Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase SMURF2

Gene

SMURF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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.By similarity

Enzyme regulationi

Activated by NDFIP1- and NDFIP2-binding.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei716Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • SMAD binding Source: BHF-UCL
  • ubiquitin protein ligase activity Source: Reactome
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108854-MONOMER.
BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-201451. Signaling by BMP.
R-HSA-2173788. Downregulation of TGF-beta receptor signaling.
R-HSA-2173795. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
R-HSA-4608870. Asymmetric localization of PCP proteins.
R-HSA-4641257. Degradation of AXIN.
R-HSA-5632684. Hedgehog 'on' state.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9HAU4.
SIGNORiQ9HAU4.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SMURF2 (EC:2.3.2.26By similarity)
Short name:
hSMURF2
Alternative name(s):
HECT-type E3 ubiquitin transferase SMURF2
SMAD ubiquitination regulatory factor 2
SMAD-specific E3 ubiquitin-protein ligase 2
Gene namesi
Name:SMURF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:16809. SMURF2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • cytosol Source: Reactome
  • membrane raft Source: UniProtKB-SubCell
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi29F → A: Increases autoubiquitination; when associated with A-30. 1 Publication1
Mutagenesisi30F → A: Increases autoubiquitination; when associated with A-29. 1 Publication1
Mutagenesisi56T → A: Increases autoubiquitination; when associated with A-57. 1 Publication1
Mutagenesisi57L → A: Increases autoubiquitination; when associated with A-56. 1 Publication1
Mutagenesisi251 – 284Missing : Abolishes interaction with SMAD2 and SMAD7. 2 PublicationsAdd BLAST34
Mutagenesisi297 – 330Missing : Abolishes interaction with SMAD7. 1 PublicationAdd BLAST34
Mutagenesisi535W → A: Loss of catalytic activity. 1 Publication1
Mutagenesisi535W → D: Loss of catalytic activity. 1 Publication1
Mutagenesisi547H → A: Partial loss of catalytic activity. 1 Publication1
Mutagenesisi547H → F or I: Activates autocatalytic activity. 1 Publication1
Mutagenesisi581Y → A: Loss of catalytic activity. 1 Publication1
Mutagenesisi716C → A: Increases Smad7-bound TGF-beta receptors in membrane rafts. 3 Publications1
Mutagenesisi716C → G: Loss of activity. Loss of ability to ubiquitinate SMAD1 and SMAD2 and no down-regulation of SMAD1 and SMAD2 protein levels. 3 Publications1

Organism-specific databases

DisGeNETi64750.
OpenTargetsiENSG00000108854.
PharmGKBiPA134985524.

Polymorphism and mutation databases

BioMutaiSMURF2.
DMDMi17865624.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203291 – 748E3 ubiquitin-protein ligase SMURF2Add BLAST748

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki375Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki377Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

Auto-ubiquitinated and ubiquitinated in the presence of RNF11 and UBE2D1. Ubiquitinated by the SCF(FBXL15) complex, leading to its degradation by the proteasome.2 Publications

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9HAU4.
MaxQBiQ9HAU4.
PaxDbiQ9HAU4.
PeptideAtlasiQ9HAU4.
PRIDEiQ9HAU4.

PTM databases

iPTMnetiQ9HAU4.
PhosphoSitePlusiQ9HAU4.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000108854.
CleanExiHS_SMURF2.
ExpressionAtlasiQ9HAU4. baseline and differential.
GenevisibleiQ9HAU4. HS.

Interactioni

Subunit structurei

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. Interacts with STAMBP and RNF11. Interacts with NDFIP1 and NDFIP2 (Probable); this interaction activates the E3 ubiquitin-protein ligase.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself6EBI-396727,EBI-396727
Q9WMX22EBI-396727,EBI-6863741From a different organism.
FBXL15Q9H4693EBI-396727,EBI-6144096
RNF11Q9Y3C55EBI-396727,EBI-396669
SMAD1Q157973EBI-396727,EBI-1567153
SMAD2Q157965EBI-396727,EBI-1040141
SMAD3P840227EBI-396727,EBI-347161
UBBP0CG474EBI-396727,EBI-413034

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • SMAD binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi122265. 125 interactors.
DIPiDIP-33061N.
IntActiQ9HAU4. 68 interactors.
MINTiMINT-1180022.
STRINGi9606.ENSP00000262435.

