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Protein

Cullin-4A

Gene

CUL4A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.8 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: GO_Central

GO - Biological processi

Keywordsi

Biological processDNA damage, DNA repair, Host-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
R-HSA-5696394 DNA Damage Recognition in GG-NER
R-HSA-5696395 Formation of Incision Complex in GG-NER
R-HSA-5696400 Dual Incision in GG-NER
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135 Dual incision in TC-NER
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-8951664 Neddylation
SIGNORiQ13619
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-4A
Short name:
CUL-4A
Gene namesi
Name:CUL4A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000139842.14
HGNCiHGNC:2554 CUL4A
MIMi603137 gene
neXtProtiNX_Q13619

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi86 – 90LYQAV → AAAAA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. 2 Publications5
Mutagenesisi139 – 142WQDH → AADA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. 2 Publications4

Organism-specific databases

DisGeNETi8451
OpenTargetsiENSG00000139842
PharmGKBiPA27050

Chemistry databases

ChEMBLiCHEMBL3833061

Polymorphism and mutation databases

BioMutaiCUL4A
DMDMi108936013

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197951 – 759Cullin-4AAdd BLAST759

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei10PhosphoserineCombined sources1
Cross-linki33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-linki705Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)By similarity

Post-translational modificationi

Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.3 Publications
(Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13619
MaxQBiQ13619
PaxDbiQ13619
PeptideAtlasiQ13619
PRIDEiQ13619
ProteomicsDBi59609
59610 [Q13619-2]

PTM databases

iPTMnetiQ13619
PhosphoSitePlusiQ13619

Expressioni

Gene expression databases

BgeeiENSG00000139842 Expressed in 232 organ(s), highest expression level in gastrocnemius
CleanExiHS_CUL4A
ExpressionAtlasiQ13619 baseline and differential
GenevisibleiQ13619 HS

Organism-specific databases

HPAiHPA058979

Interactioni

Subunit structurei

Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to consist of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the CSA complex (DCX(ERCC8) complex) containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Component of the DCX(DET1-COP1) complex with the substrate recognition component DET1 and COP1. Component of the DCX(DDB2) complex with the substrate recognition component DDB2. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Interacts with DDB1, RBX1, RNF7, CTD1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9. Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually exclusive. Interacts with DCAF1, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, COP1, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5, LRWD1 and DCAF8. May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5. Can self-associate. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655).18 Publications
(Microbial infection) Interacts with Epstein-Barr virus BPLF1.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114029, 314 interactors
ComplexPortaliCPX-477 CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant
CORUMiQ13619
DIPiDIP-31610N
IntActiQ13619, 52 interactors
MINTiQ13619
STRINGi9606.ENSP00000364589

Structurei

Secondary structure

1759
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ13619
SMRiQ13619
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13619

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2167 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00760000119212
HOVERGENiHBG003619
InParanoidiQ13619
KOiK10609
OMAiTWQKLHE
OrthoDBiEOG091G02DP
PhylomeDBiQ13619
TreeFamiTF101153

