CUL4A_HUMAN
ID CUL4A_HUMAN Reviewed; 759 AA.
AC Q13619; A2A2W2; O75834; Q589T6; Q5TC62; Q6UP08; Q9UP17;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Cullin-4A {ECO:0000305};
DE Short=CUL-4A {ECO:0000303|PubMed:9721878};
GN Name=CUL4A {ECO:0000303|PubMed:9721878, ECO:0000312|HGNC:HGNC:2554};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=9721878;
RA Chen L.-C., Manjeshwar S., Lu Y., Moore D., Ljung B.M., Kuo W.L.,
RA Dairkee S.H., Wernick M., Collins C., Smith H.S.;
RT "The human homologue for the Caenorhabditis elegans cul-4 gene is amplified
RT and overexpressed in primary breast cancers.";
RL Cancer Res. 58:3677-3683(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP CDT1.
RX PubMed=14578910; DOI=10.1038/ncb1061;
RA Higa L.A., Mihaylov I.S., Banks D.P., Zheng J., Zhang H.;
RT "Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes
RT constitutes a new checkpoint.";
RL Nat. Cell Biol. 5:1008-1015(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=15811626; DOI=10.1016/j.dnarep.2004.12.012;
RA Matsuda N., Azuma K., Saijo M., Iemura S., Hioki Y., Natsume T., Chiba T.,
RA Tanaka K., Tanaka K.;
RT "DDB2, the xeroderma pigmentosum group E gene product, is directly
RT ubiquitylated by Cullin 4A-based ubiquitin ligase complex.";
RL DNA Repair 4:537-545(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 236-759 (ISOFORMS 1/2), AND NEDDYLATION.
RX PubMed=9694792; DOI=10.1101/gad.12.15.2263;
RA Osaka F., Kawasaki H., Aida N., Saeki M., Chiba T., Kawashima S.,
RA Tanaka K., Kato S.;
RT "A new NEDD8-ligating system for cullin-4A.";
RL Genes Dev. 12:2263-2268(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 339-759 (ISOFORMS 1/2).
RX PubMed=8681378; DOI=10.1016/s0092-8674(00)81267-2;
RA Kipreos E.T., Lander L.E., Wing J.P., He W.W., Hedgecock E.M.;
RT "cul-1 is required for cell cycle exit in C. elegans and identifies a novel
RT gene family.";
RL Cell 85:829-839(1996).
RN [8]
RP NEDDYLATION.
RX PubMed=10597293; DOI=10.1038/sj.onc.1203093;
RA Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N.,
RA Kato S., Tanaka K.;
RT "Covalent modification of all members of human cullin family proteins by
RT NEDD8.";
RL Oncogene 18:6829-6834(1999).
RN [9]
RP INTERACTION WITH RBX1 AND RNF7.
RX PubMed=10230407; DOI=10.1016/s1097-2765(00)80482-7;
RA Ohta T., Michel J.J., Schottelius A.J., Xiong Y.;
RT "ROC1, a homolog of APC11, represents a family of cullin partners with an
RT associated ubiquitin ligase activity.";
RL Mol. Cell 3:535-541(1999).
RN [10]
RP IDENTIFICATION IN THE CSA COMPLEX WITH RBX1; DDB1 AND ERCC8, AND
RP INTERACTION OF THE CSA COMPLEX WITH RNA POLYMERASE II AND THE COP9
RP SIGNALOSOME.
RX PubMed=12732143; DOI=10.1016/s0092-8674(03)00316-7;
RA Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M., Drapkin R.,
RA Kisselev A.F., Tanaka K., Nakatani Y.;
RT "The ubiquitin ligase activity in the DDB2 and CSA complexes is
RT differentially regulated by the COP9 signalosome in response to DNA
RT damage.";
RL Cell 113:357-367(2003).
RN [11]
RP INTERACTION WITH HOXA9, FUNCTION IN UBIQUITINATION OF HOXA9, AND PATHWAY.
RX PubMed=14609952; DOI=10.1093/emboj/cdg577;
RA Zhang Y., Morrone G., Zhang J., Chen X., Lu X., Ma L., Moore M., Zhou P.;
RT "CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain
RT protein.";
RL EMBO J. 22:6057-6067(2003).
RN [12]
RP INTERACTION WITH TIP120A.
RX PubMed=12609982; DOI=10.1074/jbc.m213070200;
RA Min K.-W., Hwang J.-W., Lee J.-S., Park Y., Tamura T.-A., Yoon J.-B.;
RT "TIP120A associates with cullins and modulates ubiquitin ligase activity.";
RL J. Biol. Chem. 278:15905-15910(2003).
