ID   ATR_MOUSE               Reviewed;        2635 AA.
AC   Q9JKK8; Q3TBS8; Q3TNX3; Q3TZM6; Q3UT26; Q3V1V6; Q571L3;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   29-MAR-2005, sequence version 2.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=Serine/threonine-protein kinase ATR;
DE            EC=2.7.11.1;
DE   AltName: Full=Ataxia telangiectasia and Rad3-related protein;
GN   Name=Atr; Synonyms=Kiaa4069;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1134 AND 1578-2635.
RC   STRAIN=C57BL/6J, and NOD;
RC   TISSUE=Brain, Dendritic cell, Egg, Embryo, and Lung;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1684-2635.
RC   TISSUE=Embryonic intestine;
RX   PubMed=15449545; DOI=10.1093/dnares/11.2.127;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA   Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of FLJ genes: the
RT   complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified
RT   by screening of terminal sequences of cDNA clones randomly sampled from
RT   size-fractionated libraries.";
RL   DNA Res. 11:127-135(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 2362-2635, FUNCTION, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=10801416; DOI=10.1016/s0960-9822(00)00447-4;
RA   de Klein A., Muijtjens M., van Os R., Verhoeven Y., Smit B., Carr A.M.,
RA   Lehmann A.R., Hoeijmakers J.H.J.;
RT   "Targeted disruption of the cell-cycle checkpoint gene ATR leads to early
RT   embryonic lethality in mice.";
RL   Curr. Biol. 10:479-482(2000).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=8843195; DOI=10.1101/gad.10.19.2423;
RA   Keegan K.S., Holtzman D.A., Plug A.W., Christenson E.R., Brainerd E.E.,
RA   Flaggs G., Bentley N.J., Taylor E.M., Meyn M.S., Moss S.B., Carr A.M.,
RA   Ashley T., Hoekstra M.F.;
RT   "The Atr and Atm protein kinases associate with different sites along
RT   meiotically pairing chromosomes.";
RL   Genes Dev. 10:2423-2437(1996).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=10691732;
RA   Brown E.J., Baltimore D.;
RT   "ATR disruption leads to chromosomal fragmentation and early embryonic
RT   lethality.";
RL   Genes Dev. 14:397-402(2000).
RN   [7]
RP   FUNCTION.
RX   PubMed=12629044; DOI=10.1101/gad.1067403;
RA   Brown E.J., Baltimore D.;
RT   "Essential and dispensable roles of ATR in cell cycle arrest and genome
RT   maintenance.";
RL   Genes Dev. 17:615-628(2003).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Heart, Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [9]
RP   INTERACTION WITH ATRIP.
RX   PubMed=20801936; DOI=10.1101/gad.1956410;
RA   Takai H., Xie Y., de Lange T., Pavletich N.P.;
RT   "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and
RT   ATR complexes.";
RL   Genes Dev. 24:2019-2030(2010).
RN   [10]
RP   SUBCELLULAR LOCATION.
RX   PubMed=23039116; DOI=10.1111/gtc.12005;
RA   Kogo H., Tsutsumi M., Inagaki H., Ohye T., Kiyonari H., Kurahashi H.;
RT   "HORMAD2 is essential for synapsis surveillance during meiotic prophase via
RT   the recruitment of ATR activity.";
RL   Genes Cells 17:897-912(2012).
RN   [11]
RP   SUBCELLULAR LOCATION.
RX   PubMed=22549958; DOI=10.1101/gad.187559.112;
RA   Wojtasz L., Cloutier J.M., Baumann M., Daniel K., Varga J., Fu J.,
RA   Anastassiadis K., Stewart A.F., Remenyi A., Turner J.M., Toth A.;
RT   "Meiotic DNA double-strand breaks and chromosome asynapsis in mice are
RT   monitored by distinct HORMAD2-independent and -dependent mechanisms.";
RL   Genes Dev. 26:958-973(2012).
RN   [12]
RP   FUNCTION.
RX   PubMed=29125140; DOI=10.1038/cr.2017.139;
RA   Zhao B., Zhang W., Cun Y., Li J., Liu Y., Gao J., Zhu H., Zhou H.,
RA   Zhang R., Zheng P.;
RT   "Mouse embryonic stem cells have increased capacity for replication fork
RT   restart driven by the specific Filia-Floped protein complex.";
RL   Cell Res. 28:69-89(2018).