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR016157 Cullin_CS
IPR016158 Cullin_homology
IPR036317 Cullin_homology_sf
IPR001373 Cullin_N
IPR019559 Cullin_neddylation_domain
IPR016159 Cullin_repeat-like_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00888 Cullin, 1 hit
PF10557 Cullin_Nedd8, 1 hit
SMARTiView protein in SMART
SM00182 CULLIN, 1 hit
SM00884 Cullin_Nedd8, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF74788 SSF74788, 1 hit
SSF75632 SSF75632, 1 hit
PROSITEiView protein in PROSITE
PS01256 CULLIN_1, 1 hit
PS50069 CULLIN_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q13619-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MADEAPRKGS FSALVGRTNG LTKPAALAAA PAKPGGAGGS KKLVIKNFRD
60 70 80 90 100
RPRLPDNYTQ DTWRKLHEAV RAVQSSTSIR YNLEELYQAV ENLCSHKVSP
110 120 130 140 150
MLYKQLRQAC EDHVQAQILP FREDSLDSVL FLKKINTCWQ DHCRQMIMIR
160 170 180 190 200
SIFLFLDRTY VLQNSTLPSI WDMGLELFRT HIISDKMVQS KTIDGILLLI
210 220 230 240 250
ERERSGEAVD RSLLRSLLGM LSDLQVYKDS FELKFLEETN CLYAAEGQRL
260 270 280 290 300
MQEREVPEYL NHVSKRLEEE GDRVITYLDH STQKPLIACV EKQLLGEHLT
310 320 330 340 350
AILQKGLDHL LDENRVPDLA QMYQLFSRVR GGQQALLQHW SEYIKTFGTA
360 370 380 390 400
IVINPEKDKD MVQDLLDFKD KVDHVIEVCF QKNERFVNLM KESFETFINK
410 420 430 440 450
RPNKPAELIA KHVDSKLRAG NKEATDEELE RTLDKIMILF RFIHGKDVFE
460 470 480 490 500
AFYKKDLAKR LLVGKSASVD AEKSMLSKLK HECGAAFTSK LEGMFKDMEL
510 520 530 540 550
SKDIMVHFKQ HMQNQSDSGP IDLTVNILTM GYWPTYTPME VHLTPEMIKL
560 570 580 590 600
QEVFKAFYLG KHSGRKLQWQ TTLGHAVLKA EFKEGKKEFQ VSLFQTLVLL
610 620 630 640 650
MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED
660 670 680 690 700
GDKFIFNGEF KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI
710 720 730 740 750
VRIMKMRKTL GHNLLVSELY NQLKFPVKPG DLKKRIESLI DRDYMERDKD

NPNQYHYVA
Length:759
Mass (Da):87,680
Last modified:May 30, 2006 - v3
Checksum:i3C4C6A1BBD94D51B
GO
Isoform 2 (identifier: Q13619-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Show »
Length:659
Mass (Da):76,821
Checksum:i56D4D196BB1074CB
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MR50A0A0A0MR50_HUMAN
Cullin-4A
CUL4A
667Annotation score:
A0A087WWN2A0A087WWN2_HUMAN
Cullin-4A
CUL4A
174Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti281S → T in BAD93235 (PubMed:15811626).Curated1
Sequence conflicti339 – 346HWSEYIKT → NSARARAA in AAC50547 (PubMed:8681378).Curated8
Sequence conflicti496K → R in BAD93235 (PubMed:15811626).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020341644K → R. Corresponds to variant dbSNP:rs2302757Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0185771 – 100Missing in isoform 2. 1 PublicationAdd BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077188 mRNA Translation: AAD45191.1
AY365124 mRNA Translation: AAR13072.1
AB178950 mRNA Translation: BAD93235.1
AL136221 Genomic DNA No translation available.
BC008308 mRNA Translation: AAH08308.2
AB012193 mRNA Translation: BAA33146.1
U58090 mRNA Translation: AAC50547.1
CCDSiCCDS41908.1 [Q13619-1]
CCDS9533.1 [Q13619-2]
RefSeqiNP_001008895.1, NM_001008895.2 [Q13619-1]
NP_001265442.1, NM_001278513.1 [Q13619-2]
NP_003580.1, NM_003589.2 [Q13619-2]
XP_011535825.1, XM_011537523.2 [Q13619-2]
UniGeneiHs.339735
Hs.562468

Genome annotation databases

EnsembliENST00000375440; ENSP00000364589; ENSG00000139842 [Q13619-1]
ENST00000375441; ENSP00000364590; ENSG00000139842 [Q13619-2]
ENST00000451881; ENSP00000389118; ENSG00000139842 [Q13619-2]
ENST00000617546; ENSP00000481782; ENSG00000139842 [Q13619-2]
GeneIDi8451
KEGGihsa:8451
UCSCiuc021rmu.2 human [Q13619-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077188 mRNA Translation: AAD45191.1
AY365124 mRNA Translation: AAR13072.1
AB178950 mRNA Translation: BAD93235.1
AL136221 Genomic DNA No translation available.
BC008308 mRNA Translation: AAH08308.2
AB012193 mRNA Translation: BAA33146.1
U58090 mRNA Translation: AAC50547.1
CCDSiCCDS41908.1 [Q13619-1]
CCDS9533.1 [Q13619-2]
RefSeqiNP_001008895.1, NM_001008895.2 [Q13619-1]
NP_001265442.1, NM_001278513.1 [Q13619-2]
NP_003580.1, NM_003589.2 [Q13619-2]
XP_011535825.1, XM_011537523.2 [Q13619-2]
UniGeneiHs.339735
Hs.562468