RN [13]
RP INTERACTION WITH MDM2 AND TP53, FUNCTION IN UBIQUITINATION OF TP53, AND
RP PATHWAY.
RX PubMed=15548678; DOI=10.1158/0008-5472.can-04-2598;
RA Nag A., Bagchi S., Raychaudhuri P.;
RT "Cul4A physically associates with MDM2 and participates in the proteolysis
RT of p53.";
RL Cancer Res. 64:8152-8155(2004).
RN [14]
RP INTERACTION WITH DDB1, FUNCTION IN CDT1 UBIQUITINATION, AND PATHWAY.
RX PubMed=15448697; DOI=10.1038/ncb1172;
RA Hu J., McCall C.M., Ohta T., Xiong Y.;
RT "Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response
RT to DNA damage.";
RL Nat. Cell Biol. 6:1003-1009(2004).
RN [15]
RP FUNCTION, AND IDENTIFICATION IN THE DCX(DET1-COP1) COMPLEX WITH DDB1; RBX1;
RP COP1 AND DET1.
RX PubMed=14739464; DOI=10.1126/science.1093549;
RA Wertz I.E., O'Rourke K.M., Zhang Z., Dornan D., Arnott D., Deshaies R.J.,
RA Dixit V.M.;
RT "Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin
RT ligase.";
RL Science 303:1371-1374(2004).
RN [16]
RP INTERACTION WITH DDB1; DDB2 AND CAND1, AND MUTAGENESIS OF 86-LEU--VAL-90
RP AND 139-TRP--HIS-142.
RX PubMed=16482215; DOI=10.1038/sj.emboj.7601002;
RA Nishitani H., Sugimoto N., Roukos V., Nakanishi Y., Saijo M., Obuse C.,
RA Tsurimoto T., Nakayama K.I., Nakayama K., Fujita M., Lygerou Z.,
RA Nishimoto T.;
RT "Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for
RT proteolysis.";
RL EMBO J. 25:1126-1136(2006).
RN [17]
RP INTERACTION WITH DCAF1; DDB2; ERCC8; DCAF11; GRWD1; COP1; FBXW5; RBBP7;
RP GNB2; WSB1; WSB2; NUP43; PWP1; FBXW8; ATG16L1; KATNB1 AND RBBP4, AND
RP MUTAGENESIS OF 86-LEU--VAL-90 AND 139-TRP--HIS-142.
RX PubMed=17079684; DOI=10.1101/gad.1483206;
RA He Y.J., McCall C.M., Hu J., Zeng Y., Xiong Y.;
RT "DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1
RT ubiquitin ligases.";
RL Genes Dev. 20:2949-2954(2006).
RN [18]
RP IDENTIFICATION IN COMPLEX WITH DDB1; DDB2 AND RBX1, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND FUNCTION.
RX PubMed=16678110; DOI=10.1016/j.molcel.2006.03.035;
RA Wang H., Zhai L., Xu J., Joo H.-Y., Jackson S., Erdjument-Bromage H.,
RA Tempst P., Xiong Y., Zhang Y.;
RT "Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase
RT facilitates cellular response to DNA damage.";
RL Mol. Cell 22:383-394(2006).
RN [19]
RP INTERACTION WITH DCAF1; DTL; DDA1; DCAF6; DCAF4; DCAF16; DCAF17; DDB2;
RP DET1; WDTC1; DCAF5; DCAF11; WDR24A; COP1; PAFAH1B1 AND DCAF8.
RX PubMed=16949367; DOI=10.1016/j.molcel.2006.08.010;
RA Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.;
RT "A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is
RT required for S phase destruction of the replication factor Cdt1.";
RL Mol. Cell 23:709-721(2006).
RN [20]
RP INTERACTION WITH SKP2 AND CDKN1B, FUNCTION IN UBIQUITINATION OF CDKN1B, AND
RP PATHWAY.
RX PubMed=16537899; DOI=10.1128/mcb.26.7.2531-2539.2006;
RA Bondar T., Kalinina A., Khair L., Kopanja D., Nag A., Bagchi S.,
RA Raychaudhuri P.;
RT "Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis
RT involving the COP9 signalosome.";
RL Mol. Cell. Biol. 26:2531-2539(2006).
RN [21]
RP FUNCTION, AND INTERACTION WITH DDB2; WDR26; RBBP5; COP1; WDR51B; SNRNP40;
RP WDR61; WDR76 AND WDR5.