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 (PubMed:8843195, PubMed:12629044). Recognizes the
CC       substrate consensus sequence [ST]-Q (By similarity). Phosphorylates
CC       BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively
CC       inhibit DNA replication and mitosis and promote DNA repair,
CC       recombination and apoptosis (PubMed:8843195, PubMed:12629044).
CC       Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA
CC       damage, thereby regulating DNA damage response mechanism (By
CC       similarity). Required for FANCD2 ubiquitination (By similarity).
CC       Critical for maintenance of fragile site stability and efficient
CC       regulation of centrosome duplication (By similarity). Acts as a
CC       regulator of the S-G2 transition by restricting the activity of CDK1
CC       during S-phase to prevent premature entry into G2 (By similarity). Acts
CC       as a regulator of the nuclear envelope integrity in response to DNA
CC       damage and stress (By similarity). Acts as a mechanical stress sensor
CC       at the nuclear envelope: relocalizes to the nuclear envelope in
CC       response to mechanical stress and mediates a checkpoint via
CC       phosphorylation of CHEK1 (By similarity). Also promotes nuclear
CC       envelope rupture in response to DNA damage by mediating phosphorylation
CC       of LMNA at 'Ser-282', leading to lamin disassembly (By similarity).
CC       Involved in the inflammatory response to genome instability and double-
CC       stranded DNA breaks: acts by localizing to micronuclei arising from
CC       genome instability and catalyzing phosphorylation of LMNA at 'Ser-395',
CC       priming LMNA for subsequent phosphorylation by CDK1 and micronuclei
CC       envelope rupture (By similarity). The rupture of micronuclear envelope
CC       triggers the cGAS-STING pathway thereby activating the type I
CC       interferon response and innate immunity (By similarity). Positively
CC       regulates the restart of stalled replication forks following activation
CC       by the KHDC3L-OOEP scaffold complex (PubMed:29125140). Essential for
CC       preventing the occurrence of DNA damage during early embryogenesis
CC       (PubMed:10691732, PubMed:10801416). {ECO:0000250|UniProtKB:Q13535,
CC       ECO:0000269|PubMed:10691732, ECO:0000269|PubMed:10801416,
CC       ECO:0000269|PubMed:12629044, ECO:0000269|PubMed:29125140,
CC       ECO:0000269|PubMed:8843195}.
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         Evidence={ECO:0000250|UniProtKB:Q13535};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC         Evidence={ECO:0000250|UniProtKB:Q13535};
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; Evidence={ECO:0000250|UniProtKB:Q13535};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC         Evidence={ECO:0000250|UniProtKB:Q13535};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:Q13535};
CC   -!- ACTIVITY REGULATION: Serine/threonine-protein kinase activity is
CC       directly stimulated by TOPBP1. ATR kinase activity is also directly
CC       activated by ETAA1, independently of TOPBP1. Activated by DNA and
CC       inhibited by BCR-ABL oncogene. Slightly activated by ATRIP.
CC       {ECO:0000250|UniProtKB:Q13535}.
CC   -!- SUBUNIT: Forms a heterodimer with ATRIP, forming the ATR-ATRIP complex
CC       (PubMed:20801936). Present in a complex containing ATRIP and RPA-coated
CC       single-stranded DNA (By similarity). Binds to DNA, and to UV-damaged
CC       DNA with higher affinity (By similarity). Interacts with MSH2 and HDAC2
CC       (By similarity). Present in a complex containing CHD4 and HDAC2 (By
CC       similarity). Interacts with EEF1E1, the interaction is enhanced by UV
CC       irradiation (By similarity). Interacts with CLSPN and CEP164 (By
CC       similarity). Interacts with TELO2 and TTI1 (By similarity). Interacts
CC       with BCR-ABL after genotoxic stress (By similarity). Interacts with
CC       UHRF2; this interaction promotes ATR activation (By similarity).
CC       Interacts (when phosphorylated) with TOPBP1; leading to ATR activation
CC       by TOPBP1 (By similarity). {ECO:0000250|UniProtKB:Q13535,
CC       ECO:0000269|PubMed:20801936}.
CC   -!- INTERACTION:
CC       Q9JKK8; Q8BMG1: Atrip; NbExp=2; IntAct=EBI-1202426, EBI-5235246;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13535}.
