Q8NHY2 · COP1_HUMAN
- ProteinE3 ubiquitin-protein ligase COP1
- GeneCOP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids731 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
Catalytic activity
Activity regulation
TRIB1 competes with substrates for RFWD2 binding.
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 472 | Interaction with TRIB1 | ||||
Sequence: K | ||||||
Site | 491 | Interaction with TRIB1 | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | Cul4A-RING E3 ubiquitin ligase complex | |
Cellular Component | cytosol | |
Cellular Component | nuclear speck | |
Cellular Component | nucleoplasm | |
Molecular Function | metal ion binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Biological Process | positive regulation of proteasomal ubiquitin-dependent protein catabolic process | |
Biological Process | proteasome-mediated ubiquitin-dependent protein catabolic process | |
Biological Process | protein ubiquitination | |
Biological Process | response to ionizing radiation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase COP1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8NHY2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: In the nucleus, it forms nuclear speckles.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 111-113 | Abolishes localization to the nucleus. | ||||
Sequence: RKR → AKA | ||||||
Mutagenesis | 136 | Abolishes p53 ubiquitination and degradation but not that of JUN; when associated with A-139. | ||||
Sequence: C → A | ||||||
Mutagenesis | 136 | Loss of SFN and MTA1 ubiquitination and degradation; when associated with S-139. Loss of stabilization by COPS6; when associated with S-139. | ||||
Sequence: C → S | ||||||
Mutagenesis | 139 | Abolishes p53 ubiquitination and degradation but not that of JUN; when associated with A-136. | ||||
Sequence: C → A | ||||||
Mutagenesis | 139 | Loss of SFN and MTA1 ubiquitination and degradation; when associated with S-136. Loss of stabilization by COPS6; when associated with S-136. | ||||
Sequence: C → S | ||||||
Mutagenesis | 156 | Loss of MTA1 ubiquitination and degradation; when associated with S-159. | ||||
Sequence: C → S | ||||||
Mutagenesis | 159 | Loss of MTA1 ubiquitination and degradation; when associated with S-156. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 629 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000055879 | 1-731 | UniProt | E3 ubiquitin-protein ligase COP1 | |||
Sequence: MSGSRQAGSGSAGTSPGSSAASSVTSASSSLSSSPSPPSVAVSAAALVSGGVAQAAGSGGLGGPVRPVLVAPAVSGSGGGAVSTGLSRHSCAARPSAGVGGSSSSLGSGSRKRPLLAPLCNGLINSYEDKSNDFVCPICFDMIEEAYMTKCGHSFCYKCIHQSLEDNNRCPKCNYVVDNIDHLYPNFLVNELILKQKQRFEEKRFKLDHSVSSTNGHRWQIFQDWLGTDQDNLDLANVNLMLELLVQKKKQLEAESHAAQLQILMEFLKVARRNKREQLEQIQKELSVLEEDIKRVEEMSGLYSPVSEDSTVPQFEAPSPSHSSIIDSTEYSQPPGFSGSSQTKKQPWYNSTLASRRKRLTAHFEDLEQCYFSTRMSRISDDSRTASQLDEFQECLSKFTRYNSVRPLATLSYASDLYNGSSIVSSIEFDRDCDYFAIAGVTKKIKVYEYDTVIQDAVDIHYPENEMTCNSKISCISWSSYHKNLLASSDYEGTVILWDGFTGQRSKVYQEHEKRCWSVDFNLMDPKLLASGSDDAKVKLWSTNLDNSVASIEAKANVCCVKFSPSSRYHLAFGCADHCVHYYDLRNTKQPIMVFKGHRKAVSYAKFVSGEEIVSASTDSQLKLWNVGKPYCLRSFKGHINEKNFVGLASNGDYIACGSENNSLYLYYKGLSKTLLTFKFDTVKSVLDKDRKEDDTNEFVSAVCWRALPDGESNVLIAANSQGTIKVLELV | |||||||
Modified residue (large scale data) | 105 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 108 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 126 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 319 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autoubiquitinated. MTA1 destabilizes it by promoting its autoubiquitination.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed at low level. Expressed at higher level in testis, placenta, skeletal muscle and heart.
Induction
By p53/TP53.
Gene expression databases
Organism-specific databases
Interaction
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8NHY2 | COPS6 Q7L5N1 | 3 | EBI-1176214, EBI-486838 | |
BINARY | Q8NHY2 | ETS1 P14921-1 | 3 | EBI-1176214, EBI-913224 | |
BINARY | Q8NHY2 | ETS2 P15036 | 2 | EBI-1176214, EBI-1646991 | |
BINARY | Q8NHY2 | ETV1 P50549 | 4 | EBI-1176214, EBI-3905068 | |
BINARY | Q8NHY2 | ETV5 P41161 | 4 | EBI-1176214, EBI-3905093 | |
BINARY | Q8NHY2 | SFN P31947 | 6 | EBI-1176214, EBI-476295 | |
BINARY | Q8NHY2-1 | ETV1 P50549-1 | 2 | EBI-9698228, EBI-15926557 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, zinc finger, coiled coil, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-40 | Disordered | ||||
Sequence: MSGSRQAGSGSAGTSPGSSAASSVTSASSSLSSSPSPPSV | ||||||
Motif | 109-113 | Nuclear localization signal 1 | ||||
Sequence: GSRKR | ||||||
Zinc finger | 136-174 | RING-type | ||||
Sequence: CPICFDMIEEAYMTKCGHSFCYKCIHQSLEDNNRCPKCN | ||||||
Motif | 195-206 | Nuclear localization signal 2 | ||||
Sequence: KQKQRFEEKRFK | ||||||
Coiled coil | 233-301 | |||||
Sequence: LDLANVNLMLELLVQKKKQLEAESHAAQLQILMEFLKVARRNKREQLEQIQKELSVLEEDIKRVEEMSG | ||||||
Motif | 235-245 | Nuclear export signal | ||||
Sequence: LANVNLMLELL | ||||||
Region | 305-325 | Disordered | ||||
Sequence: PVSEDSTVPQFEAPSPSHSSI | ||||||
Repeat | 419-458 | WD 1 | ||||
Sequence: NGSSIVSSIEFDRDCDYFAIAGVTKKIKVYEYDTVIQDAV | ||||||
Repeat | 468-508 | WD 2 | ||||
Sequence: TCNSKISCISWSSYHKNLLASSDYEGTVILWDGFTGQRSKV | ||||||
Repeat | 511-551 | WD 3 | ||||
Sequence: EHEKRCWSVDFNLMDPKLLASGSDDAKVKLWSTNLDNSVAS | ||||||
Repeat | 553-593 | WD 4 | ||||
Sequence: EAKANVCCVKFSPSSRYHLAFGCADHCVHYYDLRNTKQPIM | ||||||
Repeat | 597-635 | WD 5 | ||||
Sequence: GHRKAVSYAKFVSGEEIVSASTDSQLKLWNVGKPYCLRS | ||||||
Repeat | 638-677 | WD 6 | ||||
Sequence: GHINEKNFVGLASNGDYIACGSENNSLYLYYKGLSKTLLT | ||||||
Region | 643-645 | Interaction with TRIB1 | ||||
Sequence: KNF | ||||||
Repeat | 691-729 | WD 7 | ||||
Sequence: RKEDDTNEFVSAVCWRALPDGESNVLIAANSQGTIKVLE |
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).
The WD40 domain (386-731) is necessary and sufficient for TRIB1 binding (PubMed:27041596).
Sequence similarities
Belongs to the COP1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
Q8NHY2-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length731
- Mass (Da)80,474
- Last updated2002-10-01 v1
- ChecksumC4B262268D01FA00
Q8NHY2-2
- Name2
- Synonymsdelta24
Q8NHY2-3
- Name3
Q8NHY2-4
- Name4
- SynonymsCOP1D
- NoteUnable to associate with other components of the CRL complex. Acts as a dominant-negative.
- Differences from canonical
- 277-296: Missing
Q8NHY2-5
- Name5
- SynonymsE
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_012026 | 1-264 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_055894 | 157 | in isoform 5 | |||
Sequence: Y → E | ||||||
Alternative sequence | VSP_055895 | 158-731 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_012024 | 211-214 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_012025 | 277-296 | in isoform 2 and isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_012027 | 342 | in isoform 3 | |||
Sequence: Q → QAGVQWRYLGSLQPPPPRYKRFSCLTLPSSWDYRRLPPHL |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF508940 EMBL· GenBank· DDBJ | AAM34692.1 EMBL· GenBank· DDBJ | mRNA | ||
BK000438 EMBL· GenBank· DDBJ | DAA01050.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF527539 EMBL· GenBank· DDBJ | AAQ08989.1 EMBL· GenBank· DDBJ | mRNA | ||
AY509921 EMBL· GenBank· DDBJ | AAS82851.1 EMBL· GenBank· DDBJ | mRNA | ||
KJ534928 EMBL· GenBank· DDBJ | AHW56568.1 EMBL· GenBank· DDBJ | mRNA | ||
KJ535076 EMBL· GenBank· DDBJ | AHW56715.1 EMBL· GenBank· DDBJ | mRNA | ||
AK025789 EMBL· GenBank· DDBJ | BAB15239.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314750 EMBL· GenBank· DDBJ | BAG37289.1 EMBL· GenBank· DDBJ | mRNA | ||
AL162736 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL359265 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL513329 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL590723 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471067 EMBL· GenBank· DDBJ | EAW91000.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC094728 EMBL· GenBank· DDBJ | AAH94728.1 EMBL· GenBank· DDBJ | mRNA |