Anti-CUL4A

Cullin proteins assemble a large number of RING E3 ubiquitin ligases,participating in the proteolysis through the ubiquitin-proteasome pathway. Two cullin 4 (CUL4) proteins,CUL4A (87 kDa) and CUL4B(104 kDa),have been identified. The two CUL4 sequences are 83% identical. They target certain proteins for degradation by binding protein DDB1 to form a CUL4-DDB1 ubiquitin ligase complex with DDB. They form two individual E3 ligases,DDB1-CUL4ADDB2 and DDB1-CUL4BDDB2 in this process. CUL4A appeared in both the nucleus and the cytosol,suggesting a more complex mechanism for entering the nucleus. CUL4B is localized in the nucleus and facilitates the transfer of DDB1 into the nucleus independently of DDB2. Protein function: 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. The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). With CUL4B, contributes to ribosome biogenesis (PubMed:26711351). [The UniProt Consortium]