372 aa)
MAP2K5Dual specificity mitogen-activated protein kinase kinase 5; Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis. (448 aa)
TNFRSF1ATumor 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)
CD74HLA class II histocompatibility antigen gamma chain; Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF. (296 aa)
GFI1Zinc finger protein Gfi-1; Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development. [...] (422 aa)
LAPTM5Lysosomal-associated transmembrane protein 5; May have a special functional role during embryogenesis and in adult hematopoietic cells; Belongs to the LAPTM4/LAPTM5 transporter family. (262 aa)
PPARGPeroxisome proliferator-activated receptor gamma; Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut ho [...] (505 aa)
OTULINUbiquitin thioesterase otulin; Deubiquitinase that specifically removes linear ('Met-1'- linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response. Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex. Acts as a negative regulator of NF-kappa-B by regulating the activity of the LUBAC complex. OTULIN function is mainly restricted to homeostasis of the LUBAC complex: acts by removing 'Met- 1'-linked autoubiquitination of the LUBAC complex, thereby p [...] (352 aa)
HPXHemopexin; Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation. (462 aa)
STAP1Signal-transducing adaptor protein 1; In BCR signaling, appears to function as a docking protein acting downstream of TEC and participates in a positive feedback loop by increasing the activity of TEC. (295 aa)
WNT5AProtein Wnt-5a; Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta- catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decre [...] (380 aa)
TXKTyrosine-protein kinase TXK; Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, inclu [...] (527 aa)
MUL1Mitochondrial ubiquitin ligase activator of NFKB 1; Exhibits weak E3 ubiquitin-protein ligase activity. 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. Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation. Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations. Plays a role in the con [...] (352 aa)
IL7Interleukin-7; Hematopoietic growth factor capable of stimulating the proliferation of lymphoid progenitors. It is important for proliferation during certain stages of B-cell maturation. (177 aa)
PIAS4E3 SUMO-protein ligase PIAS4; Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylati [...] (510 aa)
NLRC5Protein NLRC5; Probable regulator of the NF-kappa-B and type I interferon signaling pathways. May also regulate the type II interferon signaling pathway. Plays a role in homeostatic control of innate immunity and in antiviral defense mechanisms; Belongs to the NLRP family. (1866 aa)
DNAJA3DnaJ homolog subfamily A member 3, mitochondrial; Modulates apoptotic signal transduction or effector structures within the mitochondrial matrix. Affect cytochrome C release from the mitochondria and caspase 3 activation, but not caspase 8 activation. Isoform 1 increases apoptosis triggered by both TNF and the DNA-damaging agent mytomycin C; in sharp contrast, isoform 2 suppresses apoptosis. Can modulate IFN-gamma-mediated transcriptional activity. Isoform 2 may play a role in neuromuscular junction development as an effector of the MUSK signaling pathway. (480 aa)
SPPL2ASignal peptide peptidase-like 2A; Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing. Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus. Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD). May play a role in the regulation of innate and [...] (520 aa)
UBE2KUbiquitin-conjugating enzyme E2 K; Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam [...] (200 aa)
IRAK3Interleukin-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)
TLR2Toll-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)
RIPK1Receptor-interacting serine/threonine-protein kinase 1; Serine-threonine kinase which is a key regulator of both cell death and cell survival. Exhibits kinase activity- dependent functions that trigger cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Initiates ripoptocide which describes cell death that is dependent on RIPK1, be it apoptosis or necroptosis. Upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, [...] (671 aa)
IL36RNInterleukin-36 receptor antagonist protein; Inhibits the activity of interleukin-36 (IL36A,IL36B and IL36G) by binding to receptor IL1RL2 and preventing its association with the coreceptor IL1RAP for signaling. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor. Proposed to play a role in skin inflammation. May be involved in the innate immune response to fungal pathogens, such as Aspergillus fumigatus. May activate an anti- inflammatory s [...] (155 aa)
CARD8Caspase recruitment domain-containing protein 8; Inhibits NF-kappa-B activation. May participate in a regulatory mechanism that coordinates cellular responses controlled by NF-kappa-B transcription factor. May be a component of the inflammasome, a protein complex which also includes PYCARD, NALP2 and CASP1 and whose function would be the activation of proinflammatory caspases. (537 aa)
