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FLASH GENE
Symbol CUL4A contributors: mct - updated : 11-10-2017
HGNC name cullin 4A
HGNC id 2554
Location 13q34      Physical location : 113.863.085 - 113.919.391
Synonym symbol(s) CUL4, CUL-4A
DNA
TYPE functioning gene
STRUCTURE 56.31 kb     20 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC387947 13 LOC387947 LOC390426 13 similar to mKIAA0324 protein SOX1 13q34 SRY (sex determining region Y)-box 1 LOC387948 13 LOC387948 LOC122258 13q34 LOC122258 TUBGCP3 13q34 tubulin, gamma complex associated protein 3 LOC387949 13 LOC387949 ATP11A 13q34 ATPase, Class VI, type 11A LOC387950 13 LOC387950 MCF2L 13q34 MCF.2 cell line derived transforming sequence-like F7 13q34 coagulation factor VII (serum prothrombin conversion accelerator) F10 13q34 coagulation factor X PROZ 13q34 protein Z, vitamin K-dependent plasma glycoprotein FLJ11305 13q34 hypothetical protein FLJ11305 CUL4A 13q34-qter cullin 4A LAMP1 13q34 lysosomal-associated membrane protein 1 GRTP1 4q14 growth hormone regulated TBC protein 1 LOC387951 13 LOC387951 ADPRHL1 13q34 ADP-ribosylhydrolase like 1 C13orf17 13q34 chromosome 13 open reading frame 17 C13orf11 13q34 chromosome 13 open reading frame 11 TFDP1 13q34 transcription factor Dp-1 ATP4B 13q34 ATPase, H+/K+ exchanging, beta polypeptide RHOK 13q34 rhodopsin kinase LOC387952 13 hypothetical gene supported by AK126042; BC034570 GAS6 13q34 growth arrest-specific 6 MGC20579 13q34 hypothetical protein MGC20579 RASA3 13q34 RAS p21 protein activator 3 LOC390427 13 LOC390427 CDC16 13q34 CDC16 cell division cycle 16 homolog (S. cerevisiae) UPF3A 13q34 UPF3 regulator of nonsense transcripts homolog A (yeast) C13orf8 13q34 chromosome 13 open reading frame 8
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
20 - 3797 87 759 - 1998 9694792
20 - 3735 76 659 - 1998 9694792
using an alternate 5' exons
EXPRESSION
Type ubiquitous
constitutive of
   expressed in (based on citations)
organ(s)
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, checkpoint, G1S
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • ubiquitin domain
  • HOMOLOGY
    interspecies homolog to murine Cul4a (95.8pc)
    intraspecies homolog to CUL4B
    Homologene
    FAMILY
  • CRL4 proteins family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • playing a critical role in early embryonic development
  • functionning as an E3 ubiquitin ligase
  • involved in ubiquitination and proteasomal degradation of target proteins
  • playing a role in the polyubiquitination of CDT1 in response to radiation-induced DNA damage
  • may be important for subsequent DNA repair
  • involved in the MDM2-mediated proteolysis of TP53
  • novel function of CUL4A in meiotic recombination and an essential role of CUL4A in spermatogenesis
  • CUL4A and CUL4B are members of cullin family proteins that mediate ubiquitin dependent proteolysis
  • plays distinct roles in spermatogenesis from its homologous protein CUL4B
  • CUL4A and CUL4B are differentially associated with etiologic factors for pulmonary malignancies
  • CELLULAR PROCESS cell cycle, checkpoint
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, repair
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text
  • negative regulator of cell proliferation
  • G1/S transition
  • PATHWAY
    metabolism
    signaling
    DDB1-CUL4A and MLL1 complexes constitute a novel pathway that mediates CDKN2A activation during oncogenic checkpoint response and is repressed by the polycomb repression complexes during normal growth of young cells
    a component
  • component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, COP1 and CUL4A
  • part of an E3 ubiquitin ligase complex composed of RBX1, DDB1, DDB2 and CUL4A
  • FBXW5DDB1CUL4ARBX1 may function to regulate the homeostasis of TSC complexes instead of mediating a specific cellular growth condition
  • CUL4A/DTL E3 ubiquitin ligase plays an essential role in DNA replication origin licensing directing degradation of several licensing factors at the G1/S transition in order to prevent DNA re-replication
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • modifying NEDD8
  • CLECSF6, DDB2
  • interacting with RBX1, RNF7 and TIP120A/CAND1
  • associating with TP53 and MDM2
  • associating stoichiometrically with DDB1 and this association is negatively regulated by the cullin-associated and neddylation-dissociated protein, CAND1
  • directly binds to CDKN1A and silencing DDB1 blocks Ras-induced CDKN1A activation
  • TOP1 is a CUL4A-dependent substrate
  • CUL4A interacts with TP53 and induces its decay
  • CUL4A or CUL4B may regulate the stability of TUBG1
  • SUGT1-HSP90AA1 complex contributes to the E3 ligase activity of the CUL4A complex that is necessary for CENPA ubiquitylation and CENPA deposition at the centromere
  • cell & other
    REGULATION
    Other major target protein of the ubiquitin-like protein NEDD8
    regulated by DET1 (DET1 complex modulates CUL4A functions by a novel mechanism) (Pick 2007)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    amplified in breast and liver cancers
    tumoral     --over  
    in breast carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • testes of the Cul4A-/- mice exhibit extensive apoptosis