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Q9HAU4 Proteins WW domain Repeats
Uniprot ID:Q9HAU4
Protein name: E3 ubiquitin-protein ligase SMURF2
Gene : SMURF2
Protein Family:
Squence Length : 748
Sequnce
>Q9HAU4 749 MSNPGGRRNGPVKLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGSGQCHSTDTVKNTLDPKWNQHYDLYIGKSDSVTISVWNHKKIHKKQGAGFLGCVRLLSNAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQSRDRIGTGGQVVDCSRLFDNDLPDGWEERRTASGRIQYLNHITRTTQWERPTRPASEYSSPGRPLSCFVDENTPISGTNGATCGQSSDPRLAERRVRSQRHRNYMSRTHLHTPPDLPEGYEQRTTQQGQVYFLHTQTGVSTWHDPRVPRDLSNINCEELGPLPPGWEIRNTATGRVYFVDHNNRTTQFTDPRLSANLHLVLNRQNQLKDQQQQQVVSLCPDDTECLTVPRYKRDLVQKLKILRQELSQQQPQAGHCRIEVSREEIFEESYRQVMKMRPKDLWKRLMIKFRGEEGLDYGGVAREWLYLLSHEMLNPYYGLFQYSRDDIYTLQINPDSAVNPEHLSYFHFVGRIMGMAVFHGHYIDGGFTLPFYKQLLGKSITLDDMELVDPDLHNSLVWILENDITGVLDHTFCVEHNAYGEIIQHELKPNGKSIPVNEENKKEYVRLYVNWRFLRGIEAQFLALQKGFNEVIPQHLLKTFDEKELELIICGLGKIDVNDWKVNTRLKHCTPDSNIVKWFWKAVEFFDEERRARLLQFVTGSSRVPLQGFKALQGAAGPRLFTIHQIDACTNNLPKAHTCFNRIDIPPYESYEKLYEKLLTAIEETCGFAVE
Domains
DOMAIN 1 98 C2 DOMAIN 157 190 WW 1 DOMAIN 251 284 WW 2 DOMAIN 297 330 WW 3 DOMAIN 414 748 HECT
WW sequence regions
157 - 190 LPDGWEERRTASGRIQYLNHITRTTQWERPTRPA 251 - 284 LPEGYEQRTTQQGQVYFLHTQTGVSTWHDPRVPR 297 - 330 LPPGWEIRNTATGRVYFVDHNNRTTQFTDPRLSA
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. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level"
Active Site
ACT_SITE 716 716 Glycyl thioester intermediate
Mutation
"29 29 F->A: Increases autoubiquitination when associated with A-30 30 30 F->A: Increases autoubiquitination when associated with A-29 56 56 T->A: Increases autoubiquitination when associated with A-57 57 57 L->A: Increases autoubiquitination when associated with A-56 251 284 Missing: Abolishes interaction with SMAD2 and SMAD7 297 330 Missing: Abolishes interaction with SMAD7 535 535 W->A: Loss of catalytic activity 535 535 W->D: Loss of catalytic activity 547 547 H->A: Partial loss of catalytic activity 547 547 H->F,I: Activates autocatalytic activity 581 581 Y->A: Loss of catalytic activity 716 716 C->A: Increases Smad7-bound TGF-beta receptors in membrane rafts 716 716 C->G: Loss of activity"