LCD1_YEAST
ID LCD1_YEAST Reviewed; 747 AA.
AC Q04377; D6VTC1;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=DNA damage checkpoint protein LCD1;
DE AltName: Full=DNA damage checkpoint protein 2;
DE AltName: Full=Lethal, checkpoint-defective, DNA damage-sensitive protein 1;
GN Name=LCD1; Synonyms=DDC2, PIE1; OrderedLocusNames=YDR499W;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [2]
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 [3]
RP FUNCTION, AND INTERACTION WITH MEC1.
RX PubMed=11060031; DOI=10.1093/emboj/19.21.5801;
RA Rouse J., Jackson S.P.;
RT "LCD1: an essential gene involved in checkpoint control and regulation of
RT the MEC1 signalling pathway in Saccharomyces cerevisiae.";
RL EMBO J. 19:5801-5812(2000).
RN [4]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH MEC1.
RX PubMed=10950868;
RA Paciotti V., Clerici M., Lucchini G., Longhese M.P.;
RT "The checkpoint protein Ddc2, functionally related to S. pombe Rad26,
RT interacts with Mec1 and is regulated by Mec1-dependent phosphorylation in
RT budding yeast.";
RL Genes Dev. 14:2046-2059(2000).
RN [5]
RP FUNCTION.
RX PubMed=11707419; DOI=10.1093/emboj/20.22.6485;
RA Clerici M., Paciotti V., Baldo V., Romano M., Lucchini G., Longhese M.P.;
RT "Hyperactivation of the yeast DNA damage checkpoint by TEL1 and DDC2
RT overexpression.";
RL EMBO J. 20:6485-6498(2001).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=11691833; DOI=10.1101/gad.903501;
RA Melo J.A., Cohen J., Toczyski D.P.;
RT "Two checkpoint complexes are independently recruited to sites of DNA
RT damage in vivo.";
RL Genes Dev. 15:2809-2821(2001).
RN [7]
RP FUNCTION, INTERACTION WITH MEC1, AND SUBCELLULAR LOCATION.
RX PubMed=11154263; DOI=10.1128/mcb.21.3.755-764.2001;
RA Wakayama T., Kondo T., Ando S., Matsumoto K., Sugimoto K.;
RT "Pie1, a protein interacting with Mec1, controls cell growth and checkpoint
RT responses in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 21:755-764(2001).
RN [8]
RP INTERACTION WITH MEC1, AND PHOSPHORYLATION BY MEC1.
RX PubMed=11359899; DOI=10.1128/mcb.21.12.3913-3925.2001;
RA Paciotti V., Clerici M., Scotti M., Lucchini G., Longhese M.P.;
RT "Characterization of mec1 kinase-deficient mutants and of new hypomorphic
RT mec1 alleles impairing subsets of the DNA damage response pathway.";
RL Mol. Cell. Biol. 21:3913-3925(2001).
RN [9]
RP FUNCTION.
RX PubMed=12181334; DOI=10.1091/mbc.02-02-0012;
RA Enomoto S., Glowczewski L., Berman J.;
RT "MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint
RT pathway required for cell cycle arrest during senescence in Saccharomyces
RT cerevisiae.";
RL Mol. Biol. Cell 13:2626-2638(2002).
RN [10]
RP FUNCTION, RECRUITMENT TO DNA LESIONS, AND MUTAGENESIS OF LYS-177 AND
RP ARG-179.
RX PubMed=11983176; DOI=10.1016/s1097-2765(02)00507-5;
RA Rouse J., Jackson S.P.;
RT "Lcd1p recruits Mec1p to DNA lesions in vitro and in vivo.";
RL Mol. Cell 9:857-869(2002).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [12]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [13]
RP RECRUITMENT TO DNA LESIONS.
RX PubMed=12791985; DOI=10.1126/science.1083430;
RA Zou L., Elledge S.J.;
RT "Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.";
RL Science 300:1542-1548(2003).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15369670; DOI=10.1016/j.cell.2004.08.015;
RA Lisby M., Barlow J.H., Burgess R.C., Rothstein R.;
RT "Choreography of the DNA damage response: spatiotemporal relationships
RT among checkpoint and repair proteins.";
RL Cell 118:699-713(2004).
RN [15]
RP FUNCTION OF THE MEC1-LCD1 COMPLEX, AND PHOSPHORYLATION BY MEC1.
