UniProtKB - Q9HCE7 (SMUF1_HUMAN)
(max 400 entries)x
Your basket is currently empty. i
Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)
Protein
E3 ubiquitin-protein ligase SMURF1
Gene
SMURF1
Organism
Homo sapiens (Human)
Status
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
: protein ubiquitination Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 725 | Glycyl thioester intermediate | 1 |
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
- 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 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
- 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
Keywordsi
Molecular function | Transferase |
Biological process | Differentiation, Ubl conjugation pathway |
Enzyme and pathway databases
BRENDAi | 2.3.2.B9. 2681. 6.3.2.19. 2681. |
Reactomei | R-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. |
SignaLinki | Q9HCE7. |
SIGNORi | Q9HCE7. |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000198742.9. |
HGNCi | HGNC:16807. SMURF1. |
MIMi | 605568. gene. |
neXtProti | NX_Q9HCE7. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 28 | K → A: Fails to ubiquitinate RHOA; when associated with A-85. 1 Publication | 1 | |
Mutagenesisi | 85 | K → A: Fails to ubiquitinate RHOA; when associated with A-28. 1 Publication | 1 | |
Mutagenesisi | 350 | K → R: Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-381 and R-381. 1 Publication | 1 | |
Mutagenesisi | 381 | K → 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 Publication | 1 | |
Mutagenesisi | 383 | K → 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 Publication | 1 | |
Mutagenesisi | 725 | C → A: Loss of enzyme activity, without abolishing FBXL15-mediated ubiquitination. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 57154. |
OpenTargetsi | ENSG00000198742. |
PharmGKBi | PA134987175. |
Polymorphism and mutation databases
BioMutai | SMURF1. |
DMDMi | 17865625. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000120326 | 1 – 757 | E3 ubiquitin-protein ligase SMURF1Add BLAST | 757 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 200 | PhosphoserineCombined sources | 1 | |
Cross-linki | 381 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 383 | Glycyl 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 conjugationProteomic databases
EPDi | Q9HCE7. |
MaxQBi | Q9HCE7. |
PaxDbi | Q9HCE7. |
PeptideAtlasi | Q9HCE7. |
PRIDEi | Q9HCE7. |
PTM databases
iPTMneti | Q9HCE7. |
PhosphoSitePlusi | Q9HCE7. |
Expressioni
Tissue specificityi
Expressed in melanocytes (PubMed:23999003).1 Publication
Gene expression databases
Bgeei | ENSG00000198742. |
CleanExi | HS_SMURF1. |
Genevisiblei | Q9HCE7. HS. |
Organism-specific databases
HPAi | HPA055245. |
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
- activin binding Source: BHF-UCL
- I-SMAD binding Source: BHF-UCL
- R-SMAD binding Source: BHF-UCL
Protein-protein interaction databases
BioGridi | 121411. 414 interactors. |
CORUMi | Q9HCE7. |
DIPi | DIP-36709N. |
IntActi | Q9HCE7. 25 interactors. |
MINTi | Q9HCE7. |
STRINGi | 9606.ENSP00000354621. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 13 – 24 | Combined sources | 12 | |
Beta strandi | 36 – 42 | Combined sources | 7 | |
Turni | 43 – 45 | Combined sources | 3 | |
Beta strandi | 48 – 50 | Combined sources | 3 | |
Beta strandi | 61 – 71 | Combined sources | 11 | |
Beta strandi | 76 – 82 | Combined sources | 7 | |
Helixi | 83 – 85 | Combined sources | 3 | |
Turni | 90 – 93 | Combined sources | 4 | |
Beta strandi | 94 – 100 | Combined sources | 7 | |
Helixi | 102 – 108 | Combined sources | 7 | |
Beta strandi | 114 – 117 | Combined sources | 4 | |
Beta strandi | 131 – 139 | Combined sources | 9 | |
Beta strandi | 241 – 245 | Combined sources | 5 | |
Turni | 246 – 248 | Combined sources | 3 | |
Beta strandi | 249 – 254 | Combined sources | 6 | |
Turni | 255 – 258 | Combined sources | 4 | |