RX PubMed=17041588; DOI=10.1038/ncb1490;
RA Higa L.A., Wu M., Ye T., Kobayashi R., Sun H., Zhang H.;
RT "CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins
RT and regulates histone methylation.";
RL Nat. Cell Biol. 8:1277-1283(2006).
RN [22]
RP SELF-ASSOCIATION.
RX PubMed=17254749; DOI=10.1016/j.cellsig.2006.12.002;
RA Chew E.H., Poobalasingam T., Hawkey C.J., Hagen T.;
RT "Characterization of cullin-based E3 ubiquitin ligases in intact mammalian
RT cells -- evidence for cullin dimerization.";
RL Cell. Signal. 19:1071-1080(2007).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP INTERACTION WITH EPSTEIN-BARR VIRUS BPLF1 (MICROBIAL INFECTION), AND
RP DENEDDYLATION BY EPSTEIN-BARR VIRUS BPLF1 (MICROBIAL INFECTION).
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).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP INTERACTION WITH LRWD1.
RX PubMed=22935713; DOI=10.4161/cc.21870;
RA Shen Z., Prasanth S.G.;
RT "Orc2 protects ORCA from ubiquitin-mediated degradation.";
RL Cell Cycle 11:3578-3589(2012).
RN [29]
RP FUNCTION IN UBIQUITINATION OF H3, AND PATHWAY.
RX PubMed=24209620; DOI=10.1016/j.cell.2013.10.014;
RA Han J., Zhang H., Zhang H., Wang Z., Zhou H., Zhang Z.;
RT "A Cul4 E3 ubiquitin ligase regulates histone hand-off during nucleosome
RT assembly.";
RL Cell 155:817-829(2013).
RN [30]
RP INTERACTION WITH ARIH1, AND NEDDYLATION.
RX PubMed=24076655; DOI=10.1038/emboj.2013.209;
RA Kelsall I.R., Duda D.M., Olszewski J.L., Hofmann K., Knebel A.,
RA Langevin F., Wood N., Wightman M., Schulman B.A., Alpi A.F.;
RT "TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-
RT RING ligase complexes.";
RL EMBO J. 32:2848-2860(2013).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [32]
RP FUNCTION IN UBIQUITINATION OF DTL, AND PATHWAY.
RX PubMed=23478445; DOI=10.1016/j.molcel.2013.02.003;
RA Abbas T., Mueller A.C., Shibata E., Keaton M., Rossi M., Dutta A.;
RT "CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-
RT Set7/Set8-mediated cellular migration.";
RL Mol. Cell 49:1147-1158(2013).
RN [33]
RP INTERACTION WITH DCUN1D1; DCUN1D2; DCUN1D3; DCUN1D4 AND DCUN1D5.
RX PubMed=23201271; DOI=10.1016/j.str.2012.10.013;
RA Monda J.K., Scott D.C., Miller D.J., Lydeard J., King D., Harper J.W.,
RA Bennett E.J., Schulman B.A.;
RT "Structural conservation of distinctive N-terminal acetylation-dependent
RT interactions across a family of mammalian NEDD8 ligation enzymes.";
RL Structure 21:42-53(2013).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
RP FUNCTION.
RX PubMed=26711351; DOI=10.1016/j.celrep.2015.11.061;
RA Badertscher L., Wild T., Montellese C., Alexander L.T., Bammert L.,
RA Sarazova M., Stebler M., Csucs G., Mayer T.U., Zamboni N., Zemp I.,
RA Horvath P., Kutay U.;
RT "Genome-wide RNAi Screening Identifies Protein Modules Required for 40S
RT Subunit Synthesis in Human Cells.";
RL Cell Rep. 13:2879-2891(2015).
RN [36]
RP FUNCTION, AND INTERACTION WITH DDB1 AND CRY1.
RX PubMed=26431207; DOI=10.1371/journal.pone.0139725;
RA Tong X., Zhang D., Guha A., Arthurs B., Cazares V., Gupta N., Yin L.;
RT "CUL4-DDB1-CDT2 E3 ligase regulates the molecular clock activity by
RT promoting ubiquitination-dependent degradation of the mammalian CRY1.";
RL PLoS ONE 10:E0139725-E0139725(2015).
RN [37]
RP INTERACTION WITH DCUN1D1; DCUN1D2; DCUN1D3 AND DCUN1D5.
RX PubMed=26906416; DOI=10.1242/jcs.181784;
RA Keuss M.J., Thomas Y., Mcarthur R., Wood N.T., Knebel A., Kurz T.;
RT "Characterization of the mammalian family of DCN-type NEDD8 E3 ligases.";
RL J. Cell Sci. 129:1441-1454(2016).
RN [38]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-8, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [39]
RP FUNCTION, AND PATHWAY.
RX PubMed=29779948; DOI=10.1016/j.cell.2018.04.028;
RA Koren I., Timms R.T., Kula T., Xu Q., Li M.Z., Elledge S.J.;
RT "The eukaryotic proteome is shaped by E3 ubiquitin ligases targeting C-
RT terminal degrons.";
RL Cell 173:1622-1635(2018).
RN [40]
RP FUNCTION, AND PATHWAY.
RX PubMed=30166453; DOI=10.15252/embj.201797508;
RA Chen S.H., Jang G.M., Huettenhain R., Gordon D.E., Du D., Newton B.W.,
RA Johnson J.R., Hiatt J., Hultquist J.F., Johnson T.L., Liu Y.L.,
RA Burton L.A., Ye J., Reichermeier K.M., Stroud R.M., Marson A., Debnath J.,
RA Gross J.D., Krogan N.J.;
RT "CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to
RT modulate CRL5 signaling.";
RL EMBO J. 37:0-0(2018).
RN [41]
RP FUNCTION, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN
RP LIGASE COMPLEX, AND PATHWAY.
RX PubMed=33854232; DOI=10.1038/s41586-021-03422-5;
RA Maiani E., Milletti G., Nazio F., Holdgaard S.G., Bartkova J., Rizza S.,
RA Cianfanelli V., Lorente M., Simoneschi D., Di Marco M., D'Acunzo P.,
RA Di Leo L., Rasmussen R., Montagna C., Raciti M., De Stefanis C.,
RA Gabicagogeascoa E., Rona G., Salvador N., Pupo E., Merchut-Maya J.M.,
RA Daniel C.J., Carinci M., Cesarini V., O'sullivan A., Jeong Y.T., Bordi M.,
RA Russo F., Campello S., Gallo A., Filomeni G., Lanzetti L., Sears R.C.,
RA Hamerlik P., Bartolazzi A., Hynds R.E., Pearce D.R., Swanton C., Pagano M.,
RA Velasco G., Papaleo E., De Zio D., Maya-Mendoza A., Locatelli F.,
RA Bartek J., Cecconi F.;
RT "AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.";
RL Nature 592:799-803(2021).
RN [42]
RP FUNCTION, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN
RP LIGASE COMPLEX, AND PATHWAY.
RX PubMed=33854239; DOI=10.1038/s41586-021-03474-7;
RA Chaikovsky A.C., Li C., Jeng E.E., Loebell S., Lee M.C., Murray C.W.,
RA Cheng R., Demeter J., Swaney D.L., Chen S.H., Newton B.W., Johnson J.R.,
RA Drainas A.P., Shue Y.T., Seoane J.A., Srinivasan P., He A., Yoshida A.,
RA Hipkins S.Q., McCrea E., Poltorack C.D., Krogan N.J., Diehl J.A., Kong C.,
RA Jackson P.K., Curtis C., Petrov D.A., Bassik M.C., Winslow M.M., Sage J.;
RT "The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.";
RL Nature 592:794-798(2021).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) IN COMPLEX WITH DDB1; RBX1 AND
RP SV5-V.
RX PubMed=16964240; DOI=10.1038/nature05175;
RA Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N.;
RT "Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase
RT machinery.";
RL Nature 443:590-593(2006).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (5.93 ANGSTROMS) OF 38-759 IN COMPLEX WITH DDB1; RBX1
RP AND DDB2.
RX PubMed=22118460; DOI=10.1016/j.cell.2011.10.035;
RA Fischer E.S., Scrima A., Bohm K., Matsumoto S., Lingaraju G.M., Faty M.,
RA Yasuda T., Cavadini S., Wakasugi M., Hanaoka F., Iwai S., Gut H.,
RA Sugasawa K., Thoma N.H.;
RT "The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture,
RT targeting, and activation.";
RL Cell 147:1024-1039(2011).
