Reviewed, UniProtKB/Swiss-Prot Q62388 (ATM_MOUSE)

Names and origin

Protein names

Recommended name:
    Serine-protein kinase ATM
    EC=2.7.11.1
Alternative name(s):
    Ataxia telangiectasia mutated homolog
      Short name=A-T mutated homolog

Gene names

Name:

Atm

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	3066 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (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 [ST]-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 (NBN), 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. Binds DNA ends. Plays a role in replication-dependent histone mRNA degradation By similarity. Ref.5 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Inhibited by wortmannin By similarity.
Subunit structure	Dimers or tetramers in inactive state. On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active. Binds DNA ends, p53/TP53, ABL1, BRCA1, NBN/nibrin and TERF1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN 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; the interaction, induced on DNA damage, upregulates TP53. Interacts with DCLRE1C, MYST1, KAT5, OBFC2B, ATMIN and CEP164 By similarity. Interacts with AP2B1 AND AP3B2; the interaction occurs in cytoplasmic vesicles. Ref.4
Subcellular location	Nucleus By similarity. Cytoplasmic vesicle By similarity. Note: Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin By similarity. Ref.2
Tissue specificity	Expressed in brain, skeletal muscle, testis, followed by spleen, lung, kidney, heart, liver and thymus. Ubiquitously expressed in embryonal tissues.
Developmental stage	Highest expression in embryonic central nervous system, from E13.5 day and during the whole cerebellar development. Decreased expression when maturation occurs. Ref.3
Domain	The FATC domain is required for interaction with KAT5 By similarity.
Post-translational modification	Phosphorylated by NUAK1/ARK5 By similarity. Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase. Acetylated by KAT5 upon DNA damage; which is required for autophosphorylation and subsequent activation By similarity.
Involvement in disease	Atm-deficient mice show a phenotype similar to human ataxia telangiectasia (AT) and consistently develop immature T-cells malignancies. Ref.6
Sequence similarities	Belongs to the PI3/PI4-kinase family. ATM subfamily. Contains 1 FAT domain. Contains 1 FATC domain. Contains 1 PI3K/PI4K domain.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Cytoplasmic vesicle Nucleus
Disease	Tumor suppressor
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	DNA damage checkpoint Inferred from mutant phenotype. Source: MGI DNA damage response, signal transduction resulting in induction of apoptosis Inferred from mutant phenotype. Source: MGI DNA repair Inferred from direct assay. Source: MGI brain development Inferred from genetic interaction. Source: MGI cell cycle Inferred from electronic annotation. Source: UniProtKB-KW female gamete generation Inferred from mutant phenotype. Source: MGI heart development Inferred from genetic interaction. Source: MGI histone mRNA catabolic process Inferred from sequence or structural similarity. Source: UniProtKB lipoprotein catabolic process Inferred from genetic interaction. Source: MGI mitotic cell cycle spindle assembly checkpoint Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptosis Inferred from mutant phenotype. Source: MGI neuron apoptosis Inferred from genetic interaction. Source: MGI positive regulation of neuron apoptosis Inferred from genetic interaction. Source: MGI protein amino acid phosphorylation Inferred from direct assay. Source: MGI response to ionizing radiation Inferred from sequence or structural similarity. Source: UniProtKB somitogenesis Inferred from genetic interaction. Source: MGI
Cellular component	cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from Experiment. Source: Reactome spindle Inferred from direct assay. Source: MGI
Molecular function	1-phosphatidylinositol-3-kinase activity Inferred from sequence or structural similarity. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein N-terminus binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ppp1ca	P62137	1	EBI-1202183,EBI-357187

