CUL4A_MOUSE
ID CUL4A_MOUSE Reviewed; 759 AA.
AC Q3TCH7; Q3THM3; Q91Z44;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Cullin-4A {ECO:0000305};
DE Short=CUL-4A {ECO:0000303|PubMed:20190741};
GN Name=Cul4a {ECO:0000303|PubMed:20190741, ECO:0000312|MGI:MGI:1914487};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=BALB/cJ, and NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP INTERACTION WITH MURINE CYTOMEGALOVIRUS M48, DENEDDYLATION BY MURINE
RP CYTOMEGALOVIRUS M48 (MICROBIAL INFECTION), AND NEDDYLATION.
RX PubMed=20190741; DOI=10.1038/ncb2035;
RA Gastaldello S., Hildebrand S., Faridani O., Callegari S., Palmkvist M.,
RA Di Guglielmo C., Masucci M.G.;
RT "A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication
RT by regulating the activity of cullin-RING ligases.";
RL Nat. Cell Biol. 12:351-361(2010).
CC -!- FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-
CC protein ligase complexes which mediate the ubiquitination of target
CC proteins. As a scaffold protein may contribute to catalysis through
CC positioning of the substrate and the ubiquitin-conjugating enzyme. The
CC E3 ubiquitin-protein ligase activity of the complex is dependent on the
CC neddylation of the cullin subunit and is inhibited by the association
CC of the deneddylated cullin subunit with TIP120A/CAND1. The functional
CC specificity of the E3 ubiquitin-protein ligase complex depends on the
CC variable substrate recognition component. DCX(DET1-COP1) directs
CC ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC.
CC DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient
CC histone deposition during replication-coupled (H3.1) and replication-
CC independent (H3.3) nucleosome assembly, probably by facilitating the
CC transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone
CC deposition. DCX(DTL) plays a role in PCNA-dependent polyubiquitination
CC of CDT1 and MDM2-dependent ubiquitination of p53/TP53 in response to
CC radiation-induced DNA damage and during DNA replication. DCX(DTL)
CC directs autoubiquitination of DTL. In association with DDB1 and SKP2
CC probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in
CC ubiquitination of HOXA9. The DDB1-CUL4A-DTL E3 ligase complex regulates
CC the circadian clock function by mediating the ubiquitination and
CC degradation of CRY1. A number of DCX complexes (containing either
CC TRPC4AP or DCAF12 as substrate-recognition component) are part of the
CC DesCEND (destruction via C-end degrons) pathway, which recognizes a C-
CC degron located at the extreme C terminus of target proteins, leading to
CC their ubiquitination and degradation. With CUL4B, contributes to
CC ribosome biogenesis. The DCX(AMBRA1) complex is a master regulator of
CC the transition from G1 to S cell phase by mediating ubiquitination of
CC phosphorylated cyclin-D (CCND1, CCND2 and CCND3). The DCX(AMBRA1)
CC complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-
CC protein ligase complexes by mediating ubiquitination and degradation of
CC Elongin-C (ELOC) component of CRL5 complexes.
CC {ECO:0000250|UniProtKB:Q13619}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q13619}.
CC -!- SUBUNIT: Can self-associate. Component of multiple DCX (DDB1-CUL4-X-
CC box) E3 ubiquitin-protein ligase complexes that seem to consist of
CC DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition
CC component which seems to belong to a protein family described as DCAF
CC (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-
CC repeat) proteins. Component of the CSA complex (DCX(ERCC8) complex)
CC containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with
CC RNA polymerase II; upon UV irradiation it interacts with the COP9
CC signalosome and preferentially with the hyperphosphorylated form of RNA
CC polymerase II. Component of the DCX(DET1-COP1) complex with the
CC substrate recognition component DET1 and COP1. Component of the
CC DCX(DDB2) complex with the substrate recognition component DDB2.