Structurei

Secondary structure

1748
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi12 – 23Combined sources12
Beta strandi35 – 41Combined sources7
Turni42 – 44Combined sources3
Beta strandi48 – 50Combined sources3
Beta strandi60 – 69Combined sources10
Beta strandi75 – 81Combined sources7
Helixi82 – 87Combined sources6
Beta strandi93 – 99Combined sources7
Helixi101 – 110Combined sources10
Beta strandi113 – 115Combined sources3
Beta strandi131 – 138Combined sources8
Beta strandi258 – 262Combined sources5
Turni263 – 265Combined sources3
Beta strandi266 – 271Combined sources6
Turni272 – 275Combined sources4
Beta strandi276 – 280Combined sources5
Beta strandi282 – 284Combined sources3
Beta strandi286 – 288Combined sources3
Helixi293 – 295Combined sources3
Beta strandi301 – 307Combined sources7
Beta strandi309 – 311Combined sources3
Beta strandi313 – 317Combined sources5
Turni318 – 321Combined sources4
Beta strandi322 – 326Combined sources5
Turni328 – 330Combined sources3
Helixi372 – 386Combined sources15
Beta strandi392 – 397Combined sources6
Helixi402 – 411Combined sources10
Helixi415 – 419Combined sources5
Beta strandi420 – 426Combined sources7
Helixi434 – 449Combined sources16
Helixi452 – 454Combined sources3
Beta strandi455 – 460Combined sources6
Beta strandi463 – 469Combined sources7
Helixi473 – 475Combined sources3
Helixi479 – 495Combined sources17
Helixi506 – 512Combined sources7
Helixi522 – 525Combined sources4
Helixi527 – 538Combined sources12
Turni542 – 544Combined sources3
Beta strandi549 – 555Combined sources7
Beta strandi558 – 565Combined sources8
Turni574 – 577Combined sources4
Helixi578 – 590Combined sources13
Turni591 – 594Combined sources4
Helixi595 – 608Combined sources14
Helixi611 – 614Combined sources4
Helixi619 – 627Combined sources9
Beta strandi629 – 631Combined sources3
Helixi634 – 639Combined sources6
Beta strandi641 – 646Combined sources6
Helixi651 – 662Combined sources12
Helixi665 – 676Combined sources12
Beta strandi679 – 681Combined sources3
Helixi686 – 688Combined sources3
Beta strandi698 – 702Combined sources5
Beta strandi712 – 714Combined sources3
Helixi715 – 717Combined sources3
Beta strandi719 – 722Combined sources4
Helixi728 – 739Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZVDX-ray2.10A369-748[»]
2DJYNMR-A297-333[»]
2JQZNMR-A10-140[»]
2KXQNMR-A250-333[»]
2LTZNMR-A297-333[»]
ProteinModelPortaliQ9HAU4.
SMRiQ9HAU4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HAU4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 98C2PROSITE-ProRule annotationAdd BLAST98
Domaini157 – 190WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini251 – 284WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini297 – 330WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini414 – 748HECTPROSITE-ProRule annotationAdd BLAST335

Domaini

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.

Sequence similaritiesi

Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 3 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOGENOMiHOG000208451.
HOVERGENiHBG004134.
InParanoidiQ9HAU4.
KOiK04678.
OMAiQWDRPRQ.
OrthoDBiEOG091G011S.
PhylomeDBiQ9HAU4.
TreeFamiTF323658.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 3 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 3 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9HAU4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSNPGGRRNG PVKLRLTVLC AKNLVKKDFF RLPDPFAKVV VDGSGQCHST
60 70 80 90 100
DTVKNTLDPK WNQHYDLYIG KSDSVTISVW NHKKIHKKQG AGFLGCVRLL
110 120 130 140 150
SNAINRLKDT GYQRLDLCKL GPNDNDTVRG QIVVSLQSRD RIGTGGQVVD
160 170 180 190 200
CSRLFDNDLP DGWEERRTAS GRIQYLNHIT RTTQWERPTR PASEYSSPGR
210 220 230 240 250
PLSCFVDENT PISGTNGATC GQSSDPRLAE RRVRSQRHRN YMSRTHLHTP
260 270 280 290 300
PDLPEGYEQR TTQQGQVYFL HTQTGVSTWH DPRVPRDLSN INCEELGPLP
310 320 330 340 350
PGWEIRNTAT GRVYFVDHNN RTTQFTDPRL SANLHLVLNR QNQLKDQQQQ
360 370 380 390 400
QVVSLCPDDT ECLTVPRYKR DLVQKLKILR QELSQQQPQA GHCRIEVSRE
410 420 430 440 450
EIFEESYRQV MKMRPKDLWK RLMIKFRGEE GLDYGGVARE WLYLLSHEML
460 470 480 490 500
NPYYGLFQYS RDDIYTLQIN PDSAVNPEHL SYFHFVGRIM GMAVFHGHYI
510 520 530 540 550
DGGFTLPFYK QLLGKSITLD DMELVDPDLH NSLVWILEND ITGVLDHTFC
560 570 580 590 600
VEHNAYGEII QHELKPNGKS IPVNEENKKE YVRLYVNWRF LRGIEAQFLA
610 620 630 640 650
LQKGFNEVIP QHLLKTFDEK ELELIICGLG KIDVNDWKVN TRLKHCTPDS
660 670 680 690 700
NIVKWFWKAV EFFDEERRAR LLQFVTGSSR VPLQGFKALQ GAAGPRLFTI
710 720 730 740
HQIDACTNNL PKAHTCFNRI DIPPYESYEK LYEKLLTAIE ETCGFAVE
Length:748
Mass (Da):86,196
Last modified:March 1, 2001 - v1
Checksum:i3042B443A3755762
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6G → R in AAG45422 (PubMed:11016919).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF310676 mRNA. Translation: AAG45422.1.
AF301463 mRNA. Translation: AAG25641.1.
AY014180 mRNA. Translation: AAG50421.1.
BC093876 mRNA. Translation: AAH93876.1.
BC111945 mRNA. Translation: AAI11946.1.
CCDSiCCDS32707.1.
RefSeqiNP_073576.1. NM_022739.3.
UniGeneiHs.515011.

