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    CUL4A cullin 4A [ Homo sapiens ]

    Gene ID: 8451, updated on 11-May-2012
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    Summary

    Official Symbol
    CUL4Aprovided by HGNC
    Official Full Name
    cullin 4Aprovided by HGNC
    Primary source
    HGNC:2554
    Locus tag
    RP11-391H12.1
    See related
    Ensembl:ENSG00000139842; HPRD:07218; MIM:603137; Vega:OTTHUMG00000017384
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    CUL4A is the ubiquitin ligase component of a multimeric complex involved in the degradation of DNA damage-response proteins (Liu et al., 2009 [PubMed 19481525]).[supplied by OMIM, Oct 2009]
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    Genomic context

    Location :
    13q34
    Sequence :
    Chromosome: 13; NC_000013.10 (113863086..113919392)
    See CUL4A in Epigenomics, MapViewer

    Chromosome 13 - NC_000013.10Genomic Context describing neighboring genes Neighboring gene protein Z, vitamin K-dependent plasma glycoprotein Neighboring gene PCI domain containing 2 Neighboring gene lactate dehydrogenase B pseudogene 1 Neighboring gene lysosomal-associated membrane protein 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. VprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity. Kassmeier MD, et al. EMBO J, 2011 Dec 13. PMID 22157821.
    2. A cohesin-RAD21 interactome. Panigrahi AK, et al. Biochem J, 2012 Mar 15. PMID 22145905.
    3. Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia-reoxygenation injury in pheochromocytoma (PC12) cells. Tan C, et al. Biochem Biophys Res Commun, 2011 Dec 16. PMID 22120631.
    4. The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation. Fischer ES, et al. Cell, 2011 Nov 23. PMID 22118460.
    5. The stability of histone acetyltransferase general control non-derepressible (Gcn) 5 is regulated by Cullin4-RING E3 ubiquitin ligase. Li Y, et al. J Biol Chem, 2011 Dec 2. PMID 21987584.

    See all (97) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. study indicates that Cul4A amplification and overexpression play an oncogenic role in the pathogenesis of mesothelioma
      Title: Cul4A is an oncogene in malignant pleural mesothelioma.
    2. hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival.
      Title: Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia-reoxygenation injury in pheochromocytoma (PC12) cells.
    3. Studies indicate the modular architecture of DDB1-CUL4 in complex with DDB2, CSA and CDT2 in DNA repair of UV-induced DNA lesions.
      Title: Detecting UV-lesions in the genome: The modular CRL4 ubiquitin ligase does it best!
    4. the CUL4A.DDB1 E3 complex is important for regulation of RASSF1A during mitosis, and it may contribute to inactivation of RASSF1A and promoting cell cycle progression
      Title: Cullin-4A·DNA damage-binding protein 1 E3 ligase complex targets tumor suppressor RASSF1A for degradation during mitosis.
    5. Observational study of gene-disease association. (HuGE Navigator)
      Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
    6. Increased PRMT5 activity mediates key events associated with cyclin D1-dependent neoplastic growth, including CUL4 repression, CDT1 overexpression, and DNA rereplication.
      Title: Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase.
    7. This study identifies CRL4-Cdt2 ubiquitin ligase to promote the ubiquitin-dependent proteolysis of the histone H4 methyltransferase Set8 during S-phase of the cell cycle and after UV-irradiation in a reaction that is dependent on PCNA.
      Title: CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation.
    8. 13q34 amplification may be of relevance in tumor progression of breast cancers by inducing overexpression of CUL4A and TFDP1, important in cell cycle regulation. These genes were also overexpressed in non-basal-like tumor samples.
      Title: Comprehensive characterization of the DNA amplification at 13q34 in human breast cancer reveals TFDP1 and CUL4A as likely candidate target genes.
    9. DDB1 modulates the function of APC/C(Cdh1) in a manner independent of the Cul4-DDB1 complex
      Title: Damaged DNA-binding protein 1 (DDB1) interacts with Cdh1 and modulates the function of APC/CCdh1.
    10. the interplay between CUL4A and CUL4B in pathogenesis of CUL4B-deficiency in humans
      Title: Mutations in Cullin 4B result in a human syndrome associated with increased camptothecin-induced topoisomerase I-dependent DNA breaks.
    Submit: New GeneRIF Correction See all (36)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_003580.1 NP_001914.2 DDB1    BIND  PubMed DDB1 Interacts with CUL4A. 
    NP_003580.1 NP_001914.2 DDB1    BIND  PubMed DDB1 interacts with CUL4A. 
    NP_003580.1 NP_055063.1 RBX1    BIND  PubMed ROC1 interacts with Cul4A. 
    Q13619 Q86VP6 CAND1    HPRD  PubMed  
    Q13619 P46527 CDKN1B    HPRD  PubMed  
    Q13619 O14757 CHEK1    HPRD  PubMed  
    Q13619 Q16531 DDB1    HPRD  PubMed  
    Q13619 Q13309 SKP2    HPRD  PubMed  
    BioGRID:114029 BioGRID:120765 AMBRA1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:198236 Atm    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:114342 BANF1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:119828 BRWD1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:120937 CAND1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:114029 BioGRID:107460 CDKN1A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:107461 CDKN1B    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:123555 CDT1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:114029 BioGRID:107536 CHEK1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:127317 COMMD1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:114729 COPS2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:114103 COPS3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:119324 COPS4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:116183 COPS5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:116176 COPS6    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:119130 COPS7A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:122237 COPS7B    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:116124 COPS8    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:119360 CRBN    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:114029 BioGRID:114028 CUL4B    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:114029 BioGRID:122612 DCAF10    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:123251 DCAF11    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:114029 BioGRID:117377 DCAF12    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:124705 DCAF15    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:120224 DCAF16    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:123098 DCAF17    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:117545 DCAF4    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:114029 BioGRID:114343 DCAF5    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:114029 BioGRID:120933 DCAF6    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:114029 BioGRID:119121 DCAF8    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:122485 DDA1    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:114029 BioGRID:108009 DDB1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex; Two-hybrid 
    BioGRID:114029 BioGRID:108010 DDB2    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114029 BioGRID:120387 DET1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114029 BioGRID:108126 DNMT3B    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:119582 DTL    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114029 BioGRID:199074 Ddb1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:218345 Dtl    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:114265 EED    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:108325 EMD    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:107581 ERCC8    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:119967 FBXW5    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:123751 GRWD1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:113946 HIST1H3A    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114029 BioGRID:109445 HOXA9    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114029 BioGRID:109552 HSP90AA1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:109535 HSPA1A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:108918 KAT2A    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:114029 BioGRID:115156 KEAP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:110694 MYC    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:110815 NEDD8    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:110844 NF2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:111142 PCNA    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:120353 PHIP    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:129421 POC1B    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:111715 PTGS2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:111822 RAD21    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:111832 RAG1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:116356 RASSF1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:111864 RBBP5    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:115301 RBX1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Two-hybrid 
    BioGRID:114029 BioGRID:122136 RFWD2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:114977 RNF7    BioGRID  PubMed Two-hybrid 
    BioGRID:114029 BioGRID:112204 SALL2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114029 BioGRID:122735 SAP130    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:112393 SKP2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:114805 SNRNP40    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:112944 TLE2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:127870 TOR1AIP2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:117569 TRPC4AP    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:114029 BioGRID:115651 TUBA1B    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:117507 UBXN7    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114029 BioGRID:115079 VPRBP    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114029 BioGRID:123195 WDR26    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:116272 WDR5    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:120039 WDR5B    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:123255 WDR61    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:123035 WDR76    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:123245 WDR82    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114029 BioGRID:116677 WDTC1    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:114029 BioGRID:1205540 vpr    BioGRID  PubMed Affinity Capture-Western 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Cul4-DDB1-CSA complex, organism-specific biosystem (from KEGG)
      Cul4-DDB1-CSA complex, organism-specific biosystemStructural complex; Genetic information processing; Ubiquitin system
    • Cul4-DDB1-DDB2 complex, organism-specific biosystem (from KEGG)
      Cul4-DDB1-DDB2 complex, organism-specific biosystemStructural complex; Genetic information processing; Ubiquitin system
    • Nucleotide excision repair, organism-specific biosystem (from KEGG)
      Nucleotide excision repair, organism-specific biosystemNucleotide excision repair (NER) is a mechanism to recognize and repair bulky DNA damage caused by compounds, environmental carcinogens, and exposure to UV-light. In humans hereditary defects in the ...
    • Nucleotide excision repair, conserved biosystem (from KEGG)
      Nucleotide excision repair, conserved biosystemNucleotide excision repair (NER) is a mechanism to recognize and repair bulky DNA damage caused by compounds, environmental carcinogens, and exposure to UV-light. In humans hereditary defects in the ...
    • Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
      Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
    • Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
      Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    ubiquitin protein ligase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    DNA repair IEA
    Inferred from Electronic Annotation
    more info
    		  
    G1/S transition of mitotic cell cycle TAS
    Traceable Author Statement
    more info
    		 PubMed 
    cell cycle arrest TAS
    Traceable Author Statement
    more info
    		 PubMed 
    induction of apoptosis by intracellular signals TAS
    Traceable Author Statement
    more info
    		 PubMed 
    interspecies interaction between organisms IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of cell proliferation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    positive regulation of S phase of mitotic cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of mitotic cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of protein metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    CUL4 RING ubiquitin ligase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Cul4A-RING ubiquitin ligase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    cullin-4A
    Names
    cullin-4A
    CUL-4A
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001008895.1 → NP_001008895.1  cullin-4A isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      BC008308, BM835927, CA445237
      Consensus CDS
      CCDS41908.1
      UniProtKB/Swiss-Prot
      Q13619
      Related
      ENSP00000364589, OTTHUMP00000018754, ENST00000375440, OTTHUMT00000045888
      Conserved Domains (3) summary
      smart00182
      Location:442 – 582
      Blast Score: 461
      CULLIN; Cullin
      pfam00888
      Location:63 – 661
      Blast Score: 1370
      Cullin; Cullin family
      cl11186
      Location:688 – 753
      Blast Score: 255
      Cullin_Nedd8; Cullin protein neddylation domain

    2. NM_003589.2 → NP_003580.1  cullin-4A isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) utilizes an alternate 5' terminal exon, compared to variant 1, resulting in an isoform (2) with a shorter N-terminus.
      Source sequence(s)
      AF077188, BC015166, BM835927, BX439434, CA445237
      Consensus CDS
      CCDS9533.1
      UniProtKB/Swiss-Prot
      Q13619
      Related
      ENSP00000389118, ENST00000451881
      Conserved Domains (3) summary
      smart00182
      Location:342 – 482
      Blast Score: 459
      CULLIN; Cullin
      pfam00888
      Location:2 – 561
      Blast Score: 1296
      Cullin; Cullin family
      cl11186
      Location:588 – 653
      Blast Score: 254
      Cullin_Nedd8; Cullin protein neddylation domain

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000013.10 Reference GRCh37.p5 Primary Assembly

      Range
      113863086..113919392
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000145.1 Alternate HuRef

      Range
      94301970..94358301
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL136221.38 CAI13795.1
      CAM18410.1
    genomic CH471085.1 EAX09201.1
    mRNA AB012193.1 BAA33146.1
    mRNA AB178950.1 BAD93235.1
    mRNA AF077188.1 AAD45191.1
    mRNA AK296700.1 BAG59294.1
    mRNA AK314835.1 BAG37354.1
    mRNA AL833355.1 None
    mRNA AY365124.1 AAR13072.1
    mRNA BC008308.1 AAH08308.2
    mRNA BC015166.1 None
    mRNA BM835927.1 None
    mRNA BX439434.2 None
    mRNA CA445237.1 None
    mRNA U58090.1 AAC50547.1
    other-genetic EU176793.1 ABW03594.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13619.3 GenPept UniProtKB/Swiss-Prot:Q13619
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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