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Atm |
Protein FULL name:
serine-protein kinase ATM [Mus musculus].
Atm (Mus musculus) is product of expression of Atm gene.
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 plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. 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.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
ENZYME REGULATION: Inhibited by wortmannin (By similarity).
SUBUNIT: 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. Interacts with TELO2 AND TTI1 (By similarity).
INTERACTION: P62137:Ppp1ca; NbExp=1; IntAct=EBI-1202183, EBI-357187;
SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasmic vesicle (By similarity). Note=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.
DOMAIN: The FATC domain is required for interaction with KAT5 (By similarity).
PTM: Phosphorylated by NUAK1/ARK5 (By similarity). Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.
PTM: Acetylated by KAT5 upon DNA damage; which is required for autophosphorylation and subsequent activation (By similarity).
DISEASE: Note=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.
| NCBI GenPept GI number(s): |
163838660 |
| Species: | Mus musculus |
Links to other databases:
| Database | ID | Link |
| Uniprot | Q62388 |
Q62388 |
| PFAM: | - |
Q62388 (Link - using uniprot id) |
| InterPro: | - |
Q62388 (Link - using uniprot id) |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MSLALNDLLICCRQLEHDRATERRKEVDKFKRLIQDPETVQHLDRHSDSK QGKYLNWDAVFRFLQKYIQKEMESLRTAKSNVSATTQSSRQKKMQEISSL VRYFIKCANKRAPRLKCQDLLNYVMDTVKDSSNGLTYGADCSNILLKDIL SVRKYWCEVSQQQWLELFSLYFRLYLKPSQDINRVLVARIIHAVTRGCCS QTDGLPSKFLDLFSKAIQYARQEKSSPGLSHILAALNIFLKSLAVNFRKR VCEAGDEILPTLLYIWTQHRLNDSLKEVIIELIQLQIYIHHPQGARAPEE GAYESMKWKSILYNLYDLLVNEISHIGSRGKYSSGSRNIAVKENLIDLMA DICYQLFDADTRSVEISQSYVTQRESTDYSVPCKRRKIDVGWEVIKDYLQ KSQSDFDLVPWLQITTRLISKYPSSLPNCELSPLILILYQLLPQQRRGER IPYVLRCLKEVALCQGKKSNLESSQKSDLLKLWIKIWSITFRGISSGQTQ TENFGLLEAIIQGSLVELDREFWKLFTGSACKPSSPSVCCLTLALSICVV PDAIKMGTEQSVCEANRSFSVKESIMRWLLFYQLEDDLEDSTELPPILQS NFPHLVVEKILVSLTMKNSKAAMKFFQSVPECEQHCEDKEEPSFSEVEEL FLQTTFDKMDFLTTVKEYAVEKFQSSVGFSVQQNLKESLDHYLLGLSEQL LSNYSSEITSSETLVRCSSLLVGVLGCYCYMGIITEDEAHKSELFQKAKS LMQCAGESISLFKNKTNEESRIGSLRNVMHLCTSCLCIHTKHTPNKIASG FFLRLLTSKLMNDIADICKSLASCTKKPLDHGVHPGEDDEDGGGCDSLME AEGPSSTGLSTAYPASSVSDANDYGENQNAVGAMSPLAADYLSKQDHLLL DMLRFLGRSVTASQSHTVSFRGADIRRKLLLLLDSSILDLMKPLHLHMYL VLLKDLPGNEHSLPMEDVVELLQPLSLVCSLHRRDQDVCKTILSNVLHIV TNLGQGSVDMESTRIAQGHFLTVMGAFWHLTKEKKCVFSVRMALVKCLQT LLEADPYSEWAILNVKGQDFPVNEAFSQFLADDHHQVRMLAAGSVNRLFQ DMRQGDFSRSLKALPLKFQQTSFNNAYTTAEAGIRGLLCDSQNPDLLDEI YNRKSVLLMMIAVVLHCSPVCEKQALFALCKSVKENRLEPHLVKKVLEKV SESFGCRSLEDFMISHLDYLVLEWLNLQDTEYSLSSFPFMLLNYTSIEDF YRSCYKILIPHLVIRSHFDEVKSIANQIQKCWKSLLVDCFPKILVHILPY FAYEGTRDSYVSQKRETATKVYDTLKGEDFLGKQIDQVFISNLPEIVVEL LMTLHETADSADSDASQSATALCDFSGDLDPAPNPPYFPSHVIQATFAYI SNCHKTKFKSILEILSKIPDSYQKILLAICEQAAETNNVFKKHRILKIYH LFVSLLLKDIQSGLGGAWAFVLRDVIYTLIHYINKRSSHFTDVSLRSFSL CCDLLSRVCHTAVTQCKDALESHLHVIVGTLIPLVDYQEVQEQVLDLLKY LVIDNKDNKNLSVTIKLLDPFPDHVIFKDLRLTQQKIKYSGGPFSLLEEI NHFLSVSAYNPLPLTRLEGLKDLRRQLEQHKDQMLDLLRASQDNPQDGIV