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Description:
Serine-protein kinase ATM (EC 2.7.1.37) (Ataxia telangiectasia mutatedhomolog) (A-T, mutated homolog).
Molecular weight: 3494
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 47.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Glires Rodentia Sciurognathi Muroidea Muridae Murinae Mus.
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_MOUSE:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | U43678 | AAC52673.1 | - |
| Ensembl | ENSMUSG00000034218 | Mus musculus.1 | |
| MGI | MGI:107202 | Atm.1 | |
| Reactome | Q62388 | -.1 | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0005819 | C:spindle | IDA. |
| GO | GO:0004674 | F:protein serine/threonine kinase activity | TAS. |
| GO | GO:0000077 | P:DNA damage checkpoint | IMP. |
| GO | GO:0008630 | P:DNA damage response, signal transduction re... | IMP. |
| GO | GO:0006281 | P:DNA repair | IDA. |
| GO | GO:0007292 | P:female gamete generation | IMP. |
| GO | GO:0006468 | P:protein amino acid phosphorylation | IDA. |
| InterPro | IPR003151 | FAT. | |
| InterPro | IPR003152 | FATC. | |
| InterPro | IPR000403 | PI3/4_kinase_cat. | |
| Pfam | PF02259 | FAT | 1. |
| Pfam | PF02260 | FATC | 1. |
| Pfam | PF00454 | PI3_PI4_kinase | 1. |
| SMART | SM00146 | PI3Kc | 1. |
| PROSITE | PS00915 | PI3_4_KINASE_1 | 1. |
| PROSITE | PS00916 | PI3_4_KINASE_2 | 1. |
| PROSITE | PS50290 | PI3_4_KINASE_3 | 1. |
Keywords:
Anti-oncogene; Cell cycle; DNA damage; DNA repair; DNA-binding; Kinase; Nuclear protein; Phosphorylation; Serine/threonine-protein kinase; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX MEDLINE=96299738; PubMed=8661102; DOI=10.1006/geno.1996.0320;
RA Pecker I., Avraham K.B., Gilbert D.J., Savitsky K., Rotman G.,
RA Harnik R., Fukao T., Schroeck E., Hirotsume S., Tagle D.A.,
RA Collins F.S., Wynshaw-Boris A., Ried T., Copeland N.G., Jenkins N.A.,
RA Shiloh Y., Ziv Y.;
RT "Identification and chromosomal localization of Atm, the mouse homolog
RT of the ataxia-telangiectasia gene.";
RL Genomics 35:39-45(1996).
RN [2]
RP SUBCELLULAR LOCATION.
RX MEDLINE=97152562; PubMed=9000145;
RA Lakin N.D., Weber P., Stankovic T., Rottinghaus S.T., Taylor A.M.R.,
RA Jackson S.P.;
RT "Analysis of the ATM protein in wild-type and ataxia telangiectasia
RT cells.";
RL Oncogene 13:2707-2716(1996).
RN [3]
RP DEVELOPMENTAL STAGE.
RC STRAIN=B6C3-F1;
RX MEDLINE=98362438; PubMed=9697112; DOI=10.1016/S0306-4522(98)00117-1;
RA Soares H.D., Morgan J.I., McKinnon P.J.;
RT "Atm expression patterns suggest a contribution from the peripheral
RT nervous system to the phenotype of ataxia-telangiectasia.";
RL Neuroscience 86:1045-1054(1998).
RN [4]
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 [5]
RP FUNCTION.
RX PubMed=11571274; DOI=10.1074/jbc.C100466200;
RA Burma S., Chen B.P., Murphy M., Kurimasa A., Chen D.J.;
RT "ATM phosphorylates histone H2AX in response to DNA double-strand
RT breaks.";
RL J. Biol. Chem. 276:42462-42467(2001).
Feature:
CHAIN 1 3066 Serine-protein kinase ATM.
/FTId=PRO_0000088841.
DOMAIN 1972 2576 FAT.
