ID:RFWD2_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase RFWD2; EC=6.3.2.-; AltName: Full=Constitutive photomorphogenesis protein 1 homolog; Short=hCOP1; AltName: Full=RING finger and WD repeat domain protein 2; AltName: Full=RING finger protein 200; FUNCTION: 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. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Homodimer. Homodimerization is mediated by the coiled coil domain. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Isoform 2 does not interact with CUL4A but still binds to RBX1, suggesting that the interaction may be mediated by another cullin protein. Isoform 1 and isoform 2 interact with CUL5 but not with CUL1, CUL2 not CUL3. Interacts with bZIP transcription factors JUN, JUNB and JUND but not with FOS, ATF2 nor XBP1. Interacts with p53 (TP53). Interacts with COPS6; this interaction stabilizes RFWD2 through reducing its auto-ubiquitination and decelerating its turnover rate. Interacts with SFN; this interaction leads to SFN degradation. Isoform 4 forms heterodimers with isoform 1, preventing its association with DET1. INTERACTION: Q7L5N1:COPS6; NbExp=3; IntAct=EBI-1176214, EBI-486838; P31947:SFN; NbExp=5; IntAct=EBI-1176214, EBI-476295; SUBCELLULAR LOCATION: Nucleus speckle. Cytoplasm. Note=In the nucleus, it forms nuclear speckles. TISSUE SPECIFICITY: Ubiquitously expressed at low level. Expressed at higher level in testis, placenta, skeletal muscle and heart. INDUCTION: By p53/TP53. DOMAIN: The RING finger domain, in addition to its role in ubiquitination, functions as a structural scaffold to bring two clusters of positive-charged residues within spatial proximity to mimic a bipartite nuclear localization signal (NLS) (By similarity). SIMILARITY: Belongs to the COP1 family. SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 7 WD repeats.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q8NHY2
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0016740 transferase activity GO:0046872 metal ion binding GO:0061630 ubiquitin protein ligase activity
Biological Process: GO:0010212 response to ionizing radiation GO:0016567 protein ubiquitination GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043687 post-translational protein modification
US Server
