SMURF2

SMAD specific E3 ubiquitin protein ligase 2
PDB rendering based on 1zvd.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ZVD​, 2DJY​, 2JQZ​, 2KXQ​, 2LTZ​
Identifiers
Symbols	SMURF2 ; DKFZp686F0270; MGC138150
External IDs	OMIM: 605532 MGI: 1913563 HomoloGene: 41490 GeneCards: SMURF2 Gene
Gene ontology Molecular function • ubiquitin-protein transferase activity • transforming growth factor beta receptor binding • protein binding • ligase activity • identical protein binding • SMAD binding • ubiquitin protein ligase activity Cellular component • ubiquitin ligase complex • nucleus • nucleoplasm • cytoplasm • cytosol • plasma membrane • membrane raft Biological process • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • transcription initiation from RNA polymerase II promoter • ubiquitin-dependent protein catabolic process • transforming growth factor beta receptor signaling pathway • gene expression • regulation of transforming growth factor beta receptor signaling pathway • BMP signaling pathway • negative regulation of transforming growth factor beta receptor signaling pathway • ubiquitin-dependent SMAD protein catabolic process • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • negative regulation of transcription, DNA-templated • positive regulation of canonical Wnt signaling pathway • positive regulation of trophoblast cell migration Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	64750	66313
Ensembl	ENSG00000108854	ENSMUSG00000018363
UniProt	Q9HAU4	A2A5Z6
RefSeq (mRNA)	NM_022739	NM_025481
RefSeq (protein)	NP_073576	NP_079757
Location (UCSC)	Chr 17: 64.54 – 64.66 Mb	Chr 11: 106.82 – 106.92 Mb
PubMed search

E3 ubiquitin-protein ligase SMURF2 is an enzyme that in humans is encoded by the SMURF2 gene.^[1][2]

Interactions

SMURF2 has been shown to interact with:

• Mothers against decapentaplegic homolog 1,^[1]
• Mothers against decapentaplegic homolog 2,^[1][3][4]
• Mothers against decapentaplegic homolog 3,^[1][3][4]
• Mothers against decapentaplegic homolog 7,^[5][6][7]
• SCYE1,^[7]
• SMURF1,^[8] and
• Ubiquitin C.^[7][9]

References

1. Lin X, Liang M, Feng XH (Nov 2000). "Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling". The Journal of Biological Chemistry 275 (47): 36818–22. doi:10.1074/jbc.C000580200. PMID 11016919.
2. "Entrez Gene: SMURF2 SMAD specific E3 ubiquitin protein ligase 2".
3. Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, Wrana JL (Jun 2001). "TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation". Nature Cell Biology 3 (6): 587–95. doi:10.1038/35078562. PMID 11389444.
4. Nakano A, Koinuma D, Miyazawa K, Uchida T, Saitoh M, Kawabata M, Hanai J, Akiyama H, Abe M, Miyazono K, Matsumoto T, Imamura T (Mar 2009). "Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins". The Journal of Biological Chemistry 284 (10): 6109–15. doi:10.1074/jbc.M804659200. PMID 19122240.
5. Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K (Jan 2004). "Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts". The Journal of Clinical Investigation 113 (2): 253–64. doi:10.1172/JCI16269. PMC 310747. PMID 14722617.
6. Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL (Dec 2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation". Molecular Cell 6 (6): 1365–75. PMID 11163210.
7. Lee YS, Han JM, Son SH, Choi JW, Jeon EJ, Bae SC, Park YI, Kim S (Jul 2008). "AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2". Biochemical and Biophysical Research Communications 371 (3): 395–400. doi:10.1016/j.bbrc.2008.04.099. PMID 18448069.
8. 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". The Journal of Biological Chemistry 283 (51): 35660–7. doi:10.1074/jbc.M710496200. PMID 18927080.
9. Carpentier I, Coornaert B, Beyaert R (Oct 2008). "Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation". Biochemical and Biophysical Research Communications 374 (4): 752–7. doi:10.1016/j.bbrc.2008.07.103. PMID 18671942.

Further reading

• Zhang Y, Chang C, Gehling DJ, Hemmati-Brivanlou A, Derynck R (Jan 2001). "Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase". Proceedings of the National Academy of Sciences of the United States of America 98 (3): 974–9. doi:10.1073/pnas.98.3.974. PMC 14694. PMID 11158580.
• Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL (Dec 2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation". Molecular Cell 6 (6): 1365–75. doi:10.1016/S1097-2765(00)00134-9. PMID 11163210.
• Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, Wrana JL (Jun 2001). "TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation". Nature Cell Biology 3 (6): 587–95. doi:10.1038/35078562. PMID 11389444.
• Subramaniam V, Li H, Wong M, Kitching R, Attisano L, Wrana J, Zubovits J, Burger AM, Seth A (Oct 2003). "The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase". British Journal of Cancer 89 (8): 1538–44. doi:10.1038/sj.bjc.6601301. PMC 2394340. PMID 14562029.
• Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K (Jan 2004). "Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts". The Journal of Clinical Investigation 113 (2): 253–64. doi:10.1172/JCI16269. PMC 310747. PMID 14722617.
• Li H, Seth A (Mar 2004). "An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein". Oncogene 23 (10): 1801–8. doi:10.1038/sj.onc.1207319. PMID 14755250.
• Jin YH, Jeon EJ, Li QL, Lee YH, Choi JK, Kim WJ, Lee KY, Bae SC (Jul 2004). "Transforming growth factor-beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation". The Journal of Biological Chemistry 279 (28): 29409–17. doi:10.1074/jbc.M313120200. PMID 15138260.
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW (Jun 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (Jul 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (Sep 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
• Zhang H, Cohen SN (Dec 2004). "Smurf2 up-regulation activates telomere-dependent senescence". Genes & Development 18 (24): 3028–40. doi:10.1101/gad.1253004. PMC 535914. PMID 15574587.
• 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 (Mar 2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science 307 (5715): 1621–5. doi:10.1126/science.1105776. PMID 15761153.
• Ohashi N, Yamamoto T, Uchida C, Togawa A, Fukasawa H, Fujigaki Y, Suzuki S, Kitagawa K, Hattori T, Oda T, Hayashi H, Hishida A, Kitagawa M (May 2005). "Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta". FEBS Letters 579 (12): 2557–63. doi:10.1016/j.febslet.2005.03.069. PMID 15862290.
• Ogunjimi AA, Briant DJ, Pece-Barbara N, Le Roy C, Di Guglielmo GM, Kavsak P, Rasmussen RK, Seet BT, Sicheri F, Wrana JL (Aug 2005). "Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain". Molecular Cell 19 (3): 297–308. doi:10.1016/j.molcel.2005.06.028. PMID 16061177.
• Chong PA, Lin H, Wrana JL, Forman-Kay JD (Jun 2006). "An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2". The Journal of Biological Chemistry 281 (25): 17069–75. doi:10.1074/jbc.M601493200. PMID 16641086.
• Wiesner S, Ogunjimi AA, Wang HR, Rotin D, Sicheri F, Wrana JL, Forman-Kay JD (Aug 2007). "Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain". Cell 130 (4): 651–62. doi:10.1016/j.cell.2007.06.050. PMID 17719543.