Tchem CUL4A Cullin-4A

Protein Summary

Description

Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. DCX(DTL) directs autoubiquitination of DTL. 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]

Uniprot Accession IDs

• Q13619
• A2A2W2
• O75834
• Q589T6
• Q5TC62
• Q6UP08
• Q9UP17
• CUL-4A

Gene Name

• CUL4A

Ensembl ID

• ENST00000375440
• ENSP00000364589
• ENSG00000139842
• ENST00000375441
• ENSP00000364590
• ENST00000451881
• ENSP00000389118
• ENST00000617546
• ENSP00000481782

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.98
transcription factor binding site profile	0.9
biological process	0.86
protein domain	0.85
protein complex	0.84

Protein Classes

PANTHER Classes

Protein / Ligase / Ubiquitin-protein Ligase / Cullin-4a

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / Cullin-4a

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 110.86   (req: < 5)

Gene RIFs: 85   (req: <= 3)

Antibodies: 357   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 110.86   (req: >= 5)

Gene RIFs: 85   (req: > 3)

Antibodies: 357   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 28

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 9

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (9)

Explore Active Ligands

1 – 9 of 9

CHEMBL4539276

CUL4ATchem

pIC50 : 6.94

CHEMBL4585473

CUL4ATchem

pIC50 : 6.85

CHEMBL4462527

CUL4ATchem

pIC50 : 6.72

CHEMBL4444266

CUL4ATchem

pIC50 : 6.63

CHEMBL4475993

CUL4ATchem

pIC50 : 6.33

CHEMBL1532407

CUL4ATchem

pIC50 : 6.26

CHEMBL4592960

CUL4ATchem

pIC50 : 6.13

CHEMBL4442009

CUL4ATchem

pIC50 : 6.03

CHEMBL1540912

CUL4ATchem

pIC50 : 6

Protein-Protein Interactions (295)

Explore Interacting Targets

1 – 10 of 295

• See Interactions on String-DB

DCAF4

Tbio

Novelty:  0.24190895

p_int:  0.999929357

p_ni:  0.000070643

Score:  0.985

Data Source:  BioPlex,STRINGDB

DCAF8

Tbio

Novelty:  0.12456534

p_int:  0.999925487

p_ni:  0.000074513

Score:  0.934

Data Source:  BioPlex,STRINGDB

DCAF11

Tbio

Novelty:  0.08318661

p_int:  0.999923934

p_ni:  0.000076066

Score:  0.989

Data Source:  BioPlex,STRINGDB

DDB2

Tbio

Novelty:  0.00648809

p_int:  0.999896428

p_ni:  0.000103572

Score:  0.996

Data Source:  BioPlex,Reactome,STRINGDB

WDTC1

Tbio

Novelty:  0.02300849

p_int:  0.999891733

p_ni:  0.000108267

Score:  0.935

Data Source:  BioPlex,STRINGDB

DET1

Tbio

Novelty:  0.01138079

p_int:  0.999791477

p_ni:  0.000208523

Score:  0.993

Data Source:  BioPlex,STRINGDB

DCAF8L2

Tdark

Novelty:  6.73057868

p_int:  0.999786613

p_ni:  0.000213387

Data Source:  BioPlex

TRPC4AP

Tbio

Novelty:  0.02170224

p_int:  0.999678712

p_ni:  0.000321288

Score:  0.939

Data Source:  BioPlex,STRINGDB

COPS8

Tbio

Novelty:  0.0408885

p_int:  0.999640855

p_ni:  0.000359145

Score:  0.987

Data Source:  BioPlex,STRINGDB

DTL

Tbio

Novelty:  0.01659105

p_int:  0.999335019

p_ni:  0.000664981

Score:  0.992

Data Source:  BioPlex,Reactome,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (48)

Reactome (15)

KEGG (3)

UniProt (1)

WikiPathways (29)

DNA Damage Bypass (R-HSA-73893)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	DNA Damage Bypass	47 targets	R-HSA-73893
Reactome	DNA Damage Recognition in GG-NER	38 targets	R-HSA-5696394
Reactome	DNA Repair	306 targets	R-HSA-73894
Reactome	Dual Incision in GG-NER	41 targets	R-HSA-5696400
Reactome	Dual incision in TC-NER	65 targets	R-HSA-6782135

Name	Explore in Pharos	Explore in Source
DNA Damage Bypass	47 targets	R-HSA-73893
DNA Damage Recognition in GG-NER	38 targets	R-HSA-5696394
DNA Repair	306 targets	R-HSA-73894
Dual Incision in GG-NER	41 targets	R-HSA-5696400
Dual incision in TC-NER	65 targets	R-HSA-6782135

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (32)

Functions (1)

Components (4)

Processes (27)

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1 – 1 of 1

GO Term	Evidence	Assigned by
ubiquitin protein ligase binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations (null)

No disease associations found

GWAS Traits (18)

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1 – 5 of 18

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	5	7	8		99.3
prothrombin time measurement	EFO_0008390	1	3	3		98
platelet count	EFO_0004309	2	3	3		95.8
factor VII measurement	EFO_0004619	1	1	1		88.6
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		76.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	8		99.3
prothrombin time measurement	EFO_0008390	3		98
platelet count	EFO_0004309	3		95.8
factor VII measurement	EFO_0004619	1		88.6
mean corpuscular hemoglobin concentration	EFO_0004528	1		76.5

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Complete proteome
DNA damage
DNA repair
Host-virus interaction
Isopeptide bond
Phosphoprotein
Polymorphism
Reference proteome

GWAS Trait Find Similar Targets

No Header	No Header
apolipoprotein A 1 measurement
atrial fibrillation
brain aneurysm
C-reactive protein measurement
factor VII measurement
high density lipoprotein cholesterol measurement
leukocyte count
mean corpuscular hemoglobin concentration
mean corpuscular volume
mean platelet volume

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
mortality/aging
neoplasm

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cullin 4A	VGNC:5050	107968010
Macaque	cullin 4A		714302
Mouse	cullin 4A	MGI:1914487	99375
Rat	cullin 4A	RGD:1563853	361181
Dog	cullin 4A	VGNC:39731	607683

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cullin 4A
Macaque	cullin 4A
Mouse	cullin 4A
Rat	cullin 4A
Dog	cullin 4A

Publication Statistics

PubMed Score 110.86

PubMed score by year

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PubTator Score 80.95

PubTator score by year

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Related Publications

Text Mined References (122)

GeneRif Annotations (85)

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PMID	Year	Title