SMURF1

E3 ubiquitin-protein ligase SMURF1 is an enzyme that in humans is encoded by the SMURF1 gene.[5][6]

SMURF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LAZ, 2LB0, 2LB1, 2LTX, 3PYC
Identifiers
Aliases	SMURF1, SMAD specific E3 ubiquitin protein ligase 1
External IDs	OMIM: 605568 MGI: 1923038 HomoloGene: 10712 GeneCards: SMURF1
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q22.1 Start 99,027,438 bp[1] End 99,144,100 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 G2 Start 144,876,495 bp[2] End 144,965,847 bp[2]
Gene ontology Molecular function • R-SMAD binding • I-SMAD binding • activin binding • GO:0001948 protein binding • phospholipid binding • transferase activity • ubiquitin-protein transferase activity • GO:1904264, GO:1904822, GO:0090622, GO:0090302 ubiquitin protein ligase activity Cellular component • cytoplasm • cytosol • membrane • cell membrane • nucleoplasm • axon • neuronal cell body • mitochondrion • extracellular exosome Biological process • cell differentiation • engulfment of target by autophagosome • ectoderm development • protein polyubiquitination • BMP signaling pathway • receptor catabolic process • ubiquitin-dependent SMAD protein catabolic process • negative regulation of ossification • protein localization to cell surface • protein targeting to vacuole involved in autophagy • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • protein ubiquitination • protein export from nucleus • positive regulation of dendrite extension • proteasome-mediated ubiquitin-dependent protein catabolic process • negative regulation of transforming growth factor beta receptor signaling pathway • transforming growth factor beta receptor signaling pathway • Wnt signaling pathway, planar cell polarity pathway • parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization • substrate localization to autophagosome • ubiquitin-dependent protein catabolic process • negative regulation of BMP signaling pathway • protein localization to plasma membrane • positive regulation of protein catabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57154	75788
Ensembl	ENSG00000284126 ENSG00000198742	ENSMUSG00000038780
UniProt	Q9HCE7	Q9CUN6
RefSeq (mRNA)	NM_001199847 NM_020429 NM_181349	NM_001038627 NM_029438
RefSeq (protein)	NP_001186776 NP_065162 NP_851994	NP_001033716 NP_083714
Location (UCSC)	Chr 7: 99.03 – 99.14 Mb	Chr 5: 144.88 – 144.97 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a ubiquitin ligase that is specific for receptor-regulated SMAD proteins in the bone morphogenetic protein (BMP) pathway. A similar protein in Xenopus is involved in embryonic pattern formation. Alternative splicing results in multiple transcript variants encoding different isoforms. An additional transcript variant has been identified, but its full length sequence has not been determined.[6]

Interactions

SMURF1 has been shown to interact with:

• ARHGEF9,[7]
• PLEKHO1,[8] and
• SMURF2.[9]

References

1. ENSG00000198742 GRCh38: Ensembl release 89: ENSG00000284126, ENSG00000198742 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038780 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH (Sep 1999). "A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation". Nature. 400 (6745): 687–93. doi:10.1038/23293. PMID 10458166.
6. "Entrez Gene: SMURF1 SMAD specific E3 ubiquitin protein ligase 1".
7. Yamaguchi K, Ohara O, Ando A, Nagase T (Apr 2008). "Smurf1 directly targets hPEM-2, a GEF for Cdc42, via a novel combination of protein interaction modules in the ubiquitin-proteasome pathway". Biol. Chem. 389 (4): 405–13. doi:10.1515/BC.2008.036. PMID 18208356.
8. Lu K, Yin X, Weng T, Xi S, Li L, Xing G, Cheng X, Yang X, Zhang L, He F (Aug 2008). "Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1". Nat. Cell Biol. 10 (8): 994–1002. doi:10.1038/ncb1760. PMID 18641638.
9. Fukunaga E, Inoue Y, Komiya S, Horiguchi K, Goto K, Saitoh M, Miyazawa K, Koinuma D, Hanyu A, Imamura T (Dec 2008). "Smurf2 induces ubiquitin-dependent degradation of Smurf1 to prevent migration of breast cancer cells". J. Biol. Chem. 283 (51): 35660–7. doi:10.1074/jbc.M710496200. PMID 18927080.

Further reading

• Wrana JL, Attisano L (2000). "The Smad pathway". Cytokine Growth Factor Rev. 11 (1–2): 5–13. doi:10.1016/S1359-6101(99)00024-6. PMID 10708948.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O (2001). "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (4): 273–81. doi:10.1093/dnares/7.4.271. PMID 10997877.
• Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K (2001). "Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation". J. Biol. Chem. 276 (16): 12477–80. doi:10.1074/jbc.C100008200. PMID 11278251.
• Suzuki C, Murakami G, Fukuchi M, Shimanuki T, Shikauchi Y, Imamura T, Miyazono K (2002). "Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane". J. Biol. Chem. 277 (42): 39919–25. doi:10.1074/jbc.M201901200. PMID 12151385.
• Tajima Y, Goto K, Yoshida M, Shinomiya K, Sekimoto T, Yoneda Y, Miyazono K, Imamura T (2003). "Chromosomal 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 Smad7". J. Biol. Chem. 278 (12): 10716–21. doi:10.1074/jbc.M212663200. PMID 12519765.
• Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K (2004). "Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7". EMBO J. 22 (24): 6458–70. doi:10.1093/emboj/cdg632. PMC 291827. PMID 14657019.
• Wang HR, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, Thomsen GH, Wrana JL (2003). "Regulation of cell polarity and protrusion formation by targeting RhoA for degradation". Science. 302 (5651): 1775–9. doi:10.1126/science.1090772. PMID 14657501.
• Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K (2004). "Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts". J. Clin. Invest. 113 (2): 253–64. doi:10.1172/JCI16269. PMC 310747. PMID 14722617.
• Jin YH, Jeon EJ, Li QL, Lee YH, Choi JK, Kim WJ, Lee KY, Bae SC (2004). "Transforming growth factor-beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation". J. Biol. Chem. 279 (28): 29409–17. doi:10.1074/jbc.M313120200. PMID 15138260.
• Shearwin-Whyatt LM, Brown DL, Wylie FG, Stow JL, Kumar S (2005). "N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking". J. Cell Sci. 117 (Pt 16): 3679–89. doi:10.1242/jcs.01212. PMID 15252135.
• Bryan B, Cai Y, Wrighton K, Wu G, Feng XH, Liu M (2005). "Ubiquitination of RhoA by Smurf1 promotes neurite outgrowth". FEBS Lett. 579 (5): 1015–9. doi:10.1016/j.febslet.2004.12.074. PMID 15710384.
• Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL (2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science. 307 (5715): 1621–5. doi:10.1126/science.1105776. PMID 15761153.

External links

• Overview of all the structural information available in the PDB for UniProt: Q9HCE7 (E3 ubiquitin-protein ligase SMURF1) at the PDBe-KB.