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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: -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
View the complete GO annotation on QuickGO ...

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 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 localization to plasma membrane Source: ParkinsonsUK-UCL
  • protein polyubiquitination Source: UniProtKB
  • protein targeting to vacuole involved in autophagy Source: ParkinsonsUK-UCL
  • protein ubiquitination Source: BHF-UCL
  • receptor catabolic process Source: BHF-UCL
  • substrate localization to autophagosome Source: ParkinsonsUK-UCL
  • transforming growth factor beta receptor signaling pathway Source: Reactome
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
  • ubiquitin-dependent SMAD protein catabolic process Source: BHF-UCL
  • Wnt signaling pathway, planar cell polarity pathway Source: Reactome
View the complete GO annotation on QuickGO ...

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
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
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

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

  • I-SMAD binding Source: BHF-UCL
  • R-SMAD binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi121411, 415 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
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
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

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: May 23, 2018
This is version 173 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

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