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UniProtKB - Q13619 (CUL4A_HUMAN)

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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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-4A
Short name:
CUL-4A
Gene namesi
Name:CUL4A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
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
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

Show more details

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114029, 311 interactors
ComplexPortaliCPX-477 CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant
CORUMiQ13619
DIPiDIP-31610N
IntActiQ13619, 55 interactors
MINTiQ13619
STRINGi9606.ENSP00000364589

Structurei

Secondary structure

1759
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni58 – 61Combined sources4
Helixi62 – 71Combined sources10
Helixi83 – 93Combined sources11
Turni96 – 98Combined sources3
Helixi99 – 121Combined sources23
Helixi130 – 152Combined sources23
Helixi154 – 157Combined sources4
Turni158 – 162Combined sources5
Beta strandi165 – 167Combined sources3
Helixi170 – 180Combined sources11
Turni181 – 183Combined sources3
Beta strandi184 – 186Combined sources3
Helixi189 – 191Combined sources3
Helixi193 – 201Combined sources9
Turni202 – 206Combined sources5
Helixi211 – 223Combined sources13
Turni227 – 231Combined sources5
Helixi232 – 253Combined sources22
Helixi256 – 269Combined sources14
Helixi271 – 274Combined sources4
Turni275 – 277Combined sources3
Turni280 – 282Combined sources3
Helixi283 – 294Combined sources12
Turni295 – 297Combined sources3
Helixi300 – 304Combined sources5
Helixi307 – 311Combined sources5
Turni312 – 314Combined sources3
Helixi316 – 328Combined sources13
Helixi332 – 352Combined sources21
Helixi355 – 357Combined sources3
Turni358 – 360Combined sources3
Helixi361 – 377Combined sources17
Turni378 – 382Combined sources5
Helixi384 – 398Combined sources15
Helixi404 – 417Combined sources14
Helixi421 – 423Combined sources3
Helixi429 – 440Combined sources12
Helixi446 – 462Combined sources17
Helixi469 – 480Combined sources12
Turni481 – 483Combined sources3
Turni485 – 488Combined sources4
Helixi489 – 513Combined sources25
Beta strandi522 – 529Combined sources8
Turni530 – 532Combined sources3
Helixi545 – 559Combined sources15
Beta strandi564 – 566Combined sources3
Helixi571 – 573Combined sources3
Beta strandi575 – 579Combined sources5
Beta strandi588 – 592Combined sources5
Helixi593 – 601Combined sources9
Helixi610 – 616Combined sources7
Helixi621 – 629Combined sources9
Turni630 – 636Combined sources7
Beta strandi638 – 641Combined sources4
Beta strandi645 – 647Combined sources3
Beta strandi653 – 656Combined sources4
Beta strandi665 – 668Combined sources4
Helixi670 – 674Combined sources5
Helixi678 – 706Combined sources29
Beta strandi707 – 711Combined sources5
Helixi713 – 722Combined sources10
Beta strandi723 – 725Combined sources3
Helixi729 – 741Combined sources13
Beta strandi754 – 756Combined sources3

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
OMAiNLCSYKV
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

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

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

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: July 18, 2018
This is version 174 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. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

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