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 3066	3066	Serine-protein kinase ATM		PRO_0000088841
Regions
	Domain	1966 – 2576	611	FAT
	Domain	2722 – 2972	251	PI3K/PI4K
	Domain	3034 – 3066	33	FATC
	Region	1380 – 1389	10	Interaction with ABL1 By similarity
Amino acid modifications
	Modified residue	86	1	Phosphothreonine By similarity
	Modified residue	367	1	Phosphoserine; by autocatalysis Ref.6
	Modified residue	372	1	Phosphothreonine By similarity
	Modified residue	1889	1	Phosphoserine By similarity
	Modified residue	1899	1	Phosphoserine; by autocatalysis Ref.6
	Modified residue	1987	1	Phosphoserine; by autocatalysis Ref.6
	Modified residue	1991	1	Phosphothreonine By similarity
	Modified residue	3006	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	367	1	S → A: Retains genomic stability and cell cycle checkpoint correction and kinase activity towards downstream targets; when associated with A-1987. Retains genomic stability, cell cycle checkpoint correction and kinase activity on downstream targets; when associated with A-1899 and A-1987. Ref.6
	Mutagenesis	1899	1	S → A: Retains genomic stability, cell cycle checkpoint correction and kinase activity on downstream targets; when associated with A-367 and A-1987. Ref.6
	Mutagenesis	1987	1	S → A: Retains genomic stability and cell cycle checkpoint correction and kinase activity towards downstream targets; when associated with A-367. Retains genomic stability, cell cycle checkpoint correction and kinase activity on downstream targets; when associated with A-367 and A-1987. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q62388-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 1EB21EB61405577A	FASTA	3,066	349,488
	10 20 30 40 50 60 MSLALNDLLI CCRQLEHDRA TERRKEVDKF KRLIQDPETV QHLDRHSDSK QGKYLNWDAV 70 80 90 100 110 120 FRFLQKYIQK EMESLRTAKS NVSATTQSSR QKKMQEISSL VRYFIKCANK RAPRLKCQDL 130 140 150 160 170 180 LNYVMDTVKD SSNGLTYGAD CSNILLKDIL SVRKYWCEVS QQQWLELFSL YFRLYLKPSQ 190 200 210 220 230 240 DINRVLVARI IHAVTRGCCS QTDGLPSKFL DLFSKAIQYA RQEKSSPGLS HILAALNIFL 250 260 270 280 290 300 KSLAVNFRKR VCEAGDEILP TLLYIWTQHR LNDSLKEVII ELIQLQIYIH HPQGARAPEE 310 320 330 340 350 360 GAYESMKWKS ILYNLYDLLV NEISHIGSRG KYSSGSRNIA VKENLIDLMA DICYQLFDAD 370 380 390 400 410 420 TRSVEISQSY VTQRESTDYS VPCKRRKIDV GWEVIKDYLQ KSQSDFDLVP WLQITTRLIS 430 440 450 460 470 480 KYPSSLPNCE LSPLILILYQ LLPQQRRGER IPYVLRCLKE VALCQGKKSN LESSQKSDLL 490 500 510 520 530 540 KLWIKIWSIT FRGISSGQTQ TENFGLLEAI IQGSLVELDR EFWKLFTGSA CKPSSPSVCC 550 560 570 580 590 600 LTLALSICVV PDAIKMGTEQ SVCEANRSFS VKESIMRWLL FYQLEDDLED STELPPILQR 610 620 630 640 650 660 NFPHLVVEKI LVSLTMKNSK AAMKFFQSVP ECEQHCEDKE EPSFSEVEEL FLQTTFDKMD 670 680 690 700 710 720 FLTTVKEYAV EKFQSSVGFS VQQNLKESLD HYLLGLSEQL LSNYSSEITS SETLVRCSSL 730 740 750 760 770 780 LVGVLGCYCY MGIITEDEAH KSELFQKAKS LMQCAGESIS LFKNKTNEES RIGSLRNVMH 790 800 810 820 830 840 LCTSCLCIHT KHTPNKIASG FFLRLLTSKL MNDIADICKS LASCTKKPLD HGVHPGEDDE 850 860 870 880 890 900 DGGGCDSLME AEGPSSTGLS TAYPASSVSD ANDYGENQNA VGAMSPLAAD YLSKQDHLLL 910 920 930 940 950 960 DMLRFLGRSV TASQSHTVSF RGADIRRKLL LLLDSSILDL MKPLHLHMYL VLLKDLPGNE 970 980 990 1000 1010 1020 HSLPMEDVVE LLQPLSLVCS LHRRDQDVCK TILSNVLHIV TNLGQGSVDM ESTRIAQGHF 1030 1040 1050 1060 1070 1080 LTVMGAFWHL TKEKKCVFSV