ID   ATR_KLULA               Reviewed;        2287 AA.
AC   Q6CT34;
DT   21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Serine/threonine-protein kinase MEC1;
DE            EC=2.7.11.1;
DE   AltName: Full=ATR homolog;
DE   AltName: Full=DNA-damage checkpoint kinase MEC1;
DE   AltName: Full=Mitosis entry checkpoint protein 1;
GN   Name=MEC1; OrderedLocusNames=KLLA0C15785g;
OS   Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 /
OS   NRRL Y-1140 / WM37) (Yeast) (Candida sphaerica).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX   NCBI_TaxID=284590;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37;
RX   PubMed=15229592; DOI=10.1038/nature02579;
RA   Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA   de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA   Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA   Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA   Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA   Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA   Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA   Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA   Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA   Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA   Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA   Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA   Weissenbach J., Wincker P., Souciet J.-L.;
RT   "Genome evolution in yeasts.";
RL   Nature 430:35-44(2004).
CC   -!- FUNCTION: Serine/threonine protein kinase which activates checkpoint
CC       signaling upon genotoxic stresses such as ionizing radiation (IR),
CC       ultraviolet light (UV), or DNA replication stalling, thereby acting as
CC       a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-
CC       Q. Recruited to DNA lesions in order to initiate the DNA repair by
CC       homologous recombination. Phosphorylates histone H2A to form H2AS128ph
CC       (gamma-H2A) at sites of DNA damage, also involved in the regulation of
CC       DNA damage response mechanism. Required for cell growth and meiotic
CC       recombination (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Localizes to nuclear
CC       DNA repair foci in response to DNA double strand breaks. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC       {ECO:0000305}.
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DR   EMBL; CR382123; CAH01756.1; -; Genomic_DNA.
DR   RefSeq; XP_452905.1; XM_452905.1.
DR   AlphaFoldDB; Q6CT34; -.
DR   SMR; Q6CT34; -.
DR   STRING; 28985.XP_452905.1; -.
DR   PRIDE; Q6CT34; -.
DR   EnsemblFungi; CAH01756; CAH01756; KLLA0_C15785g.
DR   GeneID; 2892483; -.
DR   KEGG; kla:KLLA0_C15785g; -.
DR   eggNOG; KOG0890; Eukaryota.
DR   HOGENOM; CLU_000178_4_0_1; -.
DR   InParanoid; Q6CT34; -.
DR   OMA; YETMHEI; -.
DR   Proteomes; UP000000598; Chromosome C.
DR   GO; GO:0070310; C:ATR-ATRIP complex; IEA:EnsemblFungi.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR   GO; GO:0006975; P:DNA damage induced protein phosphorylation; IEA:EnsemblFungi.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0006260; P:DNA replication; IEA:EnsemblFungi.
DR   GO; GO:1901857; P:positive regulation of cellular respiration; IEA:EnsemblFungi.
DR   GO; GO:2000105; P:positive regulation of DNA-templated DNA replication; IEA:EnsemblFungi.
DR   GO; GO:0007131; P:reciprocal meiotic recombination; IEA:EnsemblFungi.
DR   GO; GO:0000722; P:telomere maintenance via recombination; IEA:EnsemblFungi.
DR   Gene3D; 1.10.1070.11; -; 1.
DR   Gene3D; 1.25.40.10; -; 1.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR003152; FATC_dom.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR   InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR   InterPro; IPR018936; PI3/4_kinase_CS.
DR   InterPro; IPR014009; PIK_FAT.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   InterPro; IPR012993; UME.
DR   Pfam; PF02260; FATC; 1.
DR   Pfam; PF00454; PI3_PI4_kinase; 1.
DR   Pfam; PF08064; UME; 1.
DR   SMART; SM01343; FATC; 1.
DR   SMART; SM00146; PI3Kc; 1.
DR   SMART; SM00802; UME; 1.
DR   SUPFAM; SSF48371; SSF48371; 1.
DR   SUPFAM; SSF48452; SSF48452; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS51189; FAT; 1.
DR   PROSITE; PS51190; FATC; 1.
