Human Gene SMURF1 (ENST00000361125.1) from GENCODE V41
  Description: Homo sapiens SMAD specific E3 ubiquitin protein ligase 1 (SMURF1), transcript variant 1, mRNA. (from RefSeq NM_020429)
RefSeq Summary (NM_020429): 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: ENST00000361125.1
Gencode Gene: ENSG00000198742.10
Transcript (Including UTRs)
   Position: hg38 chr7:99,027,441-99,144,100 Size: 116,660 Total Exon Count: 19 Strand: -
Coding Region
   Position: hg38 chr7:99,030,584-99,143,780 Size: 113,197 Coding Exon Count: 19 

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 (chr7:99,027,441-99,144,100)mRNA (may differ from genome)Protein (757 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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GencodeGeneCardsHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: SMUF1_HUMAN
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 -197.30320-0.617 Picture PostScript Text
3' UTR -1012.103143-0.322 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
2LAZ - NMR MuPIT 2LB0 - NMR MuPIT 2LB1 - NMR MuPIT 3PYC - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9HCE7
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-  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 BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  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, KIAA1625, NM_020429, O75853, Q547Q3, Q9HCE7, Q9UJT8, SMUF1_HUMAN, uc003upu.1, uc003upu.2, uc003upu.3
UCSC ID: ENST00000361125.1
RefSeq Accession: NM_020429
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.