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HYEX-ray3.10C1-759[»]
4A0KX-ray5.93A38-759[»]
ProteinModelPortaliQ13619
SMRiQ13619
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114029, 314 interactors
ComplexPortaliCPX-477 CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant
CORUMiQ13619
DIPiDIP-31610N
IntActiQ13619, 52 interactors
MINTiQ13619
STRINGi9606.ENSP00000364589

Chemistry databases

ChEMBLiCHEMBL3833061

PTM databases

iPTMnetiQ13619
PhosphoSitePlusiQ13619

Polymorphism and mutation databases

BioMutaiCUL4A
DMDMi108936013

Proteomic databases

EPDiQ13619
MaxQBiQ13619
PaxDbiQ13619
PeptideAtlasiQ13619
PRIDEiQ13619
ProteomicsDBi59609
59610 [Q13619-2]

Protocols and materials databases

DNASUi8451
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375440; ENSP00000364589; ENSG00000139842 [Q13619-1]
ENST00000375441; ENSP00000364590; ENSG00000139842 [Q13619-2]
ENST00000451881; ENSP00000389118; ENSG00000139842 [Q13619-2]
ENST00000617546; ENSP00000481782; ENSG00000139842 [Q13619-2]
GeneIDi8451
KEGGihsa:8451
UCSCiuc021rmu.2 human [Q13619-1]

Organism-specific databases

CTDi8451
DisGeNETi8451
EuPathDBiHostDB:ENSG00000139842.14
GeneCardsiCUL4A
HGNCiHGNC:2554 CUL4A
HPAiHPA058979
MIMi603137 gene
neXtProtiNX_Q13619
OpenTargetsiENSG00000139842
PharmGKBiPA27050
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2167 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00760000119212
HOVERGENiHBG003619
InParanoidiQ13619
KOiK10609
OMAiTWQKLHE
OrthoDBiEOG091G02DP
PhylomeDBiQ13619
TreeFamiTF101153

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
R-HSA-5696394 DNA Damage Recognition in GG-NER
R-HSA-5696395 Formation of Incision Complex in GG-NER
R-HSA-5696400 Dual Incision in GG-NER
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135 Dual incision in TC-NER
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-8951664 Neddylation
SIGNORiQ13619

Miscellaneous databases

ChiTaRSiCUL4A human
EvolutionaryTraceiQ13619
GeneWikiiCUL4A
GenomeRNAii8451
PROiPR:Q13619
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139842 Expressed in 232 organ(s), highest expression level in gastrocnemius
CleanExiHS_CUL4A
ExpressionAtlasiQ13619 baseline and differential
GenevisibleiQ13619 HS

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR016157 Cullin_CS
IPR016158 Cullin_homology
IPR036317 Cullin_homology_sf
IPR001373 Cullin_N
IPR019559 Cullin_neddylation_domain
IPR016159 Cullin_repeat-like_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00888 Cullin, 1 hit
PF10557 Cullin_Nedd8, 1 hit
SMARTiView protein in SMART
SM00182 CULLIN, 1 hit
SM00884 Cullin_Nedd8, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF74788 SSF74788, 1 hit
SSF75632 SSF75632, 1 hit
PROSITEiView protein in PROSITE
PS01256 CULLIN_1, 1 hit
PS50069 CULLIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCUL4A_HUMAN
AccessioniPrimary (citable) accession number: Q13619
Secondary accession number(s): A2A2W2
, O75834, Q589T6, Q5TC62, Q6UP08, Q9UP17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2006
Last modified: November 7, 2018
This is version 176 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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