Genome annotation databases

EnsembliENST00000262435; ENSP00000262435; ENSG00000108854.
GeneIDi64750.
KEGGihsa:64750.
UCSCiuc002jep.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF310676 mRNA. Translation: AAG45422.1.
AF301463 mRNA. Translation: AAG25641.1.
AY014180 mRNA. Translation: AAG50421.1.
BC093876 mRNA. Translation: AAH93876.1.
BC111945 mRNA. Translation: AAI11946.1.
CCDSiCCDS32707.1.
RefSeqiNP_073576.1. NM_022739.3.
UniGeneiHs.515011.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZVDX-ray2.10A369-748[»]
2DJYNMR-A297-333[»]
2JQZNMR-A10-140[»]
2KXQNMR-A250-333[»]
2LTZNMR-A297-333[»]
ProteinModelPortaliQ9HAU4.
SMRiQ9HAU4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122265. 125 interactors.
DIPiDIP-33061N.
IntActiQ9HAU4. 68 interactors.
MINTiMINT-1180022.
STRINGi9606.ENSP00000262435.

PTM databases

iPTMnetiQ9HAU4.
PhosphoSitePlusiQ9HAU4.

Polymorphism and mutation databases

BioMutaiSMURF2.
DMDMi17865624.

Proteomic databases

EPDiQ9HAU4.
MaxQBiQ9HAU4.
PaxDbiQ9HAU4.
PeptideAtlasiQ9HAU4.
PRIDEiQ9HAU4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262435; ENSP00000262435; ENSG00000108854.
GeneIDi64750.
KEGGihsa:64750.
UCSCiuc002jep.2. human.

Organism-specific databases

CTDi64750.
DisGeNETi64750.
GeneCardsiSMURF2.
HGNCiHGNC:16809. SMURF2.
MIMi605532. gene.
neXtProtiNX_Q9HAU4.
OpenTargetsiENSG00000108854.
PharmGKBiPA134985524.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOGENOMiHOG000208451.
HOVERGENiHBG004134.
InParanoidiQ9HAU4.
KOiK04678.
OMAiQWDRPRQ.
OrthoDBiEOG091G011S.
PhylomeDBiQ9HAU4.
TreeFamiTF323658.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000108854-MONOMER.
BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-201451. Signaling by BMP.
R-HSA-2173788. Downregulation of TGF-beta receptor signaling.
R-HSA-2173795. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
R-HSA-4608870. Asymmetric localization of PCP proteins.
R-HSA-4641257. Degradation of AXIN.
R-HSA-5632684. Hedgehog 'on' state.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9HAU4.
SIGNORiQ9HAU4.

Miscellaneous databases

ChiTaRSiSMURF2. human.
EvolutionaryTraceiQ9HAU4.
GeneWikiiSMURF2.
GenomeRNAii64750.
PROiQ9HAU4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108854.
CleanExiHS_SMURF2.
ExpressionAtlasiQ9HAU4. baseline and differential.
GenevisibleiQ9HAU4. HS.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 3 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 3 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSMUF2_HUMAN
AccessioniPrimary (citable) accession number: Q9HAU4
Secondary accession number(s): Q52LL1, Q9H260
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2001
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 166 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.