CC Component of the DCX(DTL) complex with the putative substrate
CC recognition component DTL. Component of DCX complexes part of the
CC DesCEND (destruction via C-end degrons) pathway, which contain either
CC TRPC4AP or DCAF12 as substrate-recognition component. Component of the
CC DCX(AMBRA1) complex with the substrate recognition component AMBRA1.
CC Interacts with DDB1, RBX1, RNF7, CDT1, TIP120A/CAND1, SKP2, CDKN1B,
CC MDM2, TP53 and HOXA9. Interacts with DDB2; the interactions with DDB2
CC and CAND1 are mutually exclusive. Interacts with DCAF1, DTL, DDA1,
CC DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, COP1,
CC PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1,
CC FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5, LRWD1 and DCAF8. May interact
CC with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5. Interacts (when
CC neddylated) with ARIH1; leading to activate the E3 ligase activity of
CC ARIH1. The DDB1-CUL4A complex interacts with CRY1. Interacts
CC (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and
CC DCUN1D5; these interactions promote the cullin neddylation.
CC {ECO:0000250|UniProtKB:Q13619}.
CC -!- SUBUNIT: (Microbial infection) Interacts with murine cytomegalovirus
CC M48. {ECO:0000269|PubMed:20190741}.
CC -!- PTM: Neddylated. Deneddylated via its interaction with the COP9
CC signalosome (CSN) complex. {ECO:0000269|PubMed:20190741}.
CC -!- PTM: (Microbial infection) Deneddylated by murine cytomegalovirus M48
CC leading to a S-phase-like environment that is required for efficient
CC replication of the viral genome. {ECO:0000269|PubMed:20190741}.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
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DR EMBL; AK168215; BAE40173.1; -; mRNA.
DR EMBL; AK170722; BAE41979.1; -; mRNA.
DR EMBL; BC010211; AAH10211.2; -; mRNA.
DR CCDS; CCDS52485.1; -.
DR RefSeq; NP_666319.2; NM_146207.2.
DR AlphaFoldDB; Q3TCH7; -.
DR SMR; Q3TCH7; -.
DR BioGRID; 221235; 111.
DR ComplexPortal; CPX-650; CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant.
DR IntAct; Q3TCH7; 37.
DR MINT; Q3TCH7; -.
DR STRING; 10090.ENSMUSP00000016680; -.
DR ChEMBL; CHEMBL4523312; -.
DR iPTMnet; Q3TCH7; -.
DR PhosphoSitePlus; Q3TCH7; -.
DR EPD; Q3TCH7; -.
DR jPOST; Q3TCH7; -.
DR MaxQB; Q3TCH7; -.
DR PaxDb; Q3TCH7; -.
DR PeptideAtlas; Q3TCH7; -.
DR PRIDE; Q3TCH7; -.
DR ProteomicsDB; 279211; -.
DR Antibodypedia; 11756; 407 antibodies from 38 providers.
DR DNASU; 99375; -.
DR Ensembl; ENSMUST00000016680; ENSMUSP00000016680; ENSMUSG00000031446.
DR GeneID; 99375; -.
DR KEGG; mmu:99375; -.
DR UCSC; uc009kww.2; mouse.
DR CTD; 8451; -.
DR MGI; MGI:1914487; Cul4a.
DR VEuPathDB; HostDB:ENSMUSG00000031446; -.
DR eggNOG; KOG2167; Eukaryota.
DR GeneTree; ENSGT00940000156905; -.
DR HOGENOM; CLU_004747_7_2_1; -.
DR InParanoid; Q3TCH7; -.
DR OMA; DNVVQSC; -.
DR OrthoDB; 1040292at2759; -.
DR PhylomeDB; Q3TCH7; -.
DR TreeFam; TF101153; -.
DR Reactome; R-MMU-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-MMU-5696394; DNA Damage Recognition in GG-NER.
DR Reactome; R-MMU-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-MMU-5696400; Dual Incision in GG-NER.
DR Reactome; R-MMU-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-MMU-6782135; Dual incision in TC-NER.
