Names & Taxonomy
- Uniprot ID:
- Q13315
- Entry Name:
- ATM_HUMAN
- Status:
- reviewed
- Protein Names:
- Serine-protein kinase ATM (EC 2.7.11.1) (Ataxia telangiectasia mutated) (A-T mutated)
- Gene Names:
- ATM
- Gene Names Primary:
- ATM
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 3056
- Sequence:
- MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGAIYGADCSNILLKDILSVRKYWCEISQQQWLELFSVYFRLYLKPSQDVHRVLVARIIHAVTKGCCSQTDGLNSKFLDFFSKAIQCARQEKSSSGLNHILAALTIFLKTLAVNFRIRVCELGDEILPTLLYIWTQHRLNDSLKEVIIELFQLQIYIHHPKGAKTQEKGAYESTKWRSILYNLYDLLVNEISHIGSRGKYSSGFRNIAVKENLIELMADICHQVFNEDTRSLEISQSYTTTQRESSDYSVPCKRKKIELGWEVIKDHLQKSQNDFDLVPWLQIATQLISKYPASLPNCELSPLLMILSQLLPQQRHGERTPYVLRCLTEVALCQDKRSNLESSQKSDLLKLWNKIWCITFRGISSEQIQAENFGLLGAIIQGSLVEVDREFWKLFTGSACRPSCPAVCCLTLALTTSIVPGTVKMGIEQNMCEVNRSFSLKESIMKWLLFYQLEGDLENSTEVPPILHSNFPHLVLEKILVSLTMKNCKAAMNFFQSVPECEHHQKDKEELSFSEVEELFLQTTFDKMDFLTIVRECGIEKHQSSIGFSVHQNLKESLDRCLLGLSEQLLNNYSSEITNSETLVRCSRLLVGVLGCYCYMGVIAEEEAYKSELFQKAKSLMQCAGESITLFKNKTNEEFRIGSLRNMMQLCTRCLSNCTKKSPNKIASGFFLRLLTSKLMNDIADICKSLASFIKKPFDRGEVESMEDDTNGNLMEVEDQSSMNLFNDYPDSSVSDANEPGESQSTIGAINPLAEEYLSKQDLLFLDMLKFLCLCVTTAQTNTVSFRAADIRRKLLMLIDSSTLEPTKSLHLHMYLMLLKELPGEEYPLPMEDVLELLKPLSNVCSLYRRDQDVCKTILNHVLHVVKNLGQSNMDSENTRDAQGQFLTVIGAFWHLTKERKYIFSVRMALVNCLKTLLEADPYSKWAILNVMGKDFPVNEVFTQFLADNHHQVRMLAAESINRLFQDTKGDSSRLLKALPLKLQQTAFENAYLKAQEGMREMSHSAENPETLDEIYNRKSVLLTLIAVVLSCSPICEKQALFALCKSVKENGLEPHLVKKVLEKVSETFGYRRLEDFMASHLDYLVLEWLNLQDTEYNLSSFPFILLNYTNIEDFYRSCYKVLIPHLVIRSHFDEVKSIANQIQEDWKSLLTDCFPKILVNILPYFAYEGTRDSGMAQQRETATKVYDMLKSENLLGKQIDHLFISNLPEIVVELLMTLHEPANSSASQSTDLCDFSGDLDPAPNPPHFPSHVIKATFAYISNCHKTKLKSILEILSKSPDSYQKILLAICEQAAETNNVYKKHRILKIYHLFVSLLLKDIKSGLGGAWAFVLRDVIYTLIHYINQRPSCIMDVSLRSFSLCCDLLSQVCQTAVTYCKDALENHLHVIVGTLIPLVYEQVEVQKQVLDLLKYLVIDNKDNENLYITIKLLDPFPDHVVFKDLRITQQKIKYSRGPFSLLEEINHFLSVSVYDALPLTRLEGLKDLRRQLELHKDQMVDIMRASQDNPQDGIMVKLVVNLLQLSKMAINHTGEKEVLEAVGSCLGEVGPIDFSTIAIQHSKDASYTKALKLFEDKELQWTFIMLTYLNNTLVEDCVKVRSAAVTCLKNILATKTGHSFWEIYKMTTDPMLAYLQPFRTSRKKFLEVPRFDKENPFEGLDDINLWIPLSENHDIWIKTLTCAFLDSGGTKCEILQLLKPMCEVKTDFCQTVLPYLIHDILLQDTNESWRNLLSTHVQGFFTSCLRHFSQTSRSTTPANLDSESEHFFRCCLDKKSQRTMLAVVDYMRRQKRPSSGTIFNDAFWLDLNYLEVAKVAQSCAAHFTALLYAEIYADKKSMDDQEKRSLAFEEGSQSTTISSLSEKSKEETGISLQDLLLEIYRSIGEPDSLYGCGGGKMLQPITRLRTYEHEAMWGKALVTYDLETAIPSSTRQAGIIQALQNLGLCHILSVYLKGLDYENKDWCPELEELHYQAAWRNMQWDHCTSVSKEVEGTSYHESLYNALQSLRDREFSTFYESLKYARVKEVEEMCKRSLESVYSLYPTLSRLQAIGELESIGELFSRSVTHRQLSEVYIKWQKHSQLLKDSDFSFQEPIMALRTVILEILMEKEMDNSQRECIKDILTKHLVELSILARTFKNTQLPERAIFQIKQYNSVSCGVSEWQLEEAQVFWAKKEQSLALSILKQMIKKLDASCAANNPSLKLTYTECLRVCGNWLAETCLENPAVIMQTYLEKAVEVAGNYDGESSDELRNGKMKAFLSLARFSDTQYQRIENYMKSSEFENKQALLKRAKEEVGLLREHKIQTNRYTVKVQRELELDELALRALKEDRKRFLCKAVENYINCLLSGEEHDMWVFRLCSLWLENSGVSEVNGMMKRDGMKIPTYKFLPLMYQLAARMGTKMMGGLGFHEVLNNLISRISMDHPHHTLFIILALANANRDEFLTKPEVARRSRITKNVPKQSSQLDEDRTEAANRIICTIRSRRPQMVRSVEALCDAYIILANLDATQWKTQRKGINIPADQPITKLKNLEDVVVPTMEIKVDHTGEYGNLVTIQSFKAEFRLAGGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEFLVNNEDGAHKRYRPNDFSAFQCQKKMMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCMEKFLDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLTRDIVDGMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWTMNPLKALYLQQRPEDETELHPTLNADDQECKRNLSDIDQSFNKVAERVLMRLQEKLKGVEEGTVLSVGGQVNLLIQQAIDPKNLSRLFPGWKAWV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Nucleus