NR1H2Oxysterols receptor LXR-beta; Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits [...] (460 aa)
STING1Stimulator 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 [...] (379 aa)
IFIH1Interferon-induced helicase C domain-containing protein 1; Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long- dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylat [...] (1025 aa)
ISG15Ubiquitin-like protein ISG15; Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhib [...] (165 aa)
SOCS1Suppressor of cytokine signaling 1; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival (By similarity). Probable substrate recognition component of an [...] (211 aa)
SAMHD1Deoxynucleoside triphosphate triphosphohydrolase SAMHD1; Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks. Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early- stage virus replication in dendritic and other myeloid cells. Likewise, suppresses LINE-1 retrotransposon activity. Not able to [...] (626 aa)
CD300LFCMRF35-like molecule 1; Acts as an inhibitory receptor for myeloid cells and mast cells. Positively regulates the phagocytosis of apoptotic cells (efferocytosis) via phosphatidylserine (PS) recognition; recognizes and binds PS as a ligand which is expressed on the surface of apoptotic cells. Plays an important role in the maintenance of immune homeostasis, by promoting macrophage-mediated efferocytosis and by inhibiting dendritic cell-mediated efferocytosis (By similarity). Negatively regulates Fc epsilon receptor-dependent mast cell activation and allergic responses via binding to cer [...] (305 aa)
IKBKEInhibitor of nuclear factor kappa-B kinase subunit epsilon; Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I- like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the [...] (716 aa)
IRF3Interferon regulatory factor 3; Key transcriptional regulator of type I interferon (IFN)- dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive [...] (452 aa)
CCL5C-C motif chemokine 5; Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second [...] (91 aa)
H2BC11Histone H2B type 1-J; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (126 aa)
NR1H3Oxysterols receptor LXR-alpha; Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES (By similarity). LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides (By similarity). Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol up [...] (453 aa)
SPPL2BSignal peptide peptidase-like 2B; Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in ITM2B and TNF processing. Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus. May play a role in the regulation of innate and adaptive immunity. Catalyzes the intramembrane cleavage of the simian foamy virus processed leader peptide gp18 of the envelope glycoprotein gp130 dependen [...] (592 aa)
YTHDF3YTH domain-containing family protein 3; Specifically recognizes and binds N6-methyladenosine (m6A)- containing RNAs and promotes RNA translation efficiency. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability. Shares m6A-containing mRNAs targets with YTHDF1 and YTHDF2, and regulates different processes depending on the context. Facilitates the translation of targeted mRNAs in cooperation with YTHDF1 by binding to m6A-containing mRNAs and interacting with 40S and 60S ribosome subu [...] (588 aa)
TNFAIP3Tumor 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 [...] (790 aa)
CD24Signal transducer CD24; May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin- like ligand to the CD24 carbohydrates, and transduced by the release of second messengers derived from the GPI-anchor. Modulates B-cell activation responses. Promotes AG-dependent proliferation of B-cells, and prevents their terminal differentiation into antibody-forming cells. In association with SIGLEC10 may be involved in the selective suppression of the immune response to danger-associated molecular patterns (DAMPs) such as HMGB1, [...] (129 aa)
USP27XUbiquitin carboxyl-terminal hydrolase 27; Deubiquitinase that can reduce the levels of BCL2L11/BIM ubiquitination and stabilize BCL2L11 in response to the RAF-MAPK- degradation signal. By acting on BCL2L11 levels, may counteract the anti-apoptotic effects of MAPK activity. (438 aa)
TREX1Three-prime repair exonuclease 1; Major cellular 3'-to-5' DNA exonuclease which digests single- stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini. Prevents cell-intrinsic initiation of autoimmunity. Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements. Unless degraded, these DNA fragments accumulate in the cytosol and activate the IFN-stimulatory DNA (ISD) response and innate immune signaling. Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the pr [...] (314 aa)
NR1H4Bile acid receptor; Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in wh [...] (486 aa)
LSM14AProtein LSM14 homolog A; Essential for formation of P-bodies, cytoplasmic structures that provide storage sites for non-translating mRNAs. (463 aa)
NLRP2NACHT, LRR and PYD domains-containing protein 2; Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature proinflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of proinflammatory caspases; Belongs to the NLRP family. (1062 aa)