DR Reactome; R-MMU-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-MMU-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 99375; 2 hits in 109 CRISPR screens.
DR ChiTaRS; Cul4a; mouse.
DR PRO; PR:Q3TCH7; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q3TCH7; protein.
DR Bgee; ENSMUSG00000031446; Expressed in ileal epithelium and 264 other tissues.
DR ExpressionAtlas; Q3TCH7; baseline and differential.
DR Genevisible; Q3TCH7; MM.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IC:ComplexPortal.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR GO; GO:0034644; P:cellular response to UV; IC:ComplexPortal.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:CACAO.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IMP:MGI.
DR GO; GO:2000819; P:regulation of nucleotide-excision repair; IMP:MGI.
DR GO; GO:0051246; P:regulation of protein metabolic process; IMP:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0042254; P:ribosome biogenesis; IMP:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:MGI.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR045093; Cullin.
DR InterPro; IPR016157; Cullin_CS.
DR InterPro; IPR016158; Cullin_homology.
DR InterPro; IPR036317; Cullin_homology_sf.
DR InterPro; IPR001373; Cullin_N.
DR InterPro; IPR019559; Cullin_neddylation_domain.
DR InterPro; IPR016159; Cullin_repeat-like_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11932; PTHR11932; 1.
DR Pfam; PF00888; Cullin; 1.
DR Pfam; PF10557; Cullin_Nedd8; 1.
DR SMART; SM00182; CULLIN; 1.
DR SMART; SM00884; Cullin_Nedd8; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF74788; SSF74788; 1.
DR SUPFAM; SSF75632; SSF75632; 1.
DR PROSITE; PS01256; CULLIN_1; 1.
DR PROSITE; PS50069; CULLIN_2; 1.
PE 1: Evidence at protein level;
KW Biological rhythms; DNA damage; DNA repair; Host-virus interaction;
KW Isopeptide bond; Phosphoprotein; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..759
FT /note="Cullin-4A"
FT /id="PRO_0000236184"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 8
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13619"
FT CROSSLNK 33
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13619"
FT CROSSLNK 705
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000250|UniProtKB:Q13616"
FT CONFLICT 756
FT /note="H -> R (in Ref. 1; BAE40173)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 759 AA; 87753 MW; 464271E22FB65F2D CRC64;
MADEGPRKGS VSALMGRTNG LTKPAALAGG PAKPGGTGGS RKLVIKNFRD RPRLPDNYTQ
DTWRKLHEAV KAIQSSTSIR YNLEELYQAV ENLCSHKVSP TLYKQLRQVC EDHVQAQILP
FREDSLDSVL FLKKINTCWQ DHCRQMIMIR SIFLFLDRTY VLQNSMLPSI WDMGLELFRN
HIISDRMVQS KTIDGILLLI GRERSGEAVD RSLLRSLLSM LSDLQVYKDS FELKFLEETN
CLYAAEGQRL MQDREVPEYL NHVSKRLEEE ADRVITYLDH STQKPLIACV EKQLLGEHLT
AILQKGLEHL LDENRVPDLT QMYQLFSRVK GGQHALLQHW SEYIKTFGTT IVINPEKDKD
MVQDLLDFKD KVDHVVEVCF QRNERFINLM KESFETFINK RPNKPAELIA KHVDSKLRAG
NKEATDEELE RILDKIMILF RFIHGKDVFE AFYKKDLAKR LLVGKSASVD AEKSMLSKLK
HECGAAFTSK LEGMFKDMEL SKDIMVHFKQ HMQNQSAPGP IDLTVNILTM GYWPTYTPME
VHLPPEMVRL QEVFKTFYLG KHSGRKLQWQ TTLGHAVLKA DFKEGKKEFQ VSLFQTLVLL
MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED GDKFIFNADF
KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI VRIMKMRKTL GHNLLVSELY
NQLKFPVKPG DLKKRIESLI DRDYMERDKD SPNQYHYVA
