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DDB1-CUL4-X-box complex
Function:
- E3 ubiquitin-protein ligase complex
- DDB1 may recruit specific substrate targeting subunits to the DCX complex
- these substrate targeting subunits are generally known as DCAF (DDB1- & CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins
- DCX complexes may associate with the COP9 signalosome, & this inhibits the E3 ubiquitin-protein ligase activity of the complex
Structure:
- subunits seem to include DDB1, CUL4A or CUL4B, RBX1 & a variable substrate recognition components DCAF or CDW (see above)
Notes:
- DDCX complexes include
a) DCX(DET1-COP1) complex with the substrate recognition component DET1 & COP1
b) DCX(DDB2) complex
1] also known as
- DDB1-CUL4-ROC1,
- CUL4-DDB-ROC1
- CUL4-DDB-RBX1)
2] substrate recognition component DDB2
3] may ubiquitinate histone H2A, histone H3 & histone H4 at sites of UV-induced DNA damage
4] ubiquitination of histones may facilitate their removal from the nucleosome & promote subsequent DNA repair
5] also ubiquitinates XPC, which may enhance DNA-binding by XPC & promote nucleotide excision repair
c) DCX(ERCC8) complex
1] putative substrate recognition component ERCC8
2] role in transcription-coupled repair (TCR)
3] role in ubiquitination of CDKN1B/p27kip when associated with CUL4 & SKP2
d) DCX(DTL) complex
1] putative substrate recognition component DTL
2] role in PCNA-dependent polyubiquitination of CDT1
3] MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage & during DNA replication
General
molecular complex
Properties
SUBUNITS: DNA damage-binding protein 1
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: CDT1 interaction {1-768}
MOTIF: Thr phosphorylation site {T8}
CUL4A interaction {391-709}
Ser phosphorylation site {S757}
Ser phosphorylation site {S766}
CDT1/CUL4A interaction {771-1140}
Cullin-4A
MOTIF: Ser phosphorylation site {S10}
Thr phosphorylation site {T22}
Ser phosphorylation site {S99}
Tyr phosphorylation site {Y227}
Cullin-4B
COMPARTMENT: cell nucleus
MOTIF: serine-rich region {3-193}
MOTIF: serine residue (SEVERAL)
Thr phosphorylation site {T48}
Thr phosphorylation site {T49}
Thr phosphorylation site {T52}
Ser phosphorylation site {S53}
nuclear translocation signal {55-58}
Ser phosphorylation site {S138}
Ser phosphorylation site {S141}
Ser phosphorylation site {S142}
Ser phosphorylation site {S143}
Ser phosphorylation site {S144}
Ser phosphorylation site {S145}
Ser phosphorylation site {S146}
Thr phosphorylation site {T148}
Ser phosphorylation site {S152}
Ser phosphorylation site {S193}
RING-box protein 1
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
Ser phosphorylation site {S11}
Zn+2-binding site
SITE: 42-42
Zn+2-binding site
SITE: 45-45
RING-finger {53-98}
MOTIF: Zn+2-binding site
SITE: 53-53
Zn+2-binding site
SITE: 56-56
Zn+2-binding site
SITE: 68-68
Zn+2-binding site
SITE: 75-75
Zn+2-binding site
SITE: 77-77
Zn+2-binding site
SITE: 80-80
Zn+2-binding site
SITE: 82-82
Zn+2-binding site
SITE: 83-83
Zn+2-binding site
SITE: 94-94
Zn+2-binding site
SITE: 97-97
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
References
UniProt :accession Q13619
Components
Cullin-4A; CUL-4A (CUL4A)
Cullin-4B; CUL-4B (CUL4B KIAA0695)
DNA damage-binding protein 1; damage-specific DNA-binding protein 1; UV-damaged DNA-binding factor; DDB p127 subunit; DNA damage-binding protein a; DDBa; UV-damaged DNA-binding protein 1; UV-DDB 1; Xeroderma pigmentosum group E-complementing protein; XPCe; XPE-binding factor; XPE-BF; HBV X-associated protein 1; XAP-1 (DDB1, XAP1)
RING-box protein 1; Rbx1; regulator of cullins 1; RING finger protein 75; protein ZYP (RBX1 RNF75 ROC1)