SMURF2 (SMAD specific E3 ubiquitin protein ligase 2)

Gene

• Entrez ID: 64750
• Gene name: SMAD specific E3 ubiquitin protein ligase 2
• Gene symbol: SMURF2
• Synonyms: -
• Chromosome: 17
• Chromosome location: 17q23.3-q24.1

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023400	hsa-miR-122-5p	Microarray	17612493
MIRT031987	hsa-miR-16-5p	Microarray	21199864
MIRT197869	hsa-miR-630	PAR-CLIP	22012620
MIRT450660	hsa-miR-511-5p	PAR-CLIP	22100165
MIRT450661	hsa-miR-203a-3p	PAR-CLIP	22100165
MIRT450662	hsa-miR-4670-3p	PAR-CLIP	22100165
MIRT450663	hsa-miR-93-3p	PAR-CLIP	22100165
MIRT450664	hsa-miR-382-5p	PAR-CLIP	22100165
MIRT450665	hsa-miR-431-5p	PAR-CLIP	22100165
MIRT534138	hsa-miR-526b-5p	PAR-CLIP	22012620
MIRT534139	hsa-miR-4635	PAR-CLIP	22012620
MIRT534140	hsa-miR-665	PAR-CLIP	22012620
MIRT534141	hsa-miR-4495	PAR-CLIP	22012620
MIRT534142	hsa-miR-3667-5p	PAR-CLIP	22012620
MIRT542375	hsa-miR-6807-5p	PAR-CLIP	21572407
MIRT542376	hsa-miR-6872-3p	PAR-CLIP	21572407
MIRT653281	hsa-miR-378a-5p	HITS-CLIP	23824327
MIRT653282	hsa-miR-4454	HITS-CLIP	23824327
MIRT653283	hsa-miR-6821-3p	HITS-CLIP	23824327
MIRT653284	hsa-miR-6790-3p	HITS-CLIP	23824327
MIRT653285	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT653286	hsa-miR-7107-5p	HITS-CLIP	23824327
MIRT653287	hsa-miR-1234-3p	HITS-CLIP	23824327
MIRT653288	hsa-miR-1224-3p	HITS-CLIP	23824327
MIRT653289	hsa-miR-186-3p	HITS-CLIP	23824327
MIRT653290	hsa-miR-3934-5p	HITS-CLIP	23824327
MIRT653291	hsa-miR-764	HITS-CLIP	23824327
MIRT653292	hsa-miR-125a-3p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	TAS
GO:0000151	Component	Ubiquitin ligase complex	IDA	14755250
GO:0000209	Process	Protein polyubiquitination	IBA	21873635
GO:0000209	Process	Protein polyubiquitination	TAS
GO:0004842	Function	Ubiquitin-protein transferase activity	IDA	14755250
GO:0004842	Function	Ubiquitin-protein transferase activity	TAS
GO:0005160	Function	Transforming growth factor beta receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	14755250, 15231748, 17719543, 18729074, 18985028, 20676133, 20937913, 21572392, 22045334, 22921829, 25438670, 28514442, 30696809, 32296183
GO:0005634	Component	Nucleus	NAS	11163210
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IEA
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IDA	14755250
GO:0016567	Process	Protein ubiquitination	IBA	21873635
GO:0016579	Process	Protein deubiquitination	TAS
GO:0016607	Component	Nuclear speck	IDA
GO:0017015	Process	Regulation of transforming growth factor beta receptor signaling pathway	NAS	11158580
GO:0030509	Process	BMP signaling pathway	TAS
GO:0030512	Process	Negative regulation of transforming growth factor beta receptor signaling pathway	IDA	19255252
GO:0030512	Process	Negative regulation of transforming growth factor beta receptor signaling pathway	TAS
GO:0030514	Process	Negative regulation of BMP signaling pathway	IBA	21873635
GO:0030579	Process	Ubiquitin-dependent SMAD protein catabolic process	IBA	21873635
GO:0030579	Process	Ubiquitin-dependent SMAD protein catabolic process	IDA	19122240
GO:0042802	Function	Identical protein binding	IPI	15231748, 17719543
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA	21873635
GO:0045121	Component	Membrane raft	IEA
GO:0045732	Process	Positive regulation of protein catabolic process	IBA	21873635
GO:0045892	Process	Negative regulation of transcription, DNA-templated	NAS	11016919
GO:0046332	Function	SMAD binding	IPI	19122240
GO:0060071	Process	Wnt signaling pathway, planar cell polarity pathway	TAS
GO:0061630	Function	Ubiquitin protein ligase activity	IBA	21873635
GO:0061630	Function	Ubiquitin protein ligase activity	TAS
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	TAS
GO:1901165	Process	Positive regulation of trophoblast cell migration	IDA	19255252

