Human Gene SMURF1 (ENST00000361368.7) from GENCODE V41
  Description: Homo sapiens SMAD specific E3 ubiquitin protein ligase 1 (SMURF1), transcript variant 2, mRNA. (from RefSeq NM_181349)
RefSeq Summary (NM_181349): This gene encodes a ubiquitin ligase that is specific for receptor-regulated SMAD proteins in the bone morphogenetic protein (BMP) pathway. This protein plays a key roll in the regulation of cell motility, cell signalling, and cell polarity. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2010].
Gencode Transcript: ENST00000361368.7
Gencode Gene: ENSG00000198742.10
Transcript (Including UTRs)
   Position: hg38 chr7:99,027,440-99,144,108 Size: 116,669 Total Exon Count: 18 Strand: -
Coding Region
   Position: hg38 chr7:99,030,584-99,143,780 Size: 113,197 Coding Exon Count: 18 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2022-05-14 09:57:26

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr7:99,027,440-99,144,108)mRNA (may differ from genome)Protein (731 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSCGAPEnsemblEntrez GeneExonPrimer

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase SMURF1; Short=hSMURF1; EC=6.3.2.-; AltName: Full=SMAD ubiquitination regulatory factor 1; AltName: Full=SMAD-specific E3 ubiquitin-protein ligase 1;
FUNCTION: 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.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: 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.
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side.
DOMAIN: The C2 domain mediates membrane localization and substrate selection.
PTM: 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.
SIMILARITY: Contains 1 C2 domain.
SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.
SIMILARITY: Contains 2 WW domains.
SEQUENCE CAUTION: Sequence=BAB13451.1; Type=Erroneous initiation;

-  MalaCards Disease Associations
  MalaCards Gene Search: SMURF1
Diseases sorted by gene-association score: cerebral cavernous malformations-2 (1), colonic benign neoplasm (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 23.35 RPKM in Testis
Total median expression: 476.26 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -200.70328-0.612 Picture PostScript Text
3' UTR -1012.103144-0.322 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000008 - C2_Ca-dep
IPR008973 - C2_Ca/lipid-bd_dom_CaLB
IPR018029 - C2_membr_targeting
IPR024928 - E3_ub_ligase_SMURF1
IPR000569 - HECT
IPR001202 - WW_Rsp5_WWP

Pfam Domains:
PF00168 - C2 domain
PF00632 - HECT-domain (ubiquitin-transferase)
PF00397 - WW domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

ModBase Predicted Comparative 3D Structure on Q9HCE7
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein SequenceProtein SequenceProtein Sequence  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0005543 phospholipid binding
GO:0016740 transferase activity
GO:0048185 activin binding
GO:0061630 ubiquitin protein ligase activity
GO:0070411 I-SMAD binding
GO:0070412 R-SMAD binding

Biological Process:
GO:0000209 protein polyubiquitination
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0006611 protein export from nucleus
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007398 ectoderm development
GO:0016567 protein ubiquitination
GO:0030154 cell differentiation
GO:0030279 negative regulation of ossification
GO:0030509 BMP signaling pathway
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030514 negative regulation of BMP signaling pathway
GO:0030579 ubiquitin-dependent SMAD protein catabolic process
GO:0032801 receptor catabolic process
GO:0034394 protein localization to cell surface
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0060071 Wnt signaling pathway, planar cell polarity pathway
GO:0061734 parkin-mediated mitophagy in response to mitochondrial depolarization
GO:0061736 engulfment of target by autophagosome
GO:0061753 substrate localization to autophagosome
GO:0071211 protein targeting to vacuole involved in autophagy
GO:0072659 protein localization to plasma membrane
GO:1903861 positive regulation of dendrite extension
GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Cellular Component:
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0030424 axon
GO:0043025 neuronal cell body
GO:0070062 extracellular exosome
GO:0005739 mitochondrion

-  Descriptions from all associated GenBank mRNAs
  BC152468 - Homo sapiens SMAD specific E3 ubiquitin protein ligase 1, mRNA (cDNA clone MGC:176726 IMAGE:8862605), complete cds.
AB046845 - Homo sapiens KIAA1625 mRNA for KIAA1625 protein.
BC136804 - Homo sapiens SMAD specific E3 ubiquitin protein ligase 1, mRNA (cDNA clone MGC:168417 IMAGE:9020794), complete cds.
BC144414 - Homo sapiens SMAD specific E3 ubiquitin protein ligase 1, mRNA (cDNA clone MGC:177952 IMAGE:9052935), complete cds.
AF464850 - Homo sapiens Smad-ubiquitin E3 ligase Smurf1-beta mRNA, complete cds; alternatively spliced.
AF199364 - Homo sapiens E3 ubiquitin ligase SMURF1 mRNA, partial cds.
AB385491 - Synthetic construct DNA, clone: pF1KA1625, Homo sapiens SMURF1 gene for E3 ubiquitin-protein ligase SMURF1, complete cds, without stop codon, in Flexi system.
AL834242 - Homo sapiens mRNA; cDNA DKFZp564H223 (from clone DKFZp564H223).
AK126471 - Homo sapiens cDNA FLJ44507 fis, clone UTERU3001571.
AL833673 - Homo sapiens mRNA; cDNA DKFZp667N0521 (from clone DKFZp667N0521).
AY007164 - Homo sapiens clone CDABP0157 mRNA sequence.
BC008574 - Homo sapiens SMAD specific E3 ubiquitin protein ligase 1, mRNA (cDNA clone IMAGE:4338957).
AK057024 - Homo sapiens cDNA FLJ32462 fis, clone SKNMC1000229.
JD480258 - Sequence 461282 from Patent EP1572962.
JD504970 - Sequence 485994 from Patent EP1572962.
JD081083 - Sequence 62107 from Patent EP1572962.
JD559445 - Sequence 540469 from Patent EP1572962.
JD100716 - Sequence 81740 from Patent EP1572962.
JD344301 - Sequence 325325 from Patent EP1572962.
JD433899 - Sequence 414923 from Patent EP1572962.
JD515668 - Sequence 496692 from Patent EP1572962.
JD273796 - Sequence 254820 from Patent EP1572962.
JD216688 - Sequence 197712 from Patent EP1572962.
JD378120 - Sequence 359144 from Patent EP1572962.
JD042561 - Sequence 23585 from Patent EP1572962.
JD409654 - Sequence 390678 from Patent EP1572962.
JD464623 - Sequence 445647 from Patent EP1572962.
DQ584827 - Homo sapiens piRNA piR-51939, complete sequence.
JD526437 - Sequence 507461 from Patent EP1572962.
JD536333 - Sequence 517357 from Patent EP1572962.
JD157553 - Sequence 138577 from Patent EP1572962.
JD272524 - Sequence 253548 from Patent EP1572962.
JD231207 - Sequence 212231 from Patent EP1572962.
JD466887 - Sequence 447911 from Patent EP1572962.
JD534570 - Sequence 515594 from Patent EP1572962.
JD443810 - Sequence 424834 from Patent EP1572962.
JD559568 - Sequence 540592 from Patent EP1572962.
JD330456 - Sequence 311480 from Patent EP1572962.
JD279236 - Sequence 260260 from Patent EP1572962.
JD184542 - Sequence 165566 from Patent EP1572962.
JD408262 - Sequence 389286 from Patent EP1572962.
JD510282 - Sequence 491306 from Patent EP1572962.
JD160584 - Sequence 141608 from Patent EP1572962.
JD500640 - Sequence 481664 from Patent EP1572962.
JD386445 - Sequence 367469 from Patent EP1572962.
JD348786 - Sequence 329810 from Patent EP1572962.
JD344905 - Sequence 325929 from Patent EP1572962.
JD423881 - Sequence 404905 from Patent EP1572962.
JD285151 - Sequence 266175 from Patent EP1572962.
JD139591 - Sequence 120615 from Patent EP1572962.
DQ590134 - Homo sapiens piRNA piR-57246, complete sequence.
JD375916 - Sequence 356940 from Patent EP1572962.
JD077468 - Sequence 58492 from Patent EP1572962.
JD295090 - Sequence 276114 from Patent EP1572962.
JD423380 - Sequence 404404 from Patent EP1572962.
JD110333 - Sequence 91357 from Patent EP1572962.
JD355292 - Sequence 336316 from Patent EP1572962.
JD090079 - Sequence 71103 from Patent EP1572962.
JD433766 - Sequence 414790 from Patent EP1572962.
JD307416 - Sequence 288440 from Patent EP1572962.
JD219374 - Sequence 200398 from Patent EP1572962.
JD540514 - Sequence 521538 from Patent EP1572962.
JD564047 - Sequence 545071 from Patent EP1572962.
JD127307 - Sequence 108331 from Patent EP1572962.
JD370483 - Sequence 351507 from Patent EP1572962.
JD538683 - Sequence 519707 from Patent EP1572962.
JD412989 - Sequence 394013 from Patent EP1572962.
JD045086 - Sequence 26110 from Patent EP1572962.
JD181823 - Sequence 162847 from Patent EP1572962.
JD267111 - Sequence 248135 from Patent EP1572962.
JD501333 - Sequence 482357 from Patent EP1572962.
JD509842 - Sequence 490866 from Patent EP1572962.
JD077028 - Sequence 58052 from Patent EP1572962.
JD038696 - Sequence 19720 from Patent EP1572962.
JD162287 - Sequence 143311 from Patent EP1572962.
CQ873712 - Sequence 131 from Patent WO2004076622.
DD413549 - Regulation of Mammalian Cells.
JD141614 - Sequence 122638 from Patent EP1572962.
JD141724 - Sequence 122748 from Patent EP1572962.
JD472120 - Sequence 453144 from Patent EP1572962.
JD141723 - Sequence 122747 from Patent EP1572962.
JD222601 - Sequence 203625 from Patent EP1572962.
JD279017 - Sequence 260041 from Patent EP1572962.
JD223389 - Sequence 204413 from Patent EP1572962.
JD344320 - Sequence 325344 from Patent EP1572962.
JD266574 - Sequence 247598 from Patent EP1572962.
JD395197 - Sequence 376221 from Patent EP1572962.
JD226887 - Sequence 207911 from Patent EP1572962.
JD211090 - Sequence 192114 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04120 - Ubiquitin mediated proteolysis
hsa04144 - Endocytosis
hsa04350 - TGF-beta signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_EfpPathway - Estrogen-responsive protein Efp controls cell cycle and breast tumors growth