CC -!- FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-
CC protein ligase complexes which mediate the ubiquitination of target
CC proteins (PubMed:14578910, PubMed:15811626, PubMed:15548678,
CC PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588,
CC PubMed:24209620, PubMed:30166453, PubMed:33854232, PubMed:33854239). As
CC a scaffold protein may contribute to catalysis through positioning of
CC the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910,
CC PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464,
CC PubMed:16678110, PubMed:17041588, PubMed:24209620). The E3 ubiquitin-
CC protein ligase activity of the complex is dependent on the neddylation
CC of the cullin subunit and is inhibited by the association of the
CC deneddylated cullin subunit with TIP120A/CAND1 (PubMed:14578910,
CC PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464,
CC PubMed:16678110, PubMed:17041588, PubMed:24209620). The functional
CC specificity of the E3 ubiquitin-protein ligase complex depends on the
CC variable substrate recognition component (PubMed:14578910,
CC PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464,
CC PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DET1-COP1)
CC directs ubiquitination of JUN (PubMed:14739464). DCX(DDB2) directs
CC ubiquitination of XPC (PubMed:15811626). DCX(DDB2) ubiquitinates
CC histones H3-H4 and is required for efficient histone deposition during
CC replication-coupled (H3.1) and replication-independent (H3.3)
CC nucleosome assembly, probably by facilitating the transfer of H3 from
CC ASF1A/ASF1B to other chaperones involved in histone deposition
CC (PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DTL) plays a
CC role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent
CC ubiquitination of p53/TP53 in response to radiation-induced DNA damage
CC and during DNA replication (PubMed:14578910, PubMed:15548678,
CC PubMed:15448697). DCX(DTL) directs autoubiquitination of DTL
CC (PubMed:23478445). In association with DDB1 and SKP2 probably is
CC involved in ubiquitination of CDKN1B/p27kip (PubMed:16537899). Is
CC involved in ubiquitination of HOXA9 (PubMed:14609952). The DDB1-CUL4A-
CC DTL E3 ligase complex regulates the circadian clock function by
CC mediating the ubiquitination and degradation of CRY1 (PubMed:26431207).
CC A number of DCX complexes (containing either TRPC4AP or DCAF12 as
CC substrate-recognition component) are part of the DesCEND (destruction
CC via C-end degrons) pathway, which recognizes a C-degron located at the
CC extreme C terminus of target proteins, leading to their ubiquitination
CC and degradation (PubMed:29779948). The DCX(AMBRA1) complex is a master
CC regulator of the transition from G1 to S cell phase by mediating
CC ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3)
CC (PubMed:33854232, PubMed:33854239). The DCX(AMBRA1) complex also acts
CC as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase
CC complexes by mediating ubiquitination and degradation of Elongin-C
CC (ELOC) component of CRL5 complexes (PubMed:30166453). With CUL4B,
CC contributes to ribosome biogenesis (PubMed:26711351).
CC {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:14609952,
CC ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15448697,
CC ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:15811626,
CC ECO:0000269|PubMed:16537899, ECO:0000269|PubMed:16678110,
CC ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:23478445,
CC ECO:0000269|PubMed:24209620, ECO:0000269|PubMed:26431207,
CC ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:29779948,
CC ECO:0000269|PubMed:30166453, ECO:0000269|PubMed:33854232,
CC ECO:0000269|PubMed:33854239}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:15448697,
CC ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:16537899,
CC ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:24209620,
CC ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30166453,
CC ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854239}.
CC -!- SUBUNIT: Can self-associate (PubMed:17254749). Component of multiple
CC DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem
CC to consist of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate
CC recognition component which seems to belong to a protein family
CC described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-
CC associated WD40-repeat) proteins (PubMed:14578910, PubMed:12732143,
CC PubMed:15548678, PubMed:14739464, PubMed:29779948, PubMed:30166453).
CC Component of the CSA complex (DCX(ERCC8) complex) containing ERCC8,
CC RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II;
CC upon UV irradiation it interacts with the COP9 signalosome and
CC preferentially with the hyperphosphorylated form of RNA polymerase II
CC (PubMed:12732143). Component of the DCX(DET1-COP1) complex with the
CC substrate recognition component DET1 and COP1 (PubMed:14739464).
CC Component of the DCX(DDB2) complex with the substrate recognition
CC component DDB2 (PubMed:15811626, PubMed:16678110). Component of the
CC DCX(DTL) complex with the putative substrate recognition component DTL
CC (PubMed:14578910, PubMed:15448697, PubMed:15548678). Component of DCX
CC complexes part of the DesCEND (destruction via C-end degrons) pathway,
CC which contain either TRPC4AP or DCAF12 as substrate-recognition
CC component (PubMed:29779948). Component of the DCX(AMBRA1) complex with
CC the substrate recognition component AMBRA1 (PubMed:30166453,
CC PubMed:33854232, PubMed:33854239). Interacts with DDB1, RBX1, RNF7,
CC CDT1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9
CC (PubMed:16964240, PubMed:16537899, PubMed:22118460, PubMed:16482215,
CC PubMed:12609982, PubMed:10230407, PubMed:14609952, PubMed:16678110).
