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CUL4A cullin 4A [ Homo sapiens (human) ]

Gene ID: 8451, updated on 15-Apr-2019

Summary

Official Symbol
CUL4Aprovided by HGNC
Official Full Name
cullin 4Aprovided by HGNC
Primary source
HGNC:HGNC:2554
See related
Ensembl:ENSG00000139842 MIM:603137
Gene type
protein coding
RefSeq status
REVIEWED
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]
Expression
Ubiquitous expression in testis (RPKM 20.5), heart (RPKM 17.9) and 25 other tissues See more
Orthologs

Genomic context

See CUL4A in Genome Data Viewer
Location:
13q34
Exon count:
25
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 13 NC_000013.11 (113208193..113267108)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (113862507..113919392)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102724474 Neighboring gene protein Z, vitamin K dependent plasma glycoprotein Neighboring gene PCI domain containing 2 Neighboring gene uncharacterized LOC107984583 Neighboring gene microRNA 8075 Neighboring gene lactate dehydrogenase B pseudogene 1 Neighboring gene lysosomal associated membrane protein 1 Neighboring gene growth hormone regulated TBC protein 1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Rev rev HIV-1 Rev interacting protein, Cullin 4A (CUL4A), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with CUL4A is increased by RRE PubMed
Vif vif Both HIV-1 Vif-induced downregulation of APOBEC3G and efficient infectivity in the presence of APOBEC3G requires CUL4A neddylation PubMed
Vpr vpr Both HIV-2 Vpr and SIVmac239 Vpr induces G2 cell cycle arrest through either CUL4A or CUL4B PubMed
vpr The interaction of Vpr with DDB1 facilitates the formation of complexes containing Cul4A-Roc1 E3 ubiquitin ligase. The association of Vpr with DDB1-containing E3 ligase mediates the degradation of UNG2 and SMUG1 PubMed
vpr Upregulation of NKG2D ligands is dependent on HIV-1 Vpr-mediated activation of the TAR DNA damage/stress pathway, which requires the recruitment of the Cul4/DDB1/DCAF1 E3 ubiquitin ligase complex PubMed
vpr HIV-1 Vpr complexes with DCAF1, DDB1, CUL4A, CUL4B, and UNG2 proteins in the cullin4 (CUL4)-containing ubiquitin ligase complex in HEK293T cells PubMed
vpr Depletion of both CUL4A and CUL4B by shRNA reduces HIV-1 Vpr-mediated G2 cell cycle arrest, which does not impact HIV-1 infectivity or cell viability PubMed
vpr HIV-1 Vpr-mediated degradation of UNG2 is dependent on CUL4A neddylation PubMed
vpr The interaction between Vpr and the Cul4A-DDB1-VprBP complex is required for the induction of G2 arrest PubMed
vpr HIV-1 Vpr-mediated upregulation of PVR (CD155) requires the interaction of Vpr with the DDB1-Cul4A E3 ligase and induction of ATR-mediated DNA damage repair and G2 arrest PubMed
vpr HIV-1 Vpr-induced downregulation of Dicer is not dependent on G2 cell cycle arrest but on the Cul4A-DCAF1-DDB1 ubiquitin ligase complex PubMed
vpr HIV-1 Vpr co-localizes with the Cul4A ubiquitin ligase complex (Cul4A, DCAF1, and DDB1) in the cellular chromatin compartment PubMed
vpr HIV-1 Vpr forms a complex by recruiting RbAp46, HAT1, ZIP/sZIP, and Cul4A PubMed
vpr HIV-1 Vpr significantly downregulates expression level of MFN2 in the mitochondria via VprBP-DDB1-CUL4A ubiquitin ligase in a proteasome-dependent manner PubMed
vpr HIV-1 Vpr(Q65R) mutant, which is defective in Cul4A-DDB1 (DCAF1) binding, undergoes proteasome-mediated degradation at a higher rate than wild-type Vpr. DCAF1 overexpression stabilizes wild-type Vpr and leads to its cytoplasmic accumulation PubMed

