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MGP005605

UniProt Annotations

Entry Information
Gene NameSMAD specific E3 ubiquitin protein ligase 1
Protein EntrySMUF1_HUMAN
UniProt IDQ9HCE7
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=Long; IsoId=Q9HCE7-1; Sequence=Displayed; Name=Short; IsoId=Q9HCE7-2; Sequence=VSP_006812;
DomainThe C2 domain mediates membrane localization and substrate selection. {ECO:0000269|PubMed:21402695}.
FunctionE3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. {ECO:0000269|PubMed:10458166, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:21402695}.
InteractionO14757:CHEK1; NbExp=4; IntAct=EBI-9845742, EBI-974488; Q9H469:FBXL15; NbExp=6; IntAct=EBI-976466, EBI-6144096; Q9H160:ING2; NbExp=4; IntAct=EBI-976466, EBI-389787; Q9Y5W3:KLF2; NbExp=4; IntAct=EBI-9845742, EBI-9846663; Q53GL0:PLEKHO1; NbExp=5; IntAct=EBI-976466, EBI-949945; P62195:PSMC5; NbExp=2; IntAct=EBI-976466, EBI-357745; P61289:PSME3; NbExp=5; IntAct=EBI-976466, EBI-355546; P61586:RHOA; NbExp=2; IntAct=EBI-9845742, EBI-446668; P62745:RHOB; NbExp=3; IntAct=EBI-9845742, EBI-602647; Q15797:SMAD1; NbExp=2; IntAct=EBI-9845742, EBI-1567153; Q9BUZ4:TRAF4; NbExp=4; IntAct=EBI-9845742, EBI-3650647;
PathwayProtein modification; protein ubiquitination.
PtmUbiquitinated by the SCF(FBXL15) complex at Lys-381 and Lys- 383, leading to its degradation by the proteasome. Lys-383 is the primary ubiquitination site. {ECO:0000269|PubMed:21572392}.
Sequence CautionSequence=BAB13451.1; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityContains 1 C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041}.
SimilarityContains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. {ECO:0000255|PROSITE-ProRule:PRU00104}.
SimilarityContains 2 WW domains. {ECO:0000255|PROSITE- ProRule:PRU00224}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:21572392}. Cell membrane {ECO:0000269|PubMed:21572392}; Peripheral membrane protein {ECO:0000269|PubMed:21572392}; Cytoplasmic side {ECO:0000269|PubMed:21572392}.
SubunitInteracts with TRAF4. Interacts (via HECT domain) with FBXL15 (via LRR repeats). Interacts with SMAD7 and TGFBR1; SMAD7 recruits SMURF1 to TGFBR1 and regulates TGF-beta receptor degradation. {ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:21572392}.
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