CC Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually
CC exclusive (PubMed:16678110, PubMed:22118460, PubMed:16482215).
CC Interacts with DCAF1, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1,
CC WDTC1, DCAF5, DCAF11, WDR24A, COP1, PAFAH1B1, ERCC8, GRWD1, FBXW5,
CC RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4,
CC RBBP5, LRWD1 and DCAF8 (PubMed:16949367, PubMed:22935713,
CC PubMed:17079684). May interact with WDR26, WDR51B, SNRNP40, WDR61,
CC WDR76, WDR5 (PubMed:17041588). Interacts (when neddylated) with ARIH1;
CC leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655).
CC The DDB1-CUL4A complex interacts with CRY1 (PubMed:26431207). Interacts
CC (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and
CC DCUN1D5; these interactions promote the cullin neddylation
CC (PubMed:23201271, PubMed:26906416). {ECO:0000269|PubMed:10230407,
CC ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:12732143,
CC ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:14609952,
CC ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15448697,
CC ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:15811626,
CC ECO:0000269|PubMed:16482215, ECO:0000269|PubMed:16537899,
CC ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16949367,
CC ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17041588,
CC ECO:0000269|PubMed:17079684, ECO:0000269|PubMed:17254749,
CC ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:22935713,
CC ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:24076655,
CC ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:26906416,
CC ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30166453,
CC ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854239}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus BPLF1.
CC {ECO:0000269|PubMed:20190741}.
CC -!- INTERACTION:
CC Q13619; P54253: ATXN1; NbExp=6; IntAct=EBI-456106, EBI-930964;
CC Q13619; Q86VP6: CAND1; NbExp=6; IntAct=EBI-456106, EBI-456077;
CC Q13619; Q16531: DDB1; NbExp=12; IntAct=EBI-456106, EBI-350322;
CC Q13619; Q92466: DDB2; NbExp=10; IntAct=EBI-456106, EBI-1176171;
CC Q13619; P08238: HSP90AB1; NbExp=2; IntAct=EBI-456106, EBI-352572;
CC Q13619; Q15291: RBBP5; NbExp=3; IntAct=EBI-456106, EBI-592823;
CC Q13619; O94888: UBXN7; NbExp=7; IntAct=EBI-456106, EBI-1993627;
CC Q13619; P55072: VCP; NbExp=2; IntAct=EBI-456106, EBI-355164;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13619-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13619-2; Sequence=VSP_018577;
CC -!- PTM: Neddylated. Deneddylated via its interaction with the COP9
CC signalosome (CSN) complex. {ECO:0000269|PubMed:10597293,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:9694792}.
CC -!- PTM: (Microbial infection) Deneddylated by Epstein-Barr virus BPLF1
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; AF077188; AAD45191.1; -; mRNA.
DR EMBL; AY365124; AAR13072.1; -; mRNA.
DR EMBL; AB178950; BAD93235.1; -; mRNA.
DR EMBL; AL136221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008308; AAH08308.2; -; mRNA.
DR EMBL; AB012193; BAA33146.1; -; mRNA.
DR EMBL; U58090; AAC50547.1; -; mRNA.
DR CCDS; CCDS41908.1; -. [Q13619-1]
DR CCDS; CCDS9533.1; -. [Q13619-2]
DR RefSeq; NP_001008895.1; NM_001008895.2. [Q13619-1]
DR RefSeq; NP_001265442.1; NM_001278513.1. [Q13619-2]
DR RefSeq; NP_003580.1; NM_003589.2. [Q13619-2]
DR RefSeq; XP_011535825.1; XM_011537523.2. [Q13619-2]
DR PDB; 2HYE; X-ray; 3.10 A; C=1-759.
DR PDB; 4A0K; X-ray; 5.93 A; A=38-759.
DR PDB; 7OKQ; EM; 8.40 A; C/G/K/O=35-759.
DR PDB; 7OPC; EM; 3.00 A; e=1-759.
DR PDB; 7OPD; EM; 3.00 A; e=1-759.
DR PDBsum; 2HYE; -.
DR PDBsum; 4A0K; -.
DR PDBsum; 7OKQ; -.
DR PDBsum; 7OPC; -.
DR PDBsum; 7OPD; -.
DR AlphaFoldDB; Q13619; -.
DR SMR; Q13619; -.
DR BioGRID; 114029; 777.