DOMAIN 2722 2972 PI3K/PI4K.
DOMAIN 3034 3066 FATC.
REGION 1380 1389 Interaction with ABL1 (By similarity).
MOD_RES 1987 1987 Phosphoserine (By similarity).
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 (By similarity).
-!- SUBUNIT: Exists in monomeric and tetrameric state. Binds DNA ends,
P53, 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 (By similarity).
-!- SUBCELLULAR LOCATION: Primarily nuclear. Found also in endocytic
vesicles in association with beta-adaptin (By similarity).
-!- 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.
-!- PTM: Phosphorylated (By similarity).
-!- DISEASE: Atm-deficient mice show a phenotype similar to human
ataxia telangiectasia (AT) and consistently develop immature T-
cells malignancies.
-!- 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.
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Sequence length: 3066
MSLALNDLLI CCRQLEHDRA TERRKEVDKF KRLIQDPETV QHLDRHSDSK QGKYLNWDAV
FRFLQKYIQK EMESLRTAKS NVSATTQSSR QKKMQEISSL VRYFIKCANK RAPRLKCQDL
LNYVMDTVKD SSNGLTYGAD CSNILLKDIL SVRKYWCEVS QQQWLELFSL YFRLYLKPSQ
DINRVLVARI IHAVTRGCCS QTDGLPSKFL DLFSKAIQYA RQEKSSPGLS HILAALNIFL
KSLAVNFRKR VCEAGDEILP TLLYIWTQHR LNDSLKEVII ELIQLQIYIH HPQGARAPEE
GAYESMKWKS ILYNLYDLLV NEISHIGSRG KYSSGSRNIA VKENLIDLMA DICYQLFDAD
TRSVEISQSY VTQRESTDYS VPCKRRKIDV GWEVIKDYLQ KSQSDFDLVP WLQITTRLIS
KYPSSLPNCE LSPLILILYQ LLPQQRRGER IPYVLRCLKE VALCQGKKSN LESSQKSDLL
KLWIKIWSIT FRGISSGQTQ TENFGLLEAI IQGSLVELDR EFWKLFTGSA CKPSSPSVCC
LTLALSICVV PDAIKMGTEQ SVCEANRSFS VKESIMRWLL FYQLEDDLED STELPPILQR
NFPHLVVEKI LVSLTMKNSK AAMKFFQSVP ECEQHCEDKE EPSFSEVEEL FLQTTFDKMD
FLTTVKEYAV EKFQSSVGFS VQQNLKESLD HYLLGLSEQL LSNYSSEITS SETLVRCSSL
LVGVLGCYCY MGIITEDEAH KSELFQKAKS LMQCAGESIS LFKNKTNEES RIGSLRNVMH
LCTSCLCIHT KHTPNKIASG FFLRLLTSKL MNDIADICKS LASCTKKPLD HGVHPGEDDE
DGGGCDSLME AEGPSSTGLS TAYPASSVSD ANDYGENQNA VGAMSPLAAD YLSKQDHLLL
DMLRFLGRSV TASQSHTVSF RGADIRRKLL LLLDSSILDL MKPLHLHMYL VLLKDLPGNE
HSLPMEDVVE LLQPLSLVCS LHRRDQDVCK TILSNVLHIV TNLGQGSVDM ESTRIAQGHF
LTVMGAFWHL TKEKKCVFSV RMALVKCLQT LLEADPYSEW AILNVKGQDF PVNEAFSQFL
ADDHHQVRML AAGSVNRLFQ DMRQGDFSRS LKALPLKFQQ TSFNNAYTTA EAGIRGLLCD
