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A2A5Z6 (SMUF2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 65. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase SMURF2

EC=6.3.2.-
Alternative name(s):
SMAD ubiquitination regulatory factor 2
SMAD-specific E3 ubiquitin-protein ligase 2
Gene names
Name:Smurf2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length748 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity.

Enzyme regulation

Activated by NDFIP1- and NDFIP2-binding By similarity.

Pathway

Protein modification; protein ubiquitination. Ref.5

Subunit structure

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.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. Cell membrane By similarity. Membrane raft By similarity. Note: Cytoplasmic in the presence of SMAD7 By similarity. Colocalizes with CAV1, SMAD7 and TGF-beta receptor in membrane rafts By similarity. Interacts with STAMBP and RNF11 By similarity.

Induction

Up-regulated about ten-fold by activation of the TNF-signaling pathway in vitro. Ref.5

Domain

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.

Post-translational modification

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.

Miscellaneous

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

Sequence similarities

Contains 1 C2 domain.

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.

Contains 3 WW domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DVL2O146418EBI-2348309,EBI-740850From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: A2A5Z6-1)

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.
Isoform 2 (identifier: A2A5Z6-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 748748E3 ubiquitin-protein ligase SMURF2
PRO_0000358318

Regions

Domain1 – 9898C2
Domain157 – 19034WW 1
Domain251 – 28434WW 2
Domain297 – 33034WW 3
Domain414 – 748335HECT
Compositional bias347 – 3515Poly-Gln

Sites

Active site7161Glycyl thioester intermediate By similarity

Natural variations

Alternative sequence18 – 3013Missing in isoform 2.
VSP_036055
Alternative sequence311R → G in isoform 2.
VSP_036056

Experimental info

Sequence conflict1301G → V in AAV87906. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 20, 2007. Version 1.
Checksum: 385AFA32D289D33F

FASTA74886,175
        10         20         30         40         50         60 
MSNPGGRRNG PVKLRLTVLC AKNLVKKDFF RLPDPFAKVV VDGSGQCHST DTVKNTLDPK 

        70         80         90        100        110        120 
WNQHYDLYIG KSDSVTISVW NHKKIHKKQG AGFLGCVRLL SNAINRLKDT GYQRLDLCKL 

       130        140        150        160        170        180 
GPNDNDTVRG QIVVSLQSRD RIGTGGQVVD CSRLFDNDLP DGWEERRTAS GRIQYLNHIT 

       190        200        210        220        230        240 
RTTQWERPTR PASEYSSPGR PLSCFVDENT PITGTNGATC GHSSDPRLAE RRVRSQRHRN 

       250        260        270        280        290        300 
YMSRTHLHTP PDLPEGYEQR TTQQGQVYFL HTQTGVSTWH DPRVPRDLSN INCEELGPLP 

       310        320        330        340        350        360 
PGWEIRNTAT GRVYFVDHNN RTTQFTDPRL SANLHLVLNR QNQLKDQQQQ QVVPLCPDDT 

       370        380        390        400        410        420 
ECLTVPRYKR DLVQKLKILR QELSQQQPQA GHCRIEVSRE EIFEESYRQV MKMRPKDLWK 

       430        440        450        460        470        480 
RLMIKFRGEE GLDYGGVARE WLYLLSHEML NPYYGLFQYS RDDIYTLQIN PDSAVNPEHL 

       490        500        510        520        530        540 
SYFHFVGRIM GMAVFHGHYI DGGFTLPFYK QLLGKSITLD DMELVDPDLH NSLVWILEND 

       550        560        570        580        590        600 
ITGVLDHTFC VEHNAYGEII QHELKPNGKS IPVTEENKKE YVRLYVNWRF LRGIEAQFLA 

       610        620        630        640        650        660 
LQKGFNEVIP QHLLKTFDEK ELELIICGLG KIDVSDWKVN TRLKHCTPDS NVVKWFWKAV 

       670        680        690        700        710        720 
EFFDEERRAR LLQFVTGSSR VPLQGFKALQ GAAGPRLFTI HQIDACTNNL PKAHTCFNRI 

       730        740 
DIPPYESYEK LYEKLLTAIE ETCGFAVE 

« Hide

Isoform 2 [UniParc].

Checksum: D8C2D02354914238
Show »

FASTA73584,569

References

« Hide 'large scale' references
[1]"Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation."
Yamashita M., Ying S.X., Zhang G.M., Li C., Cheng S.Y., Deng C.X., Zhang Y.E.
Cell 121:101-113(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: 129/SvJ.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[5]"Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts."
Kaneki H., Guo R., Chen D., Yao Z., Schwarz E.M., Zhang Y.E., Boyce B.F., Xing L.
J. Biol. Chem. 281:4326-4333(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY TNF SIGNALING PATHWAY ACTIVATION.
[6]"AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2."
Lee Y.S., Han J.M., Son S.H., Choi J.W., Jeon E.J., Bae S.-C., Park Y.I., Kim S.
Biochem. Biophys. Res. Commun. 371:395-400(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: STABILIZATION BY SCYE1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_079757.2. NM_025481.2.
XP_006533999.1. XM_006533936.1.
UniGeneMm.340955.

3D structure databases

ProteinModelPortalA2A5Z6.
SMRA2A5Z6. Positions 10-140, 155-745.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid211376. 19 interactions.
IntActA2A5Z6. 13 interactions.

PTM databases

PhosphoSiteA2A5Z6.

Proteomic databases

PaxDbA2A5Z6.
PRIDEA2A5Z6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000092517; ENSMUSP00000090177; ENSMUSG00000018363. [A2A5Z6-1]
ENSMUST00000103067; ENSMUSP00000099356; ENSMUSG00000018363. [A2A5Z6-2]
ENSMUST00000167787; ENSMUSP00000129269; ENSMUSG00000018363. [A2A5Z6-1]
GeneID66313.
KEGGmmu:66313.
UCSCuc007lzx.2. mouse. [A2A5Z6-1]
uc007lzy.2. mouse. [A2A5Z6-2]

Organism-specific databases

CTD64750.
MGIMGI:1913563. Smurf2.

Phylogenomic databases

eggNOGCOG5021.
GeneTreeENSGT00750000117667.
HOGENOMHOG000208451.
HOVERGENHBG004134.
InParanoidQ5IRE6.
KOK04678.
OMANQAARPF.
OrthoDBEOG77Q4W4.
PhylomeDBA2A5Z6.
TreeFamTF323658.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressA2A5Z6.
BgeeA2A5Z6.
GenevestigatorA2A5Z6.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view]
PIRSFPIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
SMARTSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 3 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 3 hits.
SSF56204. SSF56204. 1 hit.
PROSITEPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio321287.
PROA2A5Z6.
SOURCESearch...

Entry information

Entry nameSMUF2_MOUSE
AccessionPrimary (citable) accession number: A2A5Z6
Secondary accession number(s): A2A5Z7, Q5IRE6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 16, 2008
Last sequence update: February 20, 2007
Last modified: April 16, 2014
This is version 65 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot