ATM_MOUSE
ID ATM_MOUSE Reviewed; 3066 AA.
AC Q62388; E9QNY7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Serine-protein kinase ATM;
DE EC=2.7.11.1 {ECO:0000269|PubMed:11571274};
DE AltName: Full=Ataxia telangiectasia mutated homolog;
DE Short=A-T mutated homolog;
GN Name=Atm;
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 [MRNA].
RC TISSUE=Brain;
RX PubMed=8661102; DOI=10.1006/geno.1996.0320;
RA Pecker I., Avraham K.B., Gilbert D.J., Savitsky K., Rotman G., Harnik R.,
RA Fukao T., Schroeck E., Hirotsume S., Tagle D.A., Collins F.S.,
RA Wynshaw-Boris A., Ried T., Copeland N.G., Jenkins N.A., Shiloh Y., Ziv Y.;
RT "Identification and chromosomal localization of Atm, the mouse homolog of
RT the ataxia-telangiectasia gene.";
RL Genomics 35:39-45(1996).
RN [2]
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 [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=8689683; DOI=10.1016/s0092-8674(00)80086-0;
RA Barlow C., Hirotsune S., Paylor R., Liyanage M., Eckhaus M., Collins F.,
RA Shiloh Y., Crawley J.N., Ried T., Tagle D., Wynshaw-Boris A.;
RT "Atm-deficient mice: a paradigm of ataxia telangiectasia.";
RL Cell 86:159-171(1996).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=9000145;
RA Lakin N.D., Weber P., Stankovic T., Rottinghaus S.T., Taylor A.M.R.,
RA Jackson S.P.;
RT "Analysis of the ATM protein in wild-type and ataxia telangiectasia
RT cells.";
RL Oncogene 13:2707-2716(1996).
RN [5]
RP DEVELOPMENTAL STAGE.
RC STRAIN=B6C3-F1;
RX PubMed=9697112; DOI=10.1016/s0306-4522(98)00117-1;
RA Soares H.D., Morgan J.I., McKinnon P.J.;
RT "Atm expression patterns suggest a contribution from the peripheral nervous
RT system to the phenotype of ataxia-telangiectasia.";
RL Neuroscience 86:1045-1054(1998).
RN [6]
RP INTERACTION WITH AP2B1 AND AP3B2.
RX PubMed=9707615; DOI=10.1073/pnas.95.17.10146;
RA Lim D.-S., Kirsch D.G., Canman C.E., Ahn J.-H., Ziv Y., Newman L.S.,
RA Darnell R.B., Shiloh Y., Kastan M.B.;
RT "ATM binds to beta-adaptin in cytoplasmic vesicles.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:10146-10151(1998).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF H2AX, AND CATALYTIC ACTIVITY.
RX PubMed=11571274; DOI=10.1074/jbc.c100466200;
RA Burma S., Chen B.P., Murphy M., Kurimasa A., Chen D.J.;
RT "ATM phosphorylates histone H2AX in response to DNA double-strand breaks.";
RL J. Biol. Chem. 276:42462-42467(2001).
RN [8]
RP FUNCTION.
RX PubMed=18833288; DOI=10.1038/embor.2008.186;
RA Adams C.J., Graham A.L., Jansson M., Coutts A.S., Edelmann M., Smith L.,
RA Kessler B., La Thangue N.B.;
RT "ATM and Chk2 kinase target the p53 cofactor Strap.";
RL EMBO Rep. 9:1222-1229(2008).
RN [9]
RP PHOSPHORYLATION AT SER-367; SER-1899 AND SER-1987, FUNCTION, AND
RP MUTAGENESIS OF SER-367; SER-1899 AND SER-1987.
RX PubMed=19047460; DOI=10.1083/jcb.200805154;
RA Daniel J.A., Pellegrini M., Lee J.H., Paull T.T., Feigenbaum L.,
RA Nussenzweig A.;
RT "Multiple autophosphorylation sites are dispensable for murine ATM
RT activation in vivo.";
RL J. Cell Biol. 183:777-783(2008).
RN [10]
RP FUNCTION.
RX PubMed=19448632; DOI=10.1038/ni.1735;
RA Hewitt S.L., Yin B., Ji Y., Chaumeil J., Marszalek K., Tenthorey J.,
RA Salvagiotto G., Steinel N., Ramsey L.B., Ghysdael J., Farrar M.A.,
RA Sleckman B.P., Schatz D.G., Busslinger M., Bassing C.H., Skok J.A.;
RT "RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning
RT of immunoglobulin loci.";
RL Nat. Immunol. 10:655-664(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1987, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [12]
RP SUBCELLULAR LOCATION.
RX PubMed=25936915; DOI=10.1016/j.stem.2015.03.017;
RA Zhao B., Zhang W.D., Duan Y.L., Lu Y.Q., Cun Y.X., Li C.H., Guo K.,
RA Nie W.H., Li L., Zhang R., Zheng P.;
RT "Filia Is an ESC-Specific Regulator of DNA Damage Response and Safeguards
RT Genomic Stability.";
RL Cell Stem Cell 16:684-698(2015).
RN [13]
RP INTERACTION WITH CYREN.
RX PubMed=30017584; DOI=10.1016/j.molcel.2018.06.018;
RA Hung P.J., Johnson B., Chen B.R., Byrum A.K., Bredemeyer A.L.,
RA Yewdell W.T., Johnson T.E., Lee B.J., Deivasigamani S., Hindi I.,
RA Amatya P., Gross M.L., Paull T.T., Pisapia D.J., Chaudhuri J.,
RA Petrini J.J.H., Mosammaparast N., Amarasinghe G.K., Zha S., Tyler J.K.,
RA Sleckman B.P.;
RT "MRI is a DNA damage response adaptor during classical non-homologous end
RT joining.";
RL Mol. Cell 71:332-342(2018).
CC -!- FUNCTION: Serine/threonine protein kinase which activates checkpoint
CC signaling upon double strand breaks (DSBs), apoptosis and genotoxic
CC stresses such as ionizing ultraviolet A light (UVA), thereby acting as
CC a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-
CC Q. Phosphorylates 'Ser-139' of histone variant H2AX at double strand
CC breaks (DSBs), thereby regulating DNA damage response mechanism. Also
CC plays a role in pre-B cell allelic exclusion, a process leading to
CC expression of a single immunoglobulin heavy chain allele to enforce
CC clonality and monospecific recognition by the B-cell antigen receptor
CC (BCR) expressed on individual B-lymphocytes. After the introduction of
CC DNA breaks by the RAG complex on one immunoglobulin allele, acts by
CC mediating a repositioning of the second allele to pericentromeric
CC heterochromatin, preventing accessibility to the RAG complex and
CC recombination of the second allele. Also involved in signal
CC transduction and cell cycle control. May function as a tumor
CC suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates
CC DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CTIP, nibrin
CC (NBN), TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C. May play a role in
CC vesicle and/or protein transport. Could play a role in T-cell
CC development, gonad and neurological function. Binds DNA ends. Plays a
CC role in replication-dependent histone mRNA degradation. Phosphorylation
CC of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-
CC mediated ubiquitination and subsequent proteasome degradation.
CC Phosphorylates ATF2 which stimulates its function in DNA damage
CC response. Phosphorylates ERCC6 which is essential for its chromatin
CC remodeling activity at DNA double-strand breaks (By similarity).
CC Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to
CC DNA damage, which promotes TTC5/STRAP nuclear localization (By
CC similarity). {ECO:0000250|UniProtKB:Q13315,
CC ECO:0000269|PubMed:11571274, ECO:0000269|PubMed:19047460,
CC ECO:0000269|PubMed:19448632}.
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:0000269|PubMed:11571274};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:Q13315};
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:0000269|PubMed:11571274};
CC -!- ACTIVITY REGULATION: Inhibited by wortmannin.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- SUBUNIT: Homodimer (By similarity). Dimers or tetramers in inactive
CC state. On DNA damage, autophosphorylation dissociates ATM into monomers
CC rendering them catalytically active. Binds DNA ends, p53/TP53, ABL1,
CC BRCA1, NBN/nibrin and TERF1. Part of the BRCA1-associated genome
CC surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1,
CC ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This
CC association could be a dynamic process changing throughout the cell
CC cycle and within subnuclear domains. DNA damage promotes association
CC with RAD17. Interacts with EEF1E1; the interaction, induced on DNA
CC damage, up-regulates TP53. Interacts with DCLRE1C, MYST1, KAT5, NABP2,
CC ATMIN and CEP164 (By similarity). Interacts with AP2B1 AND AP3B2; the
CC interaction occurs in cytoplasmic vesicles (PubMed:9707615). Interacts
CC with TELO2 AND TTI1. Interacts with DDX1 (By similarity). Interacts
CC with BRAT1 (By similarity). Interacts with CYREN (via XLF motif)
CC (PubMed:30017584). {ECO:0000250|UniProtKB:Q13315,
CC ECO:0000269|PubMed:30017584, ECO:0000269|PubMed:9707615}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13315}.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q13315}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:25936915}. Note=Primarily nuclear. Found also in
CC endocytic vesicles in association with beta-adaptin.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, skeletal muscle, testis,
CC followed by spleen, lung, kidney, heart, liver and thymus. Ubiquitously
CC expressed in embryonal tissues.
CC -!- DEVELOPMENTAL STAGE: Highest expression in embryonic central nervous
CC system, from 13.5 dpc day and during the whole cerebellar development.
CC Decreased expression when maturation occurs.
CC {ECO:0000269|PubMed:9697112}.
CC -!- DOMAIN: The FATC domain is required for interaction with KAT5.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- PTM: Phosphorylated by NUAK1/ARK5 (By similarity). Autophosphorylation
CC on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated
CC activation of the kinase. {ECO:0000250, ECO:0000269|PubMed:19047460}.
CC -!- PTM: Phosphorylated by NUAK1/ARK5. Autophosphorylation on Ser-367, Ser-
CC 1899, Ser-1987 correlates with DNA damage-mediated activation of the
CC kinase. During the late stages of DNA damage response, dephosphorylated
CC following deacetylation by SIRT7, leading to ATM deactivation.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- PTM: Acetylation, on DNA damage, is required for activation of the
CC kinase activity, dimer-monomer transition, and subsequent
CC autophosphorylation on Ser-1987. Acetylated in vitro by KAT5/TIP60.
CC Deacetylated by SIRT7 during the late stages of DNA damage response,
CC promoting ATM dephosphorylation and subsequent deactivation.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- DISRUPTION PHENOTYPE: Atm-disrupted mice recapitulate the human ataxia
CC telangiectasia phenotype. Mice homozygous for the disrupted Atm allele
CC display growth retardation, neurologic dysfunction, male and female
CC infertility secondary to the absence of mature gametes, defects in T
CC lymphocyte maturation, and extreme sensitivity to gamma-irradiation.
CC {ECO:0000269|PubMed:8689683}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC {ECO:0000305}.
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DR EMBL; U43678; AAC52673.1; -; mRNA.
DR EMBL; AC079869; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC156640; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_031525.2; NM_007499.2.
DR SMR; Q62388; -.
DR BioGRID; 198236; 35.
DR IntAct; Q62388; 9.
DR STRING; 10090.ENSMUSP00000113388; -.
DR iPTMnet; Q62388; -.
DR PhosphoSitePlus; Q62388; -.
DR EPD; Q62388; -.
DR jPOST; Q62388; -.
DR MaxQB; Q62388; -.
DR PaxDb; Q62388; -.
DR PRIDE; Q62388; -.
DR ProteomicsDB; 277071; -.
DR Antibodypedia; 3596; 1469 antibodies from 48 providers.
DR DNASU; 11920; -.
DR Ensembl; ENSMUST00000232179; ENSMUSP00000156344; ENSMUSG00000034218.
DR GeneID; 11920; -.
DR KEGG; mmu:11920; -.
DR UCSC; uc009pmd.2; mouse.
DR CTD; 472; -.
DR MGI; MGI:107202; Atm.
DR VEuPathDB; HostDB:ENSMUSG00000034218; -.
DR eggNOG; KOG0892; Eukaryota.
DR GeneTree; ENSGT00670000098061; -.
DR HOGENOM; CLU_000178_3_1_1; -.
DR InParanoid; Q62388; -.
DR OMA; YSKWAVL; -.
DR OrthoDB; 80538at2759; -.
DR PhylomeDB; Q62388; -.
DR TreeFam; TF101182; -.
DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-MMU-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-MMU-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR Reactome; R-MMU-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR Reactome; R-MMU-6804760; Regulation of TP53 Activity through Methylation.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR Reactome; R-MMU-69541; Stabilization of p53.
DR Reactome; R-MMU-9664873; Pexophagy.
DR BioGRID-ORCS; 11920; 20 hits in 110 CRISPR screens.
DR ChiTaRS; Atm; mouse.
DR PRO; PR:Q62388; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q62388; protein.
DR Bgee; ENSMUSG00000034218; Expressed in parotid gland and 253 other tissues.
DR ExpressionAtlas; Q62388; baseline and differential.
DR Genevisible; Q62388; MM.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:1990391; C:DNA repair complex; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:MGI.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004677; F:DNA-dependent protein kinase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISS:UniProtKB.
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:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0007420; P:brain development; IGI:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IGI:MGI.
DR GO; GO:0071480; P:cellular response to gamma radiation; ISO:MGI.
DR GO; GO:0071500; P:cellular response to nitrosative stress; ISO:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:ARUK-UCL.
DR GO; GO:0071481; P:cellular response to X-ray; ISO:MGI.
DR GO; GO:0070192; P:chromosome organization involved in meiotic cell cycle; IMP:MGI.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:MGI.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:MGI.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IDA:MGI.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:MGI.
DR GO; GO:0097694; P:establishment of RNA localization to telomere; ISO:MGI.
DR GO; GO:0007292; P:female gamete generation; IMP:MGI.
DR GO; GO:0008585; P:female gonad development; IMP:MGI.
DR GO; GO:0007143; P:female meiotic nuclear division; IMP:MGI.
DR GO; GO:0007507; P:heart development; IGI:MGI.
DR GO; GO:0071044; P:histone mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; IEA:InterPro.
DR GO; GO:0002376; P:immune system process; IMP:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0042159; P:lipoprotein catabolic process; IGI:MGI.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:MGI.
DR GO; GO:0045141; P:meiotic telomere clustering; IMP:MGI.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISO:MGI.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:MGI.
DR GO; GO:1904354; P:negative regulation of telomere capping; ISO:MGI.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051402; P:neuron apoptotic process; IGI:MGI.
DR GO; GO:0048599; P:oocyte development; IMP:MGI.
DR GO; GO:0001541; P:ovarian follicle development; IMP:MGI.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:1903626; P:positive regulation of DNA catabolic process; ISO:MGI.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IGI:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; 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:1904358; P:positive regulation of telomere maintenance via telomere lengthening; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:ARUK-UCL.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0002331; P:pre-B cell allelic exclusion; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
DR GO; GO:1905843; P:regulation of cellular response to gamma radiation; ISO:MGI.
DR GO; GO:1903978; P:regulation of microglial cell activation; ISO:MGI.
DR GO; GO:0032210; P:regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0090399; P:replicative senescence; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0010212; P:response to ionizing radiation; IGI:MGI.
DR GO; GO:0001756; P:somitogenesis; IGI:MGI.
DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR GO; GO:0048538; P:thymus development; IMP:MGI.
DR GO; GO:0033151; P:V(D)J recombination; IGI:MGI.
DR CDD; cd05171; PIKKc_ATM; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR015519; ATM/Tel1.
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; IPR003151; PIK-rel_kinase_FAT.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR044107; PIKKc_ATM.
DR InterPro; IPR021668; TAN.
DR PANTHER; PTHR11139:SF72; PTHR11139:SF72; 1.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF11640; TAN; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SMART; SM01342; TAN; 1.
DR SUPFAM; SSF48371; SSF48371; 2.
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; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell cycle; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; DNA damage; DNA-binding; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tumor suppressor.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT CHAIN 2..3066
FT /note="Serine-protein kinase ATM"
FT /id="PRO_0000088841"
FT DOMAIN 1946..2576
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 2696..3009
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 3034..3066
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 829..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1380..1389
FT /note="Interaction with ABL1"
FT /evidence="ECO:0000250"
FT REGION 1973..2000
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2585..2607
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2702..2708
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2877..2885
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2897..2921
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2986..3007
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1983..2000
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 367
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19047460"
FT MOD_RES 1899
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19047460"
FT MOD_RES 1987
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19047460,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 3006
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 3026
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MUTAGEN 367
FT /note="S->A: Retains genomic stability and cell cycle
FT checkpoint correction and kinase activity towards
FT downstream targets; when associated with A-1987. Retains
FT genomic stability, cell cycle checkpoint correction and
FT kinase activity on downstream targets; when associated with
FT A-1899 and A-1987."
FT /evidence="ECO:0000269|PubMed:19047460"
FT MUTAGEN 1899
FT /note="S->A: Retains genomic stability, cell cycle
FT checkpoint correction and kinase activity on downstream
FT targets; when associated with A-367 and A-1987."
FT /evidence="ECO:0000269|PubMed:19047460"
FT MUTAGEN 1987
FT /note="S->A: Retains genomic stability and cell cycle
FT checkpoint correction and kinase activity towards
FT downstream targets; when associated with A-367. Retains
FT genomic stability, cell cycle checkpoint correction and
FT kinase activity on downstream targets; when associated with
FT A-367 and A-1987."
FT /evidence="ECO:0000269|PubMed:19047460"
FT CONFLICT 600
FT /note="S -> R (in Ref. 1; AAC52673)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 3066 AA; 349418 MW; 7AE54BF9801C6336 CRC64;
MSLALNDLLI CCRQLEHDRA TERRKEVDKF KRLIQDPETV QHLDRHSDSK QGKYLNWDAV
FRFLQKYIQK EMESLRTAKS NVSATTQSSR QKKMQEISSL VRYFIKCANK RAPRLKCQDL
LNYVMDTVKD SSNGLTYGAD CSNILLKDIL SVRKYWCEVS QQQWLELFSL YFRLYLKPSQ
DINRVLVARI IHAVTRGCCS QTDGLPSKFL DLFSKAIQYA RQEKSSPGLS HILAALNIFL
KSLAVNFRKR VCEAGDEILP TLLYIWTQHR LNDSLKEVII ELIQLQIYIH HPQGARAPEE
GAYESMKWKS ILYNLYDLLV NEISHIGSRG KYSSGSRNIA VKENLIDLMA DICYQLFDAD
TRSVEISQSY VTQRESTDYS VPCKRRKIDV GWEVIKDYLQ KSQSDFDLVP WLQITTRLIS
KYPSSLPNCE LSPLILILYQ LLPQQRRGER IPYVLRCLKE VALCQGKKSN LESSQKSDLL
KLWIKIWSIT FRGISSGQTQ TENFGLLEAI IQGSLVELDR EFWKLFTGSA CKPSSPSVCC
LTLALSICVV PDAIKMGTEQ SVCEANRSFS VKESIMRWLL FYQLEDDLED STELPPILQS
NFPHLVVEKI LVSLTMKNSK AAMKFFQSVP ECEQHCEDKE EPSFSEVEEL FLQTTFDKMD
FLTTVKEYAV EKFQSSVGFS VQQNLKESLD HYLLGLSEQL LSNYSSEITS SETLVRCSSL
LVGVLGCYCY MGIITEDEAH KSELFQKAKS LMQCAGESIS LFKNKTNEES RIGSLRNVMH
LCTSCLCIHT KHTPNKIASG FFLRLLTSKL MNDIADICKS LASCTKKPLD HGVHPGEDDE
DGGGCDSLME AEGPSSTGLS TAYPASSVSD ANDYGENQNA VGAMSPLAAD YLSKQDHLLL
DMLRFLGRSV TASQSHTVSF RGADIRRKLL LLLDSSILDL MKPLHLHMYL VLLKDLPGNE
HSLPMEDVVE LLQPLSLVCS LHRRDQDVCK TILSNVLHIV TNLGQGSVDM ESTRIAQGHF
LTVMGAFWHL TKEKKCVFSV RMALVKCLQT LLEADPYSEW AILNVKGQDF PVNEAFSQFL
ADDHHQVRML AAGSVNRLFQ DMRQGDFSRS LKALPLKFQQ TSFNNAYTTA EAGIRGLLCD
SQNPDLLDEI YNRKSVLLMM IAVVLHCSPV CEKQALFALC KSVKENRLEP HLVKKVLEKV
SESFGCRSLE DFMISHLDYL VLEWLNLQDT EYSLSSFPFM LLNYTSIEDF YRSCYKILIP
HLVIRSHFDE VKSIANQIQK CWKSLLVDCF PKILVHILPY FAYEGTRDSY VSQKRETATK
VYDTLKGEDF LGKQIDQVFI SNLPEIVVEL LMTLHETADS ADSDASQSAT ALCDFSGDLD
PAPNPPYFPS HVIQATFAYI SNCHKTKFKS ILEILSKIPD SYQKILLAIC EQAAETNNVF
KKHRILKIYH LFVSLLLKDI QSGLGGAWAF VLRDVIYTLI HYINKRSSHF TDVSLRSFSL
CCDLLSRVCH TAVTQCKDAL ESHLHVIVGT LIPLVDYQEV QEQVLDLLKY LVIDNKDNKN
LSVTIKLLDP FPDHVIFKDL RLTQQKIKYS GGPFSLLEEI NHFLSVSAYN PLPLTRLEGL
KDLRRQLEQH KDQMLDLLRA SQDNPQDGIV VKLVVSLLQL SKMAVNQTGE REVLEAVGRC
LGEIGPLDFS TIAVQHNKDV SYTKAYGLPE DRELQWTLIM LTALNNTLVE DSVKIRSAAA
TCLKNILATK IGHIFWENYK TSADPMLTYL QPFRTSRKKF LEVPRSVKED VLEGLDAVNL
WVPQSESHDI WIKTLTCAFL DSGGINSEIL QLLKPMCEVK TDFCQMLLPY LIHDVLLQDT
HESWRTLLSA HVRGFFTSCF KHSSQASRSA TPANSDSESE NFLRCCLDKK SQRTMLAVVD
YLRRQKRPSS GTAFDDAFWL DLNYLEVAKV AQSCSAHFTA LLYAEIYSDK KSTDEQEKRS
PTFEEGSQGT TISSLSEKSK EETGISLQDL LLEIYRSIGE PDSLYGCGGG KMLQPLTRIR
TYEHEATWEK ALVTYDLETS ISSSTRQSGI IQALQNLGLS HILSVYLKGL DYERREWCAE
LQELRYQAAW RNMQWGLCAS AGQEVEGTSY HESLYNALQC LRNREFSTFY ESLRYASLFR
VKEVEELSKG SLESVYSLYP TLSRLQAIGE LENSGELFSR SVTDRERSEA YWKWQKHSQL
LKDSDFSFQE PLMALRTVIL ETLVQKEMER SQGACSKDIL TKHLVEFSVL ARTFKNTQLP
ERAIFKIKQY NSAICGISEW HLEEAQVFWA KKEQSLALSI LKQMIKKLDS SFKDKENDAG
LKVIYAECLR VCGSWLAETC LENPAVIMQT YLEKAVKVAG SYDGNSRELR NGQMKAFLSL
ARFSDTQYQR IENYMKSSEF ENKQTLLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEC
ALRALREDRK RFLCKAVENY INCLLSGEEH DLWVFRLCSL WLENSGVSEV NGMMKKDGMK
ISSYKFLPLM YQLAARMGTK MTGGLGFHEV LNNLISRISL DHPHHTLFII LALANANKDE
FLSKPETTRR SRITKSTSKE NSHLDEDRTE AATRIIHSIR SKRCKMVKDM EALCDAYIIL
ANMDASQWRA QRKGINIPAN QPITKLKNLE DVVVPTMEIK VDPTGEYENL VTIKSFKTEF
RLAGGLNLPK IIDCVGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RNTETRKRKL
TICTYKVVPL SQRSGVLEWC TGTVPIGEYL VNSEDGAHRR YRPNDFSANQ CQKKMMEVQK
KSFEEKYDTF MTICQNFEPV FRYFCMEKFL DPAVWFEKRL AYTRSVATSS IVGYILGLGD
RHVQNILINE QSAELVHIDL GVAFEQGKIL PTPETVPFRL SRDIVDGMGI TGVEGVFRRC
CEKTMEVMRS SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDESDL HSTPNADDQE
CKQSLSDTDQ SFNKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAM DPKNLSRLFP
GWKAWV
