CUL5 (Cullin 5): A Multifaceted E3 Ubiquitin Ligase Scaffold in Health and Disease
Explore the genomic architecture, expression patterns, mutational landscape, and clinical significance of the CUL5 gene, a key regulator of proteostasis and cellular signaling.
Gene Information Card
| Symbol | CUL5 |
|---|---|
| Full Name | Cullin 5 |
| Gene Type | Protein-coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 8065 ncbi.nlm.nih.gov/gene/8065 |
| Ensembl ID | ENSG00000166226 |
| UniProt ID | Q93034 |
| OMIM ID | 601404 |
| HGNC ID | 2555 |
| Aliases | VACM-1 |
Description
CUL5 (Cullin 5) encodes a core scaffold component of the Cullin-RING E3 ubiquitin ligase complex (CRL5). This protein participates in ubiquitination and subsequent proteasomal degradation of target proteins, thereby regulating diverse cellular processes including cell cycle progression, DNA damage response, signal transduction, and antiviral defense. CUL5 is widely expressed and its dysregulation has been implicated in various cancers and viral infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered CUL5 expression disrupts ubiquitination of key oncoproteins/tumor suppressors, affecting cell proliferation and survival. | COSMIC; PMID: 25655993 |
| HIV/AIDS | CUL5 is hijacked by HIV-1 Vif protein to degrade APOBEC3G, a host antiviral factor, promoting viral infectivity. | PMID: 14532107 |
| Neuroblastoma | CUL5 downregulation correlates with poor prognosis and increased tumor aggressiveness. | PMID: 21516115 |
| VACM-1-related disorders | CUL5 (also known as VACM-1) is implicated in vascular and renal functions; mutations may affect blood pressure regulation. | OMIM: 601404 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.4 | Medium |
| Lung | 8.7 | Low |
| Liver | 6.2 | Low |
| Kidney | 10.1 | Medium |
| Testis | 15.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical carcinoma; high expression |
| A549 | 9.8 | Lung carcinoma; moderate |
| HepG2 | 7.5 | Liver carcinoma; low-moderate |
| MCF7 | 11.6 | Breast carcinoma; moderate-high |
| K562 | 8.9 | Leukemia; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | 0.01% (gnomAD) | Truncated protein, likely loss of function |
| c.1567G>A (p.Val523Met) | Missense | 0.05% (gnomAD) | Unknown; may affect protein stability |
| c.2011A>G (p.Thr671Ala) | Missense | 0.02% (gnomAD) | Potential impact on substrate binding |
| c.789_790insA (p.Gln264ThrfsTer19) | Frameshift | Rare | Loss of function, likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (nonsense, frameshift) are rare and may contribute to cancer progression by impairing ubiquitination of tumor suppressors.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression of wild-type CUL5 may enhance degradation of oncoproteins in some contexts.
Dominant Negative (DN)
Certain missense mutations in the cullin domain may act as dominant-negative by disrupting complex assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • protein ubiquitination |
| • cullin-RING ubiquitin ligase complex | • cell cycle |
| • DNA damage response | • response to virus |
| • cytoplasm | • nucleus |
Pathways
• Ubiquitin-Proteasome Pathway
• Cullin-RING E3 Ligase (CRL) Signaling
• HIV Life Cycle (Vif-mediated APOBEC3G degradation)
• Cell Cycle Regulation
• DNA Repair
Protein Summary
CUL5 is a 780-amino acid protein that serves as a molecular scaffold in CRL5 complexes. It interacts with Elongin B/C, Rbx2, and substrate receptors to ubiquitinate specific targets. CUL5 is involved in the degradation of p53, cyclin D1, and APOBEC3G, among others. Its activity is regulated by neddylation and deneddylation. CUL5 is essential for normal cell proliferation and antiviral immunity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CUL5 Knockout HEK293 Cell Line | EDJ-KQ6164 | Human | 8065 | Details Get a Quote |
| CUL5 Knockout A-549 Cell Line | EDJ-KQ29979 | Human | 8065 | Details Get a Quote |
| CUL5 Knockout HCT 116 Cell Line | EDJ-KQ29980 | Human | 8065 | Details Get a Quote |
| CUL5 Knockout HeLa Cell Line | EDJ-KQ29981 | Human | 8065 | Details Get a Quote |
