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Q3TCH7 (CUL4A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cullin-4A

Short name=CUL-4A
Gene names
Name:Cul4a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length759 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to be formed 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 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 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(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 VPRBP, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, RFWD2, 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 with murine cytomegalovirus M48. Ref.3

Post-translational modification

Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex By similarity. Deneddylated by murine cytomegalovirus M48 leading to a S-phase-like environment that is required for efficient replication of the viral genome.

Sequence similarities

Belongs to the cullin family.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Host-virus interaction
Ubl conjugation pathway
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

hemopoiesis

Inferred from mutant phenotype PubMed 18339895. Source: MGI

negative regulation of granulocyte differentiation

Inferred from direct assay PubMed 12393421. Source: MGI

positive regulation of G1/S transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 19056892. Source: MGI

positive regulation of cell proliferation

Inferred from direct assay PubMed 16467204. Source: MGI

positive regulation of protein catabolic process

Inferred from sequence orthology PubMed 19056892. Source: MGI

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 16467204. Source: MGI

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

regulation of DNA damage checkpoint

Inferred from mutant phenotype PubMed 19481525. Source: MGI

regulation of nucleotide-excision repair

Inferred from mutant phenotype PubMed 19481525. Source: MGI

regulation of protein metabolic process

Inferred from mutant phenotype PubMed 19056892. Source: MGI

somatic stem cell maintenance

Inferred from mutant phenotype PubMed 17616641. Source: MGI

ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype PubMed 19481525. Source: MGI

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCul4-RING ubiquitin ligase complex

Inferred from sequence or structural similarity. Source: UniProtKB

Cul4A-RING ubiquitin ligase complex

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 759759Cullin-4A
PRO_0000236184

Amino acid modifications

Modified residue101Phosphoserine By similarity
Cross-link33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict7561H → R in BAE40173. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q3TCH7 [UniParc].

Last modified October 11, 2005. Version 1.
Checksum: 464271E22FB65F2D

FASTA75987,753
        10         20         30         40         50         60 
MADEGPRKGS VSALMGRTNG LTKPAALAGG PAKPGGTGGS RKLVIKNFRD RPRLPDNYTQ 

        70         80         90        100        110        120 
DTWRKLHEAV KAIQSSTSIR YNLEELYQAV ENLCSHKVSP TLYKQLRQVC EDHVQAQILP 

       130        140        150        160        170        180 
FREDSLDSVL FLKKINTCWQ DHCRQMIMIR SIFLFLDRTY VLQNSMLPSI WDMGLELFRN 

       190        200        210        220        230        240 
HIISDRMVQS KTIDGILLLI GRERSGEAVD RSLLRSLLSM LSDLQVYKDS FELKFLEETN 

       250        260        270        280        290        300 
CLYAAEGQRL MQDREVPEYL NHVSKRLEEE ADRVITYLDH STQKPLIACV EKQLLGEHLT 

       310        320        330        340        350        360 
AILQKGLEHL LDENRVPDLT QMYQLFSRVK GGQHALLQHW SEYIKTFGTT IVINPEKDKD 

       370        380        390        400        410        420 
MVQDLLDFKD KVDHVVEVCF QRNERFINLM KESFETFINK RPNKPAELIA KHVDSKLRAG 

       430        440        450        460        470        480 
NKEATDEELE RILDKIMILF RFIHGKDVFE AFYKKDLAKR LLVGKSASVD AEKSMLSKLK 

       490        500        510        520        530        540 
HECGAAFTSK LEGMFKDMEL SKDIMVHFKQ HMQNQSAPGP IDLTVNILTM GYWPTYTPME 

       550        560        570        580        590        600 
VHLPPEMVRL QEVFKTFYLG KHSGRKLQWQ TTLGHAVLKA DFKEGKKEFQ VSLFQTLVLL 

       610        620        630        640        650        660 
MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED GDKFIFNADF 

       670        680        690        700        710        720 
KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI VRIMKMRKTL GHNLLVSELY 

       730        740        750 
NQLKFPVKPG DLKKRIESLI DRDYMERDKD SPNQYHYVA 

« Hide

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: BALB/c and NOD.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary tumor.
[3]"A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases."
Gastaldello S., Hildebrand S., Faridani O., Callegari S., Palmkvist M., Di Guglielmo C., Masucci M.G.
Nat. Cell Biol. 12:351-361(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MURINE CYTOMEGALOVIRUS M48, DENEDDYLATION BY MURINE CYTOMEGALOVIRUS M48.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK168215 mRNA. Translation: BAE40173.1.
AK170722 mRNA. Translation: BAE41979.1.
BC010211 mRNA. Translation: AAH10211.2.
RefSeqNP_666319.2. NM_146207.2.
UniGeneMm.212861.

3D structure databases

ProteinModelPortalQ3TCH7.
SMRQ3TCH7. Positions 41-759.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid221235. 12 interactions.
IntActQ3TCH7. 5 interactions.
MINTMINT-4122171.

PTM databases

PhosphoSiteQ3TCH7.

Proteomic databases

PaxDbQ3TCH7.
PRIDEQ3TCH7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000016680; ENSMUSP00000016680; ENSMUSG00000031446.
GeneID99375.
KEGGmmu:99375.
UCSCuc009kww.2. mouse.

Organism-specific databases

CTD8451.
MGIMGI:1914487. Cul4a.

Phylogenomic databases

eggNOGCOG5647.
GeneTreeENSGT00730000110449.
HOGENOMHOG000176712.
HOVERGENHBG003619.
InParanoidQ3TCH7.
KOK10609.
OMAHVVEVCF.
OrthoDBEOG75TMB5.
PhylomeDBQ3TCH7.
TreeFamTF101153.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ3TCH7.
BgeeQ3TCH7.
CleanExMM_CUL4A.
GenevestigatorQ3TCH7.

Family and domain databases

Gene3D1.10.10.10. 2 hits.
InterProIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMSSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCUL4A. mouse.
NextBio353901.
PROQ3TCH7.
SOURCESearch...

Entry information

Entry nameCUL4A_MOUSE
AccessionPrimary (citable) accession number: Q3TCH7
Secondary accession number(s): Q3THM3, Q91Z44
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: October 11, 2005
Last modified: April 16, 2014
This is version 79 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot