A2A5Z6A2A5Z7Q5IRE6SMUF2_MOUSEE3 ubiquitin-protein ligase SMURF22.3.2.26HECT-type E3 ubiquitin transferase SMURF2SMAD ubiquitination regulatory factor 2SMAD-specific E3 ubiquitin-protein ligase 2Smurf2Mus musculusMouseEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMusUbiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)Lineage-specific biology revealed by a finished genome assembly of the mouse.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts.INDUCTION BY TNF SIGNALING PATHWAY ACTIVATIONAIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2.STABILIZATION BY AIMP1E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1. Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation. SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation. Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation.S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.Activated by NDFIP1- and NDFIP2-binding.Protein modification; protein ubiquitination.Interacts (via WW domains) with SMAD1. Interacts (via WW domains) with SMAD2 (via PY-motif). Interacts (via WW domains) with SMAD3 (via PY-motif). Interacts with SMAD6. Interacts with SMAD7 (via PY-motif) and TGFBR1; SMAD7 recruits SMURF2 to the TGF-beta receptor and regulates its degradation. Does not interact with SMAD4; SMAD4 lacks a PY-motif. Interacts with AIMP1 (By similarity). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (By similarity). Interacts with TTC3 (By similarity).A2A5Z6O14641true8NucleusCytoplasmCell membraneMembrane raftCytoplasmic in the presence of SMAD7. Colocalizes with CAV1, SMAD7 and TGF-beta receptor in membrane rafts.A2A5Z6-11A2A5Z6-22Up-regulated about ten-fold by activation of the TNF-signaling pathway in vitro.The second and third WW domains are responsible for interaction with the PY-motif of R-SMAD (SMAD1, SMAD2 and SMAD3).The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.Auto-ubiquitinated and ubiquitinated in the presence of RNF11 and UBE2D1 (By similarity). Ubiquitinated by the SCF(FBXL15) complex and TTC3, leading to its degradation by the proteasome (By similarity). 'Lys-48'-linked polyubiquitination mediated by TRAF4 at Lys-119 leads to SMURF2 proteasomal degradation (By similarity).Level decreases under the suppression of SCYE1, suggesting that AIMP1 stabilizes SMURF2.Alternative splicingCell membraneCytoplasmIsopeptide bondMembraneNucleusReference proteomeRepeatTransferaseUbl conjugationUbl conjugation pathwayRGGVMSNPGGRRNGPVKLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGSGQCHSTDTVKNTLDPKWNQHYDLYIGKSDSVTISVWNHKKIHKKQGAGFLGCVRLLSNAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQSRDRIGTGGQVVDCSRLFDNDLPDGWEERRTASGRIQYLNHITRTTQWERPTRPASEYSSPGRPLSCFVDENTPITGTNGATCGHSSDPRLAERRVRSQRHRNYMSRTHLHTPPDLPEGYEQRTTQQGQVYFLHTQTGVSTWHDPRVPRDLSNINCEELGPLPPGWEIRNTATGRVYFVDHNNRTTQFTDPRLSANLHLVLNRQNQLKDQQQQQVVPLCPDDTECLTVPRYKRDLVQKLKILRQELSQQQPQAGHCRIEVSREEIFEESYRQVMKMRPKDLWKRLMIKFRGEEGLDYGGVAREWLYLLSHEMLNPYYGLFQYSRDDIYTLQINPDSAVNPEHLSYFHFVGRIMGMAVFHGHYIDGGFTLPFYKQLLGKSITLDDMELVDPDLHNSLVWILENDITGVLDHTFCVEHNAYGEIIQHELKPNGKSIPVTEENKKEYVRLYVNWRFLRGIEAQFLALQKGFNEVIPQHLLKTFDEKELELIICGLGKIDVSDWKVNTRLKHCTPDSNVVKWFWKAVEFFDEERRARLLQFVTGSSRVPLQGFKALQGAAGPRLFTIHQIDACTNNLPKAHTCFNRIDIPPYESYEKLYEKLLTAIEETCGFAVE
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