Reactome (by CSHL, EBI, and GO)

Protein Q9HCE7 (Reactome details) participates in the following event(s):

R-HSA-2160932 SMURF1 binds phosphorylated PARD6A
R-HSA-9009401 RUNX2 binds SMURF1
R-NUL-2176396 SMURF1 ubiquitinates Smad7 and phosphorylated TGFBR1
R-HSA-9009403 SMURF1 polyubiquitinates RUNX2
R-HSA-2167917 SMAD7 binds to SMURF1
R-NUL-2169004 Smad7 binds SMURF1
R-HSA-2160935 SMURF1 ubiquitinates RHOA
R-HSA-178215 SMAD7:SMURF1 complex is exported to the cytosol
R-NUL-2169036 Smad7:SMURF1 binds phosphorylated TGFBR1
R-NUL-2169016 Smad7:SMURF1 complex translocates to the cytosol
R-HSA-4608854 SMURF1/2 are recruited to the DVL2:PARD6A complex
R-HSA-5632646 SMURF1/2 bind PTCH1
R-HSA-5635865 SMURF1/2 dissociates from ub-PTCH1
R-HSA-2169050 SMURFs/NEDD4L ubiquitinate phosphorylated TGFBR1 and SMAD7
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-2167924 SMAD7:SMURF1 complex binds XPO1 (CRM1)
R-NUL-2169012 Smad7:SMURF1 complex binds XPO1 (CRM1)
R-HSA-201821 I-Smad binds to type I receptor, preventing Smad1/5/8 from being activated
R-HSA-5632648 SMURF1/2 ubiquitinates PTCH1
R-HSA-178218 SMAD7:SMURF complex binds to phosphorylated TGFBR1
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-8952419 SMURFs ubiquitinate RUNX3
R-HSA-4608852 SMURF1/2 ubiquitinates PRICKLE1
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-5632684 Hedgehog 'on' state
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-170834 Signaling by TGF-beta Receptor Complex
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-201451 Signaling by BMP
R-HSA-4086400 PCP/CE pathway
R-HSA-5358351 Signaling by Hedgehog
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-212436 Generic Transcription Pathway
R-HSA-8941858 Regulation of RUNX3 expression and activity
R-HSA-3858494 Beta-catenin independent WNT signaling
R-HSA-162582 Signal Transduction
R-HSA-1280218 Adaptive Immune System
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-8878159 Transcriptional regulation by RUNX3
R-HSA-195721 Signaling by WNT
R-HSA-168256 Immune System
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A4D279, B7ZMB6, B9EGV3, ENST00000361368.1, ENST00000361368.2, ENST00000361368.3, ENST00000361368.4, ENST00000361368.5, ENST00000361368.6, KIAA1625, NM_181349, O75853, Q547Q3, Q9HCE7, Q9UJT8, SMUF1_HUMAN, uc003upv.1, uc003upv.2, uc003upv.3, uc003upv.4
UCSC ID: ENST00000361368.7
RefSeq Accession: NM_181349
Protein: Q9HCE7 (aka SMUF1_HUMAN or SUF1_HUMAN)
CCDS: CCDS34689.1, CCDS34690.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.