CC       Chromosome {ECO:0000269|PubMed:22549958, ECO:0000269|PubMed:23039116,
CC       ECO:0000269|PubMed:8843195}. Nucleus envelope
CC       {ECO:0000250|UniProtKB:Q13535}. Note=Depending on the cell type, it can
CC       also be found in PML nuclear bodies. Recruited to chromatin during S-
CC       phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia
CC       or replication fork stalling. Relocalizes to the nuclear envelope in
CC       response to mechanical stress or DNA damage. Also localizes to the
CC       micronuclear envelope in response to response to genome instability.
CC       {ECO:0000250|UniProtKB:Q13535}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Expression is highest in testis, where
CC       it is restricted to primary spermatocytes. Expression decreases as
CC       spermiogenesis proceeds (at protein level).
CC       {ECO:0000269|PubMed:8843195}.
CC   -!- PTM: Phosphorylated; autophosphorylates in vitro.
CC       {ECO:0000250|UniProtKB:Q13535}.
CC   -!- DISRUPTION PHENOTYPE: Early embryonic lethality.
CC       {ECO:0000269|PubMed:10691732, ECO:0000269|PubMed:10801416}.
CC   -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AC091531; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC121499; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK132223; BAE21043.1; -; mRNA.
DR   EMBL; AK139834; BAE24154.1; -; mRNA.
DR   EMBL; AK157754; BAE34182.1; -; mRNA.
DR   EMBL; AK164916; BAE37964.1; -; mRNA.
DR   EMBL; AK171072; BAE42229.1; -; mRNA.
DR   EMBL; AK220176; BAD90361.1; -; mRNA.
DR   EMBL; AF236887; AAF61728.1; -; mRNA.
DR   AlphaFoldDB; Q9JKK8; -.
DR   SMR; Q9JKK8; -.
DR   ComplexPortal; CPX-3623; ATR-ATRIP DNA damage-sensing kinase complex.
DR   IntAct; Q9JKK8; 2.
DR   STRING; 10090.ENSMUSP00000149953; -.
DR   GlyGen; Q9JKK8; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9JKK8; -.
DR   PhosphoSitePlus; Q9JKK8; -.
DR   EPD; Q9JKK8; -.
DR   MaxQB; Q9JKK8; -.
DR   PaxDb; 10090-ENSMUSP00000034980; -.
DR   ProteomicsDB; 277199; -.
DR   Pumba; Q9JKK8; -.
DR   AGR; MGI:108028; -.
DR   MGI; MGI:108028; Atr.
DR   eggNOG; KOG0890; Eukaryota.
DR   InParanoid; Q9JKK8; -.
DR   PhylomeDB; Q9JKK8; -.
DR   Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR   Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR   Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR   Reactome; R-MMU-6783310; Fanconi Anemia Pathway.
DR   Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR   Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR   ChiTaRS; Atr; mouse.
DR   PRO; PR:Q9JKK8; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q9JKK8; Protein.
DR   GO; GO:0070310; C:ATR-ATRIP complex; IPI:ComplexPortal.
DR   GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR   GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR   GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR   GO; GO:0001741; C:XY body; IDA:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0035979; F:histone H2AXS139 kinase activity; ISS:UniProtKB.
DR   GO; GO:0032405; F:MutLalpha complex binding; ISO:MGI.
DR   GO; GO:0032407; F:MutSalpha complex binding; ISO:MGI.
DR   GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR   GO; GO:0071480; P:cellular response to gamma radiation; ISO:MGI.
DR   GO; GO:0034644; P:cellular response to UV; ISO:MGI.
DR   GO; GO:0051276; P:chromosome organization; IMP:MGI.
DR   GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:MGI.
DR   GO; GO:0006974; P:DNA damage response; IDA:MGI.
DR   GO; GO:0006281; P:DNA repair; IDA:MGI.
DR   GO; GO:0007566; P:embryo implantation; IMP:MGI.
DR   GO; GO:0097694; P:establishment of RNA localization to telomere; ISO:MGI.
DR   GO; GO:0008156; P:negative regulation of DNA replication; ISO:MGI.
DR   GO; GO:0051081; P:nuclear membrane disassembly; ISS:UniProtKB.
DR   GO; GO:0006139; P:nucleobase-containing compound metabolic process; NAS:ComplexPortal.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISO:MGI.
DR   GO; GO:1904884; P:positive regulation of telomerase catalytic core complex assembly; ISO:MGI.
DR   GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR   GO; GO:0070198; P:protein localization to chromosome, telomeric region; ISO:MGI.