Go to the HIV-1, Human Interaction Database

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-CSA complex, conserved biosystem (from KEGG)
    Cul4-DDB1-CSA complex, conserved 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
  • Cul4-DDB1-DDB2 complex, conserved biosystem (from KEGG)
    Cul4-DDB1-DDB2 complex, conserved biosystemStructural complex; Genetic information processing; Ubiquitin system
  • DNA Damage Bypass, organism-specific biosystem (from REACTOME)
    DNA Damage Bypass, organism-specific biosystemIn addition to various processes for removing lesions from the DNA, cells have developed specific mechanisms for tolerating unrepaired damage during the replication of the genome. These mechanisms ar...
  • DNA Damage Recognition in GG-NER, organism-specific biosystem (from REACTOME)
    DNA Damage Recognition in GG-NER, organism-specific biosystemIn global genome nucleotide excision repair (GG-NER), the DNA damage is recognized by two protein complexes. The first complex consists of XPC, RAD23A or RAD23B, and CETN2. This complex probes the DN...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • Dual Incision in GG-NER, organism-specific biosystem (from REACTOME)
    Dual Incision in GG-NER, organism-specific biosystemDouble incision at the damaged DNA strand excises the oligonucleotide that contains the lesion from the open bubble. The excised oligonucleotide is ~27-30 bases long. Incision 5' to the damage site, ...
  • Dual incision in TC-NER, organism-specific biosystem (from REACTOME)
    Dual incision in TC-NER, organism-specific biosystemIn transcription-coupled nucleotide excision repair (TC-NER), similar to global genome nucleotide excision repair (GG-NER), the oligonucleotide that contains the lesion is excised from the open bubbl...
  • Formation of Incision Complex in GG-NER, organism-specific biosystem (from REACTOME)
    Formation of Incision Complex in GG-NER, organism-specific biosystemAfter the XPC complex and the UV-DDB complex bind damaged DNA, a basal transcription factor TFIIH is recruited to the nucleotide excision repair (NER) site (Volker et al. 2001, Riedl et al. 2003). DN...
  • Formation of TC-NER Pre-Incision Complex, organism-specific biosystem (from REACTOME)
    Formation of TC-NER Pre-Incision Complex, organism-specific biosystemFormation of TC-NER pre-incision complex is initiated when the RNA polymerase II (RNA Pol II) complex stalls at a DNA damage site. The stalling is caused by misincorporation of a ribonucleotide oppos...
  • Gap-filling DNA repair synthesis and ligation in TC-NER, organism-specific biosystem (from REACTOME)
    Gap-filling DNA repair synthesis and ligation in TC-NER, organism-specific biosystemIn transcription-coupled nucleotide excision repair (TC-NER), similar to global genome nucleotide excision repair (GG-NER), DNA polymerases delta or epsilon, or the Y family DNA polymerase kappa, fil...
  • Global Genome Nucleotide Excision Repair (GG-NER), organism-specific biosystem (from REACTOME)
    Global Genome Nucleotide Excision Repair (GG-NER), organism-specific biosystemThe DNA damage in GG-NER is recognized by the joint action of two protein complexes. The first complex is composed of XPC, RAD23A or RAD23B and CETN2. The second complex, known as the UV-DDB complex,...
  • Nucleotide Excision Repair, organism-specific biosystem (from REACTOME)
    Nucleotide Excision Repair, organism-specific biosystemNucleotide excision repair (NER) was first described in the model organism E. coli in the early 1960s as a process whereby bulky base damage is enzymatically removed from DNA, facilitating the recove...
  • 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 ...
  • Recognition of DNA damage by PCNA-containing replication complex, organism-specific biosystem (from REACTOME)
    Recognition of DNA damage by PCNA-containing replication complex, organism-specific biosystemDamaged double strand DNA (dsDNA) cannot be successfully used as a template by replicative DNA polymerase delta (POLD) and epsilon (POLE) complexes (Hoege et al. 2002). When the replication complex c...
  • Transcription-Coupled Nucleotide Excision Repair (TC-NER), organism-specific biosystem (from REACTOME)
    Transcription-Coupled Nucleotide Excision Repair (TC-NER), organism-specific biosystemDNA damage in transcribed strands of active genes is repaired through a specialized nucleotide excision repair (NER) pathway known as transcription-coupled nucleotide excision repair (TC-NER). TC-NER...
  • 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...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
DNA damage response, detection of DNA damage TAS
Traceable Author Statement
more info
 
