CUL4B: Cullin 4B, a Core Component of the E3 Ubiquitin Ligase Complex
A critical regulator of ubiquitination, cell cycle, and neurodevelopment, implicated in X-linked intellectual disability and cancer.
Gene Information Card
| Symbol | CUL4B |
|---|---|
| Full Name | Cullin 4B |
| Gene Type | Protein coding |
| Chromosomal Location | Xq24 |
| NCBI Gene ID | 8450 ncbi.nlm.nih.gov/gene/8450 |
| Ensembl ID | ENSG00000158290 |
| UniProt ID | Q13620 |
| OMIM ID | 300304 |
| HGNC ID | 2556 |
| Aliases | CUL-4B, MRXHF2, SFM16 |
Description
CUL4B encodes cullin-4B, a core scaffold protein of the Cullin-RING E3 ubiquitin ligase complex (CRL4B). This complex targets specific substrates for ubiquitination and proteasomal degradation, regulating diverse cellular processes including cell cycle progression, DNA replication, chromatin remodeling, and gene transcription. CUL4B is essential for normal development, and mutations cause X-linked intellectual disability (XLID) and are associated with various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability, Cabezas type (MRXHF2) | Loss-of-function mutations impair CRL4B complex activity, disrupting neuronal gene expression and synaptic function. | OMIM 300304; ClinVar |
| X-linked intellectual disability with seizures and speech delay | Missense and truncating mutations in CUL4B lead to reduced protein stability or loss of E3 ligase activity, affecting brain development. | OMIM; ClinVar |
| Hepatocellular carcinoma | Overexpression of CUL4B promotes tumor cell proliferation and invasion via ubiquitination of tumor suppressors (e.g., p53) and activation of oncogenic pathways. | COSMIC; literature |
| Breast cancer | CUL4B overexpression correlates with poor prognosis, enhancing cell cycle progression and epithelial-mesenchymal transition. | COSMIC; literature |
| Gastric cancer | CUL4B upregulation promotes cancer cell growth and metastasis through regulation of cell cycle and apoptosis. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | High |
| Brain | 12.3 | Medium |
| Liver | 10.2 | Medium |
| Kidney | 9.8 | Medium |
| Lung | 7.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| HepG2 | 12.8 | Liver cancer cell line |
| MCF7 | 11.5 | Breast cancer cell line |
| A549 | 9.3 | Lung cancer cell line |
| K562 | 8.1 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg377* | Nonsense | Rare | Truncating mutation leading to loss of function, associated with XLID. |
| p.Leu496Pro | Missense | Rare | Disrupts cullin domain, impairing complex assembly and function. |
| p.Gly859Asp | Missense | Rare | Affects substrate binding, reducing ubiquitination activity. |
| c.1003+1G>A | Splice site | Rare | Aberrant splicing, leading to frameshift and premature stop codon. |
Mutation functional classification
Loss of Function (LOF)
Most CUL4B mutations in XLID are loss-of-function, reducing E3 ligase activity and leading to accumulation of substrates that disrupt neuronal development.
Gain of Function (GOF)
In cancer, CUL4B overexpression acts as a gain-of-function, enhancing degradation of tumor suppressors and promoting oncogenic signaling.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming inactive complexes with wild-type CUL4B, though this is less common.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • protein ubiquitination |
| • cell cycle | • DNA replication |
| • chromatin remodeling | • response to DNA damage stimulus |
| • nervous system development |
Pathways
• Cullin-RING E3 ubiquitin ligase pathway
• Cell cycle control
• DNA damage response
• Chromatin modification
Protein Summary
CUL4B is a 895-amino acid protein that serves as a scaffold for the CRL4B complex, which includes DDB1, RBX1, and various substrate receptors. It mediates ubiquitination of proteins such as p53, cyclin E, and histone H2A, thereby regulating cell cycle, DNA repair, and gene expression. CUL4B is widely expressed, with high levels in testis and brain, and its dysfunction is linked to neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CUL4B Knockout HEK293 Cell Line | EDJ-KQ3120 | Human | 8450 | Details Get a Quote |
| CUL4B Knockout A-549 Cell Line | EDJ-KQ25837 | Human | 8450 | Details Get a Quote |
| CUL4B Knockout HCT 116 Cell Line | EDJ-KQ25838 | Human | 8450 | Details Get a Quote |
| CUL4B Knockout HeLa Cell Line | EDJ-KQ25839 | Human | 8450 | Details Get a Quote |
