ATM_HUMAN
ID ATM_HUMAN Reviewed; 3056 AA.
AC Q13315; B2RNX5; O15429; Q12758; Q16551; Q93007; Q9NP02; Q9UCX7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 4.
DT 03-AUG-2022, entry version 252.
DE RecName: Full=Serine-protein kinase ATM;
DE EC=2.7.11.1 {ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:28508083, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:8988033, ECO:0000269|PubMed:9843217};
DE AltName: Full=Ataxia telangiectasia mutated;
DE Short=A-T mutated;
GN Name=ATM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT AT ASP-3003.
RX PubMed=8589678; DOI=10.1093/hmg/4.11.2025;
RA Savitsky K., Sfez S., Tagle D.A., Ziv Y., Sartiel A., Collins F.S.,
RA Shiloh Y., Rotman G.;
RT "The complete sequence of the coding region of the ATM gene reveals
RT similarity to cell cycle regulators in different species.";
RL Hum. Mol. Genet. 4:2025-2032(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT AT ASP-3003, AND VARIANTS
RP CYS-49; ARG-1054; PHE-1420; ILE-2079 AND ALA-2287.
RX PubMed=8665503;
RA Vorechovsky I., Rasio D., Luo L., Monaco C., Hammarstroem L.,
RA Webster A.D.B., Zaloudik J., Barbanti-Brodano G., James M.R., Russo G.,
RA Croce C.M., Negrini M.;
RT "The ATM gene and susceptibility to breast cancer: analysis of 38 breast
RT tumors reveals no evidence for mutation.";
RL Cancer Res. 56:2726-2732(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9199932; DOI=10.1101/gr.7.6.592;
RA Platzer M., Rotman G., Bauer D., Uziel T., Savitsky K., Bar-Shira A.,
RA Gilad S., Shiloh Y., Rosenthal A.;
RT "Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic
RT DNA containing the entire ATM gene.";
RL Genome Res. 7:592-605(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-1983.
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2756.
RG NIEHS SNPs program;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1369, AND VARIANT AT 2546-SER--ILE-2548
RP DEL.
RX PubMed=8789452; DOI=10.1093/hmg/5.1.145;
RA Byrd P.J., McConville C.M., Cooper P., Parkhill J., Stankovic T.,
RA McGuire G.M., Thick J.A., Taylor A.M.R.;
RT "Mutations revealed by sequencing the 5' half of the gene for ataxia
RT telangiectasia.";
RL Hum. Mol. Genet. 5:145-149(1996).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RX PubMed=9108147; DOI=10.1093/nar/25.9.1678;
RA Savitsky K., Platzer M., Uziel T., Gilad S., Sartiel A., Rosenthal A.,
RA Elroy-Stein O., Shiloh Y., Rotman G.;
RT "Ataxia-telangiectasia: structural diversity of untranslated sequences
RT suggests complex post-transcriptional regulation of ATM gene expression.";
RL Nucleic Acids Res. 25:1678-1684(1997).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1332-3056, AND VARIANTS 2427-LEU-ARG-2428
RP DEL; 2546-SER--ILE-2548 DEL; SER-2860 DEL AND ASP-3003.
RC TISSUE=Fibroblast;
RX PubMed=7792600; DOI=10.1126/science.7792600;
RA Savitsky K., Bar-Shira A., Gilad S., Rotman G., Ziv Y., Vanagaite L.,
RA Tagle D.A., Smith S., Uziel T., Sfez S., Ashkenazi M., Pecker I.,
RA Frydman M., Harnik R., Patanjali S.R., Simmons A., Clines G.A., Sartiel A.,
RA Gatti R.A., Chessa L., Sanal O., Lavin M.F., Jaspers N.G.J., Taylor A.M.R.,
RA Arlett C.F., Miki T., Weissman S.M., Lovett M., Collins F.S., Shiloh Y.;
RT "A single ataxia telangiectasia gene with a product similar to PI-3
RT kinase.";
RL Science 268:1749-1753(1995).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1332-3056.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1349-3056.
RX PubMed=8521392;
RA Rasio D., Negrini M., Croce C.M.;
RT "Genomic organization of the ATM locus involved in ataxia-telangiectasia.";
RL Cancer Res. 55:6053-6057(1995).
RN [12]
RP PHOSPHORYLATION.
RX PubMed=8969240; DOI=10.1074/jbc.271.52.33693;
RA Chen G., Lee E.Y.-H.P.;
RT "The product of the ATM gene is a 370-kDa nuclear phosphoprotein.";
RL J. Biol. Chem. 271:33693-33697(1996).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=9050866; DOI=10.1073/pnas.94.5.1840;
RA Brown K.D., Ziv Y., Sadanandan S.N., Chessa L., Collins F.S., Shiloh Y.,
RA Tagle D.A.;
RT "The ataxia-telangiectasia gene product, a constitutively expressed nuclear
RT protein that is not up-regulated following genome damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:1840-1845(1997).
RN [14]
RP SUBCELLULAR LOCATION, AND VARIANTS 2546-SER--ILE-2548 DEL AND TYR-2824.
RX PubMed=9150358; DOI=10.1038/sj.onc.1201037;
RA Watters D., Khanna K.K., Beamish H., Birrell G., Spring K., Kedar P.,
RA Gatei M., Stenzel D., Hobson K., Kozlov S., Zhang N., Farrell A.,
RA Ramsay J., Gatti R.A., Lavin M.F.;
RT "Cellular localisation of the ataxia-telangiectasia (ATM) gene product and
RT discrimination between mutated and normal forms.";
RL Oncogene 14:1911-1921(1997).
RN [15]
RP CATALYTIC ACTIVITY.
RX PubMed=8988033;
RA Jung M., Kondratyev A., Lee S.A., Dimtchev A., Dritschilo A.;
RT "ATM gene product phosphorylates I kappa B-alpha.";
RL Cancer Res. 57:24-27(1997).
RN [16]
RP INTERACTION WITH ABL1.
RX PubMed=9168117; DOI=10.1038/387520a0;
RA Shafman T., Khanna K.K., Kedar P., Spring K., Kozlov S., Yen T., Hobson K.,
RA Gatei M., Zhang N., Watters D., Egerton M., Shiloh Y., Kharbanda S.,
RA Kufe D., Lavin M.F.;
RT "Interaction between ATM protein and c-Abl in response to DNA damage.";
RL Nature 387:520-523(1997).
RN [17]
RP ACTIVITY REGULATION.
RX PubMed=9766667;
RA Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E.,
RA Abraham R.T.;
RT "Inhibition of phosphoinositide 3-kinase related kinases by the
RT radiosensitizing agent wortmannin.";
RL Cancer Res. 58:4375-4382(1998).
RN [18]
RP FUNCTION, INTERACTION WITH TP53, AND CATALYTIC ACTIVITY.
RX PubMed=9843217; DOI=10.1038/3882;
RA Khanna K.K., Keating K.E., Kozlov S., Scott S., Gatei M., Hobson K.,
RA Taya Y., Gabrielli B., Chan D., Lees-Miller S.P., Lavin M.F.;
RT "ATM associates with and phosphorylates p53: mapping the region of
RT interaction.";
RL Nat. Genet. 20:398-400(1998).
RN [19]
RP INTERACTION WITH BETA-ADAPTIN.
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 [20]
RP FUNCTION IN PHOSPHORYLATION OF TP53.
RX PubMed=9733514; DOI=10.1126/science.281.5383.1674;
RA Banin S., Moyal L., Shieh S.-Y., Taya Y., Anderson C.W., Chessa L.,
RA Smorodinsky N.I., Prives C., Reiss Y., Shiloh Y., Ziv Y.;
RT "Enhanced phosphorylation of p53 by ATM in response to DNA damage.";
RL Science 281:1674-1677(1998).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF TP53, AND MUTAGENESIS OF ASP-2870 AND
RP ASN-2875.
RX PubMed=9733515; DOI=10.1126/science.281.5383.1677;
RA Canman C.E., Lim D.-S., Cimprich K.A., Taya Y., Tamai K., Sakaguchi K.,
RA Appella E., Kastan M.B., Siliciano J.D.;
RT "Activation of the ATM kinase by ionizing radiation and phosphorylation of
RT p53.";
RL Science 281:1677-1679(1998).
RN [22]
RP DNA-BINDING.
RX PubMed=10500142; DOI=10.1073/pnas.96.20.11134;
RA Smith G.C.M., Cary R.B., Lakin N.D., Hann B.C., Teo S.-H., Chen D.J.,
RA Jackson S.P.;
RT "Purification and DNA binding properties of the ataxia-telangiectasia gene
RT product ATM.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:11134-11139(1999).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF BRCA1.
RX PubMed=10550055; DOI=10.1126/science.286.5442.1162;
RA Cortez D., Wang Y., Qin J., Elledge S.J.;
RT "Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage
RT response to double-strand breaks.";
RL Science 286:1162-1166(1999).
RN [24]
RP IDENTIFICATION OF ATM AS MEMBER OF BASC.
RX PubMed=10783165;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [25]
RP FUNCTION IN PHOSPHORYLATION OF NBN.
RX PubMed=10766245; DOI=10.1038/35007091;
RA Lim D.-S., Kim S.-T., Xu B., Maser R.S., Lin J., Petrini J.H.J.,
RA Kastan M.B.;
RT "ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.";
RL Nature 404:613-617(2000).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF NBN.
RX PubMed=10839545; DOI=10.1038/35013089;
RA Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N.,
RA O'Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G.,
RA Livingston D.M., Weaver D.T.;
RT "ATM phosphorylation of Nijmegen breakage syndrome protein is required in a
RT DNA damage response.";
RL Nature 405:477-482(2000).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF CTIP.
RX PubMed=10910365; DOI=10.1038/35018134;
RA Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y., Lee E.Y.-H.P.,
RA Lee W.-H.;
RT "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA
RT damage response.";
RL Nature 406:210-215(2000).
RN [28]
RP FUNCTION IN PHOSPHORYLATION OF NBN.
RX PubMed=10802669; DOI=10.1038/75508;
RA Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K., Kozlov S.,
RA Lavin M.F., Gatti R.A., Concannon P., Khanna K.K.;
RT "ATM-dependent phosphorylation of nibrin in response to radiation
RT exposure.";
RL Nat. Genet. 25:115-119(2000).
RN [29]
RP FUNCTION IN PHOSPHORYLATION OF CHEK2.
RX PubMed=10973490; DOI=10.1073/pnas.190030497;
RA Matsuoka S., Rotman G., Ogawa A., Shiloh Y., Tamai K., Elledge S.J.;
RT "Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10389-10394(2000).
RN [30]
RP FUNCTION IN PHOSPHORYLATION OF TERF1.
RX PubMed=11375976; DOI=10.1074/jbc.m011534200;
RA Kishi S., Zhou X.Z., Ziv Y., Khoo C., Hill D.E., Shiloh Y., Lu K.P.;
RT "Telomeric protein Pin2/TRF1 as an important ATM target in response to
RT double strand DNA breaks.";
RL J. Biol. Chem. 276:29282-29291(2001).
RN [31]
RP INTERACTION WITH RAD17.
RX PubMed=11418864; DOI=10.1038/35082110;
RA Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A., Ali A.,
RA Chen S.M., Abraham R.T., Wang X.-F.;
RT "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic
RT stress responses.";
RL Nature 411:969-974(2001).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF FANCD2.
RX PubMed=12086603; DOI=10.1016/s0092-8674(02)00747-x;
RA Taniguchi T., Garcia-Higuera I., Xu B., Andreassen P.R., Gregory R.C.,
RA Kim S.-T., Lane W.S., Kastan M.B., D'Andrea A.D.;
RT "Convergence of the Fanconi anemia and ataxia telangiectasia signaling
RT pathways.";
RL Cell 109:459-472(2002).
RN [33]
RP PHOSPHORYLATION BY NUAK1.
RX PubMed=12409306; DOI=10.1074/jbc.m206025200;
RA Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F., Esumi H.;
RT "Identification of a novel protein kinase mediating Akt survival signaling
RT to the ATM protein.";
RL J. Biol. Chem. 278:48-53(2003).
RN [34]
RP PHOSPHORYLATION AT SER-1981, SUBUNIT, FUNCTION, AND MUTAGENESIS OF
RP SER-1981.
RX PubMed=12556884; DOI=10.1038/nature01368;
RA Bakkenist C.J., Kastan M.B.;
RT "DNA damage activates ATM through intermolecular autophosphorylation and
RT dimer dissociation.";
RL Nature 421:499-506(2003).
RN [35]
RP FUNCTION IN DNA DAMAGE RESPONSE, AND INTERACTION WITH PPP5C.
RX PubMed=14871926; DOI=10.1101/gad.1176004;
RA Ali A., Zhang J., Bao S., Liu I., Otterness D., Dean N.M., Abraham R.T.,
RA Wang X.F.;
RT "Requirement of protein phosphatase 5 in DNA-damage-induced ATM
RT activation.";
RL Genes Dev. 18:249-254(2004).
RN [36]
RP FUNCTION IN PHOSPHORYLATION OF DCLRE1C, AND INTERACTION WITH DCLRE1C.
RX PubMed=15456891; DOI=10.1128/mcb.24.20.9207-9220.2004;
RA Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D.,
RA Legerski R.J.;
RT "Artemis is a phosphorylation target of ATM and ATR and is involved in the
RT G2/M DNA damage checkpoint response.";
RL Mol. Cell. Biol. 24:9207-9220(2004).
RN [37]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15448695; DOI=10.1038/ncb1170;
RA Demonacos C., Krstic-Demonacos M., Smith L., Xu D., O'Connor D.P.,
RA Jansson M., La Thangue N.B.;
RT "A new effector pathway links ATM kinase with the DNA damage response.";
RL Nat. Cell Biol. 6:968-976(2004).
RN [38]
RP INTERACTION WITH EEF1E1.
RX PubMed=15680327; DOI=10.1016/j.cell.2004.11.054;
RA Park B.-J., Kang J.W., Lee S.W., Choi S.-J., Shin Y.K., Ahn Y.H.,
RA Choi Y.H., Choi D., Lee K.S., Kim S.;
RT "The haploinsufficient tumor suppressor p18 upregulates p53 via
RT interactions with ATM/ATR.";
RL Cell 120:209-221(2005).
RN [39]
RP FUNCTION.
RX PubMed=15916964; DOI=10.1016/j.molcel.2005.04.015;
RA Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.;
RT "ATM-dependent phosphorylation of ATF2 is required for the DNA damage
RT response.";
RL Mol. Cell 18:577-587(2005).
RN [40]
RP INTERACTION WITH KAT8.
RX PubMed=15923642; DOI=10.1128/mcb.25.12.5292-5305.2005;
RA Gupta A., Sharma G.G., Young C.S.H., Agarwal M., Smith E.R., Paull T.T.,
RA Lucchesi J.C., Khanna K.K., Ludwig T., Pandita T.K.;
RT "Involvement of human MOF in ATM function.";
RL Mol. Cell. Biol. 25:5292-5305(2005).
RN [41]
RP FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY.
RX PubMed=16086026; DOI=10.1038/nsmb972;
RA Kaygun H., Marzluff W.F.;
RT "Regulated degradation of replication-dependent histone mRNAs requires both
RT ATR and Upf1.";
RL Nat. Struct. Mol. Biol. 12:794-800(2005).
RN [42]
RP INTERACTION WITH HTATIP, PHOSPHORYLATION AT SER-1981, AND ACETYLATION.
RX PubMed=16141325; DOI=10.1073/pnas.0504211102;
RA Sun Y., Jiang X., Chen S., Fernandes N., Price B.D.;
RT "A role for the Tip60 histone acetyltransferase in the acetylation and
RT activation of ATM.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13182-13187(2005).
RN [43]
RP PHOSPHORYLATION AT SER-367; SER-1893 AND SER-1981, FUNCTION, CATALYTIC
RP ACTIVITY, MUTAGENESIS OF SER-367; SER-1893 AND SER-1981, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RX PubMed=16858402; DOI=10.1038/sj.emboj.7601231;
RA Kozlov S.V., Graham M.E., Peng C., Chen P., Robinson P.J., Lavin M.F.;
RT "Involvement of novel autophosphorylation sites in ATM activation.";
RL EMBO J. 25:3504-3514(2006).
RN [44]
RP INTERACTION WITH ATMIN.
RX PubMed=17525732; DOI=10.1038/sj.emboj.7601733;
RA Kanu N., Behrens A.;
RT "ATMIN defines an NBS1-independent pathway of ATM signalling.";
RL EMBO J. 26:2933-2941(2007).
RN [45]
RP ACETYLATION AT LYS-3016, FUNCTION, AND MUTAGENESIS OF LYS-3016 AND
RP LYS-3018.
RX PubMed=17923702; DOI=10.1128/mcb.01382-07;
RA Sun Y., Xu Y., Roy K., Price B.D.;
RT "DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase
RT activity.";
RL Mol. Cell. Biol. 27:8502-8509(2007).
RN [46]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1981 AND SER-1983, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [47]
RP INTERACTION WITH CEP164.
RX PubMed=18283122; DOI=10.1101/gad.1627708;
RA Sivasubramaniam S., Sun X., Pan Y.R., Wang S., Lee E.Y.;
RT "Cep164 is a mediator protein required for the maintenance of genomic
RT stability through modulation of MDC1, RPA, and CHK1.";
RL Genes Dev. 22:587-600(2008).
RN [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2996, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [49]
RP INTERACTION WITH NABP2.
RX PubMed=18449195; DOI=10.1038/nature06883;
RA Richard D.J., Bolderson E., Cubeddu L., Wadsworth R.I.M., Savage K.,
RA Sharma G.G., Nicolette M.L., Tsvetanov S., McIlwraith M.J., Pandita R.K.,
RA Takeda S., Hay R.T., Gautier J., West S.C., Paull T.T., Pandita T.K.,
RA White M.F., Khanna K.K.;
RT "Single-stranded DNA-binding protein hSSB1 is critical for genomic
RT stability.";
RL Nature 453:677-681(2008).
RN [50]
RP INTERACTION WITH DDX1.
RX PubMed=18710941; DOI=10.1128/mcb.01053-08;
RA Li L., Monckton E.A., Godbout R.;
RT "A role for DEAD box 1 at DNA double-strand breaks.";
RL Mol. Cell. Biol. 28:6413-6425(2008).
RN [51]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2996, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [52]
RP FUNCTION AS DYRK2 KINASE.
RX PubMed=19965871; DOI=10.1074/jbc.m109.042341;
RA Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K.;
RT "ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the
RT apoptotic response to DNA damage.";
RL J. Biol. Chem. 285:4909-4919(2010).
RN [53]
RP INTERACTION WITH TTI1.
RX PubMed=20810650; DOI=10.1101/gad.1934210;
RA Hurov K.E., Cotta-Ramusino C., Elledge S.J.;
RT "A genetic screen identifies the Triple T complex required for DNA damage
RT signaling and ATM and ATR stability.";
RL Genes Dev. 24:1939-1950(2010).
RN [54]
RP INTERACTION WITH TELO2.
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 [55]
RP INTERACTION WITH TELO2 AND TTI1.
RX PubMed=20427287; DOI=10.1074/jbc.m110.121699;
RA Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K.,
RA Iemura S., Natsume T., Mizushima N.;
RT "Tti1 and Tel2 are critical factors in mammalian target of rapamycin
RT complex assembly.";
RL J. Biol. Chem. 285:20109-20116(2010).
RN [56]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [57]
RP PHOSPHORYLATION AT SER-1981.
RX PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005;
RA Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y., Jun J.Y.,
RA You H.J.;
RT "Protein phosphatase 5 is necessary for ATR-mediated DNA repair.";
RL Biochem. Biophys. Res. Commun. 404:476-481(2011).
RN [58]
RP INTERACTION WITH BRAT1.
RX PubMed=22977523; DOI=10.3892/etm.2011.232;
RA So E.Y., Ouchi T.;
RT "Functional interaction of BRCA1/ATM-associated BAAT1 with the DNA-PK
RT catalytic subunit.";
RL Exp. Ther. Med. 2:443-447(2011).
RN [59]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [60]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [61]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [62]
RP FUNCTION IN PHOSPHORYLATION OF FBXW7.
RX PubMed=26774286; DOI=10.1016/j.molcel.2015.12.010;
RA Zhang Q., Karnak D., Tan M., Lawrence T.S., Morgan M.A., Sun Y.;
RT "FBXW7 facilitates nonhomologous end-joining via K63-linked
RT polyubiquitylation of XRCC4.";
RL Mol. Cell 61:419-433(2016).
RN [63]
RP FUNCTION.
RX PubMed=29203878; DOI=10.1038/s41467-017-02114-x;
RA Batenburg N.L., Walker J.R., Noordermeer S.M., Moatti N., Durocher D.,
RA Zhu X.D.;
RT "ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair
RT pathway choice.";
RL Nat. Commun. 8:1921-1921(2017).
RN [64]
RP FUNCTION.
RX PubMed=30612738; DOI=10.1016/j.cell.2018.11.024;
RA Jachimowicz R.D., Beleggia F., Isensee J., Velpula B.B., Goergens J.,
RA Bustos M.A., Doll M.A., Shenoy A., Checa-Rodriguez C., Wiederstein J.L.,
RA Baranes-Bachar K., Bartenhagen C., Hertwig F., Teper N., Nishi T.,
RA Schmitt A., Distelmaier F., Luedecke H.J., Albrecht B., Krueger M.,
RA Schumacher B., Geiger T., Hoon D.S.B., Huertas P., Fischer M., Hucho T.,
RA Peifer M., Ziv Y., Reinhardt H.C., Wieczorek D., Shiloh Y.;
RT "UBQLN4 represses homologous recombination and is overexpressed in
RT aggressive tumors.";
RL Cell 0:0-0(2019).
RN [65]
RP FUNCTION IN PHOSPHORYLATION OF UFL1, AND CATALYTIC ACTIVITY.
RX PubMed=30886146; DOI=10.1038/s41467-019-09175-0;
RA Qin B., Yu J., Nowsheen S., Wang M., Tu X., Liu T., Li H., Wang L., Lou Z.;
RT "UFL1 promotes histone H4 ufmylation and ATM activation.";
RL Nat. Commun. 10:1242-1242(2019).
RN [66]
RP ACETYLATION AT LYS-3016, PHOSPHORYLATION AT SER-1981, AND MUTAGENESIS OF
RP LYS-3016.
RX PubMed=30944854; DOI=10.1126/sciadv.aav1118;
RA Tang M., Li Z., Zhang C., Lu X., Tu B., Cao Z., Li Y., Chen Y., Jiang L.,
RA Wang H., Wang L., Wang J., Liu B., Xu X., Wang H., Zhu W.G.;
RT "SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA
RT damage repair.";
RL Sci. Adv. 5:EAAV1118-EAAV1118(2019).
RN [67] {ECO:0007744|PDB:5NP0, ECO:0007744|PDB:5NP1}
RP STRUCTURE BY ELECTRON MICROSCOPY (5.70 ANGSTROMS), CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=28508083; DOI=10.1126/sciadv.1700933;
RA Baretic D., Pollard H.K., Fisher D.I., Johnson C.M., Santhanam B.,
RA Truman C.M., Kouba T., Fersht A.R., Phillips C., Williams R.L.;
RT "Structures of closed and open conformations of dimeric human ATM.";
RL Sci. Adv. 3:E1700933-E1700933(2017).
RN [68]
RP VARIANTS GLY-2424; 2546-SER--ILE-2548 DEL AND CYS-2827.
RX PubMed=8755918;
RA McConville C.M., Stankovic T., Byrd P.J., McGuire G.M., Yao Q.-Y.,
RA Lennox G.G., Taylor A.M.R.;
RT "Mutations associated with variant phenotypes in ataxia-telangiectasia.";
RL Am. J. Hum. Genet. 59:320-330(1996).
RN [69]
RP VARIANT AT 2546-SER--ILE-2548 DEL, AND VARIANT ILE-2438.
RX PubMed=8808599;
RA Wright J., Teraoka S., Onengut S., Tolun A., Gatti R.A., Ochs H.D.,
RA Concannon P.;
RT "A high frequency of distinct ATM gene mutations in ataxia-
RT telangiectasia.";
RL Am. J. Hum. Genet. 59:839-846(1996).
RN [70]
RP VARIANTS 705-PHE--PRO-707 AND 2546-SER--ILE-2548 DEL, AND VARIANTS CYS-49;
RP LEU-858; ARG-1054; PHE-1420 AND ARG-1691.
RX PubMed=8797579;
RA Vorechovsky I., Luo L., Lindblom A., Negrini M., Webster A.D.B.,
RA Croce C.M., Hammarstroem L.;
RT "ATM mutations in cancer families.";
RL Cancer Res. 56:4130-4133(1996).
RN [71]
RP VARIANT AT 705-PHE--PRO-707, AND VARIANTS LEU-858 AND ARG-1054.
RX PubMed=9043869; DOI=10.1159/000472231;
RA Vorechovsky I., Luo L., Prudente S., Chessa L., Russo G., Kanariou M.,
RA James M.R., Negrini M., Webster A.D.B., Hammarstroem L.;
RT "Exon-scanning mutation analysis of the ATM gene in patients with ataxia-
RT telangiectasia.";
RL Eur. J. Hum. Genet. 4:352-355(1996).
RN [72]
RP VARIANT AT ARG-2867.
RX PubMed=8698354; DOI=10.1007/s004390050202;
RA Baumer A., Bernthaler U., Wolz W., Hoehn H., Schindler D.;
RT "New mutations in the ataxia telangiectasia gene.";
RL Hum. Genet. 98:246-249(1996).
RN [73]
RP VARIANTS 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; SER-2860 DEL AND
RP GLY-2904.
RX PubMed=8845835; DOI=10.1093/hmg/5.4.433;
RA Gilad S., Khosravi R., Shkedy D., Uziel T., Ziv Y., Savitsky K., Rotman G.,
RA Smith S., Chessa L., Jorgensen T.J., Harnik R., Frydman M., Sanal O.,
RA Portnoi S., Goldwicz Z., Jaspers N.G.J., Gatti R.A., Lenoir G., Lavin M.F.,
RA Tatsumi K., Wegner R.-D., Shiloh Y., Bar-Shira A.;
RT "Predominance of null mutations in ataxia-telangiectasia.";
RL Hum. Mol. Genet. 5:433-439(1996).
RN [74]
RP POSSIBLE INVOLVEMENT IN TPLL AND BNHL, AND VARIANTS VAL-1040; THR-1407;
RP SER-1463; HIS-1682; HIS-1910; LYS-2164; SER-2396; GLY-2424; PRO-2442;
RP 2546-SER--ILE-2548 DEL; ALA-2695; ARG-2722; VAL-2725; LEU-2732; LYS-2810
RP DEL; CYS-2832 AND 2871-ARG-HIS-2872 DELINS SER AND VAL-2890.
RX PubMed=9288106; DOI=10.1038/ng0997-96;
RA Vorechovsky I., Luo L., Dyer M.J.S., Catovsky D., Amlot P.L., Yaxley J.C.,
RA Foroni L., Hammarstroem L., Webster A.D.B., Yuille M.A.R.;
RT "Clustering of missense mutations in the ataxia-telangiectasia gene in a
RT sporadic T-cell leukaemia.";
RL Nat. Genet. 17:96-99(1997).
RN [75]
RP POSSIBLE INVOLVEMENT IN TPLL, AND VARIANTS GLY-2725; PRO-3006 AND CYS-3008.
RX PubMed=9334731; DOI=10.1038/nm1097-1155;
RA Stilgenbauer S., Schaffner C., Litterst A., Liebisch P., Gilad S.,
RA Bar-Shira A., James M.R., Lichter P., Doehner H.;
RT "Biallelic mutations in the ATM gene in T-prolymphocytic leukemia.";
RL Nat. Med. 3:1155-1159(1997).
RN [76]
RP VARIANT AT CYS-2832.
RX PubMed=9443866; DOI=10.1086/301673;
RA Telatar M., Teraoka S., Wang Z., Chun H.H., Liang T., Castellvi-Bel S.,
RA Udar N., Boerresen-Dale A.-L., Chessa L., Bernatowska-Matuszkiewicz E.,
RA Porras O., Watanabe M., Junker A., Concannon P., Gatti R.A.;
RT "Ataxia-telangiectasia: identification and detection of founder-effect
RT mutations in the ATM gene in ethnic populations.";
RL Am. J. Hum. Genet. 62:86-97(1998).
RN [77]
RP POSSIBLE INVOLVEMENT IN TALL, AND VARIANTS AT LEU-292; ASP-768; GLN-1001;
RP ARG-1691; ILE-1743; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548
RP DEL; ASP-2554; GLY-2668 AND CYS-2827.
RX PubMed=9463314; DOI=10.1086/301706;
RA Stankovic T., Kidd A.M.J., Sutcliffe A., McGuire G.M., Robinson P.,
RA Weber P., Bedenham T., Bradwell A.R., Easton D.F., Lennox G.G., Haites N.,
RA Byrd P.J., Taylor A.M.R.;
RT "ATM mutations and phenotypes in ataxia-telangiectasia families in the
RT British Isles: expression of mutant ATM and the risk of leukemia, lymphoma,
RT and breast cancer.";
RL Am. J. Hum. Genet. 62:334-345(1998).
RN [78]
RP VARIANT AT 1812-ALA-PHE-1813 DELINS VAL.
RX PubMed=9497252; DOI=10.1086/301755;
RA Gilad S., Chessa L., Khosravi R., Russell P., Galanty Y., Piane M.,
RA Gatti R.A., Jorgensen T.J., Shiloh Y., Bar-Shira A.;
RT "Genotype-phenotype relationships in ataxia-telangiectasia and variants.";
RL Am. J. Hum. Genet. 62:551-561(1998).
RN [79]
RP VARIANT AT PRO-2656.
RX PubMed=9450874;
RX DOI=10.1002/(sici)1096-8628(19980113)75:2<141::aid-ajmg4>3.0.co;2-w;
RA Toyoshima M., Hara T., Zhang H., Yamamoto T., Akaboshi S., Nanba E.,
RA Ohno K., Hori N., Sato K., Takeshita K.;
RT "Ataxia-telangiectasia without immunodeficiency: novel point mutations
RT within and adjacent to the phosphatidylinositol 3-kinase-like domain.";
RL Am. J. Med. Genet. 75:141-144(1998).
RN [80]
RP VARIANT TPLL GLY-2486.
RX PubMed=9573030;
RA Stoppa-Lyonnet D., Soulier J., Lauge A., Dastot H., Garand R., Sigaux F.,
RA Stern M.-H.;
RT "Inactivation of the ATM gene in T-cell prolymphocytic leukemias.";
RL Blood 91:3920-3926(1998).
RN [81]
RP VARIANTS 2855-ARG-ILE-2856 AND CYS-3008, AND VARIANT VAL-1853.
RX PubMed=9872980; DOI=10.1101/gr.8.12.1245;
RA Hacia J.G., Sun B., Hunt N., Edgemon K., Mosbrook D., Robbins C.,
RA Fodor S.P.A., Tagle D.A., Collins F.S.;
RT "Strategies for mutational analysis of the large multiexon ATM gene using
RT high-density oligonucleotide arrays.";
RL Genome Res. 8:1245-1258(1998).
RN [82]
RP VARIANT AT 2625-GLU-PRO-2626.
RX PubMed=9521587; DOI=10.1007/s004390050675;
RA van Belzen M.J., Hiel J.A.P., Weemaes C.M.R., Gabreeels F.J.M.,
RA van Engelen B.G.M., Smeets D.F.C.M., van den Heuvel L.P.W.J.;
RT "A double missense mutation in the ATM gene of a Dutch family with ataxia
RT telangiectasia.";
RL Hum. Genet. 102:187-191(1998).
RN [83]
RP VARIANT AT LEU-2829, AND VARIANTS GLU-126; ASP-514 AND ASN-1853.
RX PubMed=9711876;
RX DOI=10.1002/(sici)1098-1004(1998)12:3<186::aid-humu6>3.0.co;2-f;
RA Sasaki T., Tian H., Kukita Y., Inazuka M., Tahira T., Imai T., Yamauchi M.,
RA Saito T., Hori T., Hashimoto-Tamaoki T., Komatsu K., Nikaido O.,
RA Hayashi K.;
RT "ATM mutations in patients with ataxia telangiectasia screened by a
RT hierarchical strategy.";
RL Hum. Mutat. 12:186-195(1998).
RN [84]
RP VARIANTS AT LEU-858; ARG-1054; ASP-1091 AND ARG-1566.
RX PubMed=9792409;
RX DOI=10.1002/(sici)1098-1004(1998)12:5<330::aid-humu6>3.0.co;2-h;
RA Broeks A., de Klein A., Floore A.N., Muijtjens M., Kleijer W.J.,
RA Jaspers N.G.J., van 't Veer L.J.;
RT "ATM germline mutations in classical ataxia-telangiectasia patients in the
RT Dutch population.";
RL Hum. Mutat. 12:330-337(1998).
RN [85]
RP VARIANTS AT ARG-2491 AND GLY-2909.
RX PubMed=9792410;
RX DOI=10.1002/(sici)1098-1004(1998)12:5<338::aid-humu7>3.0.co;2-9;
RA Fukao T., Song X.-Q., Yoshida T., Tashita H., Kaneko H., Teramoto T.,
RA Inoue R., Katamura K., Mayumi M., Hiratani M., Taniguchi N., Arai J.,
RA Wakiguchi H., Bar-Shira A., Shiloh Y., Kondo N.;
RT "Ataxia-telangiectasia in the Japanese population: identification of
RT R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being
RT relatively common mutations.";
RL Hum. Mutat. 12:338-343(1998).
RN [86]
RP VARIANTS TPLL GLY-2139; VAL-2890 AND CYS-3008.
RX PubMed=9488043; DOI=10.1038/sj.onc.1201603;
RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., Matutes E.,
RA Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., Catovsky D.;
RT "ATM is usually rearranged in T-cell prolymphocytic leukaemia.";
RL Oncogene 16:789-796(1998).
RN [87]
RP ERRATUM OF PUBMED:9488043.
RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., Matutes E.,
RA Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., Catovsky D.;
RL Oncogene 16:2955-2955(1998).
RN [88]
RP POSSIBLE INVOLVEMENT IN BCLL AND MCL, AND VARIANTS ASN-1853; VAL-1853;
RP ARG-1953; LYS-2418 INS; PRO-2420; GLY-2423; HIS-3008 AND ASN-3018.
RX PubMed=10397742;
RA Schaffner C., Stilgenbauer S., Rappold G.A., Doehner H., Lichter P.;
RT "Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic
RT lymphocytic leukemia.";
RL Blood 94:748-753(1999).
RN [89]
RP POSSIBLE INVOLVEMENT IN BCLL, AND VARIANTS CYS-332; ARG-1691 AND GLY-2424.
RX PubMed=9892178;
RA Bullrich F., Rasio D., Kitada S., Starostik P., Kipps T., Keating M.,
RA Albitar M., Reed J.C., Croce C.M.;
RT "ATM mutations in B-cell chronic lymphocytic leukemia.";
RL Cancer Res. 59:24-27(1999).
RN [90]
RP VARIANT AT PRO-1465.
RX PubMed=10234507; DOI=10.1038/sj.ejhg.5200288;
RA Izatt L., Vessey C., Hodgson S.V., Solomon E.;
RT "Rapid and efficient ATM mutation detection by fluorescent chemical
RT cleavage of mismatch: identification of four novel mutations.";
RL Eur. J. Hum. Genet. 7:310-320(1999).
RN [91]
RP VARIANTS CYS-49; LEU-182; PRO-707; LEU-858; PHE-1420; ALA-1570; ASN-1853
RP AND SER-2765.
RX PubMed=10534763;
RX DOI=10.1002/(sici)1098-2264(199912)26:4<286::aid-gcc2>3.0.co;2-x;
RA Izatt L., Greenman J., Hodgson S.V., Ellis D., Watts S., Scott G.,
RA Jacobs C., Liebmann R., Zvelebil M.J., Mathew C., Solomon E.;
RT "Identification of germline missense mutations and rare allelic variants in
RT the ATM gene in early-onset breast cancer.";
RL Genes Chromosomes Cancer 26:286-294(1999).
RN [92]
RP VARIANTS AT SER-570; CYS-785; GLY-1913; GLY-2016; ASP-2067; CYS-2227;
RP ASP-2470; VAL-2662 DEL; PRO-2849 AND ARG-2867, AND VARIANTS CYS-49;
RP LEU-858; ARG-1054; ASN-1853 AND VAL-1853.
RX PubMed=9887333; DOI=10.1093/hmg/8.1.69;
RA Sandoval N., Platzer M., Rosenthal A., Doerk T., Bendix R., Skawran B.,
RA Stuhrmann M., Wegner R.-D., Sperling K., Banin S., Shiloh Y., Baumer A.,
RA Bernthaler U., Sennefelder H., Brohm M., Weber B.H.F., Schindler D.;
RT "Characterization of ATM gene mutations in 66 ataxia telangiectasia
RT families.";
RL Hum. Mol. Genet. 8:69-79(1999).
RN [93]
RP VARIANTS AT CYS-49; 375-GLN--VAL-3056 DEL; 1466-ARG--VAL-3056 DEL;
RP 1730-ARG--VAL-3056 DEL; GLY-2016; 2224-MET--ARG-2227 DELINS ILE-SER;
RP 2246-CYS--THR-2252 DELINS HIS; VAL-2664 DEL; VAL-2726; 2849-ARG--VAL-3056
RP DEL AND ARG-2855.
RX PubMed=10425038;
RX DOI=10.1002/(sici)1098-1004(1999)14:2<156::aid-humu7>3.0.co;2-e;
RA Castellvi-Bel S., Sheikhavandi S., Telatar M., Tai L.-Q., Hwang M.J.,
RA Wang Z., Yang Z., Cheng R., Gatti R.A.;
RT "New mutations, polymorphisms, and rare variants in the ATM gene detected
RT by a novel SSCP strategy.";
RL Hum. Mutat. 14:156-162(1999).
RN [94]
RP POSSIBLE INVOLVEMENT IN BCLL, AND VARIANTS THR-350; THR-352; ARG-1054;
RP THR-2274 AND ALA-2695.
RX PubMed=10023947; DOI=10.1016/s0140-6736(98)10117-4;
RA Stankovic T., Weber P., Stewart G., Bedenham T., Murray J., Byrd P.J.,
RA Moss P.A.H., Taylor A.M.R.;
RT "Inactivation of ataxia telangiectasia mutated gene in B-cell chronic
RT lymphocytic leukaemia.";
RL Lancet 353:26-29(1999).
RN [95]
RP VARIANT ARG-1054.
RX PubMed=10217116; DOI=10.1016/s0140-6736(05)75199-0;
RA Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.;
RT "Missense mutations at ATM gene and cancer risk.";
RL Lancet 353:1276-1276(1999).
RN [96]
RP ERRATUM OF PUBMED:10217116.
RA Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.;
RL Lancet 354:780-780(1999).
RN [97]
RP VARIANTS AT GLU-224; VAL-323; PRO-1420; CYS-2218; 2546-SER--ILE-2548 DEL;
RP GLN-2625; CYS-2832; 2855-ARG-ILE-2856 AND CYS-3008, AND VARIANTS VAL-1853
RP AND ILE-2438.
RX PubMed=10817650;
RX DOI=10.1002/(sici)1096-8628(20000529)92:3<170::aid-ajmg3>3.0.co;2-#;
RA Li A., Swift M.;
RT "Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-
RT T patients.";
RL Am. J. Med. Genet. 92:170-177(2000).
RN [98]
RP VARIANTS AT 35-ARG--VAL-3056 DEL; CYS-49; 292-LEU; 393-TRP--VAL-3056 DEL;
RP LEU-1082; 1171-GLN--VAL-3056 DEL; 1839-GLN--VAL-3056 DEL; GLU-2063;
RP CYS-2227; 2246-CYS--THR-2252 DELINS HIS; 2547-AER--SER-2549 DEL; GLU-2625
RP AND PRO-2626.
RX PubMed=10873394; DOI=10.1006/mgme.2000.2998;
RA Becker-Catania S.G., Chen G., Hwang M.J., Wang Z., Sun X., Sanal O.,
RA Bernatowska-Matuszkiewicz E., Chessa L., Lee E.Y.-H.P., Gatti R.A.;
RT "Ataxia-telangiectasia: phenotype/genotype studies of ATM protein
RT expression, mutations, and radiosensitivity.";
RL Mol. Genet. Metab. 70:122-133(2000).
RN [99]
RP VARIANTS MCL LYS-2418 INS; GLY-2423 AND CYS-3008.
RX PubMed=10706620; DOI=10.1073/pnas.050400997;
RA Schaffner C., Idler I., Stilgenbauer S., Doehner H., Lichter P.;
RT "Mantle cell lymphoma is characterized by inactivation of the ATM gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2773-2778(2000).
RN [100]
RP VARIANTS TRP-45 AND CYS-49.
RX PubMed=11897822; DOI=10.1136/jmg.39.3.192;
RA Allinen M., Launonen V., Laake K., Jansen L., Huusko P., Kaeaeriaeinen H.,
RA Boerresen-Dale A.L., Winqvist R.;
RT "ATM mutations in Finnish breast cancer patients.";
RL J. Med. Genet. 39:192-196(2002).
RN [101]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-23; CYS-49; GLU-126; HIS-140; GLN-250;
RP PHE-333; CYS-337; HIS-337; ALA-410; SER-504; ASP-514; TYR-540; VAL-546;
RP LEU-582; PRO-707; GLN-848; LEU-858; SER-872; TRP-924; ALA-935; ARG-1054;
RP PHE-1179; ILE-1321; TYR-1380; SER-1382; PHE-1420; MET-1469; CYS-1475;
RP SER-1650; THR-1739; ASN-1853; VAL-1853; ILE-1916; THR-1945; CYS-1961;
RP ASP-1991; PHE-2307; PRO-2332; PHE-2356; LEU-2408; PRO-2442; GLN-2443;
RP ARG-2464; ARG-2492; ALA-2666; HIS-2719; ARG-2842 AND ASN-2870.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [102]
RP VARIANTS CYS-49; LEU-858; ARG-1054; VAL-1255; ASN-1853; THR-2105; SER-2396
RP AND HIS-2719.
RX PubMed=18384426; DOI=10.1111/j.1399-0004.2008.00987.x;
RA Brunet J., Gutierrez-Enriquez S., Torres A., Berez V., Sanjose S.,
RA Galceran J., Izquierdo A., Menendez J.A., Guma J., Borras J.;
RT "ATM germline mutations in Spanish early-onset breast cancer patients
RT negative for BRCA1/BRCA2 mutations.";
RL Clin. Genet. 73:465-473(2008).
RN [103]
RP FUNCTION, CHARACTERIZATION OF VARIANTS AT LEU-292; PRO-1465; ILE-1743;
RP THR-2274; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL;
RP ASP-2554; GLY-2668; CYS-2827; 2855-SER-VAL-2856 DELINS ARG-ILE AND
RP CYS-3008, CHARACTERIZATION OF VARIANTS VAL-546; ARG-1054; ILE-1322;
RP ARG-1691; CYS-1961 AND SER-2765, VARIANT ILE-1322, AND MUTAGENESIS OF
RP LYS-1807; VAL-1941; TYR-2019; GLU-2039; LEU-2338; SER-2394; LEU-2452;
RP SER-2685; PRO-2699; ASP-2708 AND GLN-2730.
RX PubMed=19431188; DOI=10.1002/humu.21034;
RA Barone G., Groom A., Reiman A., Srinivasan V., Byrd P.J., Taylor A.M.;
RT "Modeling ATM mutant proteins from missense changes confirms retained
RT kinase activity.";
RL Hum. Mutat. 30:1222-1230(2009).
RN [104]
RP VARIANTS ALA-661; PRO-707; LEU-858; TRP-924; ARG-1054; ARG-1691 AND
RP VAL-1853.
RX PubMed=28202063; DOI=10.1186/s12920-017-0244-7;
RA Jalkh N., Chouery E., Haidar Z., Khater C., Atallah D., Ali H.,
RA Marafie M.J., Al-Mulla M.R., Al-Mulla F., Megarbane A.;
RT "Next-generation sequencing in familial breast cancer patients from
RT Lebanon.";
RL BMC Med. Genomics 10:8-8(2017).
RN [105]
RP VARIANTS AT VAL-323; PRO-1046; ARG-2023; SER-2068; ASP-2080; HIS-2627;
RP LEU-2834 AND ASP-3003, CHARACTERIZATION OF VARIANTS AT VAL-323; PRO-1046;
RP ARG-2023; SER-2068; ASP-2080; HIS-2627; LEU-2834 AND ASP-3003, AND
RP PHOSPHORYLATION.
RX PubMed=27664052; DOI=10.1007/s12017-016-8440-8;
RA Carranza D., Vega A.K., Torres-Rusillo S., Montero E., Martinez L.J.,
RA Santamaria M., Santos J.L., Molina I.J.;
RT "Molecular and functional characterization of a cohort of Spanish patients
RT with ataxia-telangiectasia.";
RL NeuroMolecular Med. 19:161-174(2017).
RN [106]
RP VARIANTS VAL-68; ILE-341; LEU-597; GLY-699; GLY-759; SER-813; GLY-869;
RP ILE-897; ASP-1474; VAL-1488; CYS-1961; ALA-2287; PHE-2307; ARG-2464;
RP PRO-2524; THR-2531; GLN-2810; HIS-2832; LEU-2974; ASP-3029 AND LEU-3056.
RX PubMed=28726808; DOI=10.1038/gim.2017.85;
RA Chaffee K.G., Oberg A.L., McWilliams R.R., Majithia N., Allen B.A.,
RA Kidd J., Singh N., Hartman A.R., Wenstrup R.J., Petersen G.M.;
RT "Prevalence of germ-line mutations in cancer genes among pancreatic cancer
RT patients with a positive family history.";
RL Genet. Med. 20:119-127(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 (PubMed:9843217,
CC PubMed:9733515, PubMed:10550055, PubMed:10766245, PubMed:10839545,
CC PubMed:10910365, PubMed:10802669, PubMed:10973490, PubMed:11375976,
CC PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:30612738,
CC PubMed:30886146, PubMed:26774286). May play a role in vesicle and/or
CC protein transport. Could play a role in T-cell development, gonad and
CC neurological function. Plays a role in replication-dependent histone
CC mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus
CC in response to genotoxic stress prevents its MDM2-mediated
CC ubiquitination and subsequent proteasome degradation. Phosphorylates
CC ATF2 which stimulates its function in DNA damage response.
CC Phosphorylates ERCC6 which is essential for its chromatin remodeling
CC activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates
CC TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage,
CC which promotes TTC5/STRAP nuclear localization (PubMed:15448695).
CC {ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245,
CC ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545,
CC ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490,
CC ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603,
CC ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926,
CC ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891,
CC ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026,
CC ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702,
CC ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871,
CC ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878,
CC ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30886146,
CC ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515,
CC ECO:0000269|PubMed:9843217}.
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:15448695, ECO:0000269|PubMed:16858402,
CC ECO:0000269|PubMed:28508083, ECO:0000269|PubMed:30886146,
CC ECO:0000269|PubMed:8988033, ECO:0000269|PubMed:9843217};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000305|PubMed:15448695};
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:28508083,
CC ECO:0000269|PubMed:8988033, ECO:0000269|PubMed:9843217};
CC -!- ACTIVITY REGULATION: Inhibited by wortmannin.
CC {ECO:0000269|PubMed:9766667}.
CC -!- SUBUNIT: Homodimer (PubMed:28508083). Dimers or tetramers in inactive
CC state. On DNA damage, autophosphorylation dissociates ATM into monomers
CC rendering them catalytically active. Binds p53/TP53, ABL1, BRCA1,
CC NBN/nibrin and TERF1. Part of the BRCA1-associated genome surveillance
CC complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2
CC and the RAD50-MRE11-NBN protein complex. This association could be a
CC dynamic process changing throughout the cell cycle and within
CC subnuclear domains. Interacts with RAD17; DNA damage promotes the
CC association. Interacts with EEF1E1; the interaction, induced on DNA
CC damage, up-regulates TP53. Interacts with DCLRE1C, KAT8, KAT5, NABP2,
CC ATMIN and CEP164. Interacts with AP2B1 and AP3B2; the interaction
CC occurs in cytoplasmic vesicles (By similarity). Interacts with TELO2
CC and TTI1. Interacts with DDX1. Interacts with BRAT1. Interacts with
CC CYREN (via XLF motif) (By similarity). {ECO:0000250|UniProtKB:Q62388,
CC ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:12556884,
CC ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15456891,
CC ECO:0000269|PubMed:15680327, ECO:0000269|PubMed:15923642,
CC ECO:0000269|PubMed:16141325, ECO:0000269|PubMed:17525732,
CC ECO:0000269|PubMed:18283122, ECO:0000269|PubMed:18449195,
CC ECO:0000269|PubMed:18710941, ECO:0000269|PubMed:20427287,
CC ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650,
CC ECO:0000269|PubMed:22977523, ECO:0000269|PubMed:28508083,
CC ECO:0000269|PubMed:9168117, ECO:0000269|PubMed:9707615,
CC ECO:0000269|PubMed:9843217}.
CC -!- INTERACTION:
CC Q13315; Q9NY61: AATF; NbExp=3; IntAct=EBI-495465, EBI-372428;
CC Q13315; P00519: ABL1; NbExp=4; IntAct=EBI-495465, EBI-375543;
CC Q13315; O43313: ATMIN; NbExp=5; IntAct=EBI-495465, EBI-7422202;
CC Q13315; Q6PJG6: BRAT1; NbExp=3; IntAct=EBI-495465, EBI-10826195;
CC Q13315; P62508-3: ESRRG; NbExp=3; IntAct=EBI-495465, EBI-12001340;
CC Q13315; Q5XUX0: FBXO31; NbExp=2; IntAct=EBI-495465, EBI-6162477;
CC Q13315; Q9Y6K9: IKBKG; NbExp=4; IntAct=EBI-495465, EBI-81279;
CC Q13315; Q13007: IL24; NbExp=2; IntAct=EBI-495465, EBI-3915542;
CC Q13315; Q14676: MDC1; NbExp=3; IntAct=EBI-495465, EBI-495644;
CC Q13315; Q9BQ15: NABP2; NbExp=4; IntAct=EBI-495465, EBI-2120336;
CC Q13315; P11245: NAT2; NbExp=2; IntAct=EBI-495465, EBI-9057228;
CC Q13315; O60934: NBN; NbExp=2; IntAct=EBI-495465, EBI-494844;
CC Q13315; P46531: NOTCH1; NbExp=8; IntAct=EBI-495465, EBI-636374;
CC Q13315; Q9BZ95: NSD3; NbExp=3; IntAct=EBI-495465, EBI-3390132;
CC Q13315; Q7LG56: RRM2B; NbExp=3; IntAct=EBI-495465, EBI-9009083;
CC Q13315; Q9Y4R8: TELO2; NbExp=4; IntAct=EBI-495465, EBI-1043674;
CC Q13315; P54274: TERF1; NbExp=3; IntAct=EBI-495465, EBI-710997;
CC Q13315; P54274-2: TERF1; NbExp=5; IntAct=EBI-495465, EBI-711018;
CC Q13315; Q15554: TERF2; NbExp=2; IntAct=EBI-495465, EBI-706637;
CC Q13315; Q12888: TP53BP1; NbExp=2; IntAct=EBI-495465, EBI-396540;
CC Q13315; O43156: TTI1; NbExp=5; IntAct=EBI-495465, EBI-1055680;
CC Q13315; PRO_0000037577 [P27958]; Xeno; NbExp=3; IntAct=EBI-495465, EBI-6904388;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9050866,
CC ECO:0000269|PubMed:9150358}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:9050866, ECO:0000269|PubMed:9150358}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q62388}. Note=Primarily nuclear. Found also in
CC endocytic vesicles in association with beta-adaptin.
CC {ECO:0000269|PubMed:9050866, ECO:0000269|PubMed:9150358}.
CC -!- TISSUE SPECIFICITY: Found in pancreas, kidney, skeletal muscle, liver,
CC lung, placenta, brain, heart, spleen, thymus, testis, ovary, small
CC intestine, colon and leukocytes.
CC -!- INDUCTION: By ionizing radiation.
CC -!- DOMAIN: The FATC domain is required for interaction with KAT5.
CC {ECO:0000269|PubMed:16141325}.
CC -!- PTM: Phosphorylated by NUAK1/ARK5 (PubMed:12409306).
CC Autophosphorylation on Ser-367, Ser-1893, Ser-1981 correlates with DNA
CC damage-mediated activation of the kinase (PubMed:12556884,
CC PubMed:16141325, PubMed:16858402, PubMed:21144835, PubMed:27664052).
CC During the late stages of DNA damage response, dephosphorylated
CC following deacetylation by SIRT7, leading to ATM deactivation
CC (PubMed:30944854). {ECO:0000269|PubMed:12409306,
CC ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:16141325,
CC ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:21144835,
CC ECO:0000269|PubMed:27664052, ECO:0000269|PubMed:30944854}.
CC -!- PTM: Acetylation, on DNA damage, is required for activation of the
CC kinase activity, dimer-monomer transition, and subsequent
CC autophosphorylation on Ser-1981 (PubMed:12556884, PubMed:16141325,
CC PubMed:16858402, PubMed:17923702, PubMed:21144835). Acetylated in vitro
CC by KAT5/TIP60 (PubMed:16141325). Deacetylated by SIRT7 during the late
CC stages of DNA damage response, promoting ATM dephosphorylation and
CC subsequent deactivation (PubMed:30944854).
CC {ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:16141325,
CC ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702,
CC ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:30944854}.
CC -!- DISEASE: Ataxia telangiectasia (AT) [MIM:208900]: A rare recessive
CC disorder characterized by progressive cerebellar ataxia, dilation of
CC the blood vessels in the conjunctiva and eyeballs, immunodeficiency,
CC growth retardation and sexual immaturity. Patients have a strong
CC predisposition to cancer; about 30% of patients develop tumors,
CC particularly lymphomas and leukemias. Cells from affected individuals
CC are highly sensitive to damage by ionizing radiation and resistant to
CC inhibition of DNA synthesis following irradiation.
CC {ECO:0000269|PubMed:10234507, ECO:0000269|PubMed:10425038,
CC ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:10873394,
CC ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:27664052,
CC ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8589678,
CC ECO:0000269|PubMed:8665503, ECO:0000269|PubMed:8698354,
CC ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:8789452,
CC ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:8808599,
CC ECO:0000269|PubMed:8845835, ECO:0000269|PubMed:9043869,
CC ECO:0000269|PubMed:9150358, ECO:0000269|PubMed:9443866,
CC ECO:0000269|PubMed:9450874, ECO:0000269|PubMed:9463314,
CC ECO:0000269|PubMed:9497252, ECO:0000269|PubMed:9521587,
CC ECO:0000269|PubMed:9711876, ECO:0000269|PubMed:9792409,
CC ECO:0000269|PubMed:9792410, ECO:0000269|PubMed:9872980,
CC ECO:0000269|PubMed:9887333}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in ATM may contribute to T-cell acute
CC lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL).
CC TPLL is characterized by a high white blood cell count, with a
CC predominance of prolymphocytes, marked splenomegaly, lymphadenopathy,
CC skin lesions and serous effusion. The clinical course is highly
CC aggressive, with poor response to chemotherapy and short survival time.
CC TPLL occurs both in adults as a sporadic disease and in younger AT
CC patients. {ECO:0000269|PubMed:9288106, ECO:0000269|PubMed:9334731,
CC ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9488043,
CC ECO:0000269|PubMed:9573030}.
CC -!- DISEASE: Note=Defects in ATM may contribute to B-cell non-Hodgkin
CC lymphomas (BNHL), including mantle cell lymphoma (MCL).
CC {ECO:0000269|PubMed:10397742, ECO:0000269|PubMed:10706620,
CC ECO:0000269|PubMed:9288106}.
CC -!- DISEASE: Note=Defects in ATM may contribute to B-cell chronic
CC lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in
CC the elderly. It is characterized by the accumulation of mature CD5+ B-
CC lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.
CC {ECO:0000269|PubMed:10023947, ECO:0000269|PubMed:10397742,
CC ECO:0000269|PubMed:9892178}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA86520.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA86520.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=AAI37170.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI37170.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=EAW67111.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ATMID123.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/atm/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ataxia telangiectasia mutated entry;
CC URL="https://en.wikipedia.org/wiki/Ataxia_telangiectasia_mutated";
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DR EMBL; U33841; AAC50289.1; -; mRNA.
DR EMBL; U55757; AAB38309.1; -; Genomic_DNA.
DR EMBL; U55704; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55705; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55707; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55708; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55709; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55710; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55711; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55712; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55713; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55714; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55715; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55716; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55717; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55718; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55719; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55720; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55721; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55722; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55723; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55724; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55725; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55726; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55727; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55728; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55729; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55730; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55731; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55732; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55733; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55734; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55735; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55736; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55737; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55738; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55739; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55740; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55741; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55742; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55743; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55744; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55745; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55746; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55747; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55748; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55749; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55750; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55751; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55752; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55753; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55754; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55755; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55756; AAB38309.1; JOINED; Genomic_DNA.
DR EMBL; U55757; AAB38310.1; -; Genomic_DNA.
DR EMBL; U55726; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55727; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55728; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55729; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55730; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55731; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55732; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55733; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55734; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55735; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55736; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55737; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55738; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55739; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55740; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55741; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55742; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55743; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55744; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55745; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55746; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55747; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55748; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55749; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55750; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55751; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55752; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55753; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55754; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55755; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U55756; AAB38310.1; JOINED; Genomic_DNA.
DR EMBL; U82828; AAB65827.1; -; Genomic_DNA.
DR EMBL; AP001925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP005718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455499; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67111.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X91196; CAA62603.1; -; mRNA.
DR EMBL; U67092; AAC51298.1; -; Genomic_DNA.
DR EMBL; AY220758; AAO26044.1; -; Genomic_DNA.
DR EMBL; U26455; AAA86520.1; ALT_SEQ; mRNA.
DR EMBL; BC137169; AAI37170.1; ALT_SEQ; mRNA.
DR CCDS; CCDS31669.1; -.
DR PIR; A43100; A43100.
DR RefSeq; NP_000042.3; NM_000051.3.
DR RefSeq; XP_005271618.2; XM_005271561.4.
DR RefSeq; XP_005271619.2; XM_005271562.4.
DR RefSeq; XP_006718906.1; XM_006718843.3.
DR RefSeq; XP_006718908.1; XM_006718845.1.
DR RefSeq; XP_011541142.1; XM_011542840.2.
DR RefSeq; XP_016873278.1; XM_017017789.1.
DR RefSeq; XP_016873279.1; XM_017017790.1.
DR PDB; 5NP0; EM; 5.70 A; A/B=1-3056.
DR PDB; 5NP1; EM; 5.70 A; A=1-3056.
DR PDB; 6HKA; NMR; -; A=3024-3056.
DR PDB; 6K9K; EM; 7.82 A; A=1-3056.
DR PDB; 6K9L; EM; 4.27 A; A/B=1-3056.
DR PDB; 7NI4; EM; 3.00 A; A/B=1-3056.
DR PDB; 7NI5; EM; 2.78 A; A/B=1-3056.
DR PDB; 7NI6; EM; 2.80 A; A/B=1-3056.
DR PDB; 7SIC; EM; 2.51 A; A/B=1-3056.
DR PDB; 7SID; EM; 2.53 A; A/C=1-3056.
DR PDBsum; 5NP0; -.
DR PDBsum; 5NP1; -.
DR PDBsum; 6HKA; -.
DR PDBsum; 6K9K; -.
DR PDBsum; 6K9L; -.
DR PDBsum; 7NI4; -.
DR PDBsum; 7NI5; -.
DR PDBsum; 7NI6; -.
DR PDBsum; 7SIC; -.
DR PDBsum; 7SID; -.
DR SMR; Q13315; -.
DR BioGRID; 106962; 285.
DR CORUM; Q13315; -.
DR DIP; DIP-182N; -.
DR IntAct; Q13315; 100.
DR MINT; Q13315; -.
DR STRING; 9606.ENSP00000278616; -.
DR BindingDB; Q13315; -.
DR ChEMBL; CHEMBL3797; -.
DR DrugBank; DB00201; Caffeine.
DR GuidetoPHARMACOLOGY; 1934; -.
DR GlyGen; Q13315; 4 sites, 2 O-linked glycans (4 sites).
DR iPTMnet; Q13315; -.
DR PhosphoSitePlus; Q13315; -.
DR BioMuta; ATM; -.
DR DMDM; 317373479; -.
DR CPTAC; CPTAC-3210; -.
DR CPTAC; CPTAC-3211; -.
DR CPTAC; CPTAC-3212; -.
DR CPTAC; CPTAC-3213; -.
DR CPTAC; CPTAC-912; -.
DR CPTAC; CPTAC-913; -.
DR EPD; Q13315; -.
DR jPOST; Q13315; -.
DR MassIVE; Q13315; -.
DR MaxQB; Q13315; -.
DR PaxDb; Q13315; -.
DR PeptideAtlas; Q13315; -.
DR PRIDE; Q13315; -.
DR ProteomicsDB; 59303; -.
DR Antibodypedia; 3596; 1469 antibodies from 48 providers.
DR CPTC; Q13315; 4 antibodies.
DR DNASU; 472; -.
DR Ensembl; ENST00000278616.9; ENSP00000278616.4; ENSG00000149311.20.
DR Ensembl; ENST00000452508.6; ENSP00000388058.2; ENSG00000149311.20.
DR Ensembl; ENST00000675843.1; ENSP00000501606.1; ENSG00000149311.20.
DR GeneID; 472; -.
DR KEGG; hsa:472; -.
DR MANE-Select; ENST00000675843.1; ENSP00000501606.1; NM_000051.4; NP_000042.3.
DR UCSC; uc001pkb.1; human.
DR CTD; 472; -.
DR DisGeNET; 472; -.
DR GeneCards; ATM; -.
DR GeneReviews; ATM; -.
DR HGNC; HGNC:795; ATM.
DR HPA; ENSG00000149311; Low tissue specificity.
DR MalaCards; ATM; -.
DR MIM; 208900; phenotype.
DR MIM; 607585; gene.
DR neXtProt; NX_Q13315; -.
DR OpenTargets; ENSG00000149311; -.
DR Orphanet; 100; Ataxia-telangiectasia.
DR Orphanet; 370109; Ataxia-telangiectasia variant.
DR Orphanet; 67038; B-cell chronic lymphocytic leukemia.
DR Orphanet; 1331; Familial prostate cancer.
DR Orphanet; 52416; Mantle cell lymphoma.
DR PharmGKB; PA61; -.
DR VEuPathDB; HostDB:ENSG00000149311; -.
DR eggNOG; KOG0892; Eukaryota.
DR GeneTree; ENSGT00670000098061; -.
DR HOGENOM; CLU_000178_3_1_1; -.
DR InParanoid; Q13315; -.
DR OMA; YSKWAVL; -.
DR OrthoDB; 80538at2759; -.
DR PhylomeDB; Q13315; -.
DR TreeFam; TF101182; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q13315; -.
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-69541; Stabilization of p53.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR Reactome; R-HSA-9664873; Pexophagy.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; Q13315; -.
DR SIGNOR; Q13315; -.
DR BioGRID-ORCS; 472; 45 hits in 1127 CRISPR screens.
DR ChiTaRS; ATM; human.
DR GeneWiki; Ataxia_telangiectasia_mutated; -.
DR GenomeRNAi; 472; -.
DR Pharos; Q13315; Tchem.
DR PRO; PR:Q13315; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q13315; protein.
DR Bgee; ENSG00000149311; Expressed in calcaneal tendon and 205 other tissues.
DR ExpressionAtlas; Q13315; baseline and differential.
DR Genevisible; Q13315; HS.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1990391; C:DNA repair complex; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005819; C:spindle; IEA:Ensembl.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IMP: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; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
DR GO; GO:0047485; F:protein N-terminus binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:BHF-UCL.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:CAFA.
DR GO; GO:0071500; P:cellular response to nitrosative stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:ARUK-UCL.
DR GO; GO:0071481; P:cellular response to X-ray; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090398; P:cellular senescence; TAS:Reactome.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IEA:Ensembl.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; TAS:Reactome.
DR GO; GO:0097695; P:establishment of protein-containing complex localization to telomere; IC:BHF-UCL.
DR GO; GO:0097694; P:establishment of RNA localization to telomere; IMP:BHF-UCL.
DR GO; GO:0007143; P:female meiotic nuclear division; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0071044; P:histone mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; IEA:InterPro.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl.
DR GO; GO:0007140; P:male meiotic nuclear division; IEA:Ensembl.
DR GO; GO:0045141; P:meiotic telomere clustering; IEA:Ensembl.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:BHF-UCL.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:1904354; P:negative regulation of telomere capping; IMP:BHF-UCL.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0048599; P:oocyte development; IEA:Ensembl.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:1903626; P:positive regulation of DNA catabolic process; IEA:Ensembl.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1904884; P:positive regulation of telomerase catalytic core complex assembly; IMP:BHF-UCL.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISS:BHF-UCL.
DR GO; GO:1904358; P:positive regulation of telomere maintenance via telomere lengthening; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:ARUK-UCL.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0002331; P:pre-B cell allelic exclusion; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:Reactome.
DR GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL.
DR GO; GO:1905843; P:regulation of cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR GO; GO:1903978; P:regulation of microglial cell activation; IEA:Ensembl.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0032210; P:regulation of telomere maintenance via telomerase; IGI:BHF-UCL.
DR GO; GO:0090399; P:replicative senescence; IMP:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0033151; P:V(D)J recombination; IEA:Ensembl.
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; 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; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Disease variant; DNA damage;
KW DNA-binding; Kinase; Neurodegeneration; 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:0007744|PubMed:22223895"
FT CHAIN 2..3056
FT /note="Serine-protein kinase ATM"
FT /id="PRO_0000088840"
FT DOMAIN 1940..2566
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 2686..2998
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 3024..3056
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 1373..1382
FT /note="Interaction with ABL1"
FT /evidence="ECO:0000269|PubMed:9168117"
FT REGION 2692..2698
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2867..2875
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2887..2911
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 367
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16858402"
FT MOD_RES 1893
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16858402"
FT MOD_RES 1981
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12556884,
FT ECO:0000269|PubMed:16141325, ECO:0000269|PubMed:16858402,
FT ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:30944854,
FT ECO:0007744|PubMed:17525332"
FT MOD_RES 1983
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 2996
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 3016
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17923702,
FT ECO:0000269|PubMed:30944854"
FT VARIANT 23
FT /note="R -> Q (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs587779858)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041545"
FT VARIANT 35..3056
FT /note="Missing (in AT; dbSNP:rs55861249)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_085060"
FT VARIANT 45
FT /note="R -> W (found in a patient with breast cancer;
FT unknown pathological significance; dbSNP:rs3218684)"
FT /evidence="ECO:0000269|PubMed:11897822"
FT /id="VAR_056678"
FT VARIANT 49
FT /note="S -> C (in AT; increases protein abundance;
FT dbSNP:rs1800054)"
FT /evidence="ECO:0000269|PubMed:10425038,
FT ECO:0000269|PubMed:10534763, ECO:0000269|PubMed:10873394,
FT ECO:0000269|PubMed:11897822, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:18384426, ECO:0000269|PubMed:8665503,
FT ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:9887333"
FT /id="VAR_010798"
FT VARIANT 68
FT /note="I -> V (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083373"
FT VARIANT 126
FT /note="D -> E (in dbSNP:rs2234997)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9711876"
FT /id="VAR_010799"
FT VARIANT 140
FT /note="D -> H (in dbSNP:rs55633650)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041546"
FT VARIANT 182
FT /note="V -> L (in dbSNP:rs3218707)"
FT /evidence="ECO:0000269|PubMed:10534763"
FT /id="VAR_010800"
FT VARIANT 224
FT /note="K -> E (in AT; unknown pathological significance;
FT dbSNP:rs145053092)"
FT /evidence="ECO:0000269|PubMed:10817650"
FT /id="VAR_010801"
FT VARIANT 250
FT /note="R -> Q (in dbSNP:rs56123940)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041547"
FT VARIANT 292
FT /note="P -> L (in AT; associated with lymphoma; decrease
FT phosphorylation of target proteins; increases protein
FT abundance; dbSNP:rs747727055)"
FT /evidence="ECO:0000269|PubMed:10873394,
FT ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:9463314"
FT /id="VAR_010802"
FT VARIANT 323
FT /note="I -> V (in AT; loss of protein expression;
FT dbSNP:rs587781511)"
FT /evidence="ECO:0000269|PubMed:10817650,
FT ECO:0000269|PubMed:27664052"
FT /id="VAR_010803"
FT VARIANT 332
FT /note="Y -> C (in B-cell chronic lymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:9892178"
FT /id="VAR_010804"
FT VARIANT 333
FT /note="S -> F (in dbSNP:rs28904919)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041548"
FT VARIANT 337
FT /note="R -> C (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs138398778)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041549"
FT VARIANT 337
FT /note="R -> H (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs202160435)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041550"
FT VARIANT 341
FT /note="V -> I (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083374"
FT VARIANT 350
FT /note="A -> T (in B-cell chronic lymphocytic leukemia;
FT dbSNP:rs371713984)"
FT /evidence="ECO:0000269|PubMed:10023947"
FT /id="VAR_010805"
FT VARIANT 352
FT /note="I -> T (in B-cell chronic lymphocytic leukemia;
FT dbSNP:rs369203092)"
FT /evidence="ECO:0000269|PubMed:10023947"
FT /id="VAR_010806"
FT VARIANT 374..3056
FT /note="Missing (in AT; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_085061"
FT VARIANT 393..3056
FT /note="Missing (in AT; unknown pathological significance;
FT dbSNP:rs587776547)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_085062"
FT VARIANT 410
FT /note="V -> A (in dbSNP:rs56128736)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041551"
FT VARIANT 504
FT /note="N -> S (in dbSNP:rs56365018)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041552"
FT VARIANT 514
FT /note="G -> D (in dbSNP:rs2235000)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9711876"
FT /id="VAR_010807"
FT VARIANT 540
FT /note="C -> Y (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041553"
FT VARIANT 546
FT /note="L -> V (no effect on phosphorylation of target
FT proteins; dbSNP:rs2227924)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:19431188"
FT /id="VAR_041554"
FT VARIANT 570
FT /note="F -> S (in AT; dbSNP:rs777301065)"
FT /evidence="ECO:0000269|PubMed:9887333"
FT /id="VAR_010808"
FT VARIANT 582
FT /note="F -> L (in dbSNP:rs2235006)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041555"
FT VARIANT 597
FT /note="P -> L (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083375"
FT VARIANT 661
FT /note="D -> A (found in a patient with familial breast
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28202063"
FT /id="VAR_083376"
FT VARIANT 699
FT /note="E -> G (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083377"
FT VARIANT 705..707
FT /note="YSS -> FIP (in AT; might be associated with
FT susceptibility to cancer)"
FT /id="VAR_010809"
FT VARIANT 707
FT /note="S -> P (in dbSNP:rs4986761)"
FT /evidence="ECO:0000269|PubMed:10534763,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:28202063"
FT /id="VAR_010810"
FT VARIANT 759
FT /note="S -> G (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083378"
FT VARIANT 761
FT /note="T -> S (in dbSNP:rs2235011)"
FT /id="VAR_056679"
FT VARIANT 768
FT /note="N -> D (in AT)"
FT /evidence="ECO:0000269|PubMed:9463314"
FT /id="VAR_010812"
FT VARIANT 785
FT /note="R -> C (in AT; dbSNP:rs587778065)"
FT /evidence="ECO:0000269|PubMed:9887333"
FT /id="VAR_010813"
FT VARIANT 788
FT /note="S -> R (in dbSNP:rs641252)"
FT /id="VAR_056680"
FT VARIANT 813
FT /note="N -> S (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083379"
FT VARIANT 814
FT /note="D -> E (in dbSNP:rs3218695)"
FT /id="VAR_056681"
FT VARIANT 848
FT /note="E -> Q (in a lung adenocarcinoma sample; somatic
FT mutation; dbSNP:rs879254046)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041556"
FT VARIANT 858
FT /note="F -> L (in dbSNP:rs1800056)"
FT /evidence="ECO:0000269|PubMed:10534763,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:18384426,
FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8797579,
FT ECO:0000269|PubMed:9043869, ECO:0000269|PubMed:9792409,
FT ECO:0000269|PubMed:9887333"
FT /id="VAR_010814"
FT VARIANT 869
FT /note="A -> G (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083380"
FT VARIANT 872
FT /note="P -> S (in dbSNP:rs3218673)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041557"
FT VARIANT 897
FT /note="F -> I (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083381"
FT VARIANT 924
FT /note="R -> W (found in a patient with familial breast
FT cancer; unknown pathological significance;
FT dbSNP:rs55723361)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:28202063"
FT /id="VAR_041558"
FT VARIANT 935
FT /note="T -> A (in dbSNP:rs35813135)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041559"
FT VARIANT 935
FT /note="T -> M (in dbSNP:rs3218708)"
FT /id="VAR_056682"
FT VARIANT 942
FT /note="L -> F (in dbSNP:rs3218688)"
FT /id="VAR_056683"
FT VARIANT 950
FT /note="L -> R (in AT; dbSNP:rs786203054)"
FT /id="VAR_010815"
FT VARIANT 1001
FT /note="L -> Q (in AT; associated with T-cell acute
FT lymphoblastic leukemia)"
FT /evidence="ECO:0000269|PubMed:9463314"
FT /id="VAR_010816"
FT VARIANT 1040
FT /note="M -> V (found in B-cell non-Hodgkin lymphoma;
FT unknown pathological significance; dbSNP:rs3092857)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010817"
FT VARIANT 1046
FT /note="L -> P (in AT; loss of protein expression;
FT dbSNP:rs568461905)"
FT /evidence="ECO:0000269|PubMed:27664052"
FT /id="VAR_077237"
FT VARIANT 1054
FT /note="P -> R (in AT, B-cell chronic lymphocytic leukemia,
FT breast cancer patients and familial cancer patients; no
FT effect on phosphorylation of target proteins;
FT dbSNP:rs1800057)"
FT /evidence="ECO:0000269|PubMed:10023947,
FT ECO:0000269|PubMed:10217116, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:18384426, ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8665503,
FT ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:9043869,
FT ECO:0000269|PubMed:9792409, ECO:0000269|PubMed:9887333"
FT /id="VAR_010818"
FT VARIANT 1082
FT /note="H -> L (in AT; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_010819"
FT VARIANT 1091
FT /note="E -> D (in AT)"
FT /evidence="ECO:0000269|PubMed:9792409"
FT /id="VAR_010820"
FT VARIANT 1171..3056
FT /note="Missing (in AT; unknown pathological significance;
FT increases protein abundance)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_085063"
FT VARIANT 1179
FT /note="S -> F (in a gastric adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041560"
FT VARIANT 1255
FT /note="L -> V (found in a patient with early-onset breast
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:18384426"
FT /id="VAR_083382"
FT VARIANT 1313
FT /note="E -> Q (in dbSNP:rs3092841)"
FT /id="VAR_056684"
FT VARIANT 1321
FT /note="M -> I (in dbSNP:rs35184530)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041561"
FT VARIANT 1322
FT /note="L -> I (no effect on phosphorylation of target
FT proteins; dbSNP:rs144535256)"
FT /evidence="ECO:0000269|PubMed:19431188"
FT /id="VAR_080300"
FT VARIANT 1380
FT /note="H -> Y (in dbSNP:rs3092856)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041562"
FT VARIANT 1382
FT /note="P -> S (in dbSNP:rs55859590)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041563"
FT VARIANT 1407
FT /note="I -> T (in T-prolymphocytic leukemia;
FT dbSNP:rs1234250980)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010821"
FT VARIANT 1420
FT /note="L -> F (in dbSNP:rs1800058)"
FT /evidence="ECO:0000269|PubMed:10534763,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8665503,
FT ECO:0000269|PubMed:8797579"
FT /id="VAR_010822"
FT VARIANT 1420
FT /note="L -> P (in AT)"
FT /evidence="ECO:0000269|PubMed:10817650"
FT /id="VAR_010823"
FT VARIANT 1427
FT /note="A -> T (in dbSNP:rs2229021)"
FT /id="VAR_056685"
FT VARIANT 1463
FT /note="F -> S (found in B-cell non-Hodgkin lymphoma;
FT unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010825"
FT VARIANT 1465
FT /note="L -> P (in AT; decreased phosphorylation of target
FT proteins; dbSNP:rs730881391)"
FT /evidence="ECO:0000269|PubMed:10234507,
FT ECO:0000269|PubMed:19431188"
FT /id="VAR_010826"
FT VARIANT 1466..3056
FT /note="Missing (in AT; unknown pathological significance;
FT dbSNP:rs730881369)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_085064"
FT VARIANT 1469
FT /note="I -> M (in a renal papillary cancer sample; somatic
FT mutation; dbSNP:rs775047783)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041564"
FT VARIANT 1474
FT /note="H -> D (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083383"
FT VARIANT 1475
FT /note="Y -> C (in dbSNP:rs34640941)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041565"
FT VARIANT 1488
FT /note="L -> V (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083384"
FT VARIANT 1541
FT /note="L -> F (in dbSNP:rs3092849)"
FT /id="VAR_056686"
FT VARIANT 1566
FT /note="P -> R (in AT)"
FT /evidence="ECO:0000269|PubMed:9792409"
FT /id="VAR_010827"
FT VARIANT 1570
FT /note="V -> A (in dbSNP:rs140856217)"
FT /evidence="ECO:0000269|PubMed:10534763"
FT /id="VAR_010828"
FT VARIANT 1650
FT /note="N -> S (in dbSNP:rs55870064)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041566"
FT VARIANT 1682
FT /note="D -> H (in T-prolymphocytic leukemia;
FT dbSNP:rs121434217)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010829"
FT VARIANT 1691
FT /note="S -> R (in AT, B-cell chronic lymphocytic leukemia
FT and familial cancer patients; no effect on phosphorylation
FT of target proteins; dbSNP:rs1800059)"
FT /evidence="ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8797579,
FT ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9892178"
FT /id="VAR_010830"
FT VARIANT 1729
FT /note="V -> L (in dbSNP:rs3092907)"
FT /id="VAR_056687"
FT VARIANT 1730..3056
FT /note="Missing (in AT; unknown pathological significance;
FT dbSNP:rs764389018)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_085065"
FT VARIANT 1739
FT /note="N -> T (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041567"
FT VARIANT 1743
FT /note="T -> I (in AT; associated with preleukemic T-cell
FT proliferation; decreased phosphorylation of target
FT proteins; dbSNP:rs587779844)"
FT /evidence="ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:9463314"
FT /id="VAR_010831"
FT VARIANT 1812..1813
FT /note="AF -> V (in AT)"
FT /evidence="ECO:0000269|PubMed:9497252"
FT /id="VAR_010832"
FT VARIANT 1839..3056
FT /note="Missing (in AT; unknown pathological significance;
FT reduces protein abundance)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_085066"
FT VARIANT 1853
FT /note="D -> N (in dbSNP:rs1801516)"
FT /evidence="ECO:0000269|PubMed:10397742,
FT ECO:0000269|PubMed:10425038, ECO:0000269|PubMed:10534763,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:18384426,
FT ECO:0000269|PubMed:9711876, ECO:0000269|PubMed:9887333"
FT /id="VAR_010833"
FT VARIANT 1853
FT /note="D -> V (might contribute to B-cell chronic
FT lymphocytic leukemia; dbSNP:rs1801673)"
FT /evidence="ECO:0000269|PubMed:10397742,
FT ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:9872980,
FT ECO:0000269|PubMed:9887333"
FT /id="VAR_010834"
FT VARIANT 1910
FT /note="L -> H (in T-prolymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010835"
FT VARIANT 1913
FT /note="V -> G (in AT; dbSNP:rs1060501688)"
FT /evidence="ECO:0000269|PubMed:9887333"
FT /id="VAR_010836"
FT VARIANT 1916
FT /note="M -> I (in a breast pleomorphic lobular carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041568"
FT VARIANT 1945
FT /note="A -> T (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041569"
FT VARIANT 1953
FT /note="T -> R (in B-cell chronic lymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:10397742"
FT /id="VAR_010837"
FT VARIANT 1961
FT /note="Y -> C (found in a patient with familial pancreatic
FT cancer; also found in a lung adenocarcinoma sample; unknown
FT pathological significance; decreased phosphorylation of
FT target proteins; dbSNP:rs56399311)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:28726808"
FT /id="VAR_041570"
FT VARIANT 1983
FT /note="S -> N (in dbSNP:rs659243)"
FT /evidence="ECO:0000269|PubMed:16554811"
FT /id="VAR_041571"
FT VARIANT 1991
FT /note="E -> D (in a renal clear cell carcinoma sample;
FT somatic mutation; dbSNP:rs587782274)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041572"
FT VARIANT 2016
FT /note="D -> G (in AT; unknown pathological significance;
FT dbSNP:rs587781302)"
FT /evidence="ECO:0000269|PubMed:10425038,
FT ECO:0000269|PubMed:9887333"
FT /id="VAR_010838"
FT VARIANT 2023
FT /note="G -> R (in AT; loss of protein expression;
FT dbSNP:rs11212587)"
FT /evidence="ECO:0000269|PubMed:27664052"
FT /id="VAR_077238"
FT VARIANT 2034
FT /note="R -> Q (in dbSNP:rs3218670)"
FT /id="VAR_056688"
FT VARIANT 2063
FT /note="G -> E (in AT; unknown pathological significance;
FT reduces protein abundance; dbSNP:rs866290641)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_010839"
FT VARIANT 2067
FT /note="A -> D (in AT; dbSNP:rs397514577)"
FT /evidence="ECO:0000269|PubMed:9887333"
FT /id="VAR_010840"
FT VARIANT 2068
FT /note="L -> S (in AT; decreased protein abundance; loss of
FT DNA damage induced protein autophosphorylation;
FT dbSNP:rs1555114558)"
FT /evidence="ECO:0000269|PubMed:27664052"
FT /id="VAR_077239"
FT VARIANT 2079
FT /note="V -> I (in dbSNP:rs1800060)"
FT /evidence="ECO:0000269|PubMed:8665503"
FT /id="VAR_010841"
FT VARIANT 2080
FT /note="Y -> D (in AT; loss of DNA damage induced protein
FT autophosphorylation; dbSNP:rs1064795467)"
FT /evidence="ECO:0000269|PubMed:27664052"
FT /id="VAR_077240"
FT VARIANT 2105
FT /note="R -> T (found in a patient with early-onset breast
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:18384426"
FT /id="VAR_083385"
FT VARIANT 2139
FT /note="E -> G (in T-prolymphocytic leukemia; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:9488043"
FT /id="VAR_010842"
FT VARIANT 2164
FT /note="E -> K (in T-prolymphocytic leukemia;
FT dbSNP:rs1317619286)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010843"
FT VARIANT 2218
FT /note="S -> C (in AT)"
FT /evidence="ECO:0000269|PubMed:10817650"
FT /id="VAR_010844"
FT VARIANT 2224..2227
FT /note="MALR -> IS (in AT; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_010845"
FT VARIANT 2227
FT /note="R -> C (in AT; unknown pathological significance;
FT reduces protein abundance; dbSNP:rs564652222)"
FT /evidence="ECO:0000269|PubMed:10873394,
FT ECO:0000269|PubMed:9887333"
FT /id="VAR_010846"
FT VARIANT 2246..2252
FT /note="CIKDILT -> H (in AT; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:10425038,
FT ECO:0000269|PubMed:10873394"
FT /id="VAR_010847"
FT VARIANT 2274
FT /note="A -> T (in B-cell chronic lymphocytic leukemia;
FT unknown pathological significance; no effect on
FT phosphorylation of target proteins; dbSNP:rs567060474)"
FT /evidence="ECO:0000269|PubMed:10023947,
FT ECO:0000269|PubMed:19431188"
FT /id="VAR_010848"
FT VARIANT 2287
FT /note="G -> A (found in a patient with familial pancreatic
FT cancer; unknown pathological significance;
FT dbSNP:rs1800061)"
FT /evidence="ECO:0000269|PubMed:28726808,
FT ECO:0000269|PubMed:8665503"
FT /id="VAR_010849"
FT VARIANT 2307
FT /note="L -> F (found in patients with familial pancreatic
FT cancer; also found in a lung adenocarcinoma sample; unknown
FT pathological significance; dbSNP:rs56009889)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:28726808"
FT /id="VAR_041573"
FT VARIANT 2332
FT /note="L -> P (in dbSNP:rs4988111)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041574"
FT VARIANT 2335
FT /note="T -> K (in dbSNP:rs3092831)"
FT /id="VAR_056689"
FT VARIANT 2356
FT /note="I -> F (in a renal clear cell carcinoma sample;
FT somatic mutation; dbSNP:rs876658517)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041575"
FT VARIANT 2396
FT /note="T -> S (in T-prolymphocytic leukemia; also found in
FT a patient with early-onset breast cancer; unknown
FT pathological significance; dbSNP:rs370559102)"
FT /evidence="ECO:0000269|PubMed:18384426,
FT ECO:0000269|PubMed:9288106"
FT /id="VAR_010850"
FT VARIANT 2408
FT /note="S -> L (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs730881315)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041576"
FT VARIANT 2418
FT /note="K -> KK (in mantle cell lymphoma)"
FT /evidence="ECO:0000269|PubMed:10397742,
FT ECO:0000269|PubMed:10706620"
FT /id="VAR_010851"
FT VARIANT 2420
FT /note="A -> P (in B-cell chronic lymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:10397742"
FT /id="VAR_010852"
FT VARIANT 2423
FT /note="E -> G (in mantle cell lymphoma; dbSNP:rs121434221)"
FT /evidence="ECO:0000269|PubMed:10397742,
FT ECO:0000269|PubMed:10706620"
FT /id="VAR_010853"
FT VARIANT 2424
FT /note="V -> G (in AT; also found in B-cell chronic
FT lymphocytic leukemia and T-prolymphocytic leukemia; may be
FT associated with increased risk for breast cancer; decreased
FT phosphorylation of target proteins; dbSNP:rs28904921)"
FT /evidence="ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:9288106,
FT ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9892178"
FT /id="VAR_010854"
FT VARIANT 2427..2428
FT /note="Missing (in AT; also found in T-prolymphocytic
FT leukemia; lack of phosphorylation of target proteins)"
FT /evidence="ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8845835,
FT ECO:0000269|PubMed:9463314"
FT /id="VAR_010855"
FT VARIANT 2438
FT /note="T -> I (in dbSNP:rs147604227)"
FT /evidence="ECO:0000269|PubMed:10817650,
FT ECO:0000269|PubMed:8808599"
FT /id="VAR_010856"
FT VARIANT 2442
FT /note="Q -> P (in T-prolymphocytic leukemia; also in a lung
FT adenocarcinoma sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9288106"
FT /id="VAR_010857"
FT VARIANT 2443
FT /note="R -> Q (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs587782310)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041577"
FT VARIANT 2464
FT /note="C -> R (found in patients with familial pancreatic
FT cancer; also found in a small cell lung cancer sample;
FT unknown pathological significance; dbSNP:rs55801750)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:28726808"
FT /id="VAR_041578"
FT VARIANT 2470
FT /note="Y -> D (in AT; dbSNP:rs876659365)"
FT /evidence="ECO:0000269|PubMed:9887333"
FT /id="VAR_010858"
FT VARIANT 2486
FT /note="R -> G (in T-prolymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:9573030"
FT /id="VAR_010859"
FT VARIANT 2491
FT /note="W -> R (in AT)"
FT /evidence="ECO:0000269|PubMed:9792410"
FT /id="VAR_010860"
FT VARIANT 2492
FT /note="L -> R (in dbSNP:rs56399857)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041579"
FT VARIANT 2524
FT /note="A -> P (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083386"
FT VARIANT 2531
FT /note="M -> T (found in patients with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083387"
FT VARIANT 2546..2548
FT /note="Missing (in AT; also found in T-prolymphocytic
FT leukemia and T-cell acute lymphoblastic leukemia; lack of
FT phosphorylation of target proteins)"
FT /evidence="ECO:0000269|PubMed:10817650,
FT ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:7792600,
FT ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:8789452,
FT ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:8808599,
FT ECO:0000269|PubMed:8845835, ECO:0000269|PubMed:9150358,
FT ECO:0000269|PubMed:9288106, ECO:0000269|PubMed:9463314"
FT /id="VAR_010861"
FT VARIANT 2547..2549
FT /note="Missing (in AT; dbSNP:rs587776547)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_085067"
FT VARIANT 2554
FT /note="H -> D (in AT; lack of phosphorylation of target
FT proteins)"
FT /evidence="ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:9463314"
FT /id="VAR_010862"
FT VARIANT 2570
FT /note="E -> G (in dbSNP:rs28904920)"
FT /id="VAR_056690"
FT VARIANT 2625..2626
FT /note="DA -> EP (in AT; dbSNP:rs267606668)"
FT /id="VAR_010864"
FT VARIANT 2625
FT /note="D -> E (in AT; unknown pathological significance;
FT dbSNP:rs1196903858)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_085068"
FT VARIANT 2625
FT /note="D -> Q (in AT; requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:10817650"
FT /id="VAR_010863"
FT VARIANT 2626
FT /note="A -> P (in AT; unknown pathological significance;
FT dbSNP:rs267606669)"
FT /evidence="ECO:0000269|PubMed:10873394"
FT /id="VAR_085069"
FT VARIANT 2627
FT /note="Y -> H (in AT; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:27664052"
FT /id="VAR_077241"
FT VARIANT 2640
FT /note="T -> I (in dbSNP:rs4988125)"
FT /id="VAR_056691"
FT VARIANT 2656
FT /note="L -> P (in AT; dbSNP:rs121434218)"
FT /evidence="ECO:0000269|PubMed:9450874"
FT /id="VAR_010865"
FT VARIANT 2662
FT /note="Missing (in AT)"
FT /evidence="ECO:0000269|PubMed:9887333"
FT /id="VAR_010866"
FT VARIANT 2664
FT /note="Missing (in AT; unknown pathological significance;
FT dbSNP:rs1471563800)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_085070"
FT VARIANT 2666
FT /note="T -> A (in a lung adenocarcinoma sample; somatic
FT mutation; dbSNP:rs745775382)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041580"
FT VARIANT 2668
FT /note="E -> G (in AT; unknown pathological significance; no
FT effect on phosphorylation of target proteins)"
FT /evidence="ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:9463314"
FT /id="VAR_010868"
FT VARIANT 2695
FT /note="G -> A (in T-prolymphocytic leukemia and B-cell
FT chronic lymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:10023947,
FT ECO:0000269|PubMed:9288106"
FT /id="VAR_010869"
FT VARIANT 2702
FT /note="I -> R (in AT; dbSNP:rs876659735)"
FT /id="VAR_010870"
FT VARIANT 2709
FT /note="G -> S (in dbSNP:rs3218680)"
FT /id="VAR_056692"
FT VARIANT 2719
FT /note="R -> H (found in a patient with early-onset breast
FT cancer; unknown pathological significance;
FT dbSNP:rs55982963)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:18384426"
FT /id="VAR_041581"
FT VARIANT 2722
FT /note="L -> R (in T-prolymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010871"
FT VARIANT 2725
FT /note="D -> G (found in T-prolymphocytic leukemia; unknown
FT pathological significance; dbSNP:rs1555128314)"
FT /evidence="ECO:0000269|PubMed:9334731"
FT /id="VAR_010872"
FT VARIANT 2725
FT /note="D -> V (in T-prolymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010873"
FT VARIANT 2726
FT /note="A -> V (in AT; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_010874"
FT VARIANT 2732
FT /note="F -> L (in T-prolymphocytic leukemia;
FT dbSNP:rs876659619)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010875"
FT VARIANT 2765
FT /note="G -> S (may contribute to breast cancer; lack of
FT phosphorylation of target proteins; dbSNP:rs748634900)"
FT /evidence="ECO:0000269|PubMed:10534763,
FT ECO:0000269|PubMed:19431188"
FT /id="VAR_010876"
FT VARIANT 2810
FT /note="K -> Q (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083388"
FT VARIANT 2810
FT /note="Missing (in T-prolymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010877"
FT VARIANT 2824
FT /note="C -> Y (in AT; dbSNP:rs876660927)"
FT /evidence="ECO:0000269|PubMed:9150358"
FT /id="VAR_010878"
FT VARIANT 2827
FT /note="F -> C (in AT; mild; decreased phosphorylation of
FT target proteins; dbSNP:rs121434216)"
FT /evidence="ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:9463314"
FT /id="VAR_010879"
FT VARIANT 2829
FT /note="P -> L (in AT; dbSNP:rs938431501)"
FT /evidence="ECO:0000269|PubMed:9711876"
FT /id="VAR_010880"
FT VARIANT 2832
FT /note="R -> C (in AT; also found in B-cell non-Hodgkin
FT lymphoma; increases protein abundance; dbSNP:rs587779872)"
FT /evidence="ECO:0000269|PubMed:10817650,
FT ECO:0000269|PubMed:10873394, ECO:0000269|PubMed:9288106,
FT ECO:0000269|PubMed:9443866"
FT /id="VAR_010881"
FT VARIANT 2832
FT /note="R -> H (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083389"
FT VARIANT 2834
FT /note="F -> L (in AT; decreased protein abundance)"
FT /evidence="ECO:0000269|PubMed:27664052"
FT /id="VAR_077242"
FT VARIANT 2842
FT /note="P -> R (in a lung adenocarcinoma sample; somatic
FT mutation; dbSNP:rs879254065)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041582"
FT VARIANT 2849..3056
FT /note="Missing (in AT; unknown pathological significance;
FT dbSNP:rs587778080)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_085071"
FT VARIANT 2849
FT /note="R -> P (in AT; dbSNP:rs587782202)"
FT /evidence="ECO:0000269|PubMed:9887333"
FT /id="VAR_010882"
FT VARIANT 2855..2856
FT /note="SV -> RI (in AT; lack of phosphorylation of target
FT proteins; dbSNP:rs587781353)"
FT /evidence="ECO:0000269|PubMed:19431188"
FT /id="VAR_010884"
FT VARIANT 2855
FT /note="S -> R (in AT; unknown pathological significance;
FT dbSNP:rs780905851)"
FT /evidence="ECO:0000269|PubMed:10425038"
FT /id="VAR_010883"
FT VARIANT 2860
FT /note="Missing (in AT)"
FT /evidence="ECO:0000269|PubMed:7792600,
FT ECO:0000269|PubMed:8845835"
FT /id="VAR_010885"
FT VARIANT 2867
FT /note="G -> R (in AT)"
FT /evidence="ECO:0000269|PubMed:8698354,
FT ECO:0000269|PubMed:9887333"
FT /id="VAR_010886"
FT VARIANT 2870
FT /note="D -> N (in dbSNP:rs55798854)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041583"
FT VARIANT 2871..2872
FT /note="RH -> S (in T-prolymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:9288106"
FT /id="VAR_010887"
FT VARIANT 2890
FT /note="L -> V (in T-prolymphocytic leukemia;
FT dbSNP:rs587779874)"
FT /evidence="ECO:0000269|PubMed:9288106,
FT ECO:0000269|PubMed:9488043"
FT /id="VAR_010888"
FT VARIANT 2904
FT /note="E -> G (in AT; dbSNP:rs786202826)"
FT /evidence="ECO:0000269|PubMed:8845835"
FT /id="VAR_010889"
FT VARIANT 2909
FT /note="R -> G (in AT)"
FT /evidence="ECO:0000269|PubMed:9792410"
FT /id="VAR_010890"
FT VARIANT 2974
FT /note="P -> L (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083390"
FT VARIANT 3003
FT /note="N -> D (in AT; decreased protein abundance;
FT dbSNP:rs1137889)"
FT /evidence="ECO:0000269|PubMed:27664052,
FT ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8589678,
FT ECO:0000269|PubMed:8665503"
FT /id="VAR_077243"
FT VARIANT 3006
FT /note="A -> P (found in T-prolymphocytic leukemia; unknown
FT pathological significance; dbSNP:rs876658767)"
FT /evidence="ECO:0000269|PubMed:9334731"
FT /id="VAR_010892"
FT VARIANT 3008
FT /note="R -> C (in AT; also found in T-prolymphocytic
FT leukemia and mantle cell lymphoma; lack of phosphorylation
FT of target proteins; dbSNP:rs587782292)"
FT /evidence="ECO:0000269|PubMed:10706620,
FT ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:19431188,
FT ECO:0000269|PubMed:9334731, ECO:0000269|PubMed:9488043,
FT ECO:0000269|PubMed:9872980"
FT /id="VAR_010893"
FT VARIANT 3008
FT /note="R -> H (in B-cell chronic lymphocytic leukemia;
FT dbSNP:rs587781894)"
FT /evidence="ECO:0000269|PubMed:10397742"
FT /id="VAR_010894"
FT VARIANT 3018
FT /note="K -> N (in B-cell chronic lymphocytic leukemia)"
FT /evidence="ECO:0000269|PubMed:10397742"
FT /id="VAR_010895"
FT VARIANT 3029
FT /note="G -> D (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083391"
FT VARIANT 3056
FT /note="V -> L (found in a patient with familial pancreatic
FT cancer; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28726808"
FT /id="VAR_083392"
FT MUTAGEN 367
FT /note="S->A: Loss of IR-induced S-367 autophosphorylation.
FT Reduced correction of cell cycle checkpoint defects and
FT DNA-repair activity. No effect on S-1893 nor S-1981
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:16858402"
FT MUTAGEN 1807
FT /note="K->E: Decreased phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 1893
FT /note="S->A: Loss of IR-induced S-1893 autophosphorylation.
FT Reduced correction of cell cycle checkpoint defects and
FT DNA-repair activity. No effect on S-367 nor S-1981
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:16858402"
FT MUTAGEN 1941
FT /note="V->L: Decreased phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 1981
FT /note="S->A: Loss of IR-induced S-1981 autophosphorylation.
FT Reduced correction of cell cycle checkpoint defects and
FT DNA-repair activity. No effect on S-367 nor S-1893
FT autophosphorylation. No dimer disruption."
FT /evidence="ECO:0000269|PubMed:12556884,
FT ECO:0000269|PubMed:16858402"
FT MUTAGEN 1981
FT /note="S->D,E: Disrupts the dimer."
FT /evidence="ECO:0000269|PubMed:12556884,
FT ECO:0000269|PubMed:16858402"
FT MUTAGEN 2019
FT /note="Y->C: Loss of phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2039
FT /note="E->K: Decreased phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2338
FT /note="L->P: Loss of phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2394
FT /note="S->L: Loss of phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2452
FT /note="L->P: Loss of phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2685
FT /note="S->T: No effect on phosphorylation of target
FT proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2699
FT /note="P->L: Loss of phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2708
FT /note="D->N: Decreased phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2730
FT /note="Q->P: Loss of phosphorylation of target proteins."
FT /evidence="ECO:0000269|PubMed:19431188"
FT MUTAGEN 2870
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9733515"
FT MUTAGEN 2875
FT /note="N->K: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9733515"
FT MUTAGEN 3016
FT /note="K->Q: Mimics acetylation, preventing
FT dephosphorylation and subsequent ATM deactivation during
FT the late stage of DNA damage response."
FT /evidence="ECO:0000269|PubMed:30944854"
FT MUTAGEN 3016
FT /note="K->R: Loss of DNA damage-inducible acetylation.
FT Retains constitutive kinase activity, but blocks DNA
FT damage-induced kinase activation. Disrupts dimer and
FT abolishes S-1981 autophosphorylation."
FT /evidence="ECO:0000269|PubMed:17923702"
FT MUTAGEN 3018
FT /note="K->R: Retains DNA damage-inducible acetylation and
FT S-1981 autophosphorylation."
FT /evidence="ECO:0000269|PubMed:17923702"
FT CONFLICT 46
FT /note="H -> N (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="N -> I (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="Y -> N (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="W -> G (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="T -> A (in Ref. 1; AAC50289)"
FT /evidence="ECO:0000305"
FT CONFLICT 750
FT /note="K -> N (in Ref. 1; AAC50289)"
FT /evidence="ECO:0000305"
FT CONFLICT 754
FT /note="Q -> K (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 887
FT /note="E -> G (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 1003
FT /note="Q -> L (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 1049
FT /note="L -> W (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT CONFLICT 1089
FT /note="A -> V (in Ref. 7; CAA62603)"
FT /evidence="ECO:0000305"
FT HELIX 4..15
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 20..35
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 37..49
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 57..76
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 85..108
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 117..129
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 135..148
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 153..158
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 161..176
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 181..201
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 209..222
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 229..243
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 248..268
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 273..290
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 306..324
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 343..356
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 393..401
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 407..409
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 410..422
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 424..426
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 432..442
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 452..469
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 474..492
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 495..497
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 501..513
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 521..527
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 528..530
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 536..548
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 571..581
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 597..600
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 608..615
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 620..628
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 634..636
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 646..655
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 684..703
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 707..709
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 712..731
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 737..742
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 744..765
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 771..786
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 792..794
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 795..806
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 809..823
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 886..889
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 892..910
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 911..913
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 920..930
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 933..935
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 941..953
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 957..959
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 963..970
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 973..979
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 980..982
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 984..994
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 995..997
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 998..1000
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1001..1003
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1008..1030
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1031..1033
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1036..1052
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1060..1063
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1066..1069
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1070..1075
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1076..1079
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1083..1091
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1093..1096
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1113..1135
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1136..1138
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1140..1164
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1169..1181
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1187..1201
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1206..1212
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1214..1223
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1227..1229
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1237..1239
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1244..1260
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1261..1263
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1265..1274
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1279..1285
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1287..1292
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1295..1299
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1306..1323
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1325..1331
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1332..1337
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1340..1348
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1383..1395
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1405..1410
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1414..1428
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1433..1451
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1452..1454
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1456..1460
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1461..1477
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1485..1509
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1514..1516
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1517..1524
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1525..1529
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1532..1546
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1547..1551
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1556..1560
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1567..1569
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1572..1582
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1583..1585
FT /evidence="ECO:0007829|PDB:7NI6"
FT HELIX 1590..1600
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1607..1610
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1611..1621
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1625..1634
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1639..1641
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1643..1657
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1658..1660
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1664..1675
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1676..1678
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1695..1702
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1705..1707
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1708..1721
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1728..1740
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1744..1753
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1754..1756
FT /evidence="ECO:0007829|PDB:7NI4"
FT HELIX 1759..1763
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 1764..1767
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1787..1789
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1792..1795
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1802..1813
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 1815..1818
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1822..1825
FT /evidence="ECO:0007829|PDB:7NI6"
FT HELIX 1828..1833
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1836..1851
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1857..1872
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1903..1917
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1927..1931
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1938..1947
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1951..1969
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 1987..1996
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2001..2012
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2016..2019
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2024..2027
FT /evidence="ECO:0007829|PDB:7NI6"
FT HELIX 2029..2038
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2042..2051
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2057..2070
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2074..2084
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2093..2105
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2124..2136
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2140..2159
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2166..2168
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2170..2190
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2195..2211
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2212..2214
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2217..2236
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2241..2264
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2269..2281
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2290..2301
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2305..2322
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2328..2330
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2331..2348
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2353..2359
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2361..2367
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2377..2405
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2408..2418
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2443..2474
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2481..2483
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2484..2493
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2494..2496
FT /evidence="ECO:0007829|PDB:7NI6"
FT STRAND 2497..2499
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2500..2506
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2508..2510
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2513..2519
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2520..2524
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2529..2531
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2533..2535
FT /evidence="ECO:0007829|PDB:7NI6"
FT HELIX 2537..2551
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2553..2564
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2565..2567
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2569..2573
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2593..2612
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2614..2632
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2636..2638
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2652..2655
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2659..2663
FT /evidence="ECO:0007829|PDB:7NI6"
FT STRAND 2673..2675
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2682..2686
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2688..2692
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2695..2697
FT /evidence="ECO:0007829|PDB:7NI6"
FT STRAND 2700..2709
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2711..2720
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2723..2741
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2743..2748
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2757..2759
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2761..2768
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2773..2775
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2776..2780
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2783..2785
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2787..2790
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2798..2806
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2807..2810
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2813..2825
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2831..2833
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2834..2838
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2842..2865
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2873..2875
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2876..2879
FT /evidence="ECO:0007829|PDB:7NI5"
FT TURN 2880..2882
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2885..2887
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2896..2898
FT /evidence="ECO:0007829|PDB:7NI6"
FT STRAND 2899..2902
FT /evidence="ECO:0007829|PDB:7NI5"
FT STRAND 2906..2908
FT /evidence="ECO:0007829|PDB:7NI4"
FT HELIX 2912..2916
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2922..2924
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2926..2940
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2942..2953
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 2964..2970
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 3001..3018
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 3028..3039
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 3042..3045
FT /evidence="ECO:0007829|PDB:7NI5"
FT HELIX 3050..3052
FT /evidence="ECO:0007829|PDB:7NI5"
SQ SEQUENCE 3056 AA; 350687 MW; C0B4866E1E3199E2 CRC64;
MSLVLNDLLI CCRQLEHDRA TERKKEVEKF KRLIRDPETI KHLDRHSDSK QGKYLNWDAV
FRFLQKYIQK ETECLRIAKP NVSASTQASR QKKMQEISSL VKYFIKCANR RAPRLKCQEL
LNYIMDTVKD SSNGAIYGAD CSNILLKDIL SVRKYWCEIS QQQWLELFSV YFRLYLKPSQ
DVHRVLVARI IHAVTKGCCS QTDGLNSKFL DFFSKAIQCA RQEKSSSGLN HILAALTIFL
KTLAVNFRIR VCELGDEILP TLLYIWTQHR LNDSLKEVII ELFQLQIYIH HPKGAKTQEK
GAYESTKWRS ILYNLYDLLV NEISHIGSRG KYSSGFRNIA VKENLIELMA DICHQVFNED
TRSLEISQSY TTTQRESSDY SVPCKRKKIE LGWEVIKDHL QKSQNDFDLV PWLQIATQLI
SKYPASLPNC ELSPLLMILS QLLPQQRHGE RTPYVLRCLT EVALCQDKRS NLESSQKSDL
LKLWNKIWCI TFRGISSEQI QAENFGLLGA IIQGSLVEVD REFWKLFTGS ACRPSCPAVC
CLTLALTTSI VPGTVKMGIE QNMCEVNRSF SLKESIMKWL LFYQLEGDLE NSTEVPPILH
SNFPHLVLEK ILVSLTMKNC KAAMNFFQSV PECEHHQKDK EELSFSEVEE LFLQTTFDKM
DFLTIVRECG IEKHQSSIGF SVHQNLKESL DRCLLGLSEQ LLNNYSSEIT NSETLVRCSR
LLVGVLGCYC YMGVIAEEEA YKSELFQKAK SLMQCAGESI TLFKNKTNEE FRIGSLRNMM
QLCTRCLSNC TKKSPNKIAS GFFLRLLTSK LMNDIADICK SLASFIKKPF DRGEVESMED
DTNGNLMEVE DQSSMNLFND YPDSSVSDAN EPGESQSTIG AINPLAEEYL SKQDLLFLDM
LKFLCLCVTT AQTNTVSFRA ADIRRKLLML IDSSTLEPTK SLHLHMYLML LKELPGEEYP
LPMEDVLELL KPLSNVCSLY RRDQDVCKTI LNHVLHVVKN LGQSNMDSEN TRDAQGQFLT
VIGAFWHLTK ERKYIFSVRM ALVNCLKTLL EADPYSKWAI LNVMGKDFPV NEVFTQFLAD
NHHQVRMLAA ESINRLFQDT KGDSSRLLKA LPLKLQQTAF ENAYLKAQEG MREMSHSAEN
PETLDEIYNR KSVLLTLIAV VLSCSPICEK QALFALCKSV KENGLEPHLV KKVLEKVSET
FGYRRLEDFM ASHLDYLVLE WLNLQDTEYN LSSFPFILLN YTNIEDFYRS CYKVLIPHLV
IRSHFDEVKS IANQIQEDWK SLLTDCFPKI LVNILPYFAY EGTRDSGMAQ QRETATKVYD
MLKSENLLGK QIDHLFISNL PEIVVELLMT LHEPANSSAS QSTDLCDFSG DLDPAPNPPH
FPSHVIKATF AYISNCHKTK LKSILEILSK SPDSYQKILL AICEQAAETN NVYKKHRILK
IYHLFVSLLL KDIKSGLGGA WAFVLRDVIY TLIHYINQRP SCIMDVSLRS FSLCCDLLSQ
VCQTAVTYCK DALENHLHVI VGTLIPLVYE QVEVQKQVLD LLKYLVIDNK DNENLYITIK
LLDPFPDHVV FKDLRITQQK IKYSRGPFSL LEEINHFLSV SVYDALPLTR LEGLKDLRRQ
LELHKDQMVD IMRASQDNPQ DGIMVKLVVN LLQLSKMAIN HTGEKEVLEA VGSCLGEVGP
IDFSTIAIQH SKDASYTKAL KLFEDKELQW TFIMLTYLNN TLVEDCVKVR SAAVTCLKNI
LATKTGHSFW EIYKMTTDPM LAYLQPFRTS RKKFLEVPRF DKENPFEGLD DINLWIPLSE
NHDIWIKTLT CAFLDSGGTK CEILQLLKPM CEVKTDFCQT VLPYLIHDIL LQDTNESWRN
LLSTHVQGFF TSCLRHFSQT SRSTTPANLD SESEHFFRCC LDKKSQRTML AVVDYMRRQK
RPSSGTIFND AFWLDLNYLE VAKVAQSCAA HFTALLYAEI YADKKSMDDQ EKRSLAFEEG
SQSTTISSLS EKSKEETGIS LQDLLLEIYR SIGEPDSLYG CGGGKMLQPI TRLRTYEHEA
MWGKALVTYD LETAIPSSTR QAGIIQALQN LGLCHILSVY LKGLDYENKD WCPELEELHY
QAAWRNMQWD HCTSVSKEVE GTSYHESLYN ALQSLRDREF STFYESLKYA RVKEVEEMCK
RSLESVYSLY PTLSRLQAIG ELESIGELFS RSVTHRQLSE VYIKWQKHSQ LLKDSDFSFQ
EPIMALRTVI LEILMEKEMD NSQRECIKDI LTKHLVELSI LARTFKNTQL PERAIFQIKQ
YNSVSCGVSE WQLEEAQVFW AKKEQSLALS ILKQMIKKLD ASCAANNPSL KLTYTECLRV
CGNWLAETCL ENPAVIMQTY LEKAVEVAGN YDGESSDELR NGKMKAFLSL ARFSDTQYQR
IENYMKSSEF ENKQALLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEL ALRALKEDRK
RFLCKAVENY INCLLSGEEH DMWVFRLCSL WLENSGVSEV NGMMKRDGMK IPTYKFLPLM
YQLAARMGTK MMGGLGFHEV LNNLISRISM DHPHHTLFII LALANANRDE FLTKPEVARR
SRITKNVPKQ SSQLDEDRTE AANRIICTIR SRRPQMVRSV EALCDAYIIL ANLDATQWKT
QRKGINIPAD QPITKLKNLE DVVVPTMEIK VDHTGEYGNL VTIQSFKAEF RLAGGVNLPK
IIDCVGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RNTETRKRKL TICTYKVVPL
SQRSGVLEWC TGTVPIGEFL VNNEDGAHKR YRPNDFSAFQ CQKKMMEVQK KSFEEKYEVF
MDVCQNFQPV FRYFCMEKFL DPAIWFEKRL AYTRSVATSS IVGYILGLGD RHVQNILINE
QSAELVHIDL GVAFEQGKIL PTPETVPFRL TRDIVDGMGI TGVEGVFRRC CEKTMEVMRN
SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDETEL HPTLNADDQE CKRNLSDIDQ
SFNKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAI DPKNLSRLFP GWKAWV