G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
PubMed 
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell cycle arrest TAS
Traceable Author Statement
more info
PubMed 
cellular response to DNA damage stimulus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
global genome nucleotide-excision repair TAS
Traceable Author Statement
more info
 
hemopoiesis IEA
Inferred from Electronic Annotation
more info
 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
intrinsic apoptotic signaling pathway TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
negative regulation of granulocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
nucleotide-excision repair, DNA damage recognition TAS
Traceable Author Statement
more info
 
nucleotide-excision repair, DNA duplex unwinding TAS
Traceable Author Statement
more info
 
nucleotide-excision repair, DNA incision TAS
Traceable Author Statement
more info
 
nucleotide-excision repair, DNA incision, 3'-to lesion TAS
Traceable Author Statement
more info
 
nucleotide-excision repair, DNA incision, 5'-to lesion TAS
Traceable Author Statement
more info
 
nucleotide-excision repair, preincision complex assembly TAS
Traceable Author Statement
more info
 
nucleotide-excision repair, preincision complex stabilization TAS
Traceable Author Statement
more info
 
positive regulation of G1/S transition of mitotic cell cycle IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
post-translational protein modification TAS
Traceable Author Statement
more info
 
proteasome-mediated ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
proteasome-mediated ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein ubiquitination IEA
Inferred from Electronic Annotation
more info
 
protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of DNA damage checkpoint IEA
Inferred from Electronic Annotation
more info
 
regulation of nucleotide-excision repair IEA
Inferred from Electronic Annotation
more info
 
regulation of protein metabolic process IEA
Inferred from Electronic Annotation
more info
 
somatic stem cell population maintenance IEA
Inferred from Electronic Annotation
more info
 
transcription-coupled nucleotide-excision repair TAS
Traceable Author Statement
more info
 
ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Cul4-RING E3 ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Cul4-RING E3 ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
Cul4A-RING E3 ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Cul4A-RING E3 ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
SCF ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cullin-RING ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 

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_001008895.4NP_001008895.1  cullin-4A isoform 1

    See identical proteins and their annotated locations for NP_001008895.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AL136221, BC008308, BU631279, DB455959
    Consensus CDS
    CCDS41908.1
    UniProtKB/Swiss-Prot
    Q13619
    Related
    ENSP00000364589.4, ENST00000375440.9
    Conserved Domains (2) summary
    smart00884
    Location:688753
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:65657
    Cullin; Cullin family
  2. NM_001278513.2NP_001265442.1  cullin-4A isoform 2