DR ComplexPortal; CPX-477; CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant.
DR CORUM; Q13619; -.
DR DIP; DIP-31610N; -.
DR IntAct; Q13619; 209.
DR MINT; Q13619; -.
DR STRING; 9606.ENSP00000364589; -.
DR ChEMBL; CHEMBL4523598; -.
DR GlyGen; Q13619; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13619; -.
DR MetOSite; Q13619; -.
DR PhosphoSitePlus; Q13619; -.
DR BioMuta; CUL4A; -.
DR DMDM; 108936013; -.
DR EPD; Q13619; -.
DR jPOST; Q13619; -.
DR MassIVE; Q13619; -.
DR MaxQB; Q13619; -.
DR PaxDb; Q13619; -.
DR PeptideAtlas; Q13619; -.
DR PRIDE; Q13619; -.
DR ProteomicsDB; 59609; -. [Q13619-1]
DR ProteomicsDB; 59610; -. [Q13619-2]
DR Antibodypedia; 11756; 407 antibodies from 38 providers.
DR DNASU; 8451; -.
DR Ensembl; ENST00000375440.9; ENSP00000364589.4; ENSG00000139842.15. [Q13619-1]
DR Ensembl; ENST00000375441.7; ENSP00000364590.3; ENSG00000139842.15. [Q13619-2]
DR Ensembl; ENST00000451881.5; ENSP00000389118.1; ENSG00000139842.15. [Q13619-2]
DR Ensembl; ENST00000617546.4; ENSP00000481782.1; ENSG00000139842.15. [Q13619-2]
DR GeneID; 8451; -.
DR KEGG; hsa:8451; -.
DR MANE-Select; ENST00000375440.9; ENSP00000364589.4; NM_001008895.4; NP_001008895.1.
DR UCSC; uc021rmu.2; human. [Q13619-1]
DR CTD; 8451; -.
DR DisGeNET; 8451; -.
DR GeneCards; CUL4A; -.
DR HGNC; HGNC:2554; CUL4A.
DR HPA; ENSG00000139842; Tissue enhanced (skeletal).
DR MIM; 603137; gene.
DR neXtProt; NX_Q13619; -.
DR OpenTargets; ENSG00000139842; -.
DR PharmGKB; PA27050; -.
DR VEuPathDB; HostDB:ENSG00000139842; -.
DR eggNOG; KOG2167; Eukaryota.
DR GeneTree; ENSGT00940000156905; -.
DR HOGENOM; CLU_004747_7_2_1; -.
DR InParanoid; Q13619; -.
DR OMA; DNVVQSC; -.
DR OrthoDB; 1040292at2759; -.
DR PhylomeDB; Q13619; -.
DR TreeFam; TF101153; -.
DR PathwayCommons; Q13619; -.
DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-HSA-5696394; DNA Damage Recognition in GG-NER.
DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-HSA-5696400; Dual Incision in GG-NER.
DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-HSA-6781827; Transcription-Coupled Nucleotide Excision Repair (TC-NER).
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q13619; -.
DR SIGNOR; Q13619; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 8451; 17 hits in 1123 CRISPR screens.
DR ChiTaRS; CUL4A; human.
DR EvolutionaryTrace; Q13619; -.
DR GeneWiki; CUL4A; -.
DR GenomeRNAi; 8451; -.
DR Pharos; Q13619; Tchem.
DR PRO; PR:Q13619; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q13619; protein.
DR Bgee; ENSG00000139842; Expressed in gastrocnemius and 202 other tissues.
DR ExpressionAtlas; Q13619; baseline and differential.
DR Genevisible; Q13619; HS.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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; IEA:Ensembl.
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:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IEA:Ensembl.
DR GO; GO:2000819; P:regulation of nucleotide-excision repair; IEA:Ensembl.
DR GO; GO:0051246; P:regulation of protein metabolic process; IEA:Ensembl.
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; IEA:Ensembl.
DR Gene3D; 1.10.10.10; -; 1.
DR IDEAL; IID00514; -.
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 3D-structure; Alternative splicing; Biological rhythms; DNA damage;
KW DNA repair; Host-virus interaction; Isopeptide bond; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..759
FT /note="Cullin-4A"
FT /id="PRO_0000119795"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT CROSSLNK 8
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 33
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT CROSSLNK 705
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000250|UniProtKB:Q13616"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9721878"
FT /id="VSP_018577"
FT VARIANT 644
FT /note="K -> R (in dbSNP:rs2302757)"
FT /id="VAR_020341"
FT MUTAGEN 86..90
FT /note="LYQAV->AAAAA: Largely reduces interaction with DDB1;
FT abolishes interaction with DDB2."
