COP1 Gene - E3 Ubiquitin-Protein Ligase
Constitutive Photomorphogenic Protein 1: A Key Regulator of Ubiquitination and Tumor Suppression
Gene Information Card
| Symbol | COP1 |
|---|---|
| Full Name | COP1 (Constitutive Photomorphogenic Protein 1) |
| Gene Type | Protein coding |
| Chromosomal Location | 1q25.2 |
| NCBI Gene ID | 64326 ncbi.nlm.nih.gov/gene/64326 |
| Ensembl ID | ENSG00000143384 |
| UniProt ID | Q8NHY2 |
| OMIM ID | 608067 |
| HGNC ID | 16886 |
| Aliases | RFWD2, RING finger and WD repeat domain 2, DET1- and DDB1-associated protein 1 |
Description
The COP1 gene encodes an E3 ubiquitin-protein ligase that targets key regulatory proteins for proteasomal degradation. It plays a critical role in cellular processes including cell cycle progression, DNA damage response, and tumor suppression. COP1 is frequently altered in various cancers, with mutations and copy number changes contributing to oncogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Loss of COP1 function leads to accumulation of oncogenic substrates (e.g., c-Jun, ETV1), promoting proliferation and invasion. | ClinVar, COSMIC |
| Prostate Cancer | COP1 downregulation or mutation increases ETV1 stability, driving tumorigenesis. | ClinVar, COSMIC |
| Lung Cancer | Somatic mutations and copy number loss of COP1 are associated with poor prognosis. | COSMIC |
| Colorectal Cancer | COP1 alterations contribute to Wnt/β-catenin pathway dysregulation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.2 | Medium |
| Liver | 6.1 | Low |
| Kidney | 5.4 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.3 | Embryonic kidney cells; moderate expression |
| HeLa | 7.8 | Cervical cancer cells; moderate expression |
| MCF7 | 6.2 | Breast cancer cells; low expression |
| A549 | 5.1 | Lung cancer cells; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <1% | Loss of function; truncated protein |
| c.789_790del (p.Glu264fs) | Frameshift | <1% | Loss of function; premature stop |
| c.1567G>A (p.Glu523Lys) | Missense | <1% | Unknown; possibly damaging (PolyPhen-2) |
| c.2011C>T (p.Arg671Trp) | Missense | <1% | Unknown; possibly damaging (SIFT) |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the RING finger domain, impairing ubiquitin ligase activity.
Gain of Function (GOF)
Not well documented; most COP1 mutations in cancer are loss-of-function.
Dominant Negative (DN)
Hypothesized for certain missense mutations that retain substrate binding but lack catalytic activity, interfering with wild-type COP1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• p53 signaling pathway (KEGG: hsa04115)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
COP1 is a 731-amino acid protein containing a RING finger domain (E3 ligase activity) and multiple WD40 repeats (substrate recognition). It forms a complex with DET1 and DDB1 to target transcription factors such as c-Jun, ETV1, and p53 for ubiquitination and degradation. COP1 acts as a tumor suppressor by limiting the levels of oncogenic proteins. Its loss or mutation contributes to cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COP1 Knockout HEK293 Cell Line | EDJ-KQ1096 | Human | 64326 | Details Get a Quote |
| COP1 Knockout A-549 Cell Line | EDJ-KQ18118 | Human | 64326 | Details Get a Quote |
| COP1 Knockout HeLa Cell Line | EDJ-KQ18922 | Human | 64326 | Details Get a Quote |
| COP1 Knockout HCT 116 Cell Line | EDJ-KQ20265 | Human | 64326 | Details Get a Quote |
