CUL4A
CUL4A (cullin 4A) is a core component of multiple cullin-RING E3 ubiquitin-protein ligase complexes that mediate the ubiquitination of target proteins. It acts as a scaffold within these complexes and belongs to the cullin family. Browse Assay Genie's current range of CUL4A research reagents below, or read on for the biology behind the target.
CUL4A is a core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes. As a scaffold protein, it may contribute to catalysis by positioning the substrate and the ubiquitin-conjugating enzyme. Ligase activity depends on neddylation of the cullin subunit and is inhibited when the deneddylated cullin associates with TIP120A/CAND1. Functional specificity comes from the variable substrate recognition component, so different DCX complexes target different proteins.
The range of DCX complexes built on CUL4A is broad. DCX(DET1-COP1) directs ubiquitination of JUN, and DCX(DDB2) directs ubiquitination of XPC. DCX(DDB2) also ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled and replication-independent nucleosome assembly. DCX(DTL) acts in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of p53/TP53 after radiation-induced DNA damage and during DNA replication. The DDB1-CUL4A-DTL complex regulates circadian clock function by promoting ubiquitination and degradation of CRY1, and the DCX(ERCC8) complex, also called the CSA complex, plays a role in transcription-coupled repair.
Other complexes contribute to cell-cycle control and protein turnover. DCX(AMBRA1) is a master regulator of the G1 to S transition, mediating ubiquitination of phosphorylated cyclin-D, and it also regulates Cul5-RING complexes by targeting Elongin-C. Complexes containing TRPC4AP or DCAF12 form part of the DesCEND pathway, which recognises C-degrons at the extreme C terminus of target proteins. Together with CUL4B, CUL4A contributes to ribosome biogenesis. NCBI Gene describes CUL4A as the ubiquitin ligase component of a multimeric complex involved in degrading DNA damage-response proteins. The human gene is classed by HGNC in the cullins group and as a microRNA protein coding host gene; the mouse ortholog is Cul4a.
CUL4A is a scaffold for cullin-RING E3 ligases whose specificity is set by variable substrate recognition components, making it a model for studying substrate selection.
CUL4A complexes target proteins such as XPC, CDT1 and p53, and the CSA complex participates in transcription-coupled repair.
DCX(AMBRA1) regulates the G1 to S transition by ubiquitinating phosphorylated cyclin-D, linking CUL4A to cell-cycle control.
CUL4A complexes ubiquitinate histones H3-H4 to support histone deposition, and DDB1-CUL4A-DTL promotes CRY1 degradation in the circadian clock.
CUL4A is a scaffold in cullin-RING E3 ubiquitin ligase complexes, which ubiquitinate target proteins. It may position the substrate and the ubiquitin-conjugating enzyme. Activity depends on neddylation, and the substrate recognition component of each complex determines which proteins are targeted.
The HGNC symbol is CUL4A, for cullin 4A, and UniProt lists the protein as Cullin-4A. No alternative symbols are recorded in the supplied data. CUL4A belongs to the cullin family, and together with CUL4B it contributes to ribosome biogenesis.
A mouse ortholog, Cul4a, is recorded. CUL4A complexes act in DNA damage responses, including ubiquitination of p53 and CDT1 after radiation damage and the CSA complex in transcription-coupled repair. Check the datasheet of any product for its validated reactivity.
Other cullin family scaffold proteins of cullin-RING E3 ubiquitin ligases with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13619; product specifications from Assay Genie datasheets.