SQNPDLLDEI YNRKSVLLMM IAVVLHCSPV CEKQALFALC KSVKENRLEP HLVKKVLEKV
SESFGCRSLE DFMISHLDYL VLEWLNLQDT EYSLSSFPFM LLNYTSIEDF YRSCYKILIP
HLVIRSHFDE VKSIANQIQK CWKSLLVDCF PKILVHILPY FAYEGTRDSY VSQKRETATK
VYDTLKGEDF LGKQIDQVFI SNLPEIVVEL LMTLHETADS ADSDASQSAT ALCDFSGDLD
PAPNPPYFPS HVIQATFAYI SNCHKTKFKS ILEILSKIPD SYQKILLAIC EQAAETNNVF
KKHRILKIYH LFVSLLLKDI QSGLGGAWAF VLRDVIYTLI HYINKRSSHF TDVSLRSFSL
CCDLLSRVCH TAVTQCKDAL ESHLHVIVGT LIPLVDYQEV QEQVLDLLKY LVIDNKDNKN
LSVTIKLLDP FPDHVIFKDL RLTQQKIKYS GGPFSLLEEI NHFLSVSAYN PLPLTRLEGL
KDLRRQLEQH KDQMLDLLRA SQDNPQDGIV VKLVVSLLQL SKMAVNQTGE REVLEAVGRC
LGEIGPLDFS TIAVQHNKDV SYTKAYGLPE DRELQWTLIM LTALNNTLVE DSVKIRSAAA
TCLKNILATK IGHIFWENYK TSADPMLTYL QPFRTSRKKF LEVPRSVKED VLEGLDAVNL
WVPQSESHDI WIKTLTCAFL DSGGINSEIL QLLKPMCEVK TDFCQMLLPY LIHDVLLQDT
HESWRTLLSA HVRGFFTSCF KHSSQASRSA TPANSDSESE NFLRCCLDKK SQRTMLAVVD
YLRRQKRPSS GTAFDDAFWL DLNYLEVAKV AQSCSAHFTA LLYAEIYSDK KSTDEQEKRS
PTFEEGSQGT TISSLSEKSK EETGISLQDL LLEIYRSIGE PDSLYGCGGG KMLQPLTRIR
TYEHEATWEK ALVTYDLETS ISSSTRQSGI IQALQNLGLS HILSVYLKGL DYERREWCAE
LQELRYQAAW RNMQWGLCAS AGQEVEGTSY HESLYNALQC LRNREFSTFY ESLRYASLFR
VKEVEELSKG SLESVYSLYP TLSRLQAIGE LENSGELFSR SVTDRERSEA YWKWQKHSQL
LKDSDFSFQE PLMALRTVIL ETLVQKEMER SQGACSKDIL TKHLVEFSVL ARTFKNTQLP
ERAIFKIKQY NSAICGISEW HLEEAQVFWA KKEQSLALSI LKQMIKKLDS SFKDKENDAG
LKVIYAECLR VCGSWLAETC LENPAVIMQT YLEKAVKVAG SYDGNSRELR NGQMKAFLSL
ARFSDTQYQR IENYMKSSEF ENKQTLLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEC
ALRALREDRK RFLCKAVENY INCLLSGEEH DLWVFRLCSL WLENSGVSEV NGMMKKDGMK
ISSYKFLPLM YQLAARMGTK MTGGLGFHEV LNNLISRISL DHPHHTLFII LALANANKDE
FLSKPETTRR SRITKSTSKE NSHLDEDRTE AATRIIHSIR SKRCKMVKDM EALCDAYIIL
ANMDASQWRA QRKGINIPAN QPITKLKNLE DVVVPTMEIK VDPTGEYENL VTIKSFKTEF
RLAGGLNLPK IIDCVGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RNTETRKRKL
TICTYKVVPL SQRSGVLEWC TGTVPIGEYL VNSEDGAHRR YRPNDFSANQ CQKKMMEVQK
KSFEEKYDTF MTICQNFEPV FRYFCMEKFL DPAVWFEKRL AYTRSVATSS IVGYILGLGD
RHVQNILINE QSAELVHIDL GVAFEQGKIL PTPETVPFRL SRDIVDGMGI TGVEGVFRRC
CEKTMEVMRS SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDESDL HSTPNADDQE
CKQSLSDTDQ SFNKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAM DPKNLSRLFP
GWKAWV