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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-046726
UUCD1 version UUC-HoS-00379
Ensembl Protein ID ENSP00000262435.9
UniProt Accession Q9HAU4; Q52LL1; Q9H260; SMUF2_HUMAN
Genbank Protein ID AAG45422.1; AAG25641.1; AAG50421.1; AAH93876.1; AAI11946.1
Protein Name E3 ubiquitin-protein ligase SMURF2; HECT-type E3 ubiquitin transferase SMURF2; SMAD ubiquitination regulatory factor 2; SMAD-specific E3 ubiquitin-protein ligase 2
Genbank Nucleotide ID AF310676; AF301463; AY014180; BC093876; BC111945
Gene Name SMURF2
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000108854.15 ENST00000582081.5 ENSP00000463531.1
ENSG00000108854.15 ENST00000578386.5 ENSP00000464432.1
ENSG00000108854.15 ENST00000262435.13 ENSP00000262435.9
ENSG00000108854.15 ENST00000585301.1 ENSP00000463804.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
miRWalkTargetScanRepTarmiRNAMap
SomamiRmiRcodeRAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Protein 3D Structure
PDBMMDB
Disease-associated Information
GWASdbOMIM
Post-translational Modifications (PTMs)
CPLMdbPAFPhosphositePlusBioGRID
DNA Methylation
MethyCancerTCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
E3 activity/HECT HECT 16950122; 18927080; 19583833; 19255252; 20819168; 14562029; 20073064; 11389444; 11163210; 18671942; 14755250; 20858899
Classification
Family E-value Score Start End
E3 activity/HECT 5.20e-129 432.1 415 747
Active Site
Position(s) Description Evidence
716 Glycyl thioester intermediate {ECO:0000255|PROSITE-ProRule:PRU00104}
Domain Profile

   E3 activity/HECT
   S: 2    ksdlkkrlevefvgEegldlgGvtreflallskelqnpdlglflysendketlqpnpdsglknpehlklFeflGrllgkalqdgrlldlpls 93
           ++dl krl+++f+gEegld+gGv+re+l+lls+e+ np++glf+ys +d +tlq+npds + npehl++F+f+Gr++g+a+++g+++d  ++
   Q: 415  PKDLWKRLMIKFRGEEGLDYGGVAREWLYLLSHEMLNPYYGLFQYSRDDIYTLQINPDSAV-NPEHLSYFHFVGRIMGMAVFHGHYIDGGFT 505
           678999*****************************************************98.89**************************** PP
   S: 94   ksfyklllgkklsledleevdpelykslkeikenaesdieelgldltfsvseeilgetkeeeLkpgGenipVtneNkeeYvklvveyrlkeg 185
            +fyk+llgk+++l+d+e vdp+l++sl +i+en   di+   ld tf+v+++ +ge+ ++eLkp+G++ipV++eNk+eYv+l+v++r+ +g
   Q: 506  LPFYKQLLGKSITLDDMELVDPDLHNSLVWILEN---DITGV-LDHTFCVEHNAYGEIIQHELKPNGKSIPVNEENKKEYVRLYVNWRFLRG 593
           ********************************99...9***8.************************************************* PP
   S: 186  ikeqveafreGfneviplellslFteeelellicGeeeidvedlkketkykggytedspaiqwFwevleefsseerkafLqFvTgssrlPlg 277
           i+ q+ a+++Gfnevip++ll+ F+e+elel+icG  +idv+d+k +t+ k+ +t+ds+ ++wFw+++e f++e r+++LqFvTgssr+Pl+
   Q: 594  IEAQFLALQKGFNEVIPQHLLKTFDEKELELIICGLGKIDVNDWKVNTRLKH-CTPDSNIVKWFWKAVEFFDEERRARLLQFVTGSSRVPLQ 684
           **************************************************99.*************************************** PP
   S: 278  Gfaelk....prlfvirk.dasddrlPssnTCfnyLkLPeYsskeilkekLlyAieetkgFel 335
           Gf++l+    prlf+i++ da +++lP+++TCfn++++P+Y+s+e+l+ekLl+Aieet gF +
   Q: 685  GFKALQgaagPRLFTIHQiDACTNNLPKAHTCFNRIDIPPYESYEKLYEKLLTAIEETCGFAV 747
           *************************************************************76 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     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.
 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.
Protein Sequence
(Fasta)
MSNPGGRRNG PVKLRLTVLC AKNLVKKDFF RLPDPFAKVV VDGSGQCHST DTVKNTLDPK 60
WNQHYDLYIG KSDSVTISVW NHKKIHKKQG AGFLGCVRLL SNAINRLKDT GYQRLDLCKL 120
It may take some time, please wait.

