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Protein

E3 ubiquitin-protein ligase SMURF2

Gene

Smurf2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.By similarity

Miscellaneous

Level decreases under the suppression of SCYE1, suggesting that SCYE1 stabilizes SMURF2.

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Activity regulationi

Activated by NDFIP1- and NDFIP2-binding.By similarity

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

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway

Enzyme and pathway databases

BRENDAi6.3.2.19 3474
ReactomeiR-MMU-201451 Signaling by BMP
R-MMU-2173788 Downregulation of TGF-beta receptor signaling
R-MMU-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-MMU-4608870 Asymmetric localization of PCP proteins
R-MMU-4641257 Degradation of AXIN
R-MMU-5632684 Hedgehog 'on' state
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8941858 Regulation of RUNX3 expression and activity
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SMURF2 (EC:2.3.2.26By similarity)
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1913563 Smurf2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003583181 – 748E3 ubiquitin-protein ligase SMURF2Add BLAST748

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 (By similarity).By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiA2A5Z6
PaxDbiA2A5Z6
PeptideAtlasiA2A5Z6
PRIDEiA2A5Z6

PTM databases

iPTMnetiA2A5Z6
PhosphoSitePlusiA2A5Z6

Expressioni

Inductioni

Up-regulated about ten-fold by activation of the TNF-signaling pathway in vitro.1 Publication

Gene expression databases

BgeeiENSMUSG00000018363 Expressed in 247 organ(s), highest expression level in embryo
GenevisibleiA2A5Z6 MM

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 (By similarity). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
DVL2O146418EBI-2348309,EBI-740850From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi211376, 25 interactors
IntActiA2A5Z6, 16 interactors
STRINGi10090.ENSMUSP00000090177

Structurei

3D structure databases

ProteinModelPortaliA2A5Z6
SMRiA2A5Z6
ModBaseiSearch...
MobiDBiSearch...

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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi347 – 351Poly-Gln5

Domaini

The second and third WW domains are responsible for interaction with the PY-motif of R-SMAD (SMAD1, SMAD2 and SMAD3).By similarity
The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208451
HOVERGENiHBG004134
InParanoidiA2A5Z6
KOiK04678
OMAiFTVLCAK
OrthoDBiEOG091G011S
PhylomeDBiA2A5Z6
TreeFamiTF323658

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 3 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR024928 E3_ub_ligase_SMURF1
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF00397 WW, 3 hits
PIRSFiPIRSF001569 E3_ub_ligase_SMURF1, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 3 hits
SUPFAMiSSF51045 SSF51045, 3 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 1 hit
PS50020 WW_DOMAIN_2, 3 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: A2A5Z6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 PITGTNGATC GHSSDPRLAE 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
QVVPLCPDDT 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 IPVTEENKKE YVRLYVNWRF LRGIEAQFLA
610 620 630 640 650
LQKGFNEVIP QHLLKTFDEK ELELIICGLG KIDVSDWKVN TRLKHCTPDS
660 670 680 690 700
NVVKWFWKAV EFFDEERRAR LLQFVTGSSR VPLQGFKALQ GAAGPRLFTI
710 720 730 740
HQIDACTNNL PKAHTCFNRI DIPPYESYEK LYEKLLTAIE ETCGFAVE
Length:748
Mass (Da):86,175
Last modified:February 20, 2007 - v1
Checksum:i385AFA32D289D33F
GO
Isoform 2 (identifier: A2A5Z6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-30: Missing.
     31-31: R → G

Show »
Length:735
Mass (Da):84,569
Checksum:iD8C2D02354914238
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A338P709A0A338P709_MOUSE
E3 ubiquitin-protein ligase SMURF2
Smurf2
68Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti130G → V in AAV87906 (PubMed:15820682).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03605518 – 30Missing in isoform 2. CuratedAdd BLAST13
Alternative sequenceiVSP_03605631R → G in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY685230 mRNA Translation: AAV87906.1
AL593847 Genomic DNA Translation: CAM16223.1
AL593847 Genomic DNA Translation: CAM16224.1
CH466558 Genomic DNA Translation: EDL34316.1
BC138786 mRNA Translation: AAI38787.1
BC138788 mRNA Translation: AAI38789.1
CCDSiCCDS25564.1 [A2A5Z6-1]
RefSeqiNP_079757.2, NM_025481.2 [A2A5Z6-1]
XP_006533999.1, XM_006533936.3 [A2A5Z6-2]
UniGeneiMm.340955

