CDC6_YEAST
ID CDC6_YEAST Reviewed; 513 AA.
AC P09119; D6VVZ7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Cell division control protein 6;
GN Name=CDC6; OrderedLocusNames=YJL194W; ORFNames=J0347;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2656692; DOI=10.1016/s0021-9258(18)81897-x;
RA Zhou C., Huang S.H., Jong A.Y.;
RT "Molecular cloning of Saccharomyces cerevisiae CDC6 gene. Isolation,
RT identification, and sequence analysis.";
RL J. Biol. Chem. 264:9022-9029(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Colasanti J.J., Comer A.R., Bruschi C.V.;
RT "Molecular cloning and characterization of the cell division cycle gene
RT CDC6 from Saccharomyces cerevisiae.";
RL Submitted (APR-1990) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=1600944; DOI=10.1002/j.1460-2075.1992.tb05276.x;
RA Bueno A., Russell P.;
RT "Dual functions of CDC6: a yeast protein required for DNA replication also
RT inhibits nuclear division.";
RL EMBO J. 11:2167-2176(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7754713; DOI=10.1002/yea.320100912;
RA Purnelle B., Coster F., Goffeau A.;
RT "The sequence of a 36 kb segment on the left arm of yeast chromosome X
RT identifies 24 open reading frames including NUC1, PRP21 (SPP91), CDC6,
RT CRY2, the gene for S24, a homologue to the aconitase gene ACO1 and two
RT homologues to chromosome III genes.";
RL Yeast 10:1235-1249(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [6]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-48.
RX PubMed=2246267; DOI=10.1016/s0021-9258(17)45458-5;
RA Zhou C., Jong A.Y.;
RT "CDC6 mRNA fluctuates periodically in the yeast cell cycle.";
RL J. Biol. Chem. 265:19904-19909(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-513.
RX PubMed=3062576; DOI=10.1093/nar/16.24.11507;
RA Lisziewicz J., Godany A., Agoston D.V., Kuentzel H.;
RT "Cloning and characterization of the Saccharomyces cerevisiae CDC6 gene.";
RL Nucleic Acids Res. 16:11507-11520(1988).
RN [9]
RP INDUCTION, AND FUNCTION.
RX PubMed=7641697; DOI=10.1002/j.1460-2075.1995.tb00048.x;
RA Piatti S., Lengauer C., Nasmyth K.;
RT "Cdc6 is an unstable protein whose de novo synthesis in G1 is important for
RT the onset of S phase and for preventing a 'reductional' anaphase in the
RT budding yeast Saccharomyces cerevisiae.";
RL EMBO J. 14:3788-3799(1995).
RN [10]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-29, AND NUCLEAR LOCALIZATION
RP SIGNAL.
RX PubMed=8892760; DOI=10.1089/dna.1996.15.883;
RA Jong A., Young M., Chen G.C., Zhang S.Q., Chan C.;
RT "Intracellular location of the Saccharomyces cerevisiae CDC6 gene
RT product.";
RL DNA Cell Biol. 15:883-895(1996).
RN [11]
RP FUNCTION.
RX PubMed=8978693; DOI=10.1002/j.1460-2075.1996.tb01057.x;
RA Santocanale C., Diffley J.F.;
RT "ORC- and Cdc6-dependent complexes at active and inactive chromosomal
RT replication origins in Saccharomyces cerevisiae.";
RL EMBO J. 15:6671-6679(1996).
RN [12]
RP INDUCTION, AND FUNCTION.
RX PubMed=8538771; DOI=10.1038/379180a0;
RA Cocker J.H., Piatti S., Santocanale C., Nasmyth K., Diffley J.F.;
RT "An essential role for the Cdc6 protein in forming the pre-replicative
RT complexes of budding yeast.";
RL Nature 379:180-182(1996).
RN [13]
RP FUNCTION, AND INTERACTION WITH CDC4.
RX PubMed=9312054; DOI=10.1093/emboj/16.19.5966;
RA Drury L.S., Perkins G., Diffley J.F.;
RT "The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast.";
RL EMBO J. 16:5966-5976(1997).
RN [14]
RP FUNCTION.
RX PubMed=9099949; DOI=10.1242/jcs.110.6.753;
RA Detweiler C.S., Li J.J.;
RT "Cdc6p establishes and maintains a state of replication competence during
RT G1 phase.";
RL J. Cell Sci. 110:753-763(1997).
RN [15]
RP INTERACTION WITH ORC1, MUTAGENESIS OF LYS-114, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10075735; DOI=10.1074/jbc.274.12.8291;
RA Wang B., Feng L., Hu Y., Huang S.H., Reynolds C.P., Wu L., Jong A.Y.;
RT "The essential role of Saccharomyces cerevisiae CDC6 nucleotide-binding
RT site in cell growth, DNA synthesis, and Orc1 association.";
RL J. Biol. Chem. 274:8291-8298(1999).
RN [16]
RP INTERACTION WITH CDC28, PHOSPHORYLATION BY CDC28, AND UBIQUITINATION.
RX PubMed=10512865; DOI=10.1091/mbc.10.10.3263;
RA Elsasser S., Chi Y., Yang P., Campbell J.L.;
RT "Phosphorylation controls timing of Cdc6p destruction: A biochemical
RT analysis.";
RL Mol. Biol. Cell 10:3263-3277(1999).
RN [17]
RP MUTAGENESIS OF LYS-114, AND FUNCTION.
RX PubMed=9892652; DOI=10.1073/pnas.96.2.441;
RA Weinreich M., Liang C., Stillman B.;
RT "The Cdc6p nucleotide-binding motif is required for loading mcm proteins
RT onto chromatin.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:441-446(1999).
RN [18]
RP INTERACTION WITH CDC28, AND PHOSPHORYLATION BY CDC28.
RX PubMed=10734126; DOI=10.1074/jbc.275.13.9734;
RA Calzada A., Sanchez M., Sanchez E., Bueno A.;
RT "The stability of the Cdc6 protein is regulated by cyclin-dependent
RT kinase/cyclin B complexes in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 275:9734-9741(2000).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-368, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [20]
RP INTERACTION WITH DIA2 AND TOM1, UBIQUITINATION, AND SUBCELLULAR LOCATION.
RX PubMed=23129771; DOI=10.1074/jbc.m112.401778;
RA Kim D.H., Zhang W., Koepp D.M.;
RT "The Hect domain E3 ligase Tom1 and the F-box protein Dia2 control Cdc6
RT degradation in G1 phase.";
RL J. Biol. Chem. 287:44212-44220(2012).
RN [21]
RP INTERACTION WITH THE ORC AND MCM2-7 COMPLEXES, AND FUNCTION.
RX PubMed=23603117; DOI=10.1016/j.molcel.2013.03.026;
RA Fernandez-Cid A., Riera A., Tognetti S., Herrera M.C., Samel S., Evrin C.,
RA Winkler C., Gardenal E., Uhle S., Speck C.;
RT "An ORC/Cdc6/MCM2-7 complex is formed in a multistep reaction to serve as a
RT platform for MCM double-hexamer assembly.";
RL Mol. Cell 50:577-588(2013).
CC -!- FUNCTION: Plays a crucial role in forming the pre-replicative
CC complexes. Interacts with the origin recognition complex (ORC) and
CC MCM2-7 helicase complex leading to the linking of those complexes and
CC loading of the replicative helicase MCM2-7 onto the pre-replicative
CC complexes. Required for the initiation of DNA replication and then
CC actively participates in the suppression of nuclear division.
CC {ECO:0000269|PubMed:10075735, ECO:0000269|PubMed:1600944,
CC ECO:0000269|PubMed:23603117, ECO:0000269|PubMed:7641697,
CC ECO:0000269|PubMed:8538771, ECO:0000269|PubMed:8978693,
CC ECO:0000269|PubMed:9099949, ECO:0000269|PubMed:9312054,
CC ECO:0000269|PubMed:9892652}.
CC -!- SUBUNIT: Associates with the ORC complex and the MCM2-7 helicase
CC complex. Interacts with CDC4, CDC28, DIA2, ORC1, and TOM1.
CC {ECO:0000269|PubMed:10075735, ECO:0000269|PubMed:10512865,
CC ECO:0000269|PubMed:10734126, ECO:0000269|PubMed:23129771,
CC ECO:0000269|PubMed:23603117, ECO:0000269|PubMed:9312054}.
CC -!- INTERACTION:
CC P09119; P00546: CDC28; NbExp=2; IntAct=EBI-4447, EBI-4253;
CC P09119; P43603: LSB3; NbExp=2; IntAct=EBI-4447, EBI-22980;
CC P09119; P29469: MCM2; NbExp=4; IntAct=EBI-4447, EBI-10533;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- INDUCTION: Transcribed at the end of mitosis, but in cells with a
CC prolonged G1 phase there is a second burst of transcription in late G1.
CC {ECO:0000269|PubMed:7641697, ECO:0000269|PubMed:8538771}.
CC -!- PTM: Ubiquitinated by the E3 ubiquitin ligase complex SCF(CDC4), DIA2,
CC and TOM1; and targeted to the 26S proteasome for degradation.
CC -!- PTM: Phosphorylated by CDC28. Phosphorylation is a prerequisite to
CC ubiquitination and degradation. {ECO:0000269|PubMed:10512865,
CC ECO:0000269|PubMed:10734126}.
CC -!- SIMILARITY: Belongs to the CDC6/cdc18 family. {ECO:0000305}.
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DR EMBL; J04734; AAA34484.1; -; Genomic_DNA.
DR EMBL; M22858; AAA34483.1; -; Genomic_DNA.
DR EMBL; X65299; CAA46392.1; -; Genomic_DNA.
DR EMBL; X77688; CAA54766.1; -; Genomic_DNA.
DR EMBL; Z49470; CAA89490.1; -; Genomic_DNA.
DR EMBL; M61183; AAA34488.1; -; Genomic_DNA.
DR EMBL; X13118; CAA31510.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08613.1; -; Genomic_DNA.
DR PIR; S46640; RGBYC6.
DR RefSeq; NP_012341.1; NM_001181627.1.
DR PDB; 5V8F; EM; 3.90 A; 9=1-513.
DR PDB; 6WGC; EM; 4.30 A; 9=1-513.
DR PDB; 6WGG; EM; 8.10 A; 9=1-513.
DR PDB; 6WGI; EM; 10.00 A; 9=1-513.
DR PDB; 7MCA; EM; 3.60 A; I=1-513.
DR PDBsum; 5V8F; -.
DR PDBsum; 6WGC; -.
DR PDBsum; 6WGG; -.
DR PDBsum; 6WGI; -.
DR PDBsum; 7MCA; -.
DR AlphaFoldDB; P09119; -.
DR SMR; P09119; -.
DR BioGRID; 33569; 323.
DR DIP; DIP-2267N; -.
DR ELM; P09119; -.
DR IntAct; P09119; 24.
DR MINT; P09119; -.
DR STRING; 4932.YJL194W; -.
DR iPTMnet; P09119; -.
DR PaxDb; P09119; -.
DR PRIDE; P09119; -.
DR EnsemblFungi; YJL194W_mRNA; YJL194W; YJL194W.
DR GeneID; 853244; -.
DR KEGG; sce:YJL194W; -.
DR SGD; S000003730; CDC6.
DR VEuPathDB; FungiDB:YJL194W; -.
DR eggNOG; KOG2227; Eukaryota.
DR GeneTree; ENSGT00530000063498; -.
DR HOGENOM; CLU_012774_2_1_1; -.
DR InParanoid; P09119; -.
DR OMA; NDNILHP; -.
DR BioCyc; YEAST:G3O-31626-MON; -.
DR Reactome; R-SCE-68689; CDC6 association with the ORC:origin complex.
DR Reactome; R-SCE-68949; Orc1 removal from chromatin.
DR Reactome; R-SCE-68962; Activation of the pre-replicative complex.