Other IDs

• MIM: 605532
• HGNC: 16809
• e!Ensembl: ENSG00000108854

Protein

• UniProt ID: Q9HAU4
• Protein name: E3 ubiquitin-protein ligase SMURF2 (hSMURF2) (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase SMURF2) (SMAD ubiquitination regulatory factor 2) (SMAD-specific E3 ubiquitin-protein ligase 2)
• Protein function: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11016919). Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby downregulating TGF-beta signaling (PubMed:11163210, PubMed:12717440). In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1 (PubMed:18448069). Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation (PubMed:11016919, PubMed:11158580, PubMed:11389444). SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation (PubMed:11389444). Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation (PubMed:30696809). ; (Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding.
• PDB: 1ZVD, 2DJY, 2JQZ, 2KXQ, 2LTZ, 6FX4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00168	C2	12 → 114	C2 domain	Domain
  PF00397	WW	159 → 188	WW domain	Domain
  PF00397	WW	253 → 282	WW domain	Domain
  PF00397	WW	299 → 328	WW domain	Domain
  PF00632	HECT	443 → 748	HECT-domain (ubiquitin-transferase)	Domain

• Sequence:

  MSNPGGRRNGPVKLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGSGQCHSTDTVKNTLDPK
  WNQHYDLYIGKSDSVTISVWNHKKIHKKQGAGFLGCVRLLSNAINRLKDTGYQRLDLCKL
  GPNDNDTVRGQIVVSLQSRDRIGTGGQVVDCSRLFDNDLPDGWEERRTASGRIQYLNHIT
  RTTQWERPTRPASEYSSPGRPLSCFVDENTPISGTNGATCGQSSDPRLAERRVRSQRHRN
  YMSRTHLHTPPDLPEGYEQRTTQQGQVYFLHTQTGVSTWHDPRVPRDLSNINCEELGPLP
  PGWEIRNTATGRVYFVDHNNRTTQFTDPRLSANLHLVLNRQNQLKDQQQQQVVSLCPDDT
  ECLTVPRYKRDLVQKLKILRQELSQQQPQAGHCRIEVSREEIFEESYRQVMKMRPKDLWK
  RLMIKFRGEEGLDYGGVAREWLYLLSHEMLNPYYGLFQYSRDDIYTLQINPDSAVNPEHL
  SYFHFVGRIMGMAVFHGHYIDGGFTLPFYKQLLGKSITLDDMELVDPDLHNSLVWILEND
  ITGVLDHTFCVEHNAYGEIIQHELKPNGKSIPVNEENKKEYVRLYVNWRFLRGIEAQFLA
  LQKGFNEVIPQHLLKTFDEKELELIICGLGKIDVNDWKVNTRLKHCTPDSNIVKWFWKAV
  EFFDEERRARLLQFVTGSSRVPLQGFKALQGAAGPRLFTIHQIDACTNNLPKAHTCFNRI
  DIPPYESYEKLYEKLLTAIEETCGFAVE

• Sequence length: 748