ATM (ataxia telangiectasia mutated)

Identity

HGNC	ATM
Location	11q22.3-q23.1

Note	see also, in Deep Insight section: Ataxia-Telangiectasia and variants

DNA/RNA

	ATM (11q22.3) in normal cells: PAC 1053F10 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi
Description	66 exons spanning 184 kb of genomic DNA; numerous Alu and Lime sequences
Transcription	alternative exons 1a and 1b; initiation codon lies within exon 4; 12 kb transcript with a 9.2 kb of coding sequence The ATM promotor is bi-directional and also directs the transcription of the E14/NPAT/CAND3 gene

Protein

Description	3056 amino acids; 350 kDa; contains a Pl 3-kinase-like domain (phosphatidylinositol 3-prime kinase)
Expression	found in all tissues
Localisation	mostly in the nucleus throughout all stages of the cell cycle
Function	initiates cell cycle checkpoints in response to double-strand DNA breaks by phosphorylating p53, BRCA1, H2AX,cAbl,IkB-alpha and chk1, as well as other targets; in certain types of tissues ATM inhibits radiation-induced, p53-dependent apoptosis.
Homology	phosphatidylinositol 3-kinase (PI3K)-like proteins, most closely related to ATR and the DNA-PK catalytic subunit

Mutations

Germinal

various types of mutations have been described, dispersed throughout the gene, and therefore most patients are compound heterozygotes; most mutations appear to inactivate the ATM protein by truncation, large deletions, or annulation of initiation or termination, although missense mutations have been described in the PI3 kinase domain and the leucine zipper motif. Missense mutations outside of the PI3 kinase and leucine zipper domains have been described among breast cancer patients, although these mutations have not been found in A-T patients. Whether these mutations contribute to breast cancer though not to ataxia-telangiectasia remains controversial.

Somatic

biallelic mutation can occur in T-prolymphocytic leukaemia

Implicated in

Entity	ataxia telangiectasia
Disease	ataxia telangiectasia is a progressive cerebellar degenerative disease with telangiectasia, immunodeficiency, cancer risk, radiosensitivity, and chromosomal instability
Prognosis	poor: median age at death:17 yrs; survival rarely exceeds 30 yrs, though survival is imcreasing with improved medical care
Cytogenetics	spontaneous chromatid/chromosome breaks; non clonal stable chromosome rearrangements involving immunoglobulin superfamilly genes e.g. inv(7)(p14q35); clonal rearrangements.

External links

	Nomenclature
HGNC	ATM   795
Entrez_Gene	ATM  472  ataxia telangiectasia mutated
	Cards
Atlas	ATM123
GeneCards	ATM
Ensembl	ATM [Search_View]   ENSG00000149311 [Gene_View]
Genatlas	ATM
GeneLynx	ATM
eGenome	ATM
euGene	472
	Genomic and cartography
GoldenPath	ATM  -     chr11:107598769-107745036 +  11q22-q23   [Description]    (hg18-Mar_2006)
Ensembl	ATM - 11q22-q23 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	ATM
	Gene and transcription
Genbank	AB209133 [ ENTREZ ]
Genbank	AF035328 [ ENTREZ ]
Genbank	BC007023 [ ENTREZ ]
Genbank	BC022307 [ ENTREZ ]
Genbank	BC061584 [ ENTREZ ]
RefSeq	NM_000051 [ SRS ]    NM_000051 [ ENTREZ ]
RefSeq	NM_138292 [ SRS ]    NM_138292 [ ENTREZ ]
RefSeq	AC_000054 [ SRS ]    AC_000054 [ ENTREZ ]
RefSeq	AC_000143 [ SRS ]    AC_000143 [ ENTREZ ]
RefSeq	NC_000011 [ SRS ]    NC_000011 [ ENTREZ ]
RefSeq	NT_033899 [ SRS ]    NT_033899 [ ENTREZ ]
RefSeq	NW_001838042 [ SRS ]    NW_001838042 [ ENTREZ ]
RefSeq	NW_925173 [ SRS ]    NW_925173 [ ENTREZ ]
AceView	ATM AceView - NCBI
Unigene	Hs.367437 [ SRS ]    Hs.367437 [ NCBI ]     HS367437 [ spliceNest ]
Fast-db	13624 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q13315 [ SRS]    Q13315 [ EXPASY ]     Q13315 [ INTERPRO ]     Q13315 [ UNIPROT ]
Prosite	PS51189 FAT [ SRS ]    PS51189 FAT [ Expasy ]
Prosite	PS51190 FATC [ SRS ]    PS51190 FATC [ Expasy ]
Prosite	PS00915 PI3_4_KINASE_1 [ SRS ]    PS00915 PI3_4_KINASE_1 [ Expasy ]
Prosite	PS00916 PI3_4_KINASE_2 [ SRS ]    PS00916 PI3_4_KINASE_2 [ Expasy ]
Prosite	PS50290 PI3_4_KINASE_3 [ SRS ]    PS50290 PI3_4_KINASE_3 [ Expasy ]
Interpro	IPR015519 Ataxia_Telang_Mut [ SRS ]    IPR015519 Ataxia_Telang_Mut [ EBI ]
Interpro	IPR003152 FATC [ SRS ]    IPR003152 FATC [ EBI ]
Interpro	IPR000403 PI3/4_kinase_cat [ SRS ]    IPR000403 PI3/4_kinase_cat [ EBI ]
Interpro	IPR003151 PIK-rel_kinase_FAT [ SRS ]    IPR003151 PIK-rel_kinase_FAT [ EBI ]
Interpro	IPR014009 PIK_FAT [ SRS ]    IPR014009 PIK_FAT [ EBI ]
CluSTr	Q13315
Pfam	PF02259 FAT [ SRS ]    PF02259 FAT [ Sanger ]    pfam02259 [ NCBI-CDD ]
Pfam	PF02260 FATC [ SRS ]    PF02260 FATC [ Sanger ]    pfam02260 [ NCBI-CDD ]
Pfam	PF00454 PI3_PI4_kinase [ SRS ]    PF00454 PI3_PI4_kinase [ Sanger ]    pfam00454 [ NCBI-CDD ]
Smart	SM00146 PI3Kc [EMBL]
Blocks	Q13315
HPRD	06347
	Protein Interaction databases
DIP	Q13315
IntAct	Q13315
	Polymorphism : SNP, mutations, diseases
OMIM	114480;208900;607585    [ map ]
GENECLINICS	114480;208900;607585
SNP	ATM [dbSNP-NCBI]
SNP	NM_000051 [SNP-NCI]
SNP	NM_138292 [SNP-NCI]
SNP	ATM [GeneSNPs - Utah]  ATM] [HGBASE - SRS]
HAPMAP	ATM [HAPMAP]
COSMIC	ATM [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	ATM
	General knowledge
Family Browser	ATM [UCSC Family Browser]
SOURCE	NM_000051
SOURCE	NM_138292
SMD	Hs.367437
SAGE	Hs.367437
Enzyme	2.7.11.1 [ Enzyme-Expasy ]   2.7.11.1 [ Enzyme-SRS ]   2.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   2.7.11.1 [ WIT ]
GO	DNA binding [Amigo]  DNA binding
GO	protein serine/threonine kinase activity [Amigo]  protein serine/threonine kinase activity
GO	binding [Amigo]  binding
GO	nucleus [Amigo]  nucleus
GO	nucleoplasm [Amigo]  nucleoplasm
GO	DNA repair [Amigo]  DNA repair
GO	mitotic cell cycle spindle assembly checkpoint [Amigo]  mitotic cell cycle spindle assembly checkpoint
GO	meiotic recombination [Amigo]  meiotic recombination
GO	signal transduction [Amigo]  signal transduction
GO	response to ionizing radiation [Amigo]  response to ionizing radiation
GO	1-phosphatidylinositol-3-kinase activity [Amigo]  1-phosphatidylinositol-3-kinase activity
GO	transferase activity [Amigo]  transferase activity
GO	phosphotransferase activity, alcohol group as acceptor [Amigo]  phosphotransferase activity, alcohol group as acceptor
GO	cytoplasmic vesicle [Amigo]  cytoplasmic vesicle
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	protein N-terminus binding [Amigo]  protein N-terminus binding
BIOCARTA	ATM Signaling Pathway    [Genes]
BIOCARTA	Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility    [Genes]
BIOCARTA	cdc25 and chk1 Regulatory Pathway in response to DNA damage    [Genes]
BIOCARTA	Apoptotic Signaling in Response to DNA Damage    [Genes]
BIOCARTA	Cell Cycle: G1/S Check Point    [Genes]
BIOCARTA	Cell Cycle: G2/M Checkpoint    [Genes]
BIOCARTA	p53 Signaling Pathway    [Genes]
BIOCARTA	Hypoxia and p53 in the Cardiovascular system    [Genes]
BIOCARTA	Regulation of cell cycle progression by Plk3    [Genes]
BIOCARTA	RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage    [Genes]
KEGG	Cell cycle
KEGG	Apoptosis
KEGG	Toll-like receptor signaling pathway
PubGene	ATM
TreeFam	ATM
CTD	472 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	ATM (11q22.3)  in normal cells (Bari)
Probe	ATM Related clones (RZPD - Berlin)
	PubMed
PubMed	428 Pubmed reference(s) in LocusLink

Bibliography

-

Gorlin RJ et al

Oxford Monogr Med Genet ..

Cancer risks in A-T heterozygotes.

Easton DF

International journal of radiation biology. 1994 ; 66 (6 Suppl) : S177-S182.

PMID 7836845

TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene.

Greenwell PW, Kronmal SL, Porter SE, Gassenhuber J, Obermaier B, Petes TD

Cell. 1995 ; 82 (5) : 823-829.

PMID 7671310

The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene.

Hari KL, Santerre A, Sekelsky JJ, McKim KS, Boyd JB, Hawley RS

Cell. 1995 ; 82 (5) : 815-821.

PMID 7671309

A single ataxia telangiectasia gene with a product similar to PI-3 kinase.

Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y

Science (New York, N.Y.). 1995 ; 268 (5218) : 1749-1753.

PMID 7792600

The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species.

Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G

Human molecular genetics. 1995 ; 4 (11) : 2025-2032.

PMID 8589678

ATM-related genes: what do they tell us about functions of the human gene?

Zakian VA

Cell. 1995 ; 82 (5) : 685-687.

PMID 7671296

Atm-deficient mice: a paradigm of ataxia telangiectasia.

Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A

Cell. 1996 ; 86 (1) : 159-171.

PMID 8689683

The ataxia-telangiectasia gene product, a constitutively expressed nuclear protein that is not up-regulated following genome damage.

Brown KD, Ziv Y, Sadanandan SN, Chessa L, Collins FS, Shiloh Y, Tagle DA

Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (5) : 1840-1845.

PMID 9050866

Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic DNA containing the entire ATM gene.

Platzer M, Rotman G, Bauer D, Uziel T, Savitsky K, Bar-Shira A, Gilad S, Shiloh Y, Rosenthal A

Genome research. 1997 ; 7 (6) : 592-605.

PMID 9199932

Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart.

Shiloh Y

Annual review of genetics. 1997 ; 31 : 635-662.

PMID 9442910

Biallelic mutations in the ATM gene in T-prolymphocytic leukemia.

Stilgenbauer S, Schaffner C, Litterst A, Liebisch P, Gilad S, Bar-Shira A, James MR, Lichter P, Dˆ�hner H

Nature medicine. 1997 ; 3 (10) : 1155-1159.

PMID 9334731

CAND3: a ubiquitously expressed gene immediately adjacent and in opposite transcriptional orientation to the ATM gene at 11q23.1.

Chen X, Yang L, Udar N, Liang T, Uhrhammer N, Xu S, Bay JO, Wang Z, Dandakar S, Chiplunkar S, Klisak I, Telatar M, Yang H, Concannon P, Gatti RA

Mammalian genome : official journal of the International Mammalian Genome Society. 1997 ; 8 (2) : 129-133.

PMID 9060412

Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia.

Vorechovskˆ‡ I, Luo L, Dyer MJ, Catovsky D, Amlot PL, Yaxley JC, Foroni L, Hammarstrˆ�m L, Webster AD, Yuille MA

Nature genetics. 1997 ; 17 (1) : 96-99.

PMID 9288106

Cell-cycle signaling: Atm displays its many talents.

Westphal CH

Current biology : CB. 1997 ; 7 (12) : R789-R792.

PMID 9382823

Recombinant ATM protein complements the cellular A-T phenotype.

Ziv Y, Bar-Shira A, Pecker I, Russell P, Jorgensen TJ, Tsarfati I, Shiloh Y

Oncogene. 1997 ; 15 (2) : 159-167.

PMID 9244351

Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations.

Telatar M, Teraoka S, Wang Z, Chun HH, Liang T, Castellvi-Bel S, Udar N, Borresen-Dale AL, Chessa L, Bernatowska-Matuszkiewicz E, Porras O, Watanabe M, Junker A, Concannon P, Gatti RA

American journal of human genetics. 1998 ; 62 (1) : 86-97.

PMID 9443866

Requirements for p53 and the ATM gene product in the regulation of G1/S and S phase checkpoints.

Xie G, Habbersett RC, Jia Y, Peterson SR, Lehnert BE, Bradbury EM, D'Anna JA

Oncogene. 1998 ; 16 (6) : 721-736.

PMID 9488036

Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families.

Janin N, Andrieu N, Ossian K, Laugˆ© A, Croquette MF, Griscelli C, Debrˆ© M, Bressac-de-Paillerets B, Aurias A, Stoppa-Lyonnet D

British journal of cancer. 1999 ; 80 (7) : 1042-1045.

PMID 10362113

ATM-heterozygous germline mutations contribute to breast cancer-susceptibility.

Broeks A, Urbanus JH, Floore AN, Dahler EC, Klijn JG, Rutgers EJ, Devilee P, Russell NS, van Leeuwen FE, van 't Veer LJ

American journal of human genetics. 2000 ; 66 (2) : 494-500.

PMID 10677309

ATM phosphorylates histone H2AX in response to DNA double-strand breaks.

Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ

The Journal of biological chemistry. 2001 ; 276 (45) : 42462-42467.

PMID 11571274

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	04-1998	Jean Loup Huret
Updated	10-1999	Nancy Uhrhammer, Jacques-Olivier Bay and Richard A Gatti
Updated	11-2002	Nancy Uhrhammer, Jacques-Olivier Bay and Richard A Gatti

Citation

This paper should be referenced as such :

Huret JL . ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. April 1998 . URL : http://AtlasGeneticsOncology.org/Genes/ATM123.html

Uhrhammer N, Bay JO and Gatti RA . ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. October 1999 . URL : http://AtlasGeneticsOncology.org/Genes/ATM123.html

Uhrhammer N, Bay JO and Gatti RA . ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. November 2002 . URL : http://AtlasGeneticsOncology.org/Genes/ATM123.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:12:16 2008