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 SMURF1

Gene

SMURF1

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

Functioni

E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404). Plays a role in dendrite formation by melanocytes (PubMed:23999003).5 Publications

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.1 Publication

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 sitei725Glycyl thioester intermediate1

GO - Molecular functioni

  • activin binding Source: BHF-UCL
  • I-SMAD binding Source: BHF-UCL
  • phospholipid binding Source: ParkinsonsUK-UCL
  • R-SMAD binding Source: BHF-UCL
  • ubiquitin protein ligase activity Source: BHF-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processDifferentiation, Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi2.3.2.B9 2681
6.3.2.19 2681
ReactomeiR-HSA-201451 Signaling by BMP
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-5632684 Hedgehog 'on' state
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-8941858 Regulation of RUNX3 expression and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9HCE7
SIGNORiQ9HCE7
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SMURF1 (EC:2.3.2.261 Publication)
Short name:
hSMURF1
Alternative name(s):
HECT-type E3 ubiquitin transferase SMURF1
SMAD ubiquitination regulatory factor 1
SMAD-specific E3 ubiquitin-protein ligase 1
Gene namesi
Name:SMURF1
Synonyms:KIAA1625
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000198742.9
HGNCiHGNC:16807 SMURF1
MIMi605568 gene
neXtProtiNX_Q9HCE7

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28K → A: Fails to ubiquitinate RHOA; when associated with A-85. 1 Publication1
Mutagenesisi85K → A: Fails to ubiquitinate RHOA; when associated with A-28. 1 Publication1
Mutagenesisi350K → R: Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-381 and R-381. 1 Publication1
Mutagenesisi381K → R: Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-350 and R-383. Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-383. 1 Publication1
Mutagenesisi383K → R: Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-350 and R-381. Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-381. 1 Publication1
Mutagenesisi725C → A: Loss of enzyme activity, without abolishing FBXL15-mediated ubiquitination. 2 Publications1

Organism-specific databases

DisGeNETi57154
OpenTargetsiENSG00000198742
PharmGKBiPA134987175

Chemistry databases

ChEMBLiCHEMBL3879859

Polymorphism and mutation databases

BioMutaiSMURF1
DMDMi17865625

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203261 – 757E3 ubiquitin-protein ligase SMURF1Add BLAST757

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei200PhosphoserineCombined sources1
Cross-linki381Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki383Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Auto-ubiquitinated in presence of NDFIP1 (PubMed:23087404). Ubiquitinated by the SCF(FBXL15) complex at Lys-381 and Lys-383, leading to its degradation by the proteasome. Lys-383 is the primary ubiquitination site.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9HCE7
MaxQBiQ9HCE7
PaxDbiQ9HCE7
PeptideAtlasiQ9HCE7
PRIDEiQ9HCE7
ProteomicsDBi81693
81694 [Q9HCE7-2]

PTM databases

iPTMnetiQ9HCE7
PhosphoSitePlusiQ9HCE7

Expressioni

Tissue specificityi

Expressed in melanocytes (PubMed:23999003).1 Publication

Gene expression databases

BgeeiENSG00000198742 Expressed in 201 organ(s), highest expression level in testis
CleanExiHS_SMURF1
GenevisibleiQ9HCE7 HS

Organism-specific databases

HPAiHPA055245

Interactioni

Subunit structurei

Interacts with TRAF4. Interacts (via HECT domain) with FBXL15 (via LRR repeats). Interacts with SMAD7 and TGFBR1; SMAD7 recruits SMURF1 to TGFBR1 and regulates TGF-beta receptor degradation. Interacts with MAVS; the interaction is mediated by NDFIP1 (PubMed:23087404).5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121411, 416 interactors
CORUMiQ9HCE7
DIPiDIP-36709N
IntActiQ9HCE7, 25 interactors
MINTiQ9HCE7
STRINGi9606.ENSP00000354621

Structurei

Secondary structure

1757
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9HCE7
SMRiQ9HCE7
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HCE7

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 99C2PROSITE-ProRule annotationAdd BLAST99
Domaini234 – 267WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini306 – 339WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini420 – 757HECTPROSITE-ProRule annotationAdd BLAST338

Domaini

The C2 domain mediates membrane localization and substrate selection.1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208451
HOVERGENiHBG004134
InParanoidiQ9HCE7
KOiK04678
OMAiCKLNPTD
OrthoDBiEOG091G011S
PhylomeDBiQ9HCE7
TreeFamiTF323658