Protein Fasta Sequence


>IUUC-Hsa-046726|E3,HECT|Homo sapiens
Please wait for a moment...
Nucleotide Sequence
(Fasta)
GGGGAGCTCG GCGTCCCGCT CCCTCCGCGG CTCATGGCGA CGACTCTCGG CACATCCGGG 60
ACCCTCCGGC CGTGGCGGCC GAGGCGCCGG CTGCTCGGGC CCCAGCCCCG GCCGCTGTGG 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-046726|E3,HECT|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-1017--Isopeptide bond
KW-0472--Membrane
KW-0539--Nucleus
KW-1185--Reference proteome
KW-0677--Repeat
KW-0808--Transferase
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway
Interpro

IPR000008--C2_dom
IPR000569--HECT_dom
IPR001202--WW_dom
PROSITE

PS50004--C2
PS50237--HECT
PS01159--WW_DOMAIN_1
PS50020--WW_DOMAIN_2
Pfam

PF00168--C2
PF00632--HECT
PF00397--WW
SMART

SM00239--C2
SM00119--HECTc
SM00456--WW
Gene Ontology

GO:0005829--C:cytosol
GO:0045121--C:membrane raft
GO:0016607--C:nuclear speck
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0005886--C:plasma membrane
GO:0000151--C:ubiquitin ligase complex
GO:0042802--F:identical protein binding
GO:0046332--F:SMAD binding
GO:0061630--F:ubiquitin protein ligase activity
GO:0004842--F:ubiquitin-protein transferase activity
GO:0030509--P:BMP signaling pathway
GO:0000122--P:negative regulation of transcription from RNA polymerase II promoter
GO:0045892--P:negative regulation of transcription, DNA-templated
GO:0030512--P:negative regulation of transforming growth factor beta receptor signaling pathway
GO:0090263--P:positive regulation of canonical Wnt signaling pathway
GO:1901165--P:positive regulation of trophoblast cell migration
GO:0016579--P:protein deubiquitination
GO:0000209--P:protein polyubiquitination
GO:0017015--P:regulation of transforming growth factor beta receptor signaling pathway
GO:0006511--P:ubiquitin-dependent protein catabolic process
GO:0030579--P:ubiquitin-dependent SMAD protein catabolic process
GO:0060071--P:Wnt signaling pathway, planar cell polarity pathway
KEGG hsa:64750
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-001305 Ailuropoda melanoleuca 99.05 0.00e+00 1498.00
IUUC-Apl-003513 Anas platyrhynchos 97.68 0.00e+00 1478.00
IUUC-Aca-005358 Anolis carolinensis 97.21 0.00e+00 1502.00
IUUC-Ame-011320 Astyanax mexicanus 87.86 0.00e+00 1389.00
IUUC-Bta-013399 Bos taurus 99.45 0.00e+00 1491.00
IUUC-Cja-019355 Callithrix jacchus 98.92 0.00e+00 1504.00
IUUC-Cpo-022200 Cavia porcellus 99.45 0.00e+00 1499.00
IUUC-Cin-025126 Ciona intestinalis 65.79 0.00e+00 971.00
IUUC-Csv-026339 Ciona savignyi 64.91 0.00e+00 1005.00
IUUC-Dre-027650 Danio rerio 90.46 0.00e+00 1433.00
IUUC-Dno-029534 Dasypus novemcinctus 99.47 0.00e+00 1528.00
