Tbio CUL4A Cullin-4A

Protein Classes

PANTHER Classes

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

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / 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

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: 85.36   (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: 85.36   (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 Ligand: 0

Tclin

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

Active Drug: 0

Protein Data Bank (2)

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (48)

Reactome (15)

KEGG (3)

UniProt (1)

WikiPathways (29)

DNA Damage Bypass (R-HSA-73893)

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Items per page:

5

1 – 5 of 15

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

Gene Ontology Terms (32)

Functions (1)

Components (4)

Processes (27)

Items per page:

10

1 – 1 of 1

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

Protein-Protein Interactions (295)

Explore Interacting Targets

1 – 10 of 295

• See Interactions on String-DB

DCAF4

Tdark

Novelty: 0.32846715

p_int: 0.999929357

p_ni: 0.000070643

Score: 0.985

Data Source: BioPlex,STRINGDB

DCAF8

Tbio

Novelty: 0.27272727

p_int: 0.999925487

p_ni: 0.000074513

Score: 0.934

Data Source: BioPlex,STRINGDB

DCAF11

Tbio

Novelty: 0.12689461

p_int: 0.999923934

p_ni: 0.000076066

Score: 0.989

Data Source: BioPlex,STRINGDB

DDB2

Tbio

Novelty: 0.00809774

p_int: 0.999896428

p_ni: 0.000103572

Score: 0.996

Data Source: BioPlex,Reactome,STRINGDB

WDTC1

Tbio

Novelty: 0.00004184

p_int: 0.999891733

p_ni: 0.000108267

Score: 0.935

Data Source: BioPlex,STRINGDB

DET1

Tbio

Novelty: 0.01807423

p_int: 0.999791477

p_ni: 0.000208523

Score: 0.993

Data Source: BioPlex,STRINGDB

DCAF8L2

Tdark

p_int: 0.999786613

p_ni: 0.000213387

Data Source: BioPlex

TRPC4AP

Tbio

Novelty: 0.00440674

p_int: 0.999678712

p_ni: 0.000321288

Score: 0.939

Data Source: BioPlex,STRINGDB

COPS8

Tbio

Novelty: 0.05324769

p_int: 0.999640855

p_ni: 0.000359145

Score: 0.987

Data Source: BioPlex,STRINGDB

DTL

Tbio

Novelty: 0.01976973

p_int: 0.999335019

p_ni: 0.000664981

Score: 0.992

Data Source: BioPlex,Reactome,STRINGDB

Publication Statistics

PubMed Score  85.36

PubMed score by year

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PubTator Score  80.95

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MADEAPRKGSFSALVGRTNGLTKPAALAAAPAKPGGAGGSKKLVIKNFRDRPRLPDNYTQDTWRKLHEAV

1-70

RAVQSSTSIRYNLEELYQAVENLCSHKVSPMLYKQLRQACEDHVQAQILPFREDSLDSVLFLKKINTCWQ

70-140

DHCRQMIMIRSIFLFLDRTYVLQNSTLPSIWDMGLELFRTHIISDKMVQSKTIDGILLLIERERSGEAVD

140-210

RSLLRSLLGMLSDLQVYKDSFELKFLEETNCLYAAEGQRLMQEREVPEYLNHVSKRLEEEGDRVITYLDH

210-280

STQKPLIACVEKQLLGEHLTAILQKGLDHLLDENRVPDLAQMYQLFSRVRGGQQALLQHWSEYIKTFGTA

280-350

IVINPEKDKDMVQDLLDFKDKVDHVIEVCFQKNERFVNLMKESFETFINKRPNKPAELIAKHVDSKLRAG

350-420

NKEATDEELERTLDKIMILFRFIHGKDVFEAFYKKDLAKRLLVGKSASVDAEKSMLSKLKHECGAAFTSK

420-490

LEGMFKDMELSKDIMVHFKQHMQNQSDSGPIDLTVNILTMGYWPTYTPMEVHLTPEMIKLQEVFKAFYLG

490-560

KHSGRKLQWQTTLGHAVLKAEFKEGKKEFQVSLFQTLVLLMFNEGDGFSFEEIKMATGIEDSELRRTLQS

560-630

LACGKARVLIKSPKGKEVEDGDKFIFNGEFKHKLFRIKINQIQMKETVEEQVSTTERVFQDRQYQIDAAI

630-700

VRIMKMRKTLGHNLLVSELYNQLKFPVKPGDLKKRIESLIDRDYMERDKDNPNQYHYVA

700-759

MADEAPRKGSFSALVGRTNGLTKPAALAAAPAKPGGAGGSKKLVIKNFRDRPRLPDNYTQDTWRKLHEAVRAVQSSTSIRYNLEELYQAVENLCSHKVSPMLYKQLRQACEDHVQAQILPFREDSLDSVLFLKKINTCWQDHCRQMIMIRSIFLFLDRTYVLQNSTLPSIWDMGLELFRTHIISDKMVQSKTIDGILLLIERERSGEAVDRSLLRSLLGMLSDLQVYKDSFELKFLEETNCLYAAEGQRLMQEREVPEYLNHVSKRLEEEGDRVITYLDHSTQKPLIACVEKQLLGEHLTAILQKGLDHLLDENRVPDLAQMYQLFSRVRGGQQALLQHWSEYIKTFGTAIVINPEKDKDMVQDLLDFKDKVDHVIEVCFQKNERFVNLMKESFETFINKRPNKPAELIAKHVDSKLRAGNKEATDEELERTLDKIMILFRFIHGKDVFEAFYKKDLAKRLLVGKSASVDAEKSMLSKLKHECGAAFTSKLEGMFKDMELSKDIMVHFKQHMQNQSDSGPIDLTVNILTMGYWPTYTPMEVHLTPEMIKLQEVFKAFYLGKHSGRKLQWQTTLGHAVLKAEFKEGKKEFQVSLFQTLVLLMFNEGDGFSFEEIKMATGIEDSELRRTLQSLACGKARVLIKSPKGKEVEDGDKFIFNGEFKHKLFRIKINQIQMKETVEEQVSTTERVFQDRQYQIDAAIVRIMKMRKTLGHNLLVSELYNQLKFPVKPGDLKKRIESLIDRDYMERDKDNPNQYHYVA

Find similar targets by:

Uniprot Keyword

3D-structure
Alternative splicing
Complete proteome
DNA damage
DNA repair
Host-virus interaction
Isopeptide bond
Phosphoprotein
Polymorphism
Reference proteome