DR   GO; GO:2000779; P:regulation of double-strand break repair; NAS:ComplexPortal.
DR   GO; GO:0031297; P:replication fork processing; IMP:UniProtKB.
DR   GO; GO:0090399; P:replicative senescence; ISO:MGI.
DR   GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR   CDD; cd00892; PIKKc_ATR; 1.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 2.
DR   Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR003152; FATC_dom.
DR   InterPro; IPR021133; HEAT_type_2.
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; IPR003151; PIK-rel_kinase_FAT.
DR   InterPro; IPR014009; PIK_FAT.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   InterPro; IPR012993; UME.
DR   PANTHER; PTHR11139; ATAXIA TELANGIECTASIA MUTATED ATM -RELATED; 1.
DR   PANTHER; PTHR11139:SF128; SERINE_THREONINE-PROTEIN KINASE ATR; 1.
DR   Pfam; PF02259; FAT; 1.
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; ARM repeat; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF48452; TPR-like; 1.
DR   PROSITE; PS51189; FAT; 1.
DR   PROSITE; PS51190; FATC; 1.
DR   PROSITE; PS50077; HEAT_REPEAT; 1.
DR   PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR   PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Chromosome; DNA damage; DNA repair; DNA-binding; Kinase;
KW   Manganese; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Repeat; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..2635
FT                   /note="Serine/threonine-protein kinase ATR"
FT                   /id="PRO_0000088845"
FT   REPEAT          799..835
FT                   /note="HEAT 1"
FT   REPEAT          1329..1365
FT                   /note="HEAT 2"
FT   DOMAIN          1634..2179
FT                   /note="FAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT   DOMAIN          2287..2595
FT                   /note="PI3K/PI4K catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   DOMAIN          2603..2635
FT                   /note="FATC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT                   ECO:0000255|PROSITE-ProRule:PRU00535"
FT   REGION          423..447
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2293..2299
FT                   /note="G-loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          2463..2471
FT                   /note="Catalytic loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          2483..2507
FT                   /note="Activation loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   MOD_RES         431
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         438
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13535"
FT   MOD_RES         439
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13535"
FT   CONFLICT        19
FT                   /note="G -> A (in Ref. 2; BAE24154/BAE34182/BAE42229)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2208
FT                   /note="D -> E (in Ref. 2; BAE37964)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2347
FT                   /note="R -> C (in Ref. 2; BAE37964)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2556
FT                   /note="G -> W (in Ref. 2; BAE21043 and 3; BAD90361)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2563
