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
  • mental retardation syndromic X-linked type 15
  • mental retardation syndromic X-linked Cabezas type

More general terms

• cullin
• phosphoprotein
• nuclear protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8450
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8450
• OMIM: https://mirror.omim.org/entry/300304
• OMIM: https://mirror.omim.org/entry/300354
• OMIM: https://mirror.omim.org/entry/300639
• UniProt: http://www.uniprot.org/uniprot/Q13620.html