Recombinant Human E3 ubiquitin-protein ligase COP1 (COP1) Protein

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. Ubiquitinates MTA1 leading to its proteasomal degradation. Upon binding to TRIB1, ubiquitinates CEBPA, which lacks a canonical COP1-binding motif (Probable)

Subcellular Location

Nucleus speckle; Cytoplasm

Tissue Specificity

Ubiquitously expressed at low level. Expressed at higher level in testis, placenta, skeletal muscle and heart

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. Interacts with p53/TP53 and MTA1. Interacts with TRIB1 (via C-terminus) and TRIB2 (PubMed:20410507, PubMed:27041596)

Pathway

Protein modification; protein ubiquitination

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• Bianchi E. et al. Characterization of human constitutive photomorphogenesis protein 1, a RING finger ubiquitin ligase that interacts with Jun transcription factors and modulates their transcriptional activity. — J. Biol. Chem. (2003)
• Wertz I.E. et al. Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. — Science (2004)
• Corominas R. et al. Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. — Nat. Commun. (2014)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)