Genome annotation databases

EnsembliENSMUST00000092517; ENSMUSP00000090177; ENSMUSG00000018363 [A2A5Z6-1]
ENSMUST00000103067; ENSMUSP00000099356; ENSMUSG00000018363 [A2A5Z6-2]
ENSMUST00000167787; ENSMUSP00000129269; ENSMUSG00000018363 [A2A5Z6-1]
GeneIDi66313
KEGGimmu:66313
UCSCiuc007lzx.2 mouse [A2A5Z6-1]
uc007lzy.2 mouse [A2A5Z6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY685230 mRNA Translation: AAV87906.1
AL593847 Genomic DNA Translation: CAM16223.1
AL593847 Genomic DNA Translation: CAM16224.1
CH466558 Genomic DNA Translation: EDL34316.1
BC138786 mRNA Translation: AAI38787.1
BC138788 mRNA Translation: AAI38789.1
CCDSiCCDS25564.1 [A2A5Z6-1]
RefSeqiNP_079757.2, NM_025481.2 [A2A5Z6-1]
XP_006533999.1, XM_006533936.3 [A2A5Z6-2]
UniGeneiMm.340955

3D structure databases

ProteinModelPortaliA2A5Z6
SMRiA2A5Z6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211376, 25 interactors
IntActiA2A5Z6, 16 interactors
STRINGi10090.ENSMUSP00000090177

PTM databases

iPTMnetiA2A5Z6
PhosphoSitePlusiA2A5Z6

Proteomic databases

MaxQBiA2A5Z6
PaxDbiA2A5Z6
PeptideAtlasiA2A5Z6
PRIDEiA2A5Z6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000092517; ENSMUSP00000090177; ENSMUSG00000018363 [A2A5Z6-1]
ENSMUST00000103067; ENSMUSP00000099356; ENSMUSG00000018363 [A2A5Z6-2]
ENSMUST00000167787; ENSMUSP00000129269; ENSMUSG00000018363 [A2A5Z6-1]
GeneIDi66313
KEGGimmu:66313
UCSCiuc007lzx.2 mouse [A2A5Z6-1]
uc007lzy.2 mouse [A2A5Z6-2]

Organism-specific databases

CTDi64750
MGIiMGI:1913563 Smurf2

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208451
HOVERGENiHBG004134
InParanoidiA2A5Z6
KOiK04678
OMAiFTVLCAK
OrthoDBiEOG091G011S
PhylomeDBiA2A5Z6
TreeFamiTF323658

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi6.3.2.19 3474
ReactomeiR-MMU-201451 Signaling by BMP
R-MMU-2173788 Downregulation of TGF-beta receptor signaling
R-MMU-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-MMU-4608870 Asymmetric localization of PCP proteins
R-MMU-4641257 Degradation of AXIN
R-MMU-5632684 Hedgehog 'on' state
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8941858 Regulation of RUNX3 expression and activity
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

PROiPR:A2A5Z6
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000018363 Expressed in 247 organ(s), highest expression level in embryo
GenevisibleiA2A5Z6 MM

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 3 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR024928 E3_ub_ligase_SMURF1
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF00397 WW, 3 hits
PIRSFiPIRSF001569 E3_ub_ligase_SMURF1, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 3 hits
SUPFAMiSSF51045 SSF51045, 3 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 1 hit
PS50020 WW_DOMAIN_2, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiSMUF2_MOUSE
AccessioniPrimary (citable) accession number: A2A5Z6
Secondary accession number(s): A2A5Z7, Q5IRE6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 16, 2008
Last sequence update: February 20, 2007
Last modified: November 7, 2018
This is version 106 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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