Cullin-4A; CUL-4A (CUL4A)

Function

• core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate ubiquitination & subsequent proteasomal degradation of target proteins
• as a scaffold protein may contribute to catalysis through positioning of the substrate & ubiquitin-conjugating enzyme
• E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit & is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1
• functional specificity of 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
• in association with RBX1, DDB1 & DDB2 is required for histone H3 & histone H4 ubiquitination in response to ultraviolet & may be important for subsequent DNA repair
• DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 & MDM2-dependent ubiquitiantion of TP53 in response to radiation-induced DNA damage & during DNA replication
• in association with DDB1 & SKP2 probably is involved in ubiquitination of CDKN1B/p27kip
• involved in ubiquitination of HOXA9
• neddylated
• deneddylated via its interaction with the COP9 signalosome (CSN) complex (putative)
• component of multiple DDB1-CUL4-X-box (DCX) complex(es) E3 ubiquitin-protein ligase complexes
• component of the DCX(DET1-COP1) complex
• component of the DCX(DDB2) complex
• component of the DCX(ERCC8) complex
• component of the DCX(DTL) complex
• interacts with DDB1, RBX1, RNF7, CTD1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 & HOXA9
• interacts with DDB2; interactions with DDB2 & CAND1 are mutually exclusive
• interacts with VPRBP, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, RFWD2, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5 & DCAF8
• may interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5
• can self-associate

Structure

belongs to the cullin family

Alternative splicing

named isoforms=2

More general terms

• cullin
• phosphoprotein

Component of

• DDB1-CUL4-X-box complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8451
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8451
• OMIM: https://mirror.omim.org/entry/603137
• UniProt: http://www.uniprot.org/uniprot/Q13619.html