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Protein

Cullin-4A

Gene

Cul4a

Organism
Mus musculus (Mouse)
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 and subsequent proteasomal degradation 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. In association with RBX1, DDB1 and DDB2 is required for histone H3 and histone H4 ubiquitination in response to ultraviolet and may be important for subsequent DNA repair. 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 (By similarity).By similarity

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-MMU-110314 Recognition of DNA damage by PCNA-containing replication complex
R-MMU-5696394 DNA Damage Recognition in GG-NER
R-MMU-5696395 Formation of Incision Complex in GG-NER
R-MMU-5696400 Dual Incision in GG-NER
R-MMU-6781823 Formation of TC-NER Pre-Incision Complex
R-MMU-6782135 Dual incision in TC-NER
R-MMU-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-MMU-8951664 Neddylation
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-4A
Short name:
CUL-4A
Gene namesi
Name:Cul4a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1914487 Cul4a

Subcellular locationi

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002361841 – 759Cullin-4AAdd BLAST759

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei10PhosphoserineCombined sources1
Cross-linki33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
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.1 Publication
(Microbial infection) Deneddylated by murine cytomegalovirus M48 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

EPDiQ3TCH7
MaxQBiQ3TCH7
PaxDbiQ3TCH7
PeptideAtlasiQ3TCH7
PRIDEiQ3TCH7

PTM databases

iPTMnetiQ3TCH7
PhosphoSitePlusiQ3TCH7

Expressioni

Gene expression databases

BgeeiENSMUSG00000031446 Expressed in 283 organ(s), highest expression level in adrenal gland
CleanExiMM_CUL4A
ExpressionAtlasiQ3TCH7 baseline and differential
GenevisibleiQ3TCH7 MM

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.By similarity
(Microbial infection) Interacts with murine cytomegalovirus M48.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi221235, 45 interactors
ComplexPortaliCPX-650 CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant
IntActiQ3TCH7, 36 interactors
MINTiQ3TCH7
STRINGi10090.ENSMUSP00000016680

Structurei

3D structure databases

ProteinModelPortaliQ3TCH7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2167 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00760000119212
HOGENOMiHOG000176712
HOVERGENiHBG003619
InParanoidiQ3TCH7
KOiK10609
OMAiTWQKLHE
OrthoDBiEOG091G02DP
PhylomeDBiQ3TCH7
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q3TCH7-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MADEGPRKGS VSALMGRTNG LTKPAALAGG PAKPGGTGGS RKLVIKNFRD
60 70 80 90 100
RPRLPDNYTQ DTWRKLHEAV KAIQSSTSIR YNLEELYQAV ENLCSHKVSP
110 120 130 140 150
TLYKQLRQVC EDHVQAQILP FREDSLDSVL FLKKINTCWQ DHCRQMIMIR
160 170 180 190 200
SIFLFLDRTY VLQNSMLPSI WDMGLELFRN HIISDRMVQS KTIDGILLLI
210 220 230 240 250
GRERSGEAVD RSLLRSLLSM LSDLQVYKDS FELKFLEETN CLYAAEGQRL
260 270 280 290 300
MQDREVPEYL NHVSKRLEEE ADRVITYLDH STQKPLIACV EKQLLGEHLT
310 320 330 340 350
AILQKGLEHL LDENRVPDLT QMYQLFSRVK GGQHALLQHW SEYIKTFGTT
360 370 380 390 400
IVINPEKDKD MVQDLLDFKD KVDHVVEVCF QRNERFINLM KESFETFINK
410 420 430 440 450
RPNKPAELIA KHVDSKLRAG NKEATDEELE RILDKIMILF RFIHGKDVFE
460 470 480 490 500
AFYKKDLAKR LLVGKSASVD AEKSMLSKLK HECGAAFTSK LEGMFKDMEL
510 520 530 540 550
SKDIMVHFKQ HMQNQSAPGP IDLTVNILTM GYWPTYTPME VHLPPEMVRL
560 570 580 590 600
QEVFKTFYLG KHSGRKLQWQ TTLGHAVLKA DFKEGKKEFQ VSLFQTLVLL
610 620 630 640 650
MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED
660 670 680 690 700
GDKFIFNADF KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI
710 720 730 740 750
VRIMKMRKTL GHNLLVSELY NQLKFPVKPG DLKKRIESLI DRDYMERDKD

SPNQYHYVA
Length:759
Mass (Da):87,753
Last modified:October 11, 2005 - v1
Checksum:i464271E22FB65F2D
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6UV36F6UV36_MOUSE
Cullin-4A
Cul4a
87Annotation score:
E9PXT5E9PXT5_MOUSE
Cullin-4A
Cul4a
265Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti756H → R in BAE40173 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK168215 mRNA Translation: BAE40173.1
AK170722 mRNA Translation: BAE41979.1
BC010211 mRNA Translation: AAH10211.2
CCDSiCCDS52485.1
RefSeqiNP_666319.2, NM_146207.2
UniGeneiMm.212861

Genome annotation databases

EnsembliENSMUST00000016680; ENSMUSP00000016680; ENSMUSG00000031446
GeneIDi99375
KEGGimmu:99375
UCSCiuc009kww.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK168215 mRNA Translation: BAE40173.1
AK170722 mRNA Translation: BAE41979.1
BC010211 mRNA Translation: AAH10211.2
CCDSiCCDS52485.1
RefSeqiNP_666319.2, NM_146207.2
UniGeneiMm.212861

3D structure databases

ProteinModelPortaliQ3TCH7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi221235, 45 interactors
ComplexPortaliCPX-650 CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant
IntActiQ3TCH7, 36 interactors
MINTiQ3TCH7
STRINGi10090.ENSMUSP00000016680

PTM databases

iPTMnetiQ3TCH7
PhosphoSitePlusiQ3TCH7

Proteomic databases

EPDiQ3TCH7
MaxQBiQ3TCH7
PaxDbiQ3TCH7
PeptideAtlasiQ3TCH7
PRIDEiQ3TCH7

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000016680; ENSMUSP00000016680; ENSMUSG00000031446
GeneIDi99375
KEGGimmu:99375
UCSCiuc009kww.2 mouse

Organism-specific databases

CTDi8451
MGIiMGI:1914487 Cul4a

Phylogenomic databases

eggNOGiKOG2167 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00760000119212
HOGENOMiHOG000176712
HOVERGENiHBG003619
InParanoidiQ3TCH7
KOiK10609
OMAiTWQKLHE
OrthoDBiEOG091G02DP
PhylomeDBiQ3TCH7
TreeFamiTF101153

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-MMU-110314 Recognition of DNA damage by PCNA-containing replication complex
R-MMU-5696394 DNA Damage Recognition in GG-NER
R-MMU-5696395 Formation of Incision Complex in GG-NER
R-MMU-5696400 Dual Incision in GG-NER
R-MMU-6781823 Formation of TC-NER Pre-Incision Complex
R-MMU-6782135 Dual incision in TC-NER
R-MMU-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-MMU-8951664 Neddylation

Miscellaneous databases

ChiTaRSiCul4a mouse
PROiPR:Q3TCH7
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031446 Expressed in 283 organ(s), highest expression level in adrenal gland
CleanExiMM_CUL4A
ExpressionAtlasiQ3TCH7 baseline and differential
GenevisibleiQ3TCH7 MM

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_MOUSE
AccessioniPrimary (citable) accession number: Q3TCH7
Secondary accession number(s): Q3THM3, Q91Z44
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: October 11, 2005
Last modified: November 7, 2018
This is version 116 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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