RX PubMed=16365046; DOI=10.1074/jbc.m507508200;
RA Ma J.-L., Lee S.-J., Duong J.K., Stern D.F.;
RT "Activation of the checkpoint kinase Rad53 by the phosphatidyl inositol
RT kinase-like kinase Mec1.";
RL J. Biol. Chem. 281:3954-3963(2006).
RN [16]
RP FUNCTION, AND INTERACTION WITH MEC1.
RX PubMed=16148046; DOI=10.1091/mbc.e05-05-0405;
RA Nakada D., Hirano Y., Tanaka Y., Sugimoto K.;
RT "Role of the C-terminus of Mec1 checkpoint kinase in its localization to
RT sites of DNA damage.";
RL Mol. Biol. Cell 16:5227-5235(2005).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-11 AND SER-76, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [18]
RP IDENTIFICATION BY 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).
CC -!- FUNCTION: Forms a complex with the serine/threonine kinase MEC1 which
CC activates checkpoint signaling upon genotoxic stresses. The MEC1-LCD1
CC complex is recruited by the single-strand-binding protein complex RPA
CC to DNA lesions in order to initiate the DNA repair by homologous
CC recombination, after the MRX-complex and TEL1 are displaced. Required
CC for the recruitment of MEC1 to DNA lesions, the activation of CHK1 and
CC RAD53 kinases and phosphorylation of RAD9 in response to DNA damage.
CC Required for cell growth and meiotic recombination.
CC {ECO:0000269|PubMed:10950868, ECO:0000269|PubMed:11060031,
CC ECO:0000269|PubMed:11154263, ECO:0000269|PubMed:11707419,
CC ECO:0000269|PubMed:11983176, ECO:0000269|PubMed:12181334,
CC ECO:0000269|PubMed:15369670, ECO:0000269|PubMed:16148046,
CC ECO:0000269|PubMed:16365046}.
CC -!- SUBUNIT: Forms a complex with MEC1.
CC -!- INTERACTION:
CC Q04377; P47027: DPB11; NbExp=7; IntAct=EBI-35652, EBI-25984;
CC Q04377; P38111: MEC1; NbExp=10; IntAct=EBI-35652, EBI-6668;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localizes to nuclear DNA
CC repair foci with other DNA repair proteins in response to DNA double
CC strand breaks. The recruitment to DNA lesion sites requires the
CC presence of the RPA complex on DNA.
CC -!- PTM: Phosphorylated by MEC1 in a cell cycle dependent manner and in
CC response to DNA damage. {ECO:0000269|PubMed:10950868,
CC ECO:0000269|PubMed:11359899, ECO:0000269|PubMed:16365046}.
CC -!- MISCELLANEOUS: Present with 606 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; U33057; AAB64941.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA12331.1; -; Genomic_DNA.
DR PIR; S69557; S69557.
DR RefSeq; NP_010787.3; NM_001180807.3.
DR PDB; 5OMD; X-ray; 2.10 A; A=73-136.
DR PDB; 5X6O; EM; 3.90 A; G=1-747.
DR PDB; 6Z2W; EM; 2.82 A; C/D=1-747.
DR PDB; 6Z2X; EM; 3.20 A; C/D=1-747.
DR PDB; 6Z3A; EM; 3.80 A; C/D=1-747.
DR PDBsum; 5OMD; -.
DR PDBsum; 5X6O; -.
DR PDBsum; 6Z2W; -.
DR PDBsum; 6Z2X; -.
DR PDBsum; 6Z3A; -.
DR AlphaFoldDB; Q04377; -.
DR SMR; Q04377; -.
DR BioGRID; 32550; 60.
DR ComplexPortal; CPX-3621; ATR-ATRIP DNA damage-sensing kinase complex.
DR DIP; DIP-2970N; -.
DR IntAct; Q04377; 18.
DR MINT; Q04377; -.
DR STRING; 4932.YDR499W; -.
DR iPTMnet; Q04377; -.
DR MaxQB; Q04377; -.
DR PaxDb; Q04377; -.
DR PRIDE; Q04377; -.
DR EnsemblFungi; YDR499W_mRNA; YDR499W; YDR499W.
DR GeneID; 852110; -.
DR KEGG; sce:YDR499W; -.
DR SGD; S000002907; LCD1.
DR VEuPathDB; FungiDB:YDR499W; -.
DR eggNOG; ENOG502QQI0; Eukaryota.
DR HOGENOM; CLU_383646_0_0_1; -.
DR InParanoid; Q04377; -.
DR OMA; IFQYELI; -.