FT                   /note="H -> R (in Ref. 2; BAE21043)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   2635 AA;  300224 MW;  C126413D15ACB8DC CRC64;
     MGDHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VALELVKKTD
     AQPTSVMLLD FIQHIMKSSP LMFVNVNGSQ GQNEAKDSCI EFSHWIITRL LRIAATPSCH
     MLHKKICEVI CSLLFLFKSK NPAIFGVLTR ELLYLFEDLI YLHKRNAVGE VMEWPVVVSR
     FLSRLDEHMG CLQPAPLQFM NVQNVEFIEV TLLMVLIHIV PTVFFRRQEL LLWQIGCALL
     EHGSPKIRSL AISLLTELFE LGGLPAQPAS TFFSLFLELL QHLVGMDADQ LKLYEEPLSK
     LLKTLFPFEA EAYRNIEPVY LNVLLEKLSV MFEDRVLMRL KSDLLKAALC HLLQYFLTFV
     PAGYESALQV RKVYVTNICR ALVDALGVQK HVGYLLGPFY AALKMESKEI IERIQCQAQQ
     ENLSGNNDEV SPKRRKLSSS LSSYKKPSRQ PEEIIHVDMD KKSILWNVLK QKAESLQISL
     ECGTLKNSVA EALEGITVVL QLTALCTVHC SHQDMDGHNV KDHQHKYKKK PPVVVTWMSL
     DFYTKVLKSC RSLLESVQKL ELELVIDSMV RICDALMYMQ VKSSFKDHVL EELCGMLSLP
     WIYSYSDDNS LKMTTFATNL LPLSQRVWDS YSPQAQSKCV FLLTLFPRRI FLEWRTAVYN
     WALKSSHEVI RASCVKGFFI LLHQQNSCNQ IPKMLVDRVK DDSDMVKKEF ASVLGQLVCT
     LHGMFYLSSS VEPCFEHMDL FSKNLKATSQ HECSSSQVKA STCKPFLFLL TKNTPSPVKL
     AFIDNLHHLC KHLDFQEDER EVKAVLGTLL NLMEDPDKDV RIAFSGNIKY ILESLNSEDG
     FVKELFVLRM KEAYTHAQIA RNNELKDTLI LTTGDIGRAA KGDLIPFALL HLLHCLLSKS
     ASVSGAAYTE IRALVAAKSV KLQNFFSQYK KPICQFLVES LHSSQMTALP SAPCQSSEIR
     KQDVAHHREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP DLAAKASPAA SALIRTLGKQ
     LNVSRREILI NNFKYIFSHL VCSCSKDELE RALHYLKNET EIELGSLLRQ DFQGLHNELL
     LRIGEHYQQV FNGLSILASF ASSDDPYQGP RDITSPELMA DYLQPKLLGI LAFFNMQLLS
     SSVGIEDKKM ALTSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV
     RCLDHAYLGP LLSHVIVALL PLIHMQPKET AAIFHYLIIE NRDAVQDFLH EIYFLPDHPE
     LEKIKAVLQE YRKETSETTD LQTTLQLSMK AIQHENVDVR IHALTSLKET LYKNQEKLIK
     YATDSETVEP VISQLVTVIL KGCQDANSQA RLLCGECLGE LGAIDPGRLD FSTTETQGKD
     FTFVTGVEDL SFAYGLLMEL TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMQSNGPGY
     QLWKRFPEHV REILEPHLNT RYKSSQKSTD WSGVTKPIYL SKLGNNFAEW SSSWAGYLIT
     KVRDNLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA EIMAVLKHDE
     QHAISTQDSA SDLCQLSTQT VFSVLDHLTQ WARHKFQALN AEKLAQNKPK GVSNVNFEDY
     QSVTRFLDLI PQDTLAVASF RSKAYTRAVM HFESFITEKK QNIQKHLGFL QKLYAAMHEP
     DGVAGVSAIR KAEPSLKEQI LEHESIGLLR DATACYDRAI QLEPDQIIHY HGVVKSMLGL
     GQLSTVITQV NGVHANRSEW TDELNTYRVE AAWKLSQWDL VENYLAADGK STTWSVRLGQ
     LLLSAKKRDT TTFYDTLKLV RAEQIVPLSA ASFERGSYQR GYEFIVRLHM LCELEHSLKP
     LFRKSPGDSC NEDSLNWGAR LEMTQNSYRA KEPILALRRA LLSLNKRPDY NEMVGECWLQ
     SARVARKAGH HQTAYNALLN AGESRLAELY VERAKWLWSK GDVHQALIVL QKGVELCFPE
     NKSPSESKHM LIHGRATLLV GRFMEETANF ESNAVMKKYK DVTLFLPEWE DGHFYLAKYY
     DKLMPMVTDN KMEKQGDLIR YIVLHFGRSL QYGNQFIYQS MPRMLSLWLD FGAKAYEWEK
     GGRSDRLQMR NDLAKINSVL TEHTNRLAPY QFLTAFSQLI SRICHSHDEV FVVLMEIIAK
     VFLAYPQQAM WMMTAVSKSS YPMRVNRCKE ILTKAIHMKK SLEKFVGDAT RLTDKLLELC
     NKSVDGSNST LSMSTHFKML KRLVEDPTFS EILIPLQSVM IPTLPSVLGA HANHDPFPGH
     WAYLAGFDDV VEILSSLQKP KKISLKGSDG KFYIMMCKPK DDLRKDCRLM EFNSLINKSL
     RKDAESRRRE LHIRTYAVIP LNDECGIIEW VNNTAGLRPI LTKIYKEKGV YMTGKELRQC
     MLPKSAALSE KLKVFQELLL PRHPPVFHEW FLRTFPDPTS WYSSRSAYCR STAVMSMVGY
     ILGLGDRHGE NILFDSFTGE CVHVDFNCLF NKGETFEVPE IVPFRLTHNM VNGMGPMGTE
     GLFRRACEVT LRLMRDQREP LMSVLKTFLH DPLVEGSKPV KGHSKAPLNE TGEVVNEKAK
     THVLDIEQRL QGVIKTRNRV TGLPLSIEGH VHYLIQEATD ENLLCQMYLG WTPYM
//