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FLASH GENE
Symbol CUL4B contributors: mct - updated : 09-10-2017
HGNC name cullin 4B
HGNC id 2555
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)