IUUC-Ete-032715 Echinops telfairi 94.66 0.00e+00 1408.00
IUUC-Eca-033580 Equus caballus 99.73 0.00e+00 1503.00
IUUC-Eeu-034945 Erinaceus europaeus 97.56 0.00e+00 1390.00
IUUC-Fal-037275 Ficedula albicollis 96.90 0.00e+00 1469.00
IUUC-Gga-041060 Gallus gallus 94.29 0.00e+00 1431.00
IUUC-Gac-041295 Gasterosteus aculeatus 91.67 0.00e+00 1399.00
IUUC-Lch-050026 Latimeria chalumnae 95.49 0.00e+00 1467.00
IUUC-Loc-051760 Lepisosteus oculatus 88.52 0.00e+00 1375.00
IUUC-Laf-053753 Loxodonta africana 99.59 0.00e+00 1501.00
IUUC-Mcc-054815 Macaca mulatta 99.73 0.00e+00 1533.00
IUUC-Meu-056436 Macropus eugenii 76.13 0.00e+00 1102.00
IUUC-Mmr-060806 Microcebus murinus 99.45 0.00e+00 1499.00
IUUC-Mdo-062805 Monodelphis domestica 97.46 0.00e+00 1493.00
IUUC-Mmu-064034 Mus musculus 99.20 0.00e+00 1523.00
IUUC-Mpu-066762 Mustela putorius furo 99.05 0.00e+00 1497.00
IUUC-Mlu-066981 Myotis lucifugus 99.59 0.00e+00 1500.00
IUUC-Nle-069804 Nomascus leucogenys 100.00 0.00e+00 1531.00
IUUC-Opr-070591 Ochotona princeps 93.97 0.00e+00 1397.00
IUUC-Ont-071239 Oreochromis niloticus 91.99 0.00e+00 1407.00
IUUC-Oan-072699 Ornithorhynchus anatinus 95.71 0.00e+00 1498.00
IUUC-Ocu-074913 Oryctolagus cuniculus 99.73 0.00e+00 1534.00
IUUC-Ola-086597 Oryzias latipes 85.62 0.00e+00 1285.00
IUUC-Oga-089116 Otolemur garnettii 95.90 0.00e+00 1432.00
IUUC-Oar-089366 Ovis aries 99.18 0.00e+00 1493.00
IUUC-Ptr-091382 Pan troglodytes 100.00 0.00e+00 1537.00
IUUC-Psi-093298 Pelodiscus sinensis 97.96 0.00e+00 1457.00
IUUC-Pma-094354 Petromyzon marinus 73.51 0.00e+00 1125.00
IUUC-Pfo-096071 Poecilia formosa 90.40 0.00e+00 1421.00
IUUC-Pab-098682 Pongo abelii 100.00 0.00e+00 1537.00
IUUC-Pca-100516 Procavia capensis 89.83 0.00e+00 637.00
IUUC-Pva-102754 Pteropus vampyrus 98.49 0.00e+00 1462.00
IUUC-Rno-105600 Rattus norvegicus 99.06 0.00e+00 1292.00
IUUC-Sha-107144 Sarcophilus harrisii 97.36 0.00e+00 1355.00
IUUC-Spo-108171 Schizosaccharomyces pombe 40.37 1.00e-163 570.00
IUUC-Sar-113122 Sorex araneus 88.36 0.00e+00 1281.00
IUUC-Tgu-117112 Taeniopygia guttata 97.08 0.00e+00 1497.00
IUUC-Tru-118497 Takifugu rubripes 88.99 0.00e+00 1366.00
IUUC-Tsy-118819 Tarsius syrichta 99.03 0.00e+00 1038.00
IUUC-Tni-120781 Tetraodon nigroviridis 89.77 0.00e+00 1179.00
IUUC-Tme-126897 Tuber melanosporum 39.30 4.00e-153 535.00
IUUC-Tbe-127371 Tupaia belangeri 89.28 0.00e+00 1220.00
IUUC-Ttr-129305 Tursiops truncatus 91.68 0.00e+00 1288.00
IUUC-Vpa-130591 Vicugna pacos 89.32 0.00e+00 1302.00
IUUC-Xtr-132979 Xenopus tropicalis 77.06 0.00e+00 1105.00
Created Date 25-Jun-2017

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