RMALVKCLQT LLEADPYSEW AILNVKGQDF PVNEAFSQFL 1090 1100 1110 1120 1130 1140 ADDHHQVRML AAGSVNRLFQ DMRQGDFSRS LKALPLKFQQ TSFNNAYTTA EAGIRGLLCD 1150 1160 1170 1180 1190 1200 SQNPDLLDEI YNRKSVLLMM IAVVLHCSPV CEKQALFALC KSVKENRLEP HLVKKVLEKV 1210 1220 1230 1240 1250 1260 SESFGCRSLE DFMISHLDYL VLEWLNLQDT EYSLSSFPFM LLNYTSIEDF YRSCYKILIP 1270 1280 1290 1300 1310 1320 HLVIRSHFDE VKSIANQIQK CWKSLLVDCF PKILVHILPY FAYEGTRDSY VSQKRETATK 1330 1340 1350 1360 1370 1380 VYDTLKGEDF LGKQIDQVFI SNLPEIVVEL LMTLHETADS ADSDASQSAT ALCDFSGDLD 1390 1400 1410 1420 1430 1440 PAPNPPYFPS HVIQATFAYI SNCHKTKFKS ILEILSKIPD SYQKILLAIC EQAAETNNVF 1450 1460 1470 1480 1490 1500 KKHRILKIYH LFVSLLLKDI QSGLGGAWAF VLRDVIYTLI HYINKRSSHF TDVSLRSFSL 1510 1520 1530 1540 1550 1560 CCDLLSRVCH TAVTQCKDAL ESHLHVIVGT LIPLVDYQEV QEQVLDLLKY LVIDNKDNKN 1570 1580 1590 1600 1610 1620 LSVTIKLLDP FPDHVIFKDL RLTQQKIKYS GGPFSLLEEI NHFLSVSAYN PLPLTRLEGL 1630 1640 1650 1660 1670 1680 KDLRRQLEQH KDQMLDLLRA SQDNPQDGIV VKLVVSLLQL SKMAVNQTGE REVLEAVGRC 1690 1700 1710 1720 1730 1740 LGEIGPLDFS TIAVQHNKDV SYTKAYGLPE DRELQWTLIM LTALNNTLVE DSVKIRSAAA 1750 1760 1770 1780 1790 1800 TCLKNILATK IGHIFWENYK TSADPMLTYL QPFRTSRKKF LEVPRSVKED VLEGLDAVNL 1810 1820 1830 1840 1850 1860 WVPQSESHDI WIKTLTCAFL DSGGINSEIL QLLKPMCEVK TDFCQMLLPY LIHDVLLQDT 1870 1880 1890 1900 1910 1920 HESWRTLLSA HVRGFFTSCF KHSSQASRSA TPANSDSESE NFLRCCLDKK SQRTMLAVVD 1930 1940 1950 1960 1970 1980 YLRRQKRPSS GTAFDDAFWL DLNYLEVAKV AQSCSAHFTA LLYAEIYSDK KSTDEQEKRS 1990 2000 2010 2020 2030 2040 PTFEEGSQGT TISSLSEKSK EETGISLQDL LLEIYRSIGE PDSLYGCGGG KMLQPLTRIR 2050 2060 2070 2080 2090 2100 TYEHEATWEK ALVTYDLETS ISSSTRQSGI IQALQNLGLS HILSVYLKGL DYERREWCAE 2110 2120 2130 2140 2150 2160 LQELRYQAAW RNMQWGLCAS AGQEVEGTSY HESLYNALQC LRNREFSTFY ESLRYASLFR 2170 2180 2190 2200 2210 2220 VKEVEELSKG SLESVYSLYP TLSRLQAIGE LENSGELFSR SVTDRERSEA YWKWQKHSQL 2230 2240 2250 2260 2270 2280 LKDSDFSFQE PLMALRTVIL ETLVQKEMER SQGACSKDIL TKHLVEFSVL ARTFKNTQLP 2290 2300 2310 2320 2330 2340 ERAIFKIKQY NSAICGISEW HLEEAQVFWA KKEQSLALSI LKQMIKKLDS SFKDKENDAG 2350 2360 2370 2380 2390 2400 LKVIYAECLR VCGSWLAETC LENPAVIMQT YLEKAVKVAG SYDGNSRELR NGQMKAFLSL 2410 2420 2430 2440 2450 2460 ARFSDTQYQR IENYMKSSEF ENKQTLLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEC 2470 2480 2490 2500 2510 2520 ALRALREDRK RFLCKAVENY INCLLSGEEH DLWVFRLCSL WLENSGVSEV NGMMKKDGMK 2530 2540 2550 2560 2570 2580 ISSYKFLPLM YQLAARMGTK MTGGLGFHEV LNNLISRISL DHPHHTLFII LALANANKDE 2590 2600 2610 2620 2630 2640 FLSKPETTRR SRITKSTSKE NSHLDEDRTE AATRIIHSIR SKRCKMVKDM EALCDAYIIL 2650 2660 2670 2680 2690 2700 ANMDASQWRA QRKGINIPAN QPITKLKNLE DVVVPTMEIK VDPTGEYENL VTIKSFKTEF 2710 2720 2730 2740 2750 2760 RLAGGLNLPK IIDCVGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RNTETRKRKL 2770 2780 2790 2800 2810 2820 TICTYKVVPL SQRSGVLEWC TGTVPIGEYL VNSEDGAHRR YRPNDFSANQ CQKKMMEVQK 2830 2840 2850 2860 2870 2880 KSFEEKYDTF MTICQNFEPV FRYFCMEKFL DPAVWFEKRL AYTRSVATSS IVGYILGLGD 2890 2900 2910 2920 2930 2940 RHVQNILINE QSAELVHIDL GVAFEQGKIL PTPETVPFRL SRDIVDGMGI TGVEGVFRRC 2950 2960 2970 2980 2990 3000 CEKTMEVMRS SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDESDL HSTPNADDQE 3010 3020 3030 3040 3050 3060 CKQSLSDTDQ SFNKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAM DPKNLSRLFP GWKAWV

References

[1]	"Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene." Pecker I., Avraham K.B., Gilbert D.J., Savitsky K., Rotman G., Harnik R., Fukao T., Schroeck E., Hirotsume S., Tagle D.A., Collins F.S., Wynshaw-Boris A., Ried T., Copeland N.G., Jenkins N.A., Shiloh Y., Ziv Y. Genomics 35:39-45(1996) [PubMed: 8661102] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Analysis of the ATM protein in wild-type and ataxia telangiectasia cells." Lakin N.D., Weber P., Stankovic T., Rottinghaus S.T., Taylor A.M.R., Jackson S.P. Oncogene 13:2707-2716(1996) [PubMed: 9000145] [Abstract] Cited for: SUBCELLULAR LOCATION.
[3]	"Atm expression patterns suggest a contribution from the peripheral nervous system to the phenotype of ataxia-telangiectasia." Soares H.D., Morgan J.I., McKinnon P.J. Neuroscience 86:1045-1054(1998) [PubMed: 9697112] [Abstract] Cited for: DEVELOPMENTAL STAGE. Strain: B6C3-F1.
[4]	"ATM binds to beta-adaptin in cytoplasmic vesicles." Lim D.-S., Kirsch D.G., Canman C.E., Ahn J.-H., Ziv Y., Newman L.S., Darnell R.B., Shiloh Y., Kastan M.B. Proc. Natl. Acad. Sci. U.S.A. 95:10146-10151(1998) [PubMed: 9707615] [Abstract] Cited for: INTERACTION WITH AP2B1 AND AP3B2.
[5]	"ATM phosphorylates histone H2AX in response to DNA double-strand breaks." Burma S., Chen B.P., Murphy M., Kurimasa A., Chen D.J. J. Biol. Chem. 276:42462-42467(2001) [PubMed: 11571274] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF H2AFX.
[6]	"Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo." Daniel J.A., Pellegrini M., Lee J.H., Paull T.T., Feigenbaum L., Nussenzweig A. J. Cell Biol. 183:777-783(2008) [PubMed: 19047460] [Abstract] Cited for: AUTOPHOSPHORYLATION AT SER-367; SER-1899 AND SER-1987, FUNCTION, MUTAGENESIS OF SER-367; SER-1899 AND SER-1987.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U43678 mRNA. Translation: AAC52673.1.
IPI	IPI00124810.
RefSeq	NP_031525.2.
UniGene	Mm.5088
3D structure databases
SMR	Q62388. Positions 2706-2972, 3035-3065.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q62388. 2 interactions.
STRING	Q62388.
PTM databases
PhosphoSite	Q62388.
Proteomic databases
PRIDE	Q62388.
Genome annotation databases
Ensembl	ENSMUST00000037440; ENSMUSP00000045039; ENSMUSG00000034218; Mus musculus. [Genome view] ENSMUST00000118282; ENSMUSP00000113388; ENSMUSG00000034218; Mus musculus. [Genome view]
GeneID	11920.
KEGG	mmu:11920.
UCSC	uc009pmd.1. mouse.
Organism-specific databases
CTD	11920.
MGI	MGI:107202. Atm.
Phylogenomic databases
HOGENOM	HBG402889.
HOVERGEN	Q62388.
InParanoid	Q62388.
Enzyme and pathway databases
BRENDA	2.7.11.1. 244.
Gene expression databases
ArrayExpress	Q62388.
Bgee	Q62388.
CleanEx	MM_ATM.
Genevestigator	Q62388.
GermOnline	ENSMUSG00000034218. Mus musculus.
Family and domain databases
InterPro	IPR016024. ARM-type_fold. IPR015519. Ataxia_Telang_Mut. IPR003152. FATC. IPR011009. Kinase-like_dom. IPR000403. PI3/4_kinase_cat. IPR018936. PI3/4_kinase_CS. IPR003151. PIK-rel_kinase_FAT. IPR014009. PIK_FAT. [Graphical view]
PANTHER	PTHR11139:SF3. Ataxia_Telang_Mut. 1 hit.
Pfam	PF02259. FAT. 1 hit. PF02260. FATC. 1 hit. PF00454. PI3_PI4_kinase. 1 hit. [Graphical view]
SMART	SM00146. PI3Kc. 1 hit. [Graphical view]
PROSITE	PS51189. FAT. 1 hit. PS51190. FATC. 1 hit. PS00915. PI3_4_KINASE_1. 1 hit. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	279985.
SOURCE	Search...

Entry information

Entry name

ATM_MOUSE

Accession

Primary (citable) accession number: Q62388

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)