BioPAX pathway converted from "SMAD7 binds to SMURF1" in the Reactome database.SMAD7 binds to SMURF1

SMAD7 binds to SMURF1

SMAD7 binds to SMURF1 in the nucleus (Ebisawa et al. 2001, Tajima et al. 2003). SMURF1 domains WW1 and WW2, highly similar to WW2 and WW3 domains of SMURF2, are involved in SMAD7 binding. SMURF1 has two splicing isoforms. The shorter splicing isoform of SMURF1 has an inter-WW domain linker of the same length as the WW2-WW3 domain linker of SMURF2. The longer isoform of SMURF1 has a longer WW1-WW2 domain linker, resulting in decreased affinity of the longer SMURF1 isoform for SMAD7 (Chong et al. 2010). This is based on experiments with recombinant mouse Smad7 and recombinant human SMURF1.

Authored: Heldin, CH, Moustakas, A, Huminiecki, L, Jassal, B, 2006-02-02Reviewed: Huang, Tao, 2012-05-14Edited: Jassal, B, 2012-04-10

Reactome DB_ID: 178197

nucleoplasmGO0005654

UniProt:O15105 SMAD7

SMAD7

MADH7MADH8SMAD7FUNCTION Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.SUBUNIT Interacts with WWP1 (By similarity). Interacts with COPS5. Interacts with NEDD4L. Interacts with STAMBP. Interacts with RNF111, AXIN1 and AXIN2. Interacts with PPP1R15A. Interacts (via MH2 domain) with EP300. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7 recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its degradation. Interacts with PDPK1 (via PH domain).TISSUE SPECIFICITY Ubiquitous with higher expression in the lung and vascular endothelium.INDUCTION By TGFB1.PTM Phosphorylation on Ser-249 does not affect its stability, nuclear localization or inhibitory function in TGFB signaling; however it affects its ability to regulate transcription (By similarity). Phosphorylated by PDPK1.PTM Ubiquitinated by WWP1 (By similarity). Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation (PubMed:14657019, PubMed:16601693). In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation (PubMed:11278251).PTM Acetylation prevents ubiquitination and degradation mediated by SMURF1.SIMILARITY Belongs to the dwarfin/SMAD family.

Reactomehttp://www.reactome.orgHomo sapiens

NCBI Taxonomy9606UniProtO15105

Chain Coordinates

EQUAL

426

EQUAL

Reactome DB_ID: 3004548

UniProt:Q9HCE7 SMURF1

SMURF1

KIAA1625SMURF1FUNCTION 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).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. Interacts with MAVS; the interaction is mediated by NDFIP1 (PubMed:23087404).TISSUE SPECIFICITY Expressed in melanocytes (PubMed:23999003).DOMAIN The C2 domain mediates membrane localization and substrate selection.PTM 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.

UniProtQ9HCE7

EQUAL

757

EQUAL

Reactome DB_ID: 2167913

SMAD7:SMURF1 [nucleoplasm]

SMAD7:SMURF1

Reactome DB_ID: 178197

EQUAL

426

EQUAL

Reactome DB_ID: 3004548

EQUAL

757

EQUAL

Reactome Database ID Release 712167913Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167913ReactomeR-HSA-2167913

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2167913.1Reactome Database ID Release 712167917Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167917ReactomeR-HSA-2167917

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2167917.120937913Pubmed2010Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificityChong, PALin, HWrana, JLForman-Kay, JDProc Natl Acad Sci U S A 107:18404-911278251Pubmed2001Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradationEbisawa, TFukuchi, MMurakami, GChiba, TTanaka, KImamura, TMiyazono, KJ Biol Chem 276:12477-8012519765Pubmed2003Chromosomal region maintenance 1 (CRM1)-dependent nuclear export of Smad ubiquitin regulatory factor 1 (Smurf1) is essential for negative regulation of transforming growth factor-beta signaling by Smad7Tajima, YGoto, KYoshida, MShinomiya, KSekimoto, TYoneda, YMiyazono, KImamura, TJ Biol Chem 278:10716-21