SMURF2
entrez
64750
canonical
uniprot
Q9HAU4
canonical
ensembl
ENSG00000108854
resolver
ensp
ENSP00000262435
resolver
enst
ENST00000262435
resolver
genesymbol
SMURF2
resolver
hgnc
HGNC:16809
resolver
uniprot
Q52LL1
resolver
uniprot
Q96DE7
resolver
uniprot
Q9H260
resolver
uniprot_entry
Q96DE7_HUMAN
resolver
uniprot_entry
SMUF2_HUMAN
resolver
uniprot_sec
Q52LL1
resolver
uniprot_sec
Q9H260
resolver
activity_regulation
ACTIVITY REGULATION: Activated by NDFIP1- and NDFIP2-binding. {ECO:0000269|PubMed:19343052}.
uniprot
proteins
amino_acid_sequence
MSNPGGRRNGPVKLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGSGQCHSTDTVKNTLDPKWNQHYDLYIGKSDSVTISVWNHKKIHKKQGAGFLGCVRLLSNAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQSRDRIGTGGQVVDCSRLFDNDLPDGWEERRTASGRIQYLNHITRTTQWERPTRPASEYSSPGRPLSCFVDENTPISGTNGATCGQSSDPRLAERRVRSQRHRNYMSRTHLHTPPDLPEGYEQRTTQQGQVYFLHTQTGVSTWHDPRVPRDLSNINCEELGPLPPGWEIRNTATGRVYFVDHNNRTTQFTDPRLSANLHLVLNRQNQLKDQQQQQVVSLCPDDTECLTVPRYKRDLVQKLKILRQELSQQQPQAGHCRIEVSREEIFEESYRQVMKMRPKDLWKRLMIKFRGEEGLDYGGVAREWLYLLSHEMLNPYYGLFQYSRDDIYTLQINPDSAVNPEHLSYFHFVGRIMGMAVFHGHYIDGGFTLPFYKQLLGKSITLDDMELVDPDLHNSLVWILENDITGVLDHTFCVEHNAYGEIIQHELKPNGKSIPVNEENKKEYVRLYVNWRFLRGIEAQFLALQKGFNEVIPQHLLKTFDEKELELIICGLGKIDVNDWKVNTRLKHCTPDSNIVKWFWKAVEFFDEERRARLLQFVTGSSRVPLQGFKALQGAAGPRLFTIHQIDACTNNLPKAHTCFNRIDIPPYESYEKLYEKLLTAIEETCGFAVE
uniprot
proteins
ec_number
2.3.2.26
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11016919, PubMed:38016474). Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling (PubMed:11163210, PubMed:12717440, PubMed:21791611). In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1 (PubMed:18448069). 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 (PubMed:11016919, PubMed:11158580, PubMed:11389444). SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation (PubMed:11389444). Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation (PubMed:30696809). Acts as an activator of ferroptosis by mediating ubiquitination and degradation of GSTP1, thereby preventing detoxification of 4-hydroxynonenal (4-HNE) reactive aldehyde (PubMed:38016474). Acts as a positive regulator of smoothened signaling pathway by mediating ubiquitination of PTCH1, leading to endocytosis and lysosomal degradation of PTCH1 (By similarity). {ECO:0000250|UniProtKB:A2A5Z6, ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11158580, ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:11389444, ECO:0000269|PubMed:12717440, ECO:0000269|PubMed:18448069, ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:30696809, ECO:0000269|PubMed:38016474}.; FUNCTION: (Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding. {ECO:0000269|PubMed:33673144}.
uniprot
proteins
mass_dalton
86196
uniprot
proteins
mutagenesis
MUTAGEN 29..30; /note="FF->AA: Increases auto-ubiquitination."; /evidence="ECO:0000269|PubMed:17719543, ECO:0000269|PubMed:30696809"; MUTAGEN 56; /note="T->A: Increases auto-ubiquitination; when associated with A-57."; /evidence="ECO:0000269|PubMed:17719543"; MUTAGEN 57; /note="L->A: Increases auto-ubiquitination; when associated with A-56."; /evidence="ECO:0000269|PubMed:17719543"; MUTAGEN 251..284; /note="Missing: Abolishes interaction with SMAD2 and SMAD7."; /evidence="ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11163210"; MUTAGEN 297..330; /note="Missing: Abolishes interaction with SMAD7."; /evidence="ECO:0000269|PubMed:11163210"; MUTAGEN 535; /note="W->A: Loss of catalytic activity."; /evidence="ECO:0000269|PubMed:16061177"; MUTAGEN 535; /note="W->D: Loss of catalytic activity."; /evidence="ECO:0000269|PubMed:16061177"; MUTAGEN 547; /note="H->A: Partial loss of catalytic activity."; /evidence="ECO:0000269|PubMed:16061177"; MUTAGEN 547; /note="H->F,I: Activates autocatalytic activity."; /evidence="ECO:0000269|PubMed:16061177"; MUTAGEN 581; /note="Y->A: Loss of catalytic activity."; /evidence="ECO:0000269|PubMed:16061177"; MUTAGEN 716; /note="C->A: Loss of catalytic activity. Increases SMAD7-bound TGF-beta receptors in membrane rafts. Decreases interaction with TTC3. Decreased VP40 virus-like particle budding."; /evidence="ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11158580, ECO:0000269|PubMed:12717440, ECO:0000269|PubMed:30696809, ECO:0000269|PubMed:33673144, ECO:0000269|PubMed:38016474"; MUTAGEN 716; /note="C->G: Loss of activity. Loss of ability to ubiquitinate SMAD1 and SMAD2 and no down-regulation of SMAD1 and SMAD2 protein levels."; /evidence="ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11158580, ECO:0000269|PubMed:12717440
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:38016474}.
uniprot
proteins
post_translational_modification
PTM: Auto-ubiquitinated and ubiquitinated in the presence of RNF11 and UBE2D1 (PubMed:19343052, PubMed:30696809). Ubiquitinated by the SCF(FBXL15) complex and TTC3, leading to its degradation by the proteasome (PubMed:21572392, PubMed:30696809). 'Lys-48'-linked polyubiquitination mediated by TRAF4 at Lys-119 leads to SMURF2 proteasomal degradation (PubMed:31076633). {ECO:0000269|PubMed:19343052, ECO:0000269|PubMed:21572392, ECO:0000269|PubMed:30696809, ECO:0000269|PubMed:31076633}.
uniprot
proteins
pubmed
11016919
uniprot
proteins
pubmed
11158580
uniprot
proteins
pubmed
11163210
uniprot
proteins
pubmed
11389444
uniprot
proteins
pubmed
12717440
uniprot
proteins
pubmed
14562029
uniprot
proteins
pubmed
14755250
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16061177
uniprot
proteins
pubmed
16641086
uniprot
proteins
pubmed
17719543
uniprot
proteins
pubmed
18448069
uniprot
proteins
pubmed
19343052
uniprot
proteins
pubmed
21572392
uniprot
proteins
pubmed
21791611
uniprot
proteins
pubmed
30696809
uniprot
proteins
pubmed
31076633
uniprot
proteins
pubmed
33673144
uniprot
proteins
pubmed
38016474
uniprot
proteins
sequence_length
748
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12717440}. Cytoplasm {ECO:0000269|PubMed:12717440}. Cell membrane {ECO:0000269|PubMed:12717440}. Membrane raft {ECO:0000269|PubMed:12717440}. Note=Cytoplasmic in the presence of SMAD7. Colocalizes with CAV1, SMAD7 and TGF-beta receptor in membrane rafts.
uniprot
proteins