DR BioCyc; YEAST:G3O-30022-MON; -.
DR PRO; PR:Q04377; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; Q04377; protein.
DR GO; GO:0070310; C:ATR-ATRIP complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000228; C:nuclear chromosome; IDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0003684; F:damaged DNA binding; IDA:SGD.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:SGD.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0045184; P:establishment of protein localization; IDA:SGD.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; IC:ComplexPortal.
DR GO; GO:2000779; P:regulation of double-strand break repair; IC:ComplexPortal.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IMP:SGD.
DR InterPro; IPR018622; DNA_damage_chkpnt_Lcd1.
DR Pfam; PF09798; LCD1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromatin regulator; Coiled coil; Cytoplasm; DNA damage;
KW DNA repair; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..747
FT /note="DNA damage checkpoint protein LCD1"
FT /id="PRO_0000227715"
FT REGION 145..180
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 62..139
FT /evidence="ECO:0000255"
FT COMPBIAS 145..171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 177
FT /note="K->A: Impairs dsDNA and ssDNA binding of the MEC1-
FT LCD1 complex."
FT /evidence="ECO:0000269|PubMed:11983176"
FT MUTAGEN 179
FT /note="R->A: Impairs dsDNA and ssDNA binding of the MEC1-
FT LCD1 complex."
FT /evidence="ECO:0000269|PubMed:11983176"
FT HELIX 73..129
FT /evidence="ECO:0007829|PDB:5OMD"
FT HELIX 202..211
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 222..226
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 250..264
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 267..286
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 295..307
FT /evidence="ECO:0007829|PDB:6Z2W"
FT TURN 311..313
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 316..332
FT /evidence="ECO:0007829|PDB:6Z2W"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 356..380
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 393..406
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 415..433
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 438..444
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 447..461
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 467..469
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:6Z2W"
FT TURN 476..478
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 491..493
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 502..505
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 536..562
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 568..572
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 573..592
FT /evidence="ECO:0007829|PDB:6Z2W"
FT TURN 593..595
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 601..621
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 623..625
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 628..631
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 632..634
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 636..646
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 647..649
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 655..657
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 658..667
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 669..680
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 684..688
FT /evidence="ECO:0007829|PDB:6Z2W"
FT STRAND 691..694
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 697..708
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 715..725
FT /evidence="ECO:0007829|PDB:6Z2W"
FT HELIX 735..742
FT /evidence="ECO:0007829|PDB:6Z2W"
FT TURN 743..745
FT /evidence="ECO:0007829|PDB:6Z2W"
SQ SEQUENCE 747 AA; 86425 MW; E981C1A38F3310BF CRC64;
MRRETVGEFS SDDDDDILLE LGTRPPRFTQ IPPSSAALQT QIPTTLEVTT TTLNNKQSKN
DNQLVNQLNK AQGEASMLRD KINFLNIERE KEKNIQAVKV NELQVKHLQE LAKLKQELQK
LEDEKKFLQM EARGKSKREV ITNVKPPSTT LSTNTNTITP DSSSVAIEAK PQSPQSKKRK
ISDNLLKKNM VPLNPNRIIP DETSLFLESI LLHQIIGADL STIEILNRLK LDYITEFKFK
NFVIAKGAPI GKSIVSLLLR CKKTLTLDRF IDTLLEDIAV LIKEISVHPN ESKLAVPFLV
ALMYQIVQFR PSATHNLALK DCFLFICDLI RIYHHVLKVP IHESNMNLHV EPQIFQYELI
DYLIISYSFD LLEGILRVLQ SHPKQTYMEF FDENILKSFE FVYKLALTIS YKPMVNVIFS
AVEVVNIITS IILNMDNSSD LKSLISGSWW RDCITRLYAL LEKEIKSGDV YNENVDTTTL
HMSKYHDFFG LIRNIGDNEL GGLISKLIYT DRLQSVPRVI SKEDIGMDSD KFTAPIIGYK
MEKWLLKLKD EVLNIFENLL MIYGDDATIV NGEMLIHSSK FLSREQALMI ERYVGQDSPN
LDLRCHLIEH TLTIIYRLWK DHFKQLREEQ IKQVESQLIM SLWRFLVCQT ETVTANEREM
RDHRHLVDSL HDLTIKDQAS YYEDAFEDLP EYIEEELKMQ LNKRTGRIMQ VKYDEKFQEM
ARTILESKSF DLTTLEEADS LYISMGL
