Overview
| Uniprot ID | Q9HAU4 |
|---|
| Protein Name | E3 ubiquitin-protein ligase SMURF2 |
|---|
| Gene Name | SMURF2 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 88 |
NHKKIHKKQGAGFLG |
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)
Protein Sequence
10
MSNPGGRRNG
20
PVKLRLTVLC
30
AKNLVKKDFF
40
RLPDPFAKVV
50
VDGSGQCHST
60
DTVKNTLDPK
70
WNQHYDLYIG
80
KSDSVTISVW
90
NHKKIHKKQG
100
AGFLGCVRLL
110
SNAINRLKDT
120
GYQRLDLCKL
130
GPNDNDTVRG
140
QIVVSLQSRD
150
RIGTGGQVVD
160
CSRLFDNDLP
170
DGWEERRTAS
180
GRIQYLNHIT
190
RTTQWERPTR
200
PASEYSSPGR
210
PLSCFVDENT
220
PISGTNGATC
230
GQSSDPRLAE
240
RRVRSQRHRN
250
YMSRTHLHTP
260
PDLPEGYEQR
270
TTQQGQVYFL
280
HTQTGVSTWH
290
DPRVPRDLSN
300
INCEELGPLP
310
PGWEIRNTAT
320
GRVYFVDHNN
330
RTTQFTDPRL
340
SANLHLVLNR
350
QNQLKDQQQQ
360
QVVSLCPDDT
370
ECLTVPRYKR
380
DLVQKLKILR
390
QELSQQQPQA
400
GHCRIEVSRE
410
EIFEESYRQV
420
MKMRPKDLWK
430
RLMIKFRGEE
440
GLDYGGVARE
450
WLYLLSHEML
460
NPYYGLFQYS
470
RDDIYTLQIN
480
PDSAVNPEHL
490
SYFHFVGRIM
500
GMAVFHGHYI
510
DGGFTLPFYK
520
QLLGKSITLD
530
DMELVDPDLH
540
NSLVWILEND
550
ITGVLDHTFC
560
VEHNAYGEII
570
QHELKPNGKS
580
IPVNEENKKE
590
YVRLYVNWRF
600
LRGIEAQFLA
610
LQKGFNEVIP
620
QHLLKTFDEK
630
ELELIICGLG
640
KIDVNDWKVN
650
TRLKHCTPDS
660
NIVKWFWKAV
670
EFFDEERRAR
680
LLQFVTGSSR
690
VPLQGFKALQ
700
GAAGPRLFTI
710
HQIDACTNNL
720
PKAHTCFNRI
730
DIPPYESYEK
740
LYEKLLTAIE
ETCGFAVE
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0045121 |
membrane raft |
| Cellular Component |
GO:0016607 |
nuclear speck |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0000151 |
ubiquitin ligase complex |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Molecular Function |
GO:0046332 |
SMAD binding |
| Molecular Function |
GO:0061630 |
ubiquitin protein ligase activity |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Biological Process |
GO:0030514 |
negative regulation of BMP signaling pathway |
| Biological Process |
GO:0045892 |
negative regulation of DNA-templated transcription |
| Biological Process |
GO:0000122 |
negative regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0030512 |
negative regulation of transforming growth factor beta receptor signaling pathway |
| Biological Process |
GO:0090263 |
positive regulation of canonical Wnt signaling pathway |
| Biological Process |
GO:0160020 |
positive regulation of ferroptosis |
| Biological Process |
GO:1901165 |
positive regulation of trophoblast cell migration |
| Biological Process |
GO:0043161 |
proteasome-mediated ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:0017015 |
regulation of transforming growth factor beta receptor signaling pathway |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0060071 |
Wnt signaling pathway, planar cell polarity pathway |
Reference
[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.