VKLVVSLLQLSKMAVNQTGEREVLEAVGRCLGEIGPLDFSTIAVQHNKDV SYTKAYGLPEDRELQWTLIMLTALNNTLVEDSVKIRSAAATCLKNILATK IGHIFWENYKTSADPMLTYLQPFRTSRKKFLEVPRSVKEDVLEGLDAVNL WVPQSESHDIWIKTLTCAFLDSGGINSEILQLLKPMCEVKTDFCQMLLPY LIHDVLLQDTHESWRTLLSAHVRGFFTSCFKHSSQASRSATPANSDSESE NFLRCCLDKKSQRTMLAVVDYLRRQKRPSSGTAFDDAFWLDLNYLEVAKV AQSCSAHFTALLYAEIYSDKKSTDEQEKRSPTFEEGSQGTTISSLSEKSK EETGISLQDLLLEIYRSIGEPDSLYGCGGGKMLQPLTRIRTYEHEATWEK ALVTYDLETSISSSTRQSGIIQALQNLGLSHILSVYLKGLDYERREWCAE LQELRYQAAWRNMQWGLCASAGQEVEGTSYHESLYNALQCLRNREFSTFY ESLRYASLFRVKEVEELSKGSLESVYSLYPTLSRLQAIGELENSGELFSR SVTDRERSEAYWKWQKHSQLLKDSDFSFQEPLMALRTVILETLVQKEMER SQGACSKDILTKHLVEFSVLARTFKNTQLPERAIFKIKQYNSAICGISEW HLEEAQVFWAKKEQSLALSILKQMIKKLDSSFKDKENDAGLKVIYAECLR VCGSWLAETCLENPAVIMQTYLEKAVKVAGSYDGNSRELRNGQMKAFLSL ARFSDTQYQRIENYMKSSEFENKQTLLKRAKEEVGLLREHKIQTNRYTVK VQRELELDECALRALREDRKRFLCKAVENYINCLLSGEEHDLWVFRLCSL WLENSGVSEVNGMMKKDGMKISSYKFLPLMYQLAARMGTKMTGGLGFHEV LNNLISRISLDHPHHTLFIILALANANKDEFLSKPETTRRSRITKSTSKE NSHLDEDRTEAATRIIHSIRSKRCKMVKDMEALCDAYIILANMDASQWRA QRKGINIPANQPITKLKNLEDVVVPTMEIKVDPTGEYENLVTIKSFKTEF RLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQ RNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEYLVNSEDGAHRR YRPNDFSANQCQKKMMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFL DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDL GVAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRS SQETLLTIVEVLLYDPLFDWTMNPLKALYLQQRPEDESDLHSTPNADDQE CKQSLSDTDQSFNKVAERVLMRLQEKLKGVEEGTVLSVGGQVNLLIQQAM DPKNLSRLFPGWKAWV |
Atm (Mus musculus) belongs to following protein families:
References:
| Title | Authors | Journal |
| Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene. | Pecker I, Avraham KB, Gilbert DJ, Savitsky K, Rotman G, Harnik R, Fukao T, Schrock E, Hirotsune S, Tagle DA, Collins FS, Wynshaw-Boris A, Ried T, Copeland NG, Jenkins NA, Shiloh Y, Ziv Y | Genomics July 1, 1996 |
| Analysis of the ATM protein in wild-type and ataxia telangiectasia cells. | Lakin ND, Weber P, Stankovic T, Rottinghaus ST, Taylor AM, Jackson SP | Oncogene Dec. 19, 1996 |
| ATM binds to beta-adaptin in cytoplasmic vesicles. | Lim DS, Kirsch DG, Canman CE, Ahn JH, Ziv Y, Newman LS, Darnell RB, Shiloh Y, Kastan MB | Proc Natl Acad Sci U S A Aug. 18, 1998 |
| Atm expression patterns suggest a contribution from the peripheral nervous system to the phenotype of ataxia-telangiectasia. | Soares HD, Morgan JI, McKinnon PJ | Neuroscience Oct. 1, 1998 |
| ATM phosphorylates histone H2AX in response to DNA double-strand breaks. | Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ | J Biol Chem Nov. 9, 2001 |
| Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo. | Daniel JA, Pellegrini M, Lee JH, Paull TT, Feigenbaum L, Nussenzweig A | J Cell Biol Dec. 1, 2008 |
| RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. | Hewitt SL, Yin B, Ji Y, Chaumeil J, Marszalek K, Tenthorey J, Salvagiotto G, Steinel N, Ramsey LB, Ghysdael J, Farrar MA, Sleckman BP, Schatz DG, Busslinger M, Bassing CH, Skok JA | Nat Immunol June 1, 2009 |
Last modification of this entry: Oct. 6, 2010.
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