Beta strandi | 259 – 263 | Combined sources | 5 | |
Beta strandi | 312 – 317 | Combined sources | 6 | |
Turni | 318 – 320 | Combined sources | 3 | |
Beta strandi | 321 – 326 | Combined sources | 6 | |
Turni | 327 – 330 | Combined sources | 4 | |
Beta strandi | 331 – 334 | Combined sources | 4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2LAZ | NMR | - | A | 235-267 | [»] | |
2LB0 | NMR | - | A | 235-267 | [»] | |
2LB1 | NMR | - | A | 305-340 | [»] | |
2LTX | NMR | - | A | 306-340 | [»] | |
3PYC | X-ray | 1.96 | A | 13-140 | [»] | |
ProteinModelPortali | Q9HCE7. | |||||
SMRi | Q9HCE7. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9HCE7. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 99 | C2PROSITE-ProRule annotationAdd BLAST | 99 | |
Domaini | 234 – 267 | WW 1PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 306 – 339 | WW 2PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 420 – 757 | HECTPROSITE-ProRule annotationAdd BLAST | 338 |
Domaini
The C2 domain mediates membrane localization and substrate selection.1 Publication
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0940. Eukaryota. COG5021. LUCA. |
GeneTreei | ENSGT00760000118966. |
HOGENOMi | HOG000208451. |
HOVERGENi | HBG004134. |
InParanoidi | Q9HCE7. |
KOi | K04678. |
OMAi | CKLNPTD. |
OrthoDBi | EOG091G011S. |
PhylomeDBi | Q9HCE7. |
TreeFami | TF323658. |
Family and domain databases
CDDi | cd00078. HECTc. 1 hit. cd00201. WW. 2 hits. |
Gene3Di | 2.60.40.150. 1 hit. |
InterProi | View 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. |
Pfami | View protein in Pfam PF00168. C2. 1 hit. PF00632. HECT. 1 hit. PF00397. WW. 2 hits. |
PIRSFi | PIRSF001569. E3_ub_ligase_SMURF1. 1 hit. |
SMARTi | View protein in SMART SM00239. C2. 1 hit. SM00119. HECTc. 1 hit. SM00456. WW. 2 hits. |
SUPFAMi | SSF51045. SSF51045. 2 hits. SSF56204. SSF56204. 1 hit. |
PROSITEi | View protein in PROSITE PS50004. C2. 1 hit. PS50237. HECT. 1 hit. PS01159. WW_DOMAIN_1. 1 hit. PS50020. WW_DOMAIN_2. 2 hits. |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative 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.
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
Isoform Short (identifier: Q9HCE7-2) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
269-294: Missing.
Sequence cautioni
The sequence BAB13451 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 447 | W → G in AAI44415 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 697 – 699 | Missing in AAI36805 (PubMed:15489334).Curated | 3 | |
Sequence conflicti | 697 – 699 | Missing in AAI44415 (PubMed:15489334).Curated | 3 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052959 | 466 | S → Y. Corresponds to variant dbSNP:rs13246077Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_006812 | 269 – 294 | Missing in isoform Short. 2 PublicationsAdd BLAST | 26 |
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. |
CCDSi | CCDS34689.1. [Q9HCE7-2] CCDS34690.1. [Q9HCE7-1] |
RefSeqi | NP_001186776.1. NM_001199847.1. NP_065162.1. NM_020429.2. [Q9HCE7-1] NP_851994.1. NM_181349.2. [Q9HCE7-2] |
UniGenei | Hs.189329. |
Genome annotation databases
Ensembli | ENST00000361125; ENSP00000354621; ENSG00000198742. [Q9HCE7-1] ENST00000361368; ENSP00000355326; ENSG00000198742. [Q9HCE7-2] ENST00000638461; ENSP00000491036; ENSG00000284126. [Q9HCE7-2] ENST00000638647; ENSP00000492201; ENSG00000284126. [Q9HCE7-1] |
GeneIDi | 57154. |
KEGGi | hsa:57154. |
UCSCi | uc003upu.3. human. [Q9HCE7-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | SMUF1_HUMAN | |
Accessioni | Q9HCE7Primary (citable) accession number: Q9HCE7 Secondary accession number(s): A4D279 Q9UJT8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 13, 2001 |
Last sequence update: | December 13, 2001 | |
Last modified: | March 28, 2018 | |
This is version 171 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |