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Description:
Serine-protein kinase ATM (EC 2.7.1.37) (Ataxia telangiectasiamutated) (A-T, mutated).
Molecular weight: 3506
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 )
Important dates:
27-APR-2001, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
07-MAR-2006, entry version 71.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein ATM_HUMAN:
Keywords:
Anti-oncogene; Cell cycle; Disease mutation; DNA damage; DNA repair; DNA-binding; Kinase; Nuclear protein; Phosphorylation; Polymorphism; Serine/threonine-protein kinase; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX MEDLINE=96154672; PubMed=8589678;
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].
RX MEDLINE=97343327; PubMed=9199932;
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
RT genomic DNA containing the entire ATM gene.";
RL Genome Res. 7:592-605(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RX MEDLINE=97263790; 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
RT expression.";
RL Nucleic Acids Res. 25:1678-1684(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1369, AND VARIANT AT
RP 2546-SER--ILE-2548 DEL.
RX MEDLINE=96381439; 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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2756, AND VARIANT MCL LYS-750.
RA Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W.,
RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1349-3056, AND VARIANT ASN-3003.
RX MEDLINE=96105020; PubMed=8521392;
RA Rasio D., Negrini M., Croce C.M.;
RT "Genomic organization of the ATM locus involved in ataxia-
RT telangiectasia.";
RL Cancer Res. 55:6053-6057(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1349-3056, AND VARIANTS AT
RP 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL AND SER-2860 DEL.
RC TISSUE=Fibroblast;
RX MEDLINE=95312868; PubMed=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.,
RA Sartiel A., Gatti R.A., Chessa L., Sanal O., Lavin M.F.,
RA Jaspers N.G.J., Taylor A.M.R., Arlett C.F., Miki T., Weissman S.M.,
RA 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 [8]
RP PARTIAL NUCLEOTIDE SEQUENCE, AND VARIANTS CYS-49; ARG-1054; PHE-1420;
RP ILE-2079 AND ALA-2287.
RX MEDLINE=96275738; 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.,
RA Russo G., Croce C.M., Negrini M.;
RT "The ATM gene and susceptibility to breast cancer: analysis of 38
RT breast tumors reveals no evidence for mutation.";
RL Cancer Res. 56:2726-2732(1996).
RN [9]
RP PHOSPHORYLATION.
RX MEDLINE=97126018; 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 [10]
RP SUBCELLULAR LOCATION.
RX MEDLINE=97203148; PubMed=9050866; DOI=10.1073/pnas.94.5.1840;
RA Brown K.D., Ziv Y., Sadanandan S.N., Chessa L., Collins F.S.,
RA Shiloh Y., Tagle D.A.;
RT "The ataxia-telangiectasia gene product, a constitutively expressed
RT nuclear protein that is not up-regulated following genome damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:1840-1845(1997).
RN [11]
RP SUBCELLULAR LOCATION, AND VARIANTS AT 2546-SER--ILE-2548 DEL AND
RP TYR-2824.
RX MEDLINE=97294602; 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
RT and discrimination between mutated and normal forms.";
RL Oncogene 14:1911-1921(1997).
RN [12]
RP KINASE ACTIVITY.
RX MEDLINE=97141775; 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 [13]
RP C-ABL BINDING.
RX MEDLINE=97311400; PubMed=9168117; DOI=10.1038/387520a0;
RA Shafman T., Khanna K.K., Kedar P., Spring K., Kozlov S., Yen T.,
RA Hobson K., Gatei M., Zhang N., Watters D., Egerton M., Shiloh Y.,
RA Kharbanda S., Kufe D., Lavin M.F.;
RT "Interaction between ATM protein and c-Abl in response to DNA
RT damage.";
RL Nature 387:520-523(1997).
RN [14]
RP ENZYME REGULATION.
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 [15]
RP TP53-BINDING, AND KINASE ACTIVITY.
RX MEDLINE=99057351; 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 [16]
RP BETA-ADAPTIN BINDING.
RX MEDLINE=98374320; 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 [17]
RP PHOSPHORYLATION OF TP53.
RX MEDLINE=98404273; 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 [18]
RP PHOSPHORYLATION OF TP53, AND MUTAGENESIS OF ASP-2870 AND ASN-2875.
RX MEDLINE=98404274; PubMed=9733515; DOI=10.1126/science.281.5383.1677;
RA Canman C.E., Lim D.-S., Cimprich K.A., Taya Y., Tamai K.,
RA Sakaguchi K., Appella E., Kastan M.B., Siliciano J.D.;
RT "Activation of the ATM kinase by ionizing radiation and
RT phosphorylation of p53.";
RL Science 281:1677-1679(1998).
RN [19]
RP DNA-BINDING.
RX MEDLINE=99432198; 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
RT gene product ATM.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:11134-11139(1999).
RN [20]
RP PHOSPHORYLATION OF BRCA1.
RX MEDLINE=20018333; 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
RT damage response to double-strand breaks.";
RL Science 286:1162-1166(1999).
RN [21]
RP IDENTIFICATION OF ATM AS MEMBER OF BASC.
RX MEDLINE=20245492; PubMed=10783165; DOI=10.1101/gad.827000;
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 [22]
RP PHOSPHORYLATION OF NBS1.
RX MEDLINE=20227312; 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 [23]
RP PHOSPHORYLATION OF NIBRIN.
RX MEDLINE=20296355; 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
RT in a DNA damage response.";
RL Nature 405:477-482(2000).
RN [24]
RP PHOSPHORYLATION OF NIBRIN.
RX MEDLINE=20264381; PubMed=10802669; DOI=10.1038/75508;
RA Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K.,
RA Kozlov S., 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 [25]
RP PHOSPHORYLATION OF CTIP.
RX MEDLINE=20365735; PubMed=10910365; DOI=10.1038/35018134;
RA Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y.,
RA Lee E.Y.-H.P., Lee W.-H.;
RT "Functional link of BRCA1 and ataxia telangiectasia gene product in
RT DNA damage response.";
RL Nature 406:210-215(2000).
RN [26]
RP PHOSPHORYLATION OF TERF1.
RX MEDLINE=21369915; 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 [27]
RP INTERACTION WITH RAD17.
RX MEDLINE=21312051; PubMed=11418864; DOI=10.1038/35082110;
RA Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A.,
RA Ali A., Chen S.M., Abraham R.T., Wang X.-F.;
RT "ATR/ATM-mediated phosphorylation of human Rad17 is required for
RT genotoxic stress responses.";
RL Nature 411:969-974(2001).
RN [28]
RP 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 [29]
RP PHOSPHORYLATION BY ARK5.
RX MEDLINE=22393479; PubMed=12409306; DOI=10.1074/jbc.M206025200;
RA Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F.,
RA Esumi H.;
RT "Identification of a novel protein kinase mediating Akt survival
RT signaling to the ATM protein.";
RL J. Biol. Chem. 278:48-53(2003).
RN [30]
RP 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
RT the G2/M DNA damage checkpoint response.";
RL Mol. Cell. Biol. 24:9207-9220(2004).
RN [31]
RP PHOSPHORYLATION SITE SER-1981.
RX PubMed=15302935; DOI=10.1073/pnas.0404720101;
RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,
RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
RT "Large-scale characterization of HeLa cell nuclear phosphoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
RN [32]
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 [33]
RP VARIANTS AT GLY-2424; 2546-SER--ILE-2548 DEL AND CYS-2827.
RX MEDLINE=96335701; 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-
RT telangiectasia.";
RL Am. J. Hum. Genet. 59:320-330(1996).
RN [34]
RP VARIANT AT 2546-SER--ILE-2548 DEL, AND VARIANT ILE-2438.
RX MEDLINE=96404417; 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 [35]
RP VARIANTS AT 705-PHE--PRO-707 AND 2546-SER--ILE-2548 DEL, AND VARIANTS
RP CYS-49; LEU-858; ARG-1054; PHE-1420 AND ARG-1691.
RX MEDLINE=96390593; 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 [36]
RP VARIANT AT 705-PHE--PRO-707, AND VARIANTS LEU-858 AND ARG-1054.
RX MEDLINE=97196780; PubMed=9043869;
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
RT ataxia-telangiectasia.";
RL Eur. J. Hum. Genet. 4:352-355(1996).
RN [37]
RP VARIANT AT ARG-2867.
RX MEDLINE=96305462; 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 [38]
RP VARIANTS AT 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; SER-2860
RP DEL AND GLY-2904.
RX MEDLINE=96254972; PubMed=8845835; DOI=10.1093/hmg/5.4.433;
RA Gilad S., Khosravi R., Shkedy D., Uziel T., Ziv Y., Savitsky K.,
RA Rotman G., Smith S., Chessa L., Jorgensen T.J., Harnik R., Frydman M.,
RA Sanal O., Portnoi S., Goldwicz Z., Jaspers N.G.J., Gatti R.A.,
RA Lenoir G., Lavin M.F., Tatsumi K., Wegner R.-D., Shiloh Y.,
RA Bar-Shira A.;
RT "Predominance of null mutations in ataxia-telangiectasia.";
RL Hum. Mol. Genet. 5:433-439(1996).
RN [39]
RP VARIANTS TPLL THR-1407; HIS-1682; HIS-1910; LYS-2164; SER-2396;
RP GLY-2424; PRO-2442; 2546-SER--ILE-2548 DEL; ALA-2695; ARG-2722;
RP VAL-2725; LEU-2732; LYS-2810 DEL; 2871-ARG-HIS-2872 DELINS SER AND
RP VAL-2890, AND VARIANTS BNHL VAL-1040; SER-1463 AND CYS-2832.
RX MEDLINE=97434220; PubMed=9288106;
RA Vorechovsky I., Luo L., Dyer M.J.S., Catovsky D., Amlot P.L.,
RA Yaxley J.C., Foroni L., Hammarstroem L., Webster A.D.B.,
RA Yuille M.A.R.;
RT "Clustering of missense mutations in the ataxia-telangiectasia gene in
RT a sporadic T-cell leukaemia.";
RL Nat. Genet. 17:96-99(1997).
RN [40]
RP VARIANTS TPLL GLY-2725; PRO-3006 AND CYS-3008.
RX MEDLINE=97475207; 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 [41]
RP VARIANT AT CYS-2832.
RX MEDLINE=98107941; PubMed=9443866;
RA Telatar M., Teraoka S., Wang Z., Chun H.H., Liang T.,
RA Castellvi-Bel S., Udar N., Borresen-Dale A.-L., Chessa L.,
RA Bernatowska-Matuszkiewicz E., Porras O., Watanabe M., Junker A.,
RA 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 [42]
RP VARIANTS AT LEU-292; ASP-768; GLN-1001; ARG-1691; ILE-1743; GLY-2424;
RP 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; ASP-2554; GLY-2668 AND
RP CYS-2827.
RX MEDLINE=98130536; PubMed=9463314;
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.,
RA Haites N., 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,
RT lymphoma, and breast cancer.";
RL Am. J. Hum. Genet. 62:334-345(1998).
RN [43]
RP VARIANT AT 1812-ALA-PHE-1813 DELINS VAL.
RX MEDLINE=98163439; PubMed=9497252;
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
RT variants.";
RL Am. J. Hum. Genet. 62:551-561(1998).
RN [44]
RP VARIANT AT PRO-2656.
RX MEDLINE=98111350; PubMed=9450874;
RX DOI=10.1002/(SICI)1096-8628(19980113)75:2<141::AID-AJMG4>3.3.CO;2-8;
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
RT domain.";
RL Am. J. Med. Genet. 75:141-144(1998).
RN [45]
RP VARIANT TPLL GLY-2486.
RX MEDLINE=98241437; PubMed=9573030;
RA Stoppa-Lyonnet D., Soulier J., Lauge A., Dastot H., Garand R.,
RA Sigaux F., Stern M.-H.;
RT "Inactivation of the ATM gene in T-cell prolymphocytic leukemias.";
RL Blood 91:3920-3926(1998).
RN [46]
RP VARIANTS AT 2855-ARG-ILE-2856 AND CYS-3008, AND VARIANT VAL-1853.
RX MEDLINE=99091900; PubMed=9872980;
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
RT using high-density oligonucleotide arrays.";
RL Genome Res. 8:1245-1258(1998).
RN [47]
RP VARIANT AT 2625-GLU-PRO-2626.
RX MEDLINE=98180886; 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
RT ataxia telangiectasia.";
RL Hum. Genet. 102:187-191(1998).
RN [48]
RP VARIANT AT LEU-2829, AND VARIANTS GLU-126; ASP-514 AND ASN-1853.
RX MEDLINE=98375694; PubMed=9711876;
RX DOI=10.1002/(SICI)1098-1004(1998)12:3<186::AID-HUMU6>3.3.CO;2-3;
RA Sasaki T., Tian H., Kukita Y., Inazuka M., Tahira T., Imai T.,
RA Yamauchi M., Saito T., Hori T., Hashimoto-Tamaoki T., Komatsu K.,
RA Nikaido O., Hayashi K.;
RT "ATM mutations in patients with ataxia telangiectasia screened by a
RT hierarchical strategy.";
RL Hum. Mutat. 12:186-195(1998).
RN [49]
RP VARIANTS AT ASP-1091 AND ARG-1566, AND VARIANTS LEU-858 AND ARG-1054.
RX MEDLINE=99006895; 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
RT the Dutch population.";
RL Hum. Mutat. 12:330-337(1998).
RN [50]
RP VARIANTS AT ARG-2491 AND GLY-2909.
RX MEDLINE=99006896; 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
RT being relatively common mutations.";
RL Hum. Mutat. 12:338-343(1998).
RN [51]
RP VARIANTS TPLL GLY-2139; VAL-2890 AND CYS-3008.
RX MEDLINE=98147367; PubMed=9488043; DOI=10.1038/sj.onc.1201603;
RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L.,
RA Matutes E., Brito-Babapulle V., Vorechovsky I., Dyer M.J.S.,
RA Catovsky D.;
RT "ATM is usually rearranged in T-cell prolymphocytic leukaemia.";
RL Oncogene 16:789-796(1998).
RN [52]
RP ERRATUM.
RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L.,
RA Matutes E., Brito-Babapulle V., Vorechovsky I., Dyer M.J.S.,
RA Catovsky D.;
RL Oncogene 16:2955-2955(1998).
RN [53]
RP VARIANTS BCLL VAL-1853; ARG-1953; PRO-2420; HIS-3008 AND ASN-3018,
RP VARIANTS MCL LYS-2418 INS AND GLY-2423, AND VARIANT ASN-1853.
RX MEDLINE=99326327; 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
RT chronic lymphocytic leukemia.";
RL Blood 94:748-753(1999).
RN [54]
RP VARIANTS BCLL CYS-332; ARG-1691 AND GLY-2424.
RX MEDLINE=99107196; 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 [55]
RP VARIANT AT PRO-1465.
RX MEDLINE=99250766; 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 [56]
RP VARIANTS CYS-49; LEU-182; PRO-707; LEU-858; PHE-1420; ALA-1570;
RP ASN-1853 AND SER-2765.
RX MEDLINE=20005806; PubMed=10534763;
RX DOI=10.1002/(SICI)1098-2264(199912)26:4<286::AID-GCC2>3.3.CO;2-O;
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
RT variants in the ATM gene in early-onset breast cancer.";
RL Genes Chromosomes Cancer 26:286-294(1999).
RN [57]
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 MEDLINE=99105918; PubMed=9887333; DOI=10.1093/hmg/8.1.69;
RA Sandoval N., Platzer M., Rosenthal A., Doerk T., Bendix R.,
RA Skawran B., Stuhrmann M., Wegner R.-D., Sperling K., Banin S.,
RA Shiloh Y., Baumer A., Bernthaler U., Sennefelder H., Brohm M.,
RA 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 [58]
RP VARIANTS AT, AND VARIANTS ASN-1454 AND ASN-1853.
RX MEDLINE=99355715; 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
RT detected by a novel SSCP strategy.";
RL Hum. Mutat. 14:156-162(1999).
RN [59]
RP VARIANTS BCLL THR-350; THR-352; ARG-1054; THR-2274 AND ALA-2695, AND
RP VARIANT ASN-3003.
RX MEDLINE=99146552; 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 [60]
RP VARIANT ARG-1054.
RX MEDLINE=99231468; PubMed=10217116;
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 [61]
RP ERRATUM.
RA Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.;
RL Lancet 354:780-780(1999).
RN [62]
RP VARIANTS AT GLU-224; VAL-323; PRO-1420; CYS-2218; 2546-SER--ILE-2548
RP DEL; GLN-2625; CYS-2832; 2855-ARG-ILE-2856 AND CYS-3008, AND VARIANTS
RP VAL-1853 AND ILE-2438.
RX MEDLINE=20275351; 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
RT of A-T patients.";
RL Am. J. Med. Genet. 92:170-177(2000).
RN [63]
RP VARIANTS AT.
RX MEDLINE=20334897; 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 [64]
RP VARIANTS MCL LYS-750; LYS-2418 INS; GLY-2423 AND CYS-3008.
RX MEDLINE=20183964; 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
RT gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2773-2778(2000).
Feature:
CHAIN 1 3056 Serine-protein kinase ATM.
/FTId=PRO_0000088840.
DOMAIN 1966 2566 FAT.
DOMAIN 2712 2962 PI3K/PI4K.
DOMAIN 3024 3056 FATC.
REGION 1373 1382 Interaction with ABL1.
MOD_RES 1981 1981 Phosphoserine.
VARIANT 49 49 S -> C (in dbSNP:1800054).
/FTId=VAR_010798.
VARIANT 126 126 D -> E.
/FTId=VAR_010799.
VARIANT 182 182 V -> L.
/FTId=VAR_010800.
VARIANT 224 224 K -> E (in AT).
/FTId=VAR_010801.
VARIANT 292 292 P -> L (in AT; associated with lymphoma).
/FTId=VAR_010802.
VARIANT 323 323 I -> V (in AT).
/FTId=VAR_010803.
VARIANT 332 332 Y -> C (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010804.
VARIANT 350 350 A -> T (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010805.
VARIANT 352 352 I -> T (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010806.
VARIANT 514 514 G -> D.
/FTId=VAR_010807.
VARIANT 570 570 F -> S (in AT).
/FTId=VAR_010808.
VARIANT 705 707 YSS -> FIP (in AT; might be associated
with susceptibility to cancer).
/FTId=VAR_010809.
VARIANT 707 707 S -> P.
/FTId=VAR_010810.
VARIANT 750 750 N -> K (in mantle cell lymphoma).
/FTId=VAR_010811.
VARIANT 768 768 N -> D (in AT).
/FTId=VAR_010812.
VARIANT 785 785 R -> C (in AT).
/FTId=VAR_010813.
VARIANT 858 858 F -> L (rare polymorphism;
dbSNP:1800056).
/FTId=VAR_010814.
VARIANT 950 950 L -> R (in AT).
/FTId=VAR_010815.
VARIANT 1001 1001 L -> Q (in AT; associated with T-cell
acute lymphoblastic leukemia).
/FTId=VAR_010816.
VARIANT 1040 1040 M -> V (in B-cell non-Hodgkin lymphoma).
/FTId=VAR_010817.
VARIANT 1054 1054 P -> R (in dbSNP:1800057).
/FTId=VAR_010818.
VARIANT 1082 1082 H -> L (in AT).
/FTId=VAR_010819.
VARIANT 1091 1091 E -> D (in AT).
/FTId=VAR_010820.
VARIANT 1407 1407 I -> T (in T-prolymphocytic leukemia).
/FTId=VAR_010821.
VARIANT 1420 1420 L -> F (rare polymorphism;
dbSNP:1800058).
/FTId=VAR_010822.
VARIANT 1420 1420 L -> P (in AT).
/FTId=VAR_010823.
VARIANT 1454 1454 K -> N.
/FTId=VAR_010824.
VARIANT 1463 1463 F -> S (in B-cell non-Hodgkin lymphoma).
/FTId=VAR_010825.
VARIANT 1465 1465 L -> P (in AT).
/FTId=VAR_010826.
VARIANT 1566 1566 P -> R (in AT).
/FTId=VAR_010827.
VARIANT 1570 1570 V -> A.
/FTId=VAR_010828.
VARIANT 1682 1682 D -> H (in T-prolymphocytic leukemia).
/FTId=VAR_010829.
VARIANT 1691 1691 S -> R (in AT and B-cell chronic
lymphocytic leukemia; could be a rare
polymorphism; dbSNP:1800059).
/FTId=VAR_010830.
VARIANT 1743 1743 T -> I (in AT; associated with
preleukemic T-cell proliferation).
/FTId=VAR_010831.
VARIANT 1812 1813 AF -> V (in AT).
/FTId=VAR_010832.
VARIANT 1853 1853 D -> N (common polymorphism;
dbSNP:1801516).
/FTId=VAR_010833.
VARIANT 1853 1853 D -> V (might contribute to B-cell
chronic lymphocytic leukemia;
dbSNP:1801673).
/FTId=VAR_010834.
VARIANT 1910 1910 L -> H (in T-prolymphocytic leukemia).
/FTId=VAR_010835.
VARIANT 1913 1913 V -> G (in AT).
/FTId=VAR_010836.
VARIANT 1953 1953 T -> R (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010837.
VARIANT 2016 2016 D -> G (in AT).
/FTId=VAR_010838.
VARIANT 2063 2063 G -> E (in AT).
/FTId=VAR_010839.
VARIANT 2067 2067 A -> D (in AT).
/FTId=VAR_010840.
VARIANT 2079 2079 V -> I (in dbSNP:1800060).
/FTId=VAR_010841.
VARIANT 2139 2139 E -> G (in T-prolymphocytic leukemia;
somatic mutation).
/FTId=VAR_010842.
VARIANT 2164 2164 E -> K (in T-prolymphocytic leukemia).
/FTId=VAR_010843.
VARIANT 2218 2218 S -> C (in AT).
/FTId=VAR_010844.
VARIANT 2224 2227 MALR -> IS (in AT).
/FTId=VAR_010845.
VARIANT 2227 2227 R -> C (in AT).
/FTId=VAR_010846.
VARIANT 2246 2252 CIKDILT -> H (in AT).
/FTId=VAR_010847.
VARIANT 2274 2274 A -> T (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010848.
VARIANT 2287 2287 G -> A (in dbSNP:1800061).
/FTId=VAR_010849.
VARIANT 2396 2396 T -> S (in T-prolymphocytic leukemia).
/FTId=VAR_010850.
VARIANT 2418 2418 K -> KK (in mantle cell lymphoma).
/FTId=VAR_010851.
VARIANT 2420 2420 A -> P (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010852.
VARIANT 2423 2423 E -> G (in mantle cell lymphoma).
/FTId=VAR_010853.
VARIANT 2424 2424 V -> G (in AT, B-cell chronic lymphocytic
leukemia and T-prolymphocytic leukemia;
associated with increased risk for breast
cancer).
/FTId=VAR_010854.
VARIANT 2427 2428 Missing (in AT; associated with T-
prolymphocytic leukemia).
/FTId=VAR_010855.
VARIANT 2438 2438 T -> I.
/FTId=VAR_010856.
VARIANT 2442 2442 Q -> P (in T-prolymphocytic leukemia).
/FTId=VAR_010857.
VARIANT 2470 2470 Y -> D (in AT).
/FTId=VAR_010858.
VARIANT 2486 2486 R -> G (in T-prolymphocytic leukemia).
/FTId=VAR_010859.
VARIANT 2491 2491 W -> R (in AT).
/FTId=VAR_010860.
VARIANT 2546 2548 Missing (in AT, T-prolymphocytic leukemia
and T-cell acute lymphoblastic leukemia).
/FTId=VAR_010861.
VARIANT 2554 2554 H -> D (in AT).
/FTId=VAR_010862.
VARIANT 2625 2626 DA -> EP (in AT).
/FTId=VAR_010864.
VARIANT 2625 2625 D -> Q (in AT; requires 2 nucleotide
substitutions).
/FTId=VAR_010863.
VARIANT 2656 2656 L -> P (in AT; partial functional loss).
/FTId=VAR_010865.
VARIANT 2662 2662 Missing (in AT).
/FTId=VAR_010866.
VARIANT 2663 2663 Missing (in AT).
/FTId=VAR_010867.
VARIANT 2668 2668 E -> G (in AT).
/FTId=VAR_010868.
VARIANT 2695 2695 G -> A (in T-prolymphocytic leukemia and
B-cell chronic lymphocytic leukemia).
/FTId=VAR_010869.
VARIANT 2702 2702 I -> R (in AT).
/FTId=VAR_010870.
VARIANT 2722 2722 L -> R (in T-prolymphocytic leukemia).
/FTId=VAR_010871.
VARIANT 2725 2725 D -> G (in T-prolymphocytic leukemia).
/FTId=VAR_010872.
VARIANT 2725 2725 D -> V (in T-prolymphocytic leukemia).
/FTId=VAR_010873.
VARIANT 2726 2726 A -> V (in AT).
/FTId=VAR_010874.
VARIANT 2732 2732 F -> L (in T-prolymphocytic leukemia).
/FTId=VAR_010875.
VARIANT 2765 2765 G -> S (may contribute to breast cancer).
/FTId=VAR_010876.
VARIANT 2810 2810 Missing (in T-prolymphocytic leukemia).
/FTId=VAR_010877.
VARIANT 2824 2824 C -> Y (in AT).
/FTId=VAR_010878.
VARIANT 2827 2827 F -> C (in AT; mild).
/FTId=VAR_010879.
VARIANT 2829 2829 P -> L (in AT).
/FTId=VAR_010880.
VARIANT 2832 2832 R -> C (in AT and B-cell non-Hodgkin
lymphoma).
/FTId=VAR_010881.
VARIANT 2849 2849 R -> P (in AT).
/FTId=VAR_010882.
VARIANT 2855 2856 SV -> RI (in AT).
/FTId=VAR_010884.
VARIANT 2855 2855 S -> R (in AT).
/FTId=VAR_010883.
VARIANT 2860 2860 Missing (in AT).
/FTId=VAR_010885.
VARIANT 2867 2867 G -> R (in AT).
/FTId=VAR_010886.
VARIANT 2871 2872 RH -> S (in T-prolymphocytic leukemia).
/FTId=VAR_010887.
VARIANT 2890 2890 L -> V (in T-prolymphocytic leukemia).
/FTId=VAR_010888.
VARIANT 2904 2904 E -> G (in AT).
/FTId=VAR_010889.
VARIANT 2909 2909 R -> G (in AT).
/FTId=VAR_010890.
VARIANT 3003 3003 D -> N.
/FTId=VAR_010891.
VARIANT 3006 3006 A -> P (in T-prolymphocytic leukemia).
/FTId=VAR_010892.
VARIANT 3008 3008 R -> C (in AT, T-prolymphocytic leukemia
and mantle cell lymphoma).
/FTId=VAR_010893.
VARIANT 3008 3008 R -> H (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010894.
VARIANT 3018 3018 K -> N (in B-cell chronic lymphocytic
leukemia).
/FTId=VAR_010895.
MUTAGEN 2870 2870 D->A: Loss of kinase activity.
MUTAGEN 2875 2875 N->K: Loss of kinase activity.
CONFLICT 46 46 H -> N (in Ref. 4).
CONFLICT 56 56 N -> I (in Ref. 4).
CONFLICT 313 313 Y -> N (in Ref. 4).
CONFLICT 488 488 W -> G (in Ref. 4).
CONFLICT 554 554 A -> T (in Ref. 2, 4, 5 and 8).
CONFLICT 754 754 Q -> K (in Ref. 4).
CONFLICT 887 887 E -> G (in Ref. 4).
CONFLICT 1003 1003 Q -> L (in Ref. 4).
CONFLICT 1049 1049 L -> W (in Ref. 4).
CONFLICT 1089 1089 A -> V (in Ref. 4).
Comments:
-!- FUNCTION: Serine/threonine protein kinase which activates
checkpoint signaling upon double strand breaks (DSBs), apoptosis
and genotoxic stresses such as ionizing ultraviolet A light (UVA),
thereby acting as a DNA damage sensor. Recognizes the substrate
consensus sequence [S/T-Q]. Phosphorylates Ser-139 of histone
variant H2AX/H2AFX at double strand breaks (DSBs), thereby
regulating DNA damage response mechanism. Also involved in signal
transduction and cell cycle control. May function as a tumor
suppressor. Necessary for activation of ABL1 and SAPK.
Phosphorylates p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin
(NBS1), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or
protein transport. Could play a role in T-cell development, gonad
and neurological function.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- ENZYME REGULATION: Inhibited by wortmannin.
-!- SUBUNIT: Exists in monomeric and tetrameric state. Binds DNA ends,
p53/TP53, ABL1, BRCA1, NIBRIN (NBS1) and TERF1. Part of the BRCA1-
associated genome surveillance complex (BASC), which contains
BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1
protein complex. This association could be a dynamic process
changing throughout the cell cycle and within subnuclear domains.
DNA damage promotes association with RAD17. Interacts with EEF1E1.
This interaction, which takes place independently of TP53, is
induced by DNA damage that may occur during genotoxic stress or
cell growth. Interacts with DCLRE1C.
-!- INTERACTION:
Q14676:MDC1; NbExp=1; IntAct=EBI-495465, EBI-495453;
-!- SUBCELLULAR LOCATION: Primarily nuclear. Found also in endocytic
vesicles in association with beta-adaptin.
-!- TISSUE SPECIFICITY: Found in pancreas, kidney, skeletal muscle,
liver, lung, placenta, brain, heart, spleen, thymus, testis,
ovary, small intestine, colon and leukocytes.
-!- INDUCTION: By ionizing radiation.
-!- PTM: Phosphorylated by ARK5.
-!- DISEASE: Defects in ATM are the cause of ataxia talangiectasia
(AT) [MIM:208900]; also known as Louis-Bar syndrome, which
includes four complementation groups: A, C, D and E. This rare
recessive disorder is characterized by progressive cerebellar
ataxia, dilation of the blood vessels in the conjunctiva and
eyeballs, immunodeficiency, growth retardation and sexual
immaturity. AT patients have a strong predisposition to cancer;
about 30% of patients develop tumors, particularly lymphomas and
leukemias. Cells from affected individuals are highly sensitive to
damage by ionizing radiation and resistant to inhibition of DNA
synthesis following irradiation.
-!- DISEASE: Defects in ATM contribute to T-cell acute lymphoblastic
leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is
characterized by a high white blood cell count, with a
predominance of prolymphocytes, marked splenomegaly,
lymphadenopathy, skin lesions and serous effusion. The clinical
course is highly aggressive, with poor response to chemoterapy and
short survival time. TPLL occurs both in adults as a sporadic
disease and in younger AT patients.
-!- DISEASE: Defects in ATM contribute to B-cell non-Hodgkin lymphomas
(BNHL), including mantle cell lymphoma (MCL).
-!- DISEASE: Defects in ATM contribute to B-cell chronic lymphocytic
leukemia (BCLL). BCLL is the commonest form of leukemia in the
elderly. It is characterized by the accumulation of mature CD5+ B
lymphocytes, lymphadenopathy, immunodeficiency and bone marrow
failure.
-!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
-!- SIMILARITY: Contains 1 FAT domain.
-!- SIMILARITY: Contains 1 FATC domain.
-!- SIMILARITY: Contains 1 PI3K/PI4K domain.
-!- DATABASE: NAME=Ataxia talangiectasia mutation db;
WWW="http://benaroyaresearch.org/investigators/concannon_patrick/atm.htm".
-!- DATABASE: NAME=Atlas Genet. Cytogenet. Oncol. Haematol.;
WWW="http://www.infobiogen.fr/services/chromcancer/Genes/ATM123.html".
-----------------------------------------------------------------------
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Sequence length: 3056
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 VPGAVKMGIE QNMCEVNRSF SLKESIMKWL LFYQLEGDLE NSTEVPPILH
SNFPHLVLEK ILVSLTMKNC KAAMNFFQSV PECEHHQKDK EELSFSEVEE LFLQTTFDKM
DFLTIVRECG IEKHQSSIGF SVHQNLKESL DRCLLGLSEQ LLNNYSSEIT NSETLVRCSR
LLVGVLGCYC YMGVIAEEEA YKSELFQKAN 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
SFDKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAI DPKNLSRLFP GWKAWV