Function
- 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 -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 DYRK2, CHEK2, 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. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Enzyme Regulation:
- ENZYME REGULATION: Inhibited by wortmannin.
- Cross Reference Drug Bank:
- DB00201
- Gene Ontology Go:
- cytoplasmic, membrane-bounded vesicle
DNA repair complex
nucleoplasm
spindle
1-phosphatidylinositol-3-kinase activity
ATP binding
DNA binding
DNA-dependent protein kinase activity
protein complex binding
protein dimerization activity
protein N-terminus binding
protein serine/threonine kinase activity
brain development
cell cycle arrest
cellular response to DNA damage stimulus
cellular response to gamma radiation
cellular response to heat
cellular response to nitrosative stress
determination of adult lifespan
DNA damage induced protein phosphorylation
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
DNA repair
double-strand break repair
double-strand break repair via homologous recombination
double-strand break repair via nonhomologous end joining
double-strand break repair via synthesis-dependent strand annealing
establishment of macromolecular complex localization to telomere
establishment of RNA localization to telomere
heart development
histone mRNA catabolic process
histone phosphorylation
intrinsic apoptotic signaling pathway in response to DNA damage
lipoprotein catabolic process
meiotic telomere clustering
mitotic spindle assembly checkpoint
negative regulation of B cell proliferation
negative regulation of telomere capping
negative regulation of TORC1 signaling
neuron apoptotic process
oocyte development
peptidyl-serine autophosphorylation
peptidyl-serine phosphorylation
phosphatidylinositol-3-phosphate biosynthetic process
positive regulation of apoptotic process
positive regulation of DNA damage response, signal transduction by p53 class mediator
positive regulation of histone phosphorylation
positive regulation of neuron apoptotic process
positive regulation of telomerase catalytic core complex assembly
positive regulation of telomere maintenance via telomerase
positive regulation of telomere maintenance via telomere lengthening
pre-B cell allelic exclusion
protein autophosphorylation
protein phosphorylation
reciprocal meiotic recombination
regulation of autophagy
regulation of cellular response to heat
replicative senescence
response to hypoxia
response to ionizing radiation
signal transduction
signal transduction involved in mitotic G2 DNA damage checkpoint
somitogenesis
telomere maintenance via telomerase
V(D)J recombination - Gene Ontology Biological Process:
- brain development
cell cycle arrest
cellular response to DNA damage stimulus
cellular response to gamma radiation
cellular response to heat
cellular response to nitrosative stress
determination of adult lifespan
DNA damage induced protein phosphorylation
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
DNA repair
double-strand break repair
double-strand break repair via homologous recombination
double-strand break repair via nonhomologous end joining
double-strand break repair via synthesis-dependent strand annealing
establishment of macromolecular complex localization to telomere
establishment of RNA localization to telomere
heart development
histone mRNA catabolic process
histone phosphorylation
intrinsic apoptotic signaling pathway in response to DNA damage
lipoprotein catabolic process
meiotic telomere clustering
mitotic spindle assembly checkpoint
negative regulation of B cell proliferation
negative regulation of telomere capping
negative regulation of TORC1 signaling
neuron apoptotic process
oocyte development
peptidyl-serine autophosphorylation
peptidyl-serine phosphorylation
phosphatidylinositol-3-phosphate biosynthetic process
positive regulation of apoptotic process
positive regulation of DNA damage response, signal transduction by p53 class mediator
positive regulation of histone phosphorylation
positive regulation of neuron apoptotic process
positive regulation of telomerase catalytic core complex assembly
positive regulation of telomere maintenance via telomerase
positive regulation of telomere maintenance via telomere lengthening
pre-B cell allelic exclusion
protein autophosphorylation
protein phosphorylation
reciprocal meiotic recombination
regulation of autophagy
regulation of cellular response to heat
replicative senescence
response to hypoxia
response to ionizing radiation
signal transduction
signal transduction involved in mitotic G2 DNA damage checkpoint
somitogenesis
telomere maintenance via telomerase
V(D)J recombination - Gene Ontology Molecular Function:
- 1-phosphatidylinositol-3-kinase activity
ATP binding
DNA binding
DNA-dependent protein kinase activity
protein complex binding
protein dimerization activity
protein N-terminus binding
protein serine/threonine kinase activity - Gene Ontology Cellular Component:
- cytoplasmic, membrane-bounded vesicle
DNA repair complex
nucleoplasm
spindle - Keywords:
- ATP-binding
Acetylation
Cell cycle
Complete proteome
Cytoplasmic vesicle
DNA damage
DNA-binding
Disease mutation
Kinase
Neurodegeneration
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
Tumor suppressor - Interacts With:
- P27958; Q9NY61; O43313; Q6PJG6; Q9Y6K9; Q13007; Q14676; Q9BQ15; P11245; Q9Y4R8; P54274; P54274-2; O43156; Q9BZ95
Publication
- PubMed ID:
- 8589678 8665503 9199932 16554811 8789452 9108147 7792600 15489334 8521392 8969240 9050866 9150358 8988033 9168117 9766667 9843217 9707615 9733514 9733515 10500142 10550055 10783165 10766245 10839545 10910365 10802669 10973490 11375976 11418864 12086603 12409306 12556884 14871926 15456891 15680327 15916964 15923642 16086026 16141325 16858402 17525732 17923702 17525332 18283122 18691976 18449195 18710941 19369195 19965871 20810650 20801936 20427287 21269460 21144835 22977523 22223895 24275569 8755918 8808599 8797579 9043869 8698354 8845835 9288106 9334731 9443866 9463314 9497252 9450874 9573030 9872980 9521587 9711876 9792409 9792410 9488043 10397742 9892178 10234507 10534763 9887333 10425038 10023947 10217116 10817650 10873394 10706620 17344846