DR   PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR   PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE   3: Inferred from homology;
KW   ATP-binding; Chromatin regulator; DNA damage; DNA repair; Kinase; Meiosis;
KW   Nucleotide-binding; Nucleus; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..2287
FT                   /note="Serine/threonine-protein kinase MEC1"
FT                   /id="PRO_0000227711"
FT   DOMAIN          1310..1864
FT                   /note="FAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT   DOMAIN          1968..2271
FT                   /note="PI3K/PI4K catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   DOMAIN          2255..2287
FT                   /note="FATC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT                   ECO:0000255|PROSITE-ProRule:PRU00535"
FT   REGION          1974..1980
FT                   /note="G-loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          2140..2148
FT                   /note="Catalytic loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          2160..2184
FT                   /note="Activation loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
SQ   SEQUENCE   2287 AA;  263121 MW;  8A73EB9EE9774995 CRC64;
     MDNPRVKYLE ELILALKSAG TVGNGIELDS TLQLDEKNGK LLQTLLKNTQ STNTDEVIFH
     KSFQALDLFL RCNQHLFSAN VKEITMIEVI LNNMVSCSLM HWSNMQYIWL INKYVSAWLK
     AYSFASTSNL QIWFTEQMVQ YEKLLVTCLR GKLEKPTFHS LLKKIVIVNG WIMRDGLLRN
     YSYRRWQSQF QKLMRLLAFV LKSTNEPSVE VASILQLLVR YISLSKESLS IFRFSFDLIQ
     TLIKDHHQHI SPTILAKTLL RTLYLCIHDE SKLAEIKNTF ELHEWINTNK NADPLFIRSI
     KYVSVKLGFL ESMEEFTFSN KQLHWLHQAI ENPKLRLVSG NVRNCIADSA DIRSFYDKVK
     ESLLNTIKDG DTAKLTHSMH SIRQLAIKEK FVNNNLVRSP QVEFNASQNM RLSSLNLVPL
     HKSLAFQLLA KHVIKSIPIT DMPEAMLTGV VLILIEVFSR FEPPKLEETS DLIQQSDGYG
     CLQVFQRASN SRSRFLRLLS VRLLPYFASL GSKYEDINLK FLIIFLQKPK APYLTETLHM
     SWINLIINCN SEYFDDLLLK LIDLFNSSDF AEHTMMAAQL RYLSKIQGKS PYQLLSPILP
     VLFKKMGRSL VEKKLGLQRI VQLVDYPAKT LLENFQRYVV PSALGQYKSD VITEVARIMS
     GNDKSLVEEK KLKLLDRNSR QIFAVALVKH GFFSIETIQT LFLNTAPKFR KNYITLYLPD
     YKTLAEVLKM SKQILTLDGQ ITETERCVLS SLRFLLITNF SKDKRRGTRF KNIEDWNEEM
     EEQFQQKLEQ NVLGIFQVFS NDMHDSDGKT SYYEKLRVLN GISFLMKYAS KKSIISALAQ
     LSICLQTGSE IPEIQHNTLE CWHLLIKLLN EEQITAIIND LFCLILQKWS TFSSSCKLEC
     QAIFDTLLKD RQKLVLEGRP FILLAFLNNP EFQVLERHPT VARKVLKVIS TTNWLKVFTE
     NLGSNNRYVI LQTLLELEKY FSTTIHRKHV DVVTKHDDSS HLSTLLGALL DSTYKFRNRD
     LKICQIAASC ISLIGLLDVT KHALPRNTNL SEEICDFNNH SQTVKFLISI VNNILVPAFW
     QSENPTKQLF VALVMQESLK YCGLSSVNWD INRPDDYPVE AKLWSRFNDI SKTTLFPLLS
     SLYLAQSWKE YVPLSYPSFK VKDGYQVWIR NLTLDLLKIG TEEDHPLHVF SSLIREDDGT
     LSNFLLPFIT MDIILRANKH NEYSKIIENL SIEFEFIFNF DLQQLNHFQI DSLKMAYNTI
     FRVYEYCKKW VSSFKQDYQA ANGTYMIQED KVLQVLDRTE RFVNTIPSDT LAKKSLETDS
     FERSALYLEQ SYREHGTSSL ASTDLLQCIQ NTYAEIGDVD AVGGVLKMFS TGNLTTKIEE
     LQYSKNWKMA QDCFEALGDF KLSANSTTSS ELVKSSNMKM LKSMYSHQLY EELLMKVKVH
     LPETKGFLVD NDGDLLNMGI EAVSQTGNIV ELTRWIERVE HIQMFNDPSL LLHYNIAKVL
     QAVSRNQQQN VERYINKCFT LIGAQFTIPS TSTTLLKNRE VLQKLHALTD IKLLCSAHTQ
     SEFSNASKAL DGRLSHVGSD FSPNHYLLSI RKTVEIISKN QHLQNDISNV YFQLSQLDRK
     ENRLDLAAED LMNALKYNHH SAELEFAEIL WKQGEKDMAL KTVAEITKRF KDDPSTASSE
     NQDFKEVLLK YTEWLDLSNS SVSEQIIKQY NELIRFDKNW DAPFYSMGLY YSKLLEKKKA
     EGYVSDGSLE YRSITNFLTS FEKGSPNIRQ SLPKVVTLWL DTAKNDVNNS ISDVSNYSSR
     ICNKIDTAVK NCGIHIWYTV LTQLLSRLMH PHTATIHTIV NILFHMTLEY PSVMLWYISI
     LLNSESLERR NIGKQIVEAF QKKNPRTKLP GTAISLVQSL TRVCIKDVKN TASRSGRSID
     SDFKFNLELA PNDMCVPVNI NLKKLLPSTA TSMNSDLFKS VMVSIARFSS QYMVFNSLKK
     PKKLTVIGSD GNIYGIMCKK EDVRQDNQYM QFANTMSFLL SKDVESRKRN LGITTYGVLS
     LREDCGLLEI VPNVVTLRSL LSMKYESMKI KYSLKSLQEK WQSIPSDQKL AFHKDCLKKF
     PPVLYQWFLD NFPDPITWYN ARNGFVRSYS VMAMVGHILG LGDRHCENIL LDVLTGRVLH
     VDFDCLFEKG KKLPVPEIVP FRLTQNITDA FGIIGTEGTF KKSSEVTLRV MRNNEIGLVN
     IIETIMYDRK IDESIQNALK VLRDKIRGID ARDGLALSVS GQVEALTQES CSVENLSKMY
     IGWLPFW