    See identical proteins and their annotated locations for NP_001265442.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) utilizes an alternate 5' terminal exon, compared to variant 1, resulting in an isoform (2) with a shorter N-terminus. Variants 2, 3, 5, 6, and 7 all encode the same isoform (2).
    Source sequence(s)
    AK314835, AL136221, BC008308, BU631279, DA478924
    Consensus CDS
    CCDS9533.1
    UniProtKB/Swiss-Prot
    Q13619
    Related
    ENSP00000364590.3, ENST00000375441.7
    Conserved Domains (2) summary
    smart00884
    Location:588653
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:2557
    Cullin; Cullin family
  3. NM_001278514.2NP_001265443.1  cullin-4A isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) utilizes an alternate 5' terminal exon and an alternate in-frame splice junction, compared to variant 1. This results in an isoform (3) with a shorter N-terminus and an alternate internal segment compared to isoform 1.
    Source sequence(s)
    AL136221, AL833355, BU631279, DA574202
    Consensus CDS
    CCDS73604.1
    UniProtKB/TrEMBL
    A0A0A0MR50
    Related
    ENSP00000322132.5, ENST00000326335.8
    Conserved Domains (2) summary
    smart00884
    Location:596661
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:2565
    Cullin; Cullin family
  4. NM_001354938.1NP_001341867.1  cullin-4A isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) utilizes an alternate 5' terminal exon, compared to variant 1, resulting in an isoform (2) with a shorter N-terminus. Variants 2, 3, 5, 6, and 7 all encode the same isoform (2).
    Source sequence(s)
    AK314835, AL136221, BC008308, BU631279, DA574202
    Consensus CDS
    CCDS9533.1
    Conserved Domains (2) summary
    smart00884
    Location:588653
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:2557
    Cullin; Cullin family
  5. NM_001354939.1NP_001341868.1  cullin-4A isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) utilizes an alternate 5' terminal exon, compared to variant 1, resulting in an isoform (2) with a shorter N-terminus. Variants 2, 3, 5, 6, and 7 all encode the same isoform (2).
    Source sequence(s)
    AF077188, AL136221, BC015166, BU631279, BX439434, CA445237
    Consensus CDS
    CCDS9533.1
    Related
    ENSP00000481782.1, ENST00000617546.4
    Conserved Domains (2) summary
    smart00884
    Location:588653
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:2557
    Cullin; Cullin family
  6. NM_001354940.1NP_001341869.1  cullin-4A isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) uses an alternate splice site, resulting in the use of a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus than isoform 1. Variants 2, 3, 5, 6, and 7 all encode the same isoform (2).
    Source sequence(s)
    AF077188, AL136221, BC015166, BU631279, CA445237, DA394068, DB455959
    Consensus CDS
    CCDS9533.1
    Conserved Domains (2) summary
    smart00884
    Location:588653
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:2557
    Cullin; Cullin family
  7. NM_001354941.1NP_001341870.1  cullin-4A isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL136221, BC008308, BU631279, DA394068, DB455959
    Conserved Domains (2) summary
    smart00884
    Location:543608
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:1512
    Cullin; Cullin family
  8. NM_001354942.1NP_001341871.1  cullin-4A isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL136221, BC008308, BU631279, DA946208, DB455959
    Conserved Domains (2) summary
    smart00884
    Location:543608
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:1512
    Cullin; Cullin family
  9. NM_001354943.1NP_001341872.1  cullin-4A isoform 5

    Status: REVIEWED

    Source sequence(s)
    BC008308, BQ185339, CK300635, DB455959
    Consensus CDS
    CCDS86363.1
    Related
    ENSP00000480367.1, ENST00000488558.2
    Conserved Domains (1) summary
    cl26515
    Location:65170
    Cullin; Cullin family
  10. NM_001354944.1NP_001341873.1  cullin-4A isoform 6

    Status: REVIEWED

    Source sequence(s)
    BC008308, BQ185339, BX439434, CK300635
    Conserved Domains (1) summary
    cl26515
    Location:270
    Cullin; Cullin family
  11. NM_003589.3NP_003580.1  cullin-4A isoform 2

    See identical proteins and their annotated locations for NP_003580.1

    Status: REVIEWED

    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. Variants 2, 3, 5, 6, and 7 all encode the same isoform (2).
    Source sequence(s)
    AF077188, AL136221, BC015166, BU631279, BX439434, CA445237
    Consensus CDS
    CCDS9533.1
    UniProtKB/Swiss-Prot
    Q13619
    Related
    ENSP00000389118.1, ENST00000451881.5
    Conserved Domains (2) summary
    smart00884
    Location:588653
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:2557
    Cullin; Cullin family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p12 Primary Assembly

    Range
    113208193..113267108
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011537523.2XP_011535825.1  cullin-4A isoform X1

    See identical proteins and their annotated locations for XP_011535825.1

    UniProtKB/Swiss-Prot
    Q13619
    Conserved Domains (2) summary
    smart00884
    Location:588653
    Cullin_Nedd8; Cullin protein neddylation domain
    pfam00888
    Location:2557
    Cullin; Cullin family
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