Tchem CUL4A Cullin-4A

Protein Summary

Description

Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. DCX(DTL) directs autoubiquitination of DTL. CUL4A is the ubiquitin ligase component of a multimeric complex involved in the degradation of DNA damage-response proteins (Liu et al., 2009 [PubMed 19481525]).[supplied by OMIM, Oct 2009]

Uniprot Accession IDs

• Q13619
• A2A2W2
• O75834
• Q589T6
• Q5TC62
• Q6UP08
• Q9UP17
• CUL-4A

Gene Name

• CUL4A

Ensembl ID

• ENST00000375440
• ENSP00000364589
• ENSG00000139842
• ENST00000375441
• ENSP00000364590
• ENST00000451881
• ENSP00000389118
• ENST00000617546
• ENSP00000481782

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.98
transcription factor binding site profile	0.9
biological process	0.86
protein domain	0.85
protein complex	0.84

Protein Classes

PANTHER Classes

Protein / Ligase / Ubiquitin-protein Ligase / Cullin-4a

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / Cullin-4a

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 119.43   (req: < 5)

Gene RIFs: 109   (req: <= 3)

Antibodies: 357   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 119.43   (req: >= 5)

Gene RIFs: 109   (req: > 3)

Antibodies: 357   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 28

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 9

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0