UniProt Accession

 RFWD2_HUMAN; Q8NHY2; Q504W6; Q6H103; Q9H6L7 

Genbank Protein ID

 AF508940; BK000438; AF527539; AY509921; AK025789; AK314750; AL359265; AL162736; AL513329; AL590723; AL513329; AL162736; AL359265; AL590723; AL162736; AL359265; AL513329; AL590723; AL590723; AL162736; AL359265; AL513329; CH471067; BC094728 

Genbank Nucleotide ID

 AAM34692.1; DAA01050.1; AAQ08989.1; AAS82851.1; BAB15239.1; BAG37289.1; CAH71140.1; CAH71140.1; CAH71140.1; CAH71140.1; CAH72425.1; CAH72425.1; CAH72425.1; CAH72425.1; CAH73625.1; CAH73625.1; CAH73625.1; CAH73625.1; CAI14643.1; CAI14643.1; CAI14643.1; CAI14643.1; EAW91000.1; AAH94728.1 

Protein Name

 E3 ubiquitin-protein ligase RFWD2 

Protein Synonyms/Alias

 Constitutive photomorphogenesis protein 1 homolog; hCOP1; RING finger and WD repeat domain protein 2; RING finger protein 200 

Gene Name

 RFWD2 

Gene Synonyms/Alias

 COP1; RNF200 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
345	SGSSQTKKQPWYNST	ubiquitination	[1]
398	EFQECLSKFTRYNSV	ubiquitination	[1]
629	LKLWNVGKPYCLRSF	ubiquitination	[2, 3]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. 

Sequence Annotation

 REPEAT 419 458 WD 1.
 REPEAT 468 508 WD 2.
 REPEAT 511 551 WD 3.
 REPEAT 553 593 WD 4.
 REPEAT 597 635 WD 5.
 REPEAT 638 677 WD 6.
 REPEAT 691 729 WD 7.
 ZN_FING 136 174 RING-type.
 MOTIF 109 113 Nuclear localization signal 1.
 MOTIF 195 206 Nuclear localization signal 2.
 MOTIF 235 245 Nuclear export signal (By similarity).  

Keyword

 Alternative splicing; Coiled coil; Complete proteome; Cytoplasm; Ligase; Metal-binding; Nucleus; Reference proteome; Repeat; Ubl conjugation pathway; WD repeat; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 731 AA 

Protein Sequence

Gene Ontology

 GO:0005813; C:centrosome; IDA:HPA.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005925; C:focal adhesion; IDA:HPA.
 GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
 GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. 

Interpro

 IPR015943; WD40/YVTN_repeat-like_dom.
 IPR001680; WD40_repeat.
 IPR019775; WD40_repeat_CS.
 IPR017986; WD40_repeat_dom.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 

Pfam

 PF00400; WD40 

SMART

 SM00184; RING
 SM00320; WD40 

PROSITE

 PS00678; WD_REPEATS_1
 PS50082; WD_REPEATS_2
 PS50294; WD_REPEATS_REGION
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS