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FLASH GENE
Symbol CUL4B contributors: mct - updated : 09-10-2017
HGNC name cullin 4B
HGNC id 2555
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   moderately Homo sapiens
Digestiveliver   moderately Homo sapiens
Endocrinepancreas   moderately Homo sapiens
Lymphoid/Immunespleen   moderately Homo sapiens
Nervousbrain   moderately Homo sapiens
Reproductivefemale systemovary  moderately Homo sapiens
 male systemtestis  moderately Homo sapiens
Respiratorylung   moderately Homo sapiens
Urinarykidney   moderately Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal moderately Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, checkpoint, G1S
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a variable N-terminal helical domain
  • a nuclear localization signal in the N-terminus (
  • globular C-terminal domain
  • HOMOLOGY
    interspecies ortholog to Cul4b, Mus musculus
    ortholog to Cul4b, Rattus norvegicus
    ortholog to cul4b, Danio rerio
    intraspecies homolog to HS-CUL4A
    Homologene
    FAMILY
  • CRL4 proteins family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • probably involved in ubiquitination and subsequent proteasomal degradation of target proteins
  • plays a role in the polyubiquitination of CDT1 in response to radiation-induced DNA damage
  • ubiquitin E3 ligase subunit implicated in the regulation of several biological processes
  • scaffold protein that organizes a cullin-RING (really interesting new gene) ubiquitin ligase (E3) complex in ubiquitylation
  • required for H3 and H4 ubiquitination in response to ultraviolet and may be important for subsequent DNA repair
  • targeting cyclin E for ubiquitination and involved in cell cycle progression
  • unneddylated CUL4B isoforms exist in the brain and are necessary for mitosis progression in neural progenitor cells
  • scaffold protein involved in the assembly of cullin-RING ubiquitin ligase (E3) complexes
  • role of CUL4B in the regulation of replication licensing
  • might promote the progression of colon cancer
  • CUL4A and CUL4B are members of cullin family proteins that mediate ubiquitin dependent proteolysis
  • plays a crucial role in post-meiotic sperm development
  • it is possible that CUL4B-selective substrates are required for post-meiotic sperm morphogenesis
  • plays distinct roles in spermatogenesis from its homologous protein CUL4A
  • CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness
  • CUL4A and CUL4B are differentially associated with etiologic factors for pulmonary malignancies
  • CELLULAR PROCESS cell cycle, checkpoint
    cell cycle, progression
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, repair
    protein, degradation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text
  • negative regulator of proliferation
  • G1/S transition
  • PATHWAY
    metabolism
    signaling
    ubiquitin conjugation, third step
    a component
  • part of a complex with RBX1 and TIP120A/CAND1
  • part of an E3 ligase complex which interacts with and ubiquitinates CDT1
  • CUL4B-CDK2-CDC6 cascade in the regulation of DNA replication licensing
  • component of the CUL4B-Ring E3 ligase complex (CRL4B)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TIP120A (
  • multiple WD40-repeat proteins (WDRs) including TLE1-3, WDR5, L2DTL, Polycomb-group protein EED, H3 methylated mononucleosomes and peptides (
  • UV-damaged chromatin and ubiquitinates histone H2A (
  • TOP1 is a CUL4B-dependent substrate
  • WDR5 and core subunit of histone H3 lysine 4 (H3K4) methyltransferase complexes (
  • CUL4B E3 ubiquitin ligase plays a key role in targeting COPS5 for degradation, potentially revealing a previously undocumented mechanism for regulation of the BMP signaling pathway involved with the CUL4B-based E3 complex
  • CDC6, the licensing factor in replication, was positively regulated by CUL4B and contributed to the loading of MCM2 to chromatin
  • important negative regulatory role of CUL4B on TP53 stability
  • CUL4A or CUL4B may regulate the stability of TUBG1
  • INSL6 is a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase
  • cell & other
    REGULATION
    Other neddylated and deneddylated via its interaction with the COP9 signalosome complex
    ASSOCIATED DISORDERS
    corresponding disease(s) MRXSC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    led to upregulation of PPARG-regulated genes and facilitated adipogenesis
    tumoral        
    can effectively inhibit osteosarcoma cell proliferation and induce apoptosis
    tumoral     --over  
    high mRNA expression of CUL2, CUL4B, and CUL5 were correlated with better survival for breast cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • can be served as a novel independent prognostic marker for the prediction of recurrence in colon cancer
  • Therapy target
    SystemTypeDisorderPubmed
    obesity  
    could be a potential therapeutic target for combating obesity and metabolic syndromes
    cancerbone 
    biomarker for the treatment of osteosarcoma
    cancer  
    target for cancer therapy
    ANIMAL & CELL MODELS
  • RNA interference silencing of CUL4B led to an inhibition of cell proliferation and a prolonged S phase, due to the overaccumulation of cyclin E (
  • Knocking down CUL4B increases WDR5 and trimethylated H3K4 on the neuronal gene promoters and induces their expression (
  • CUL4B depletion suppresses neurite outgrowth of PC12 neuroendocrine cells (
  • Cul4b null mouse embryos show severe developmental arrest and usually die before embryonic day 9.5 (E9.5)