CUL4A cullin 4A [Homo sapiens (human)] - Gene

Summary

Official Symbol: CUL4Aprovided by HGNC
Official Full Name: cullin 4Aprovided by HGNC
Primary source: HGNC:HGNC:2554
See related: Ensembl:ENSG00000139842 MIM:603137; AllianceGenome:HGNC:2554
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: mouse all
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Genomic context

Location:: 13q34

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (113208193..113267108)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (112460539..112520767)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (113862507..113921422)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

circSNTB2 and CUL4A Induces Dysfunction of Nucleus Pulposus Cells by Competitively Binding miR-665.
Title: circSNTB2 and CUL4A Induces Dysfunction of Nucleus Pulposus Cells by Competitively Binding miR-665.
CUL4A Ubiquitin Ligase Is an Independent Predictor of Overall Survival in Pancreatic Adenocarcinoma.
Title: CUL4A Ubiquitin Ligase Is an Independent Predictor of Overall Survival in Pancreatic Adenocarcinoma.
S100 Calcium Binding Protein A16 Promotes Cell Proliferation by triggering LATS1 ubiquitin degradation mediated by CUL4A ligase to inhibit Hippo pathway in Glioma development.
Title: S100 Calcium Binding Protein A16 Promotes Cell Proliferation by triggering LATS1 ubiquitin degradation mediated by CUL4A ligase to inhibit Hippo pathway in Glioma development.
Lentivirus-mediated short hairpin RNA interference of CENPK inhibits growth of colorectal cancer cells with overexpression of Cullin 4A.
Title: Lentivirus-mediated short hairpin RNA interference of CENPK inhibits growth of colorectal cancer cells with overexpression of Cullin 4A.
Cullin 4A/protein arginine methyltransferase 5 (CUL4A/PRMT5) promotes cell malignant phenotypes and tumor growth in nasopharyngeal carcinoma.
Title: Cullin 4A/protein arginine methyltransferase 5 (CUL4A/PRMT5) promotes cell malignant phenotypes and tumor growth in nasopharyngeal carcinoma.
Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma.
Title: Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma.
Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine.
Title: Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine.
lncRNA NEAT1 facilitates the progression of colorectal cancer via the KDM5A/Cul4A and Wnt signaling pathway.
Title: lncRNA NEAT1 facilitates the progression of colorectal cancer via the KDM5A/Cul4A and Wnt signaling pathway.
CRL4A(DTL) degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation.
Title: CRL4A(DTL) degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation.
CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma.
Title: CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (111)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-W68080 (e-PCR)
- UniSTS:29269

WI-21043 (e-PCR)
- UniSTS:65880

SHGC-112141 (e-PCR)
- UniSTS:182674

CUL4A_1335 (e-PCR)
- UniSTS:277140

CUL4A_v414 (e-PCR)
- UniSTS:277140

WI-16281 (e-PCR)
- UniSTS:52904

D13S828E (e-PCR)
- UniSTS:151505

SHGC-110591 (e-PCR)
- UniSTS:167923

STS-W80462 (e-PCR)
- UniSTS:28152

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin ligase complex scaffold activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	EXP Inferred from Experiment more info	PubMed
involved_in DNA damage response	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in G1/S transition of mitotic cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in T cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to UV	EXP Inferred from Experiment more info	PubMed
involved_in hemopoiesis	IEA Inferred from Electronic Annotation more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of granulocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of G1/S transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA damage checkpoint	IEA Inferred from Electronic Annotation more info
involved_in regulation of nucleotide-excision repair	IEA Inferred from Electronic Annotation more info
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info
involved_in ribosome biogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in somatic stem cell population maintenance	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of Cul4-RING E3 ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
part_of Cul4A-RING E3 ubiquitin ligase complex	EXP Inferred from Experiment more info	PubMed
part_of Cul4A-RING E3 ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of Cul4A-RING E3 ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IC Inferred by Curator more info	PubMed
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: cullin-4A

Names: CUL-4A

NCBI Reference Sequences (RefSeq)

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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)

NM_001008895.4 → NP_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

A2A2W2, O75834, Q13619, Q589T6, Q5TC62, Q6UP08, Q9UP17

UniProtKB/TrEMBL

B2RBV7

Related

ENSP00000364589.4, ENST00000375440.9

Conserved Domains (2) summary

smart00884
Location:688 → 753

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:63 → 660

Cullin; Cullin family
NM_001278513.3 → NP_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)

AL136221, AL137002

Consensus CDS

CCDS9533.1

UniProtKB/TrEMBL

B2RBV7

Related

ENSP00000364590.3, ENST00000375441.7

Conserved Domains (2) summary

smart00884
Location:588 → 653

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:2 → 557

Cullin; Cullin family
NM_001278514.3 → NP_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, B2RBV7

Related

ENSP00000322132.5, ENST00000326335.8

Conserved Domains (2) summary

smart00884
Location:596 → 661

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:2 → 565

Cullin; Cullin family
NM_001354938.2 → NP_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

UniProtKB/TrEMBL

B2RBV7

Conserved Domains (2) summary

smart00884
Location:588 → 653

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:2 → 557

Cullin; Cullin family
NM_001354939.2 → NP_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

UniProtKB/TrEMBL

B2RBV7

Related

ENSP00000481782.1, ENST00000617546.4

Conserved Domains (2) summary

smart00884
Location:588 → 653

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:2 → 557

Cullin; Cullin family
NM_001354940.2 → NP_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

UniProtKB/TrEMBL

B2RBV7

Conserved Domains (2) summary

smart00884
Location:588 → 653

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:2 → 557

Cullin; Cullin family
NM_001354941.2 → NP_001341870.1 cullin-4A isoform 4

Status: REVIEWED

Source sequence(s)

AL136221, BC008308, BU631279, DA394068, DB455959

UniProtKB/TrEMBL

B2RBV7

Conserved Domains (2) summary

smart00884
Location:543 → 608

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:1 → 515

Cullin; Cullin family
NM_001354942.2 → NP_001341871.1 cullin-4A isoform 4

Status: REVIEWED

Source sequence(s)

AL136221, BC008308, BU631279, DA946208, DB455959

UniProtKB/TrEMBL

B2RBV7

Conserved Domains (2) summary

smart00884
Location:543 → 608

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:1 → 515

Cullin; Cullin family
NM_001354943.2 → NP_001341872.1 cullin-4A isoform 5

Status: REVIEWED

Source sequence(s)

BC008308, BQ185339, CK300635, DB455959

Consensus CDS

CCDS86363.1

UniProtKB/TrEMBL

A0A087WWN2

Related

ENSP00000480367.1, ENST00000488558.2

Conserved Domains (1) summary

pfam00888
Location:63 → 170

Cullin; Cullin family
NM_001354944.2 → NP_001341873.1 cullin-4A isoform 6

Status: REVIEWED

Source sequence(s)

BC008308, BQ185339, BX439434, CK300635

Conserved Domains (1) summary

cl26515
Location:2 → 70

Cullin; Cullin family
NM_003589.4 → NP_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/TrEMBL

B2RBV7

Related

ENSP00000389118.1, ENST00000451881.5

Conserved Domains (2) summary

smart00884
Location:588 → 653

Cullin_Nedd8; Cullin protein neddylation domain

pfam00888
Location:2 → 557

Cullin; Cullin family