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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
General
cullin
phosphoprotein
Properties
SIZE: entity length = 759 aa
MW = 88 kD
MOTIF: Ser phosphorylation site {S10}
Thr phosphorylation site {T22}
Ser phosphorylation site {S99}
Tyr phosphorylation site {Y227}
Database Correlations
OMIM 603137
UniProt Q13619
PFAM correlations
Entrez Gene 8451
Kegg hsa:8451
References
- UniProt :accession Q13619
- Entrez Gene :accession 8451
Component-of
DDB1-CUL4-X-box complex