DR Reactome; R-SCE-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR PRO; PR:P09119; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P09119; protein.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0031261; C:DNA replication preinitiation complex; IDA:SGD.
DR GO; GO:0005656; C:nuclear pre-replicative complex; IDA:SGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0005524; F:ATP binding; IDA:SGD.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:SGD.
DR GO; GO:0003682; F:chromatin binding; IDA:SGD.
DR GO; GO:0003688; F:DNA replication origin binding; IDA:SGD.
DR GO; GO:0005525; F:GTP binding; IDA:SGD.
DR GO; GO:0003924; F:GTPase activity; IDA:SGD.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006270; P:DNA replication initiation; IEA:InterPro.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:SGD.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IBA:GO_Central.
DR GO; GO:0006267; P:pre-replicative complex assembly involved in nuclear cell cycle DNA replication; IDA:SGD.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IMP:SGD.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR016314; Cdc6/18.
DR InterPro; IPR015163; Cdc6_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF13401; AAA_22; 1.
DR Pfam; PF09079; Cdc6_C; 1.
DR PIRSF; PIRSF001767; Cdc6; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Cell division; Chromosome;
KW DNA replication; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..513
FT /note="Cell division control protein 6"
FT /id="PRO_0000150977"
FT REGION 1..47
FT /note="Interaction with CDC4; required for degradation"
FT /evidence="ECO:0000269|PubMed:9312054"
FT MOTIF 27..33
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:8892760"
FT BINDING 108..115
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 368
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MUTAGEN 29
FT /note="K->R,T: Impairs nuclear localization."
FT /evidence="ECO:0000269|PubMed:8892760"
FT MUTAGEN 114
FT /note="K->E: Impairs ORC1-binding and leads to defective
FT association with chromatin."
FT /evidence="ECO:0000269|PubMed:10075735,
FT ECO:0000269|PubMed:9892652"
FT CONFLICT 3
FT /note="A -> G (in Ref. 1; AAA34484)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="M -> I (in Ref. 1; AAA34484)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="M -> I (in Ref. 1; AAA34484)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="L -> P (in Ref. 8; CAA31510)"
FT /evidence="ECO:0000305"
FT CONFLICT 277
FT /note="L -> F (in Ref. 1; AAA34484)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="R -> S (in Ref. 1; AAA34484)"
FT /evidence="ECO:0000305"
FT CONFLICT 395..396
FT /note="SK -> LQN (in Ref. 8; CAA31510)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="S -> L (in Ref. 8; CAA31510)"
FT /evidence="ECO:0000305"
FT CONFLICT 410
FT /note="L -> S (in Ref. 8; CAA31510)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="S -> L (in Ref. 8; CAA31510)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 513 AA; 58037 MW; 13645F65BEAB5EE8 CRC64;
MSAIPITPTK RIRRNLFDDA PATPPRPLKR KKLQFTDVTP ESSPEKLQFG SQSIFLRTKA
LLQKSSELVN LNSSDGALPA RTAEYEQVMN FLAKAISEHR SDSLYITGPP GTGKTAQLDM
IIRQKFQSLP LSLSTPRSKD VLRHTNPNLQ NLSWFELPDG RLESVAVTSI NCISLGEPSS
IFQKIFDSFQ DLNGPTLQIK NMQHLQKFLE PYHKKTTFVV VLDEMDRLLH ANTSETQSVR
TILELFLLAK LPTVSFVLIG MANSLDMKDR FLSRLNLDRG LLPQTIVFQP YTAEQMYEIV
IQKMSSLPTI IFQPMAIKFA AKKCAGNTGD LRKLFDVLRG SIEIYELEKR FLLSPTRGSL
NSAQVPLTPT TSPVKKSYPE PQGKIGLNYI AKVFSKFVNN NSTRTRIAKL NIQQKLILCT
IIQSLKLNSD ATIDESFDHY IKAITKTDTL APLQRNEFLE ICTILETCGL VSIKKTKCKG
KTKRFVDKID VDLDMREFYD EMTKISILKP FLH
