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Database: UniProt
Entry: Q13619
LinkDB: Q13619
Original site: Q13619 
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   07-APR-2021, entry version 194.
DE   RecName: Full=Cullin-4A;
DE            Short=CUL-4A;
GN   Name=CUL4A;
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).
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, AND FUNCTION IN UBIQUITINATION OF HOXA9.
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, AND FUNCTION IN UBIQUITINATION OF TP53.
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, AND FUNCTION IN CTD1 UBIQUITINATION.
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   IDENTIFICATION IN THE DCX(DET1-COP1) COMPLEX WITH DDB1; RBX1; COP1 AND
RP   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, AND FUNCTION IN UBIQUITINATION OF CDKN1B.
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   INTERACTION WITH DDB2; WDR26; RBBP5; COP1; WDR51B; SNRNP40; WDR61; WDR76
RP   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.
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.
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   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   [40]
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. 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 TP53 in response to
CC       radiation-induced DNA damage and during DNA replication. In association
CC       with DDB1 and SKP2 probably is involved in ubiquitination of
CC       CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. DCX(DTL) directs
CC       autoubiquitination of DTL. The DDB1-CUL4A-DTL E3 ligase complex
CC       regulates the circadian clock function by mediating the ubiquitination
CC       and degradation of CRY1 (PubMed:26431207). With CUL4B, contributes to
CC       ribosome biogenesis (PubMed:26711351). {ECO:0000269|PubMed:14578910,
CC       ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:15448697,
CC       ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:16537899,
CC       ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:23478445,
CC       ECO:0000269|PubMed:24209620, ECO:0000269|PubMed:26431207,
CC       ECO:0000269|PubMed:26711351}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-
CC       protein ligase complexes that seem to consist of DDB1, CUL4A or CUL4B,
CC       RBX1 and a variable substrate recognition component which seems to
CC       belong to a protein family described as DCAF (Ddb1- and Cul4-associated
CC       factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component
CC       of the CSA complex (DCX(ERCC8) complex) containing ERCC8, RBX1, DDB1
CC       and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV
CC       irradiation it interacts with the COP9 signalosome and preferentially
CC       with the hyperphosphorylated form of RNA polymerase II. Component of
CC       the DCX(DET1-COP1) complex with the substrate recognition component
CC       DET1 and COP1. Component of the DCX(DDB2) complex with the substrate
CC       recognition component DDB2. Component of the DCX(DTL) complex with the
CC       putative substrate recognition component DTL. Interacts with DDB1,
CC       RBX1, RNF7, CTD1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9.
CC       Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually
CC       exclusive. Interacts with DCAF1, DTL, DDA1, DCAF6, DCAF4, DCAF16,
CC       DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, COP1, PAFAH1B1, ERCC8,
CC       GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1,
CC       KATNB1, RBBP4, RBBP5, LRWD1 and DCAF8. May interact with WDR26, WDR51B,
CC       SNRNP40, WDR61, WDR76, WDR5. Can self-associate. Interacts (when
CC       neddylated) with ARIH1; leading to activate the E3 ligase activity of
CC       ARIH1 (PubMed:24076655). The DDB1-CUL4A complex interacts with CRY1
CC       (PubMed:26431207). Interacts (unneddylated form) with DCUN1D1, DCUN1D2,
CC       DCUN1D3, DCUN1D4 and DCUN1D5; these interacti ons promote the cullin
CC       neddylation (PubMed:26906416, PubMed:23201271).
CC       {ECO:0000269|PubMed:10230407, ECO:0000269|PubMed:12609982,
CC       ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:14578910,
CC       ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:14739464,
CC       ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15548678,
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:22118460,
CC       ECO:0000269|PubMed:22935713, ECO:0000269|PubMed:23201271,
CC       ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:26431207,
CC       ECO:0000269|PubMed:26906416}.
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   PDBsum; 2HYE; -.
DR   PDBsum; 4A0K; -.
DR   SMR; Q13619; -.
DR   BioGRID; 114029; 460.
DR   ComplexPortal; CPX-477; CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant.
DR   CORUM; Q13619; -.
DR   DIP; DIP-31610N; -.
DR   IntAct; Q13619; 206.
DR   MINT; Q13619; -.
DR   STRING; 9606.ENSP00000364589; -.
DR   ChEMBL; CHEMBL3833061; -.
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; 387 antibodies.
DR   DNASU; 8451; -.
DR   Ensembl; ENST00000375440; ENSP00000364589; ENSG00000139842. [Q13619-1]
DR   Ensembl; ENST00000375441; ENSP00000364590; ENSG00000139842. [Q13619-2]
DR   Ensembl; ENST00000451881; ENSP00000389118; ENSG00000139842. [Q13619-2]
DR   Ensembl; ENST00000617546; ENSP00000481782; ENSG00000139842. [Q13619-2]
DR   GeneID; 8451; -.
DR   KEGG; hsa:8451; -.
DR   UCSC; uc021rmu.2; human. [Q13619-1]
DR   CTD; 8451; -.
DR   DisGeNET; 8451; -.
DR   GeneCards; CUL4A; -.
DR   HGNC; HGNC:2554; CUL4A.
DR   HPA; ENSG00000139842; Low tissue specificity.
DR   MIM; 603137; gene.
DR   neXtProt; NX_Q13619; -.
DR   OpenTargets; ENSG00000139842; -.
DR   PharmGKB; PA27050; -.
DR   VEuPathDB; HostDB:ENSG00000139842.14; -.
DR   eggNOG; KOG2167; Eukaryota.
DR   GeneTree; ENSGT00940000156905; -.
DR   HOGENOM; CLU_004747_7_2_1; -.
DR   InParanoid; Q13619; -.
DR   OMA; KETPNQY; -.
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   SIGNOR; Q13619; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 8451; 11 hits in 998 CRISPR screens.
DR   ChiTaRS; CUL4A; human.
DR   EvolutionaryTrace; Q13619; -.
DR   GeneWiki; CUL4A; -.
DR   GenomeRNAi; 8451; -.
DR   Pharos; Q13619; Tbio.
DR   PRO; PR:Q13619; -.
DR   Proteomes; UP000005640; Chromosome 13.
DR   RNAct; Q13619; protein.
DR   Bgee; ENSG00000139842; Expressed in skeletal muscle tissue and 244 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:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR   GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR   GO; GO:0042769; P:DNA damage response, detection of DNA damage; TAS:Reactome.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
DR   GO; GO:0070911; P:global genome nucleotide-excision repair; TAS:Reactome.
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:0000715; P:nucleotide-excision repair, DNA damage recognition; TAS:Reactome.
DR   GO; GO:0000717; P:nucleotide-excision repair, DNA duplex unwinding; TAS:Reactome.
DR   GO; GO:0033683; P:nucleotide-excision repair, DNA incision; TAS:Reactome.
DR   GO; GO:0006295; P:nucleotide-excision repair, DNA incision, 3'-to lesion; TAS:Reactome.
DR   GO; GO:0006296; P:nucleotide-excision repair, DNA incision, 5'-to lesion; TAS:Reactome.
DR   GO; GO:0006294; P:nucleotide-excision repair, preincision complex assembly; TAS:Reactome.
DR   GO; GO:0006293; P:nucleotide-excision repair, preincision complex stabilization; TAS:Reactome.
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:0043687; P:post-translational protein modification; TAS:Reactome.
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   GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; TAS:Reactome.
DR   GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.10.10; -; 1.
DR   IDEAL; IID00514; -.
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   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   TURN            58..61
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           62..71
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           83..93
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            96..98
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           99..121
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           130..152
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           154..157
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            158..162
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          165..167
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           170..180
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            181..183
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          184..186
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           189..191
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           193..201
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            202..206
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           211..223
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            227..231
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           232..253
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           256..269
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           271..274
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            275..277
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            280..282
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           283..294
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            295..297
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           300..304
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           307..311
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            312..314
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           316..328
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           332..352
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           355..357
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            358..360
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           361..377
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            378..382
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           384..398
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           404..417
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           421..423
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           429..440
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           446..462
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           469..480
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            481..483
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            485..488
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           489..513
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          522..529
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            530..532
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           545..559
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          564..566
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           571..573
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          575..579
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          588..592
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           593..601
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           610..616
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           621..629
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   TURN            630..636
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          638..641
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          645..647
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          653..656
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          665..668
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           670..674
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           678..706
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          707..711
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           713..722
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          723..725
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   HELIX           729..741
FT                   /evidence="ECO:0007744|PDB:2HYE"
FT   STRAND          754..756
FT                   /evidence="ECO:0007744|PDB:2HYE"
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
//
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