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 2 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, 2 hits
PIRSFiPIRSF001569 E3_ub_ligase_SMURF1, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 2 hits
SUPFAMiSSF51045 SSF51045, 2 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, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform Long (identifier: Q9HCE7-1) [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
MSNPGTRRNG SSIKIRLTVL CAKNLAKKDF FRLPDPFAKI VVDGSGQCHS
60 70 80 90 100
TDTVKNTLDP KWNQHYDLYV GKTDSITISV WNHKKIHKKQ GAGFLGCVRL
110 120 130 140 150
LSNAISRLKD TGYQRLDLCK LNPSDTDAVR GQIVVSLQTR DRIGTGGSVV
160 170 180 190 200
DCRGLLENEG TVYEDSGPGR PLSCFMEEPA PYTDSTGAAA GGGNCRFVES
210 220 230 240 250
PSQDQRLQAQ RLRNPDVRGS LQTPQNRPHG HQSPELPEGY EQRTTVQGQV
260 270 280 290 300
YFLHTQTGVS TWHDPRIPSP SGTIPGGDAA FLYEFLLQGH TSEPRDLNSV
310 320 330 340 350
NCDELGPLPP GWEVRSTVSG RIYFVDHNNR TTQFTDPRLH HIMNHQCQLK
360 370 380 390 400
EPSQPLPLPS EGSLEDEELP AQRYERDLVQ KLKVLRHELS LQQPQAGHCR
410 420 430 440 450
IEVSREEIFE ESYRQIMKMR PKDLKKRLMV KFRGEEGLDY GGVAREWLYL
460 470 480 490 500
LCHEMLNPYY GLFQYSTDNI YMLQINPDSS INPDHLSYFH FVGRIMGLAV
510 520 530 540 550
FHGHYINGGF TVPFYKQLLG KPIQLSDLES VDPELHKSLV WILENDITPV
560 570 580 590 600
LDHTFCVEHN AFGRILQHEL KPNGRNVPVT EENKKEYVRL YVNWRFMRGI
610 620 630 640 650
EAQFLALQKG FNELIPQHLL KPFDQKELEL IIGGLDKIDL NDWKSNTRLK
660 670 680 690 700
HCVADSNIVR WFWQAVETFD EERRARLLQF VTGSTRVPLQ GFKALQGSTG
710 720 730 740 750
AAGPRLFTIH LIDANTDNLP KAHTCFNRID IPPYESYEKL YEKLLTAVEE

TCGFAVE
Length:757
Mass (Da):86,114
Last modified:December 13, 2001 - v2
Checksum:i89A171CFC47B40E9
GO
Isoform Short (identifier: Q9HCE7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     269-294: Missing.

Show »
Length:731
Mass (Da):83,440
Checksum:iF106E00CA3C210AA
GO

Sequence cautioni

The sequence BAB13451 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti447W → G in AAI44415 (PubMed:15489334).Curated1
Sequence conflicti697 – 699Missing in AAI36805 (PubMed:15489334).Curated3
Sequence conflicti697 – 699Missing in AAI44415 (PubMed:15489334).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052959466S → Y. Corresponds to variant dbSNP:rs13246077Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006812269 – 294Missing in isoform Short. 2 PublicationsAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046845 mRNA Translation: BAB13451.1 Different initiation.
AC004893 Genomic DNA Translation: AAC62434.1
AF464850 mRNA Translation: AAM90910.1
AC073468 Genomic DNA No translation available.
AC114500 Genomic DNA No translation available.
CH236956 Genomic DNA Translation: EAL23885.1
CH236956 Genomic DNA Translation: EAL23886.1
CH471091 Genomic DNA Translation: EAW76687.1
CH471091 Genomic DNA Translation: EAW76688.1
BC136804 mRNA Translation: AAI36805.1
BC144414 mRNA Translation: AAI44415.1
BC152468 mRNA Translation: AAI52469.1
AF199364 mRNA Translation: AAF08298.2
CCDSiCCDS34689.1 [Q9HCE7-2]
CCDS34690.1 [Q9HCE7-1]
RefSeqiNP_001186776.1, NM_001199847.1
NP_065162.1, NM_020429.2 [Q9HCE7-1]
NP_851994.1, NM_181349.2 [Q9HCE7-2]
UniGeneiHs.189329

