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FLASH GENE
Symbol CUL4B contributors: mct - updated : 09-10-2017
HGNC name cullin 4B
HGNC id 2555
Corresponding disease
MRXSC X-linked mental retardation, syndromic 15 (Cabezas type)
Location Xq24      Physical location : 119.658.447 - 119.709.684
Synonym name
  • CUL-4B
  • cullin-4B
  • Synonym symbol(s) KIAA0695, DKFZp686F1470, SFM2, MRXHF2, MRXS15, MRXSC
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 51.24 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - DXS8064 - DXS8067 - CUL4B - DXS1001 - GATA165B12 - qter
    Physical map
    LOC389883 X similar to Hnrpa1 protein PGRMC1 Xq22-q24 progesterone receptor membrane component 1 LOC139516 Xq24 similar to DNA segment on chromosome X and Y (unique) 155 expressed sequence; Pseudoautosomal gene XE7 (Y chromosome) MRPS17P9 Xq24 similar to DNA segment on chromosome X and Y (unique) 155 expressed sequence; Pseudoautosomal gene XE7 (Y chromosome) LOC203427 Xq24 similar to solute carrier family 25 , member 16 SLC25A5 Xq24-q26 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5 FLJ22965 Xq23 hypothetical protein FLJ22965 UBE2A Xq24-q25 ubiquitin-conjugating enzyme E2A (RAD6 homolog) NRF Xq24-q25 ubiquitin-conjugating enzyme E2A (RAD6 homolog) SEPT6 Xq24 ubiquitin-conjugating enzyme E2A (RAD6 homolog) LOC347454 Xq25 similar to hypothetical protein A630014H24 RPL39 Xq22.1-q22.2 ribosomal protein L39 LOC158796 Xq25 similar to UPF3 regulator of nonsense transcripts homolog B isoform 2 UPF3B Xq25-q26 UPF3 regulator of nonsense transcripts homolog B (yeast) ZNF183 Xq24-q25 zinc finger protein 183 (RING finger, C3HC4 type) NDUFA1 Xq24 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa AKAP28 Xq25 A-kinase anchor protein 28 NKAP Xq25 NF-kappaB activating protein OTEX Xq25 paired-like homeobox protein OTEX LOC392530 X similar to hypothetical protein FLJ22626 PEPP-2 Xq25 PEPP subfamily gene 2 LOC340576 Xq25 similar to eukaryotic translation elongation factor 1 alpha 1; CTCL tumor antigen; translation elongation factor 1 alpha 1-like 14; prostate tumor-inducing protein 1; EF1a-like protein; glucocorticoid receptor AF-1 specific elongati FLJ36576 Xq25 hypothetical protein FLJ36576 ZNF-kaiso Xq23 kaiso FLJ20716 Xq25 hypothetical protein FLJ20716 ATP1B4 Xq24 ATPase, (Na+)/K+ transporting, beta 4 polypeptide LAMP2 Xq24 lysosomal-associated membrane protein 2 RNU7P1 Xq25 RNA, U7 small nuclear pseudogene 1 RNU7P2 Xq25 RNA, U7 small nuclear pseudogene 2 CUL4B Xq23 cullin 4B MCTS1 Xq22-24 malignant T cell amplified sequence 1 C1GALT2 Xq25 core 1 UDP-galactose:N-acetylgalactosamine-alpha-R beta 1,3-galactosyltransferase 2 LOC392531 X similar to RIKEN cDNA 2900070E19 LOC389884 X similar to Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog) (hG4-1) LOC255313 Xq25 hypothetical protein LOC255313 GLUD2 Xq25 glutamate dehydrogenase 2 LOC158714 Xq25 heat shock 70kDa protein 8 pseudogene LOC392532 X similar to Translationally controlled tumor protein (TCTP) (p23) (Histamine-releasing factor) (HRF)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 5365 - 913 more abundant in the brain 2012 22992378
  • isoform 1, CUL4B-1, unneddylated
  • 20 - 5198 - 895 - 2012 22992378
  • isoform 2
  • Cul4B-3 that misses the N-terminus present in the other two isoforms, and is neddylated
  • - - 5019 - 900 more abundant in the brain 2012 22992378
  • CUL4B-2, unneddylated
  • 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
    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)