SMURF2

SMAD specific E3 ubiquitin protein ligase 2

PDB rendering based on 1zvd.

Available structures
PDB	1ZVD, 2DJY, 2JQZ, 2KXQ

Identifiers

Symbols

SMURF2; DKFZp686F0270; MGC138150

External IDs

OMIM: 605532 MGI: 1913563 HomoloGene: 41490 GeneCards: SMURF2 Gene

Gene Ontology
Molecular function	• ubiquitin-protein ligase activity • protein binding • ligase activity • acid-amino acid ligase activity • identical protein binding • SMAD binding
Cellular component	• ubiquitin ligase complex • intracellular • nucleus • cytoplasm • cytosol • plasma membrane • membrane raft
Biological process	• protein modification process • ubiquitin-dependent protein catabolic process • transforming growth factor beta receptor signaling pathway • protein ubiquitination • regulation of transforming growth factor beta receptor signaling pathway • BMP signaling pathway • ubiquitin-dependent SMAD protein catabolic process • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • negative regulation of transcription, DNA-dependent
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

n/a

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 17:
62.54 – 62.66 Mb

Chr 11:
106.68 – 106.78 Mb

PubMed search

[1]

[2]

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

References

^ ^a ^b ^c ^d Lin X, Liang M, Feng XH (Jan 2001). "Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling". J Biol Chem 275 (47): 36818–22. doi:10.1074/jbc.C000580200. PMID 11016919.
^ "Entrez Gene: SMURF2 SMAD specific E3 ubiquitin protein ligase 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64750.
^ Asano, Yoshihide; Ihn Hironobu, Yamane Kenichi, Kubo Masahide, Tamaki Kunihiko (Jan. 2004). "Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts". J. Clin. Invest. (United States) 113 (2): 253–64. doi:10.1172/JCI16269. ISSN 0021-9738. PMC 310747. PMID 14722617. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310747.
^ Kavsak, P; Rasmussen R K, Causing C G, Bonni S, Zhu H, Thomsen G H, Wrana J L (Dec. 2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation". Mol. Cell (United States) 6 (6): 1365–75. doi:10.1016/S1097-2765(00)00134-9. ISSN 1097-2765. PMID 11163210.
^ ^a ^b ^c Lee, Yeon Sook; Han Jung Min, Son Sung Hwa, Choi Jin Woo, Jeon Eun Ju, Bae Suk-Chul, Park Young In, Kim Sunghoon (Jul. 2008). "AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2". Biochem. Biophys. Res. Commun. (United States) 371 (3): 395–400. doi:10.1016/j.bbrc.2008.04.099. PMID 18448069.
^ Fukunaga, Erina; Inoue Yasumichi, Komiya Setsuro, Horiguchi Kana, Goto Kouichiro, Saitoh Masao, Miyazawa Keiji, Koinuma Daizo, Hanyu Aki, Imamura Takeshi (Dec. 2008). "Smurf2 induces ubiquitin-dependent degradation of Smurf1 to prevent migration of breast cancer cells". J. Biol. Chem. (United States) 283 (51): 35660–7. doi:10.1074/jbc.M710496200. ISSN 0021-9258. PMID 18927080.
^ ^a ^b Bonni, S; Wang H R, Causing C G, Kavsak P, Stroschein S L, Luo K, Wrana J L (Jun. 2001). "TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation". Nat. Cell Biol. (England) 3 (6): 587–95. doi:10.1038/35078562. ISSN 1465-7392. PMID 11389444.
^ ^a ^b Nakano, Ayako; Koinuma Daizo, Miyazawa Keiji, Uchida Takafumi, Saitoh Masao, Kawabata Masahiro, Hanai Jun-ichi, Akiyama Hirotada, Abe Masahiro, Miyazono Kohei, Matsumoto Toshio, Imamura Takeshi (Mar. 2009). "Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins". J. Biol. Chem. (United States) 284 (10): 6109–15. doi:10.1074/jbc.M804659200. ISSN 0021-9258. PMID 19122240.
^ Carpentier, Isabelle; Coornaert Beatrice, Beyaert Rudi (Oct. 2008). "Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation". Biochem. Biophys. Res. Commun. (United States) 374 (4): 752–7. doi:10.1016/j.bbrc.2008.07.103. PMID 18671942.

Zhang Y, Chang C, Gehling DJ, et al. (2001). "Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase.". Proc. Natl. Acad. Sci. U.S.A. 98 (3): 974–9. doi:10.1073/pnas.98.3.974. PMC 14694. PMID 11158580. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14694.
Kavsak P, Rasmussen RK, Causing CG, et al. (2001). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation.". Mol. Cell 6 (6): 1365–75. doi:10.1016/S1097-2765(00)00134-9. PMID 11163210.
Bonni S, Wang HR, Causing CG, et al. (2001). "TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation.". Nat. Cell Biol. 3 (6): 587–95. doi:10.1038/35078562. PMID 11389444.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Subramaniam V, Li H, Wong M, et al. (2003). "The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase.". Br. J. Cancer 89 (8): 1538–44. doi:10.1038/sj.bjc.6601301. PMC 2394340. PMID 14562029. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2394340.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Asano Y, Ihn H, Yamane K, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310747.
Li H, Seth A (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, et al. (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.
Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway.". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442148.
Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=515316.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
Zhang H, Cohen SN (2005). "Smurf2 up-regulation activates telomere-dependent senescence.". Genes Dev. 18 (24): 3028–40. doi:10.1101/gad.1253004. PMC 535914. PMID 15574587. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=535914.
Barrios-Rodiles M, Brown KR, Ozdamar B, et al. (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, et al. (2005). "Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta.". FEBS Lett. 579 (12): 2557–63. doi:10.1016/j.febslet.2005.03.069. PMID 15862290.
Ogunjimi AA, Briant DJ, Pece-Barbara N, et al. (2005). "Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain.". Mol. Cell 19 (3): 297–308. doi:10.1016/j.molcel.2005.06.028. PMID 16061177.
Chong PA, Lin H, Wrana JL, Forman-Kay JD (2006). "An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2.". J. Biol. Chem. 281 (25): 17069–75. doi:10.1074/jbc.M601493200. PMID 16641086.
Wiesner S, Ogunjimi AA, Wang HR, et al. (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.

PDB gallery

1zvd: Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain

2djy: Solution structure of Smurf2 WW3 domain-Smad7 PY peptide complex

SMURF2

Interactions

References

Further reading