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UniProtKB - Q9HCE7 (SMUF1_HUMAN)

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Protein

E3 ubiquitin-protein ligase SMURF1

Gene

SMURF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

GO - Biological processi

  • BMP signaling pathway Source: UniProtKB
  • cell differentiation Source: UniProtKB
  • ectoderm development Source: UniProtKB
  • engulfment of target by autophagosome Source: ParkinsonsUK-UCL
  • negative regulation of BMP signaling pathway Source: BHF-UCL
  • negative regulation of ossification Source: Ensembl
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization Source: Ensembl
  • positive regulation of dendrite extension Source: UniProtKB
  • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: CACAO
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • protein export from nucleus Source: BHF-UCL
  • protein localization to cell surface Source: BHF-UCL
  • protein polyubiquitination Source: UniProtKB
  • protein targeting to plasma membrane Source: ParkinsonsUK-UCL
  • protein targeting to vacuole involved in autophagy Source: ParkinsonsUK-UCL
  • protein ubiquitination Source: BHF-UCL
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • receptor catabolic process Source: BHF-UCL
  • substrate localization to autophagosome Source: ParkinsonsUK-UCL
  • transforming growth factor beta receptor signaling pathway Source: Reactome
  • ubiquitin-dependent SMAD protein catabolic process Source: BHF-UCL
  • Wnt signaling pathway, planar cell polarity pathway Source: Reactome
Complete GO annotation...

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-8941858. Regulation of RUNX3 expression and activity.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9HCE7.
SIGNORiQ9HCE7.
UniPathwayiUPA00143.

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000198742.9.
HGNCiHGNC:16807. SMURF1.

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.

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.

PTM databases

iPTMnetiQ9HCE7.
PhosphoSitePlusiQ9HCE7.

Expressioni

Tissue specificityi

Expressed in melanocytes (PubMed:23999003).1 Publication

Gene expression databases

BgeeiENSG00000198742.
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

Show more details

GO - Molecular functioni

  • activin binding Source: BHF-UCL
  • I-SMAD binding Source: BHF-UCL
  • R-SMAD binding Source: BHF-UCL
Complete GO annotation...

Protein-protein interaction databases

BioGridi121411. 414 interactors.
CORUMiQ9HCE7.
DIPiDIP-36709N.
IntActiQ9HCE7. 24 interactors.
MINTiMINT-102628.
STRINGi9606.ENSP00000354621.

Structurei

Secondary structure

1757
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 24Combined sources12
Beta strandi36 – 42Combined sources7
Turni43 – 45Combined sources3
Beta strandi48 – 50Combined sources3
Beta strandi61 – 71Combined sources11
Beta strandi76 – 82Combined sources7
Helixi83 – 85Combined sources3
Turni90 – 93Combined sources4
Beta strandi94 – 100Combined sources7
Helixi102 – 108Combined sources7
Beta strandi114 – 117Combined sources4
Beta strandi131 – 139Combined sources9
Beta strandi241 – 245Combined sources5
Turni246 – 248Combined sources3
Beta strandi249 – 254Combined sources6
Turni255 – 258Combined sources4
Beta strandi259 – 263Combined sources5
Beta strandi312 – 317Combined sources6
Turni318 – 320Combined sources3
Beta strandi321 – 326Combined sources6
Turni327 – 330Combined sources4
Beta strandi331 – 334Combined sources4

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...

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.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT_dom.
IPR001202. WW_dom.
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.
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. 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

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: September 27, 2017
This is version 166 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 chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references