Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:15314065, PubMed:23542699, PubMed:34425109).Does not cleave 'Lys-48'-linked polyubiquitin chains (PubMed:15314065).Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF (PubMed:10383417).Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7 (PubMed:11483516).Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes (PubMed:15314065, PubMed:17261583).Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (PubMed:15314065, PubMed:17261583).Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways (PubMed:23542699).
Protein names:
STAM-binding protein
Alternative name:
Associated molecule with the SH3 domain of STAM;Endosome-associated ubiquitin isopeptidase
Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa.
Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines (PubMed:15208624, PubMed:16125763, PubMed:15708988, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:29117565, PubMed:28469175, PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726).Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988).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 (PubMed:28469175, PubMed:31006531).Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons (PubMed:28469175, PubMed:31006531).Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966).In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966).Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966).A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966).Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV) (PubMed:21616437, PubMed:21884169).It also detects rotaviruses and reoviruses (PubMed:21616437, PubMed:21884169).Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.68). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370).Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration
Protein names:
Antiviral innate immune response receptor RIG-I
Alternative name:
ATP-dependent RNA helicase DDX58 (EC:3.6.4.13);DEAD box protein 58;RIG-I-like receptor 1 (RLR-1);RNA sensor RIG-I;Retinoic acid-inducible gene 1 protein (RIG-1);Retinoic acid-inducible gene I protein (RIG-I)
Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436).
Deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis (PubMed:22212137, PubMed:23359680).Abrogates the ubiquitination of multiple proteins including WWTR1/TAZ, EGFR, HIF1A and beta-site amyloid precursor protein cleaving enzyme 1/BACE1 (PubMed:22212137, PubMed:25615526).In addition, recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin to maintain a stable pool of monoubiquitin that is a key requirement for the ubiquitin-proteasome and the autophagy-lysosome pathways (PubMed:9774100, PubMed:8639624, PubMed:12408865).Regulates amyloid precursor protein/APP processing by promoting BACE1 degradation resulting in decreased amyloid beta production (PubMed:22212137).Plays a role in the immune response by regulating the ability of MHC I molecules to reach cross-presentation compartments competent for generating Ag-MHC I complexes (By similarity).Mediates the 'Lys-48'-linked deubiquitination of the transcriptional coactivator WWTR1/TAZ leading to its stabilization and inhibition of osteoclastogenesis (By similarity).Deubiquitinates and stabilizes epidermal growth factor receptor EGFR to prevent its degradation and to activate its downstream mediators (By similarity).Modulates oxidative activity in skeletal muscle by regulating key mitochondrial oxidative proteins (By similarity).Enhances the activity of hypoxia-inducible factor 1-alpha/HIF1A by abrogateing its VHL E3 ligase-mediated ubiquitination and consequently inhibiting its degradation (PubMed:25615526).
Protein names:
Ubiquitin carboxyl-terminal hydrolase isozyme L1
Alternative name:
Neuron cytoplasmic protein 9.5;PGP 9.5 (PGP9.5);Ubiquitin thioesterase L1
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg2+ (By similarity).Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg2+ (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A.
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 IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of pro-inflammatory cytokines and IFN beta in LPS-tolerized macrophages.
Protein names:
Tumor necrosis factor alpha-induced protein 3
Alternative name:
OTU domain-containing protein 7C;Putative DNA-binding protein A20;Zinc finger protein A20
Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways (PubMed:14563850, PubMed:15047686, PubMed:23023224, PubMed:25588840, PubMed:26320582, PubMed:31371777).Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures (PubMed:23023224).Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes (PubMed:23023224).MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (PubMed:31371777).Binds to polyubiquitinated proteins via its GAT domain (PubMed:14563850).In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes (PubMed:15047686).The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin (PubMed:14563850, PubMed:15047686).Mediates clathrin recruitment to early endosomes by ZFYVE16 (PubMed:15657082).Modulates binding of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns3P) via binding competition; the association with TOLLIP may favor the release of TOLLIP from endosomal membranes, allowing TOLLIP to commit to cargo trafficking (PubMed:26320582).Acts as a phosphatidylinositol 5-phosphate (PtdIns5P) effector by binding to PtdIns5P, thereby regulating endosomal maturation (PubMed:25588840).PtdIns5P-dependent recruitment to signaling endosomes may block endosomal maturation (PubMed:25588840).Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling (PubMed:15047686, PubMed:26320582).
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. May be involved in degradation of muscle-specific proteins. Mediates polyubiquitination of CYP3A4.
Protein names:
Ubiquitin-conjugating enzyme E2 G1
Alternative name:
E2 ubiquitin-conjugating enzyme G1;E217K;UBC7;Ubiquitin carrier protein G1;Ubiquitin-protein ligase G1