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Cullin-4B; CUL-4B (CUL4B KIAA0695)
Function:
- core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination & subsequent proteasomal degradation of target proteins.
- functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit
- CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate & the ubiquitin-conjugating enzyme
- plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 & histone H4 in response to radiation-induced DNA damage
- targeted to UV damaged chromatin by DDB2
- may be important for DNA repair & DNA replication
- required for ubiquitination of cyclin E, & consequently, normal G1 cell cycle progression
- regulates mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size & metabolism
- specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function & requires interaction between CUL4B & MLST8
- protein modification; protein ubiquitination
- neddylated. deneddylated via its interaction with the COP9 signalosome (CSN complex)
- component of multiple DDB1-CUL4-X-box (DCX) complex(es)
- component of the DCX(DDB2) complex
- part of a complex with RBX1 & TIP120A/CAND1
- interacts with RBX1 GRWD1, MLST8, SMU1, TLE2, TLE3, VPRBP, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 & TMEM113
- interacts with cyclin E & with importin alpha-1 (KPNA2), importin alpha-3 (KPNA4), importin alpha-5 (KPNA1) & importin beta-1 (KPNB1)
- may interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 & WDR5
Structure: belongs to the cullin family
Compartment: nucleus
Alternative splicing: named isoforms=3
Pathology:
- defects in CUL4B are the cause of
a) mental retardation syndromic X-linked type 15
b) mental retardation syndromic X-linked Cabezas type
General
cullin
nuclear protein
phosphoprotein
Properties
SIZE: entity length = 913 aa
MW = 104 kD
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}
Database Correlations
OMIM correlations
UniProt Q13620
PFAM correlations
Entrez Gene 8450
Kegg hsa:8450
References
- UniProt :accession Q13620
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/CUL4B
- Entrez Gene :accession 8450
Component-of
DDB1-CUL4-X-box complex