FT /evidence="ECO:0000269|PubMed:16482215,
FT ECO:0000269|PubMed:17079684"
FT MUTAGEN 139..142
FT /note="WQDH->AADA: Largely reduces interaction with DDB1;
FT abolishes interaction with DDB2."
FT /evidence="ECO:0000269|PubMed:16482215,
FT ECO:0000269|PubMed:17079684"
FT CONFLICT 281
FT /note="S -> T (in Ref. 3; BAD93235)"
FT /evidence="ECO:0000305"
FT CONFLICT 339..346
FT /note="HWSEYIKT -> NSARARAA (in Ref. 7; AAC50547)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="K -> R (in Ref. 3; BAD93235)"
FT /evidence="ECO:0000305"
FT HELIX 56..73
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 84..92
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 96..98
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 99..116
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 131..150
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:2HYE"
FT HELIX 170..181
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 182..185
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 187..203
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 211..223
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 224..228
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 232..253
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 256..276
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 280..294
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 301..303
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 305..312
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 316..325
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 328..331
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 332..352
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 355..357
FT /evidence="ECO:0007829|PDB:2HYE"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 362..377
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 378..382
FT /evidence="ECO:0007829|PDB:2HYE"
FT HELIX 385..398
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 405..416
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:2HYE"
FT HELIX 426..440
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 446..461
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 462..464
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 469..480
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 481..483
FT /evidence="ECO:0007829|PDB:2HYE"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 490..511
FT /evidence="ECO:0007829|PDB:7OPC"
FT TURN 512..516
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 522..529
FT /evidence="ECO:0007829|PDB:2HYE"
FT TURN 530..532
FT /evidence="ECO:0007829|PDB:2HYE"
FT HELIX 545..559
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 560..563
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 566..568
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 571..573
FT /evidence="ECO:0007829|PDB:2HYE"
FT STRAND 575..580
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 587..592
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 593..604
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 610..615
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 621..627
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 630..634
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 637..639
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 645..647
FT /evidence="ECO:0007829|PDB:2HYE"
FT STRAND 653..656
FT /evidence="ECO:0007829|PDB:2HYE"
FT STRAND 665..667
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 672..674
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 678..689
FT /evidence="ECO:0007829|PDB:7OPC"
FT HELIX 692..706
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 707..711
FT /evidence="ECO:0007829|PDB:2HYE"
FT HELIX 712..722
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 723..725
FT /evidence="ECO:0007829|PDB:2HYE"
FT HELIX 729..741
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 746..748
FT /evidence="ECO:0007829|PDB:7OPC"
FT STRAND 754..757
FT /evidence="ECO:0007829|PDB:7OPC"
SQ SEQUENCE 759 AA; 87680 MW; 3C4C6A1BBD94D51B CRC64;
MADEAPRKGS FSALVGRTNG LTKPAALAAA PAKPGGAGGS KKLVIKNFRD RPRLPDNYTQ
DTWRKLHEAV RAVQSSTSIR YNLEELYQAV ENLCSHKVSP MLYKQLRQAC EDHVQAQILP
FREDSLDSVL FLKKINTCWQ DHCRQMIMIR SIFLFLDRTY VLQNSTLPSI WDMGLELFRT
HIISDKMVQS KTIDGILLLI ERERSGEAVD RSLLRSLLGM LSDLQVYKDS FELKFLEETN
CLYAAEGQRL MQEREVPEYL NHVSKRLEEE GDRVITYLDH STQKPLIACV EKQLLGEHLT
AILQKGLDHL LDENRVPDLA QMYQLFSRVR GGQQALLQHW SEYIKTFGTA IVINPEKDKD
MVQDLLDFKD KVDHVIEVCF QKNERFVNLM KESFETFINK RPNKPAELIA KHVDSKLRAG
NKEATDEELE RTLDKIMILF RFIHGKDVFE AFYKKDLAKR LLVGKSASVD AEKSMLSKLK
HECGAAFTSK LEGMFKDMEL SKDIMVHFKQ HMQNQSDSGP IDLTVNILTM GYWPTYTPME
VHLTPEMIKL QEVFKAFYLG KHSGRKLQWQ TTLGHAVLKA EFKEGKKEFQ VSLFQTLVLL
MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED GDKFIFNGEF
KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI VRIMKMRKTL GHNLLVSELY
NQLKFPVKPG DLKKRIESLI DRDYMERDKD NPNQYHYVA