Genome annotation databases

EnsembliENST00000361125; ENSP00000354621; ENSG00000198742 [Q9HCE7-1]
ENST00000361368; ENSP00000355326; ENSG00000198742 [Q9HCE7-2]
ENST00000638461; ENSP00000491036; ENSG00000284126 [Q9HCE7-2]
ENST00000638647; ENSP00000492201; ENSG00000284126 [Q9HCE7-1]
GeneIDi57154
KEGGihsa:57154
UCSCiuc003upu.3 human [Q9HCE7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046845 mRNA Translation: BAB13451.1 Different initiation.
AC004893 Genomic DNA Translation: AAC62434.1
AF464850 mRNA Translation: AAM90910.1
AC073468 Genomic DNA No translation available.
AC114500 Genomic DNA No translation available.
CH236956 Genomic DNA Translation: EAL23885.1
CH236956 Genomic DNA Translation: EAL23886.1
CH471091 Genomic DNA Translation: EAW76687.1
CH471091 Genomic DNA Translation: EAW76688.1
BC136804 mRNA Translation: AAI36805.1
BC144414 mRNA Translation: AAI44415.1
BC152468 mRNA Translation: AAI52469.1
AF199364 mRNA Translation: AAF08298.2
CCDSiCCDS34689.1 [Q9HCE7-2]
CCDS34690.1 [Q9HCE7-1]
RefSeqiNP_001186776.1, NM_001199847.1
NP_065162.1, NM_020429.2 [Q9HCE7-1]
NP_851994.1, NM_181349.2 [Q9HCE7-2]
UniGeneiHs.189329

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LAZNMR-A235-267[»]
2LB0NMR-A235-267[»]
2LB1NMR-A305-340[»]
2LTXNMR-A306-340[»]
3PYCX-ray1.96A13-140[»]
ProteinModelPortaliQ9HCE7
SMRiQ9HCE7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121411, 416 interactors
CORUMiQ9HCE7
DIPiDIP-36709N
IntActiQ9HCE7, 25 interactors
MINTiQ9HCE7
STRINGi9606.ENSP00000354621

Chemistry databases

ChEMBLiCHEMBL3879859

PTM databases

iPTMnetiQ9HCE7
PhosphoSitePlusiQ9HCE7

Polymorphism and mutation databases

BioMutaiSMURF1
DMDMi17865625

Proteomic databases

EPDiQ9HCE7
MaxQBiQ9HCE7
PaxDbiQ9HCE7
PeptideAtlasiQ9HCE7
PRIDEiQ9HCE7
ProteomicsDBi81693
81694 [Q9HCE7-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361125; ENSP00000354621; ENSG00000198742 [Q9HCE7-1]
ENST00000361368; ENSP00000355326; ENSG00000198742 [Q9HCE7-2]
ENST00000638461; ENSP00000491036; ENSG00000284126 [Q9HCE7-2]
ENST00000638647; ENSP00000492201; ENSG00000284126 [Q9HCE7-1]
GeneIDi57154
KEGGihsa:57154
UCSCiuc003upu.3 human [Q9HCE7-1]

Organism-specific databases

CTDi57154
DisGeNETi57154
EuPathDBiHostDB:ENSG00000198742.9
GeneCardsiSMURF1
HGNCiHGNC:16807 SMURF1
HPAiHPA055245
MIMi605568 gene
neXtProtiNX_Q9HCE7
OpenTargetsiENSG00000198742
PharmGKBiPA134987175
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208451
HOVERGENiHBG004134
InParanoidiQ9HCE7
KOiK04678
OMAiCKLNPTD
OrthoDBiEOG091G011S
PhylomeDBiQ9HCE7
TreeFamiTF323658

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi2.3.2.B9 2681
6.3.2.19 2681
ReactomeiR-HSA-201451 Signaling by BMP
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-5632684 Hedgehog 'on' state
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-8941858 Regulation of RUNX3 expression and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9HCE7
SIGNORiQ9HCE7

Miscellaneous databases

ChiTaRSiSMURF1 human
EvolutionaryTraceiQ9HCE7
GeneWikiiSMURF1
GenomeRNAii57154
PROiPR:Q9HCE7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198742 Expressed in 201 organ(s), highest expression level in testis
CleanExiHS_SMURF1
GenevisibleiQ9HCE7 HS

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 2 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, 2 hits
PIRSFiPIRSF001569 E3_ub_ligase_SMURF1, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 2 hits
SUPFAMiSSF51045 SSF51045, 2 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, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiSMUF1_HUMAN
AccessioniPrimary (citable) accession number: Q9HCE7
Secondary accession number(s): A4D279
, B7ZMB6, B9EGV3, O75853, Q547Q3, Q9UJT8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 13, 2001
Last sequence update: December 13, 2001
Last modified: November 7, 2018
This is version 178 of the entry and version 2 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again