YTHDF2YTH domain-containing family protein 2; Specifically recognizes and binds N6-methyladenosine (m6A)- containing RNAs, and regulates mRNA stability. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing. Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context. M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cle [...] (579 aa)
HIF1AHypoxia-inducible factor 1-alpha; Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequenc [...] (850 aa)
CASP1Caspase-1 subunit p10; Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis. Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive. In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracell [...] (404 aa)
IKBKBInhibitor 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. 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 translocated [...] (756 aa)
NAIPBaculoviral IAP repeat-containing protein 1; Anti-apoptotic protein which acts by inhibiting the activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the rate of auto proteolysis at 'Asp-330'. Acts as a mediator of neuronal survival in pathological conditions. Prevents motor-neuron apoptosis induced by a variety of signals. Possible role in the prevention of spinal muscular atrophy that seems to be caused by inappropriate persistence of motor- neuron ap [...] (1403 aa)
ANGPT1Angiopoietin-1; Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Required for normal angiogenesis and heart development during embryogenesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells [...] (498 aa)
IRGMImmunity-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)
SLIT2Slit homolog 2 protein C-product; Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons [...] (1529 aa)
ROBO1Roundabout homolog 1; Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its intera [...] (1651 aa)
PARP14Protein mono-ADP-ribosyltransferase PARP14; ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate residues on target proteins. In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation. Has been shown to catalyze the mono-ADP-ribosylation of STAT1 at 'Glu-657' and 'Glu-705', thus decreasing STAT1 phosphorylation which negatively regulates pro-inflammatory cytokine production in macrophages in response to IFNG stimulation. However, the role of ADP-ribosylation in the prevention of STAT1 phosphorylation has been called into question and it has been [...] (1801 aa)
SPATA2Spermatogenesis-associated protein 2; Bridging factor that mediates the recruitment of CYLD to the LUBAC complex, thereby regulating TNF-alpha-induced necroptosis. Acts as a direct binding intermediate that bridges RNF31/HOIP, the catalytic subunit of the LUBAC complex, and the deubiquitinase (CYLD), thereby recruiting CYLD to the TNF-R1 signaling complex (TNF-RSC). Required to activate the 'Met-1'- (linear) and 'Lys-63'-linked deubiquitinase activities of CYLD. Controls the kinase activity of RIPK1 and TNF-alpha-induced necroptosis by promoting 'Met-1'-linked deubiquitination of RIPK1 [...] (520 aa)
TICAM2TIR domain-containing adapter molecule 2; Functions as sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction. In TLR4 signaling, physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement. Involved in IL-18 signaling and is proposed to function as a sorting adapter for MYD88 in IL-18 signaling during adapt [...] (235 aa)
CACTINCactin; Involved in the regulation of innate immune response. Acts as negative regulator of Toll-like receptor, interferon-regulatory factor (IRF) and canonical NF-kappa-B signaling pathways. Contributes to the regulation of transcriptional activation of NF-kappa-B target genes in response to endogenous proinflammatory stimuli. (758 aa)
PTPRCReceptor-type tyrosine-protein phosphatase C; Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity); Belongs to the protein-tyrosine phosphatase family. Receptor class 1/6 subfamily. (1306 aa)
OTUD4OTU domain-containing protein 4; Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein. May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators. Independently of the catalytic ac [...] (1049 aa)
TRIM32E3 ubiquitin-protein ligase TRIM32; Has an E3 ubiquitin ligase activity. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May ubiquitinate BBS2. May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo; Belongs to the TRIM/RBCC family. (653 aa)
VRK2Serine/threonine-protein kinase VRK2; Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen- activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 [...] (508 aa)
HIPK1Homeodomain-interacting protein kinase 1; Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by [...] (1210 aa)
SIGIRRSingle 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)
MAVSMitochondrial 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. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that [...] (540 aa)
LRRC70Leucine-rich repeat-containing protein 70; Renders cells highly sensitive to the activation by cytokines and lipopolysaccharide (LPS). (622 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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