Names & Taxonomy

Uniprot ID:
Q13535
Entry Name:
ATR_HUMAN
Status:
reviewed
Protein Names:
Serine/threonine-protein kinase ATR (EC 2.7.11.1) (Ataxia telangiectasia and Rad3-related protein) (FRAP-related protein 1)
Gene Names:
ATR FRP1
Gene Names Primary:
ATR
Organism:
Homo sapiens (Human)

Structure

Length:
2644
Sequence:
MGEHGLELASMIPALRELGSATPEEYNTVVQKPRQILCQFIDRILTDVNVVAVELVKKTDSQPTSVMLLDFIQHIMKSSPLMFVNVSGSHEAKGSCIEFSNWIITRLLRIAATPSCHLLHKKICEVICSLLFLFKSKSPAIFGVLTKELLQLFEDLVYLHRRNVMGHAVEWPVVMSRFLSQLDEHMGYLQSAPLQLMSMQNLEFIEVTLLMVLTRIIAIVFFRRQELLLWQIGCVLLEYGSPKIKSLAISFLTELFQLGGLPAQPASTFFSSFLELLKHLVEMDTDQLKLYEEPLSKLIKTLFPFEAEAYRNIEPVYLNMLLEKLCVMFEDGVLMRLKSDLLKAALCHLLQYFLKFVPAGYESALQVRKVYVRNICKALLDVLGIEVDAEYLLGPLYAALKMESMEIIEEIQCQTQQENLSSNSDGISPKRRRLSSSLNPSKRAPKQTEEIKHVDMNQKSILWSALKQKAESLQISLEYSGLKNPVIEMLEGIAVVLQLTALCTVHCSHQNMNCRTFKDCQHKSKKKPSVVITWMSLDFYTKVLKSCRSLLESVQKLDLEATIDKVVKIYDALIYMQVNSSFEDHILEDLCGMLSLPWIYSHSDDGCLKLTTFAANLLTLSCRISDSYSPQAQSRCVFLLTLFPRRIFLEWRTAVYNWALQSSHEVIRASCVSGFFILLQQQNSCNRVPKILIDKVKDDSDIVKKEFASILGQLVCTLHGMFYLTSSLTEPFSEHGHVDLFCRNLKATSQHECSSSQLKASVCKPFLFLLKKKIPSPVKLAFIDNLHHLCKHLDFREDETDVKAVLGTLLNLMEDPDKDVRVAFSGNIKHILESLDSEDGFIKELFVLRMKEAYTHAQISRNNELKDTLILTTGDIGRAAKGDLVPFALLHLLHCLLSKSASVSGAAYTEIRALVAAKSVKLQSFFSQYKKPICQFLVESLHSSQMTALPNTPCQNADVRKQDVAHQREMALNTLSEIANVFDFPDLNRFLTRTLQVLLPDLAAKASPAASALIRTLGKQLNVNRREILINNFKYIFSHLVCSCSKDELERALHYLKNETEIELGSLLRQDFQGLHNELLLRIGEHYQQVFNGLSILASFASSDDPYQGPRDIISPELMADYLQPKLLGILAFFNMQLLSSSVGIEDKKMALNSLMSLMKLMGPKHVSSVRVKMMTTLRTGLRFKDDFPELCCRAWDCFVRCLDHACLGSLLSHVIVALLPLIHIQPKETAAIFHYLIIENRDAVQDFLHEIYFLPDHPELKKIKAVLQEYRKETSESTDLQTTLQLSMKAIQHENVDVRIHALTSLKETLYKNQEKLIKYATDSETVEPIISQLVTVLLKGCQDANSQARLLCGECLGELGAIDPGRLDFSTTETQGKDFTFVTGVEDSSFAYGLLMELTRAYLAYADNSRAQDSAAYAIQELLSIYDCREMETNGPGHQLWRRFPEHVREILEPHLNTRYKSSQKSTDWSGVKKPIYLSKLGSNFAEWSASWAGYLITKVRHDLASKIFTCCSIMMKHDFKVTIYLLPHILVYVLLGCNQEDQQEVYAEIMAVLKHDDQHTINTQDIASDLCQLSTQTVFSMLDHLTQWARHKFQALKAEKCPHSKSNRNKVDSMVSTVDYEDYQSVTRFLDLIPQDTLAVASFRSKAYTRAVMHFESFITEKKQNIQEHLGFLQKLYAAMHEPDGVAGVSAIRKAEPSLKEQILEHESLGLLRDATACYDRAIQLEPDQIIHYHGVVKSMLGLGQLSTVITQVNGVHANRSEWTDELNTYRVEAAWKLSQWDLVENYLAADGKSTTWSVRLGQLLLSAKKRDITAFYDSLKLVRAEQIVPLSAASFERGSYQRGYEYIVRLHMLCELEHSIKPLFQHSPGDSSQEDSLNWVARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMVGECWLQSARVARKAGHHQTAYNALLNAGESRLAELYVERAKWLWSKGDVHQALIVLQKGVELCFPENETPPEGKNMLIHGRAMLLVGRFMEETANFESNAIMKKYKDVTACLPEWEDGHFYLAKYYDKLMPMVTDNKMEKQGDLIRYIVLHFGRSLQYGNQFIYQSMPRMLTLWLDYGTKAYEWEKAGRSDRVQMRNDLGKINKVITEHTNYLAPYQFLTAFSQLISRICHSHDEVFVVLMEIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILNKAIHMKKSLEKFVGDATRLTDKLLELCNKPVDGSSSTLSMSTHFKMLKKLVEEATFSEILIPLQSVMIPTLPSILGTHANHASHEPFPGHWAYIAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTGKELRQCMLPKSAALSEKLKVFREFLLPRHPPIFHEWFLRTFPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSKPVKGHSKAPLNETGEVVNEKAKTHVLDIEQRLQGVIKTRNRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGWTPYM
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus

Function

Function:
Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence -Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication.
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Cofactor:
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
Enzyme Regulation:
ENZYME REGULATION: Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002.
Gene Ontology Go:
chromosome
Golgi apparatus
nucleoplasm
PML body
ATP binding
DNA binding
MutLalpha complex binding
MutSalpha complex binding
protein kinase activity
protein serine/threonine kinase activity
cell cycle
cellular response to DNA damage stimulus
cellular response to gamma radiation
cellular response to heat
cellular response to UV
DNA damage checkpoint
DNA repair
DNA replication
double-strand break repair
double-strand break repair via homologous recombination
establishment of macromolecular complex localization to telomere
establishment of RNA localization to telomere
interstrand cross-link repair
multicellular organism development
negative regulation of DNA replication
peptidyl-serine phosphorylation
positive regulation of DNA damage response, signal transduction by p53 class mediator
positive regulation of telomerase catalytic core complex assembly
positive regulation of telomere maintenance via telomerase
protein autophosphorylation
protein localization to chromosome, telomeric region
regulation of cellular response to heat
replicative senescence
response to drug
Gene Ontology Biological Process:
cell cycle
cellular response to DNA damage stimulus
cellular response to gamma radiation
cellular response to heat
cellular response to UV
DNA damage checkpoint
DNA repair
DNA replication
double-strand break repair
double-strand break repair via homologous recombination
establishment of macromolecular complex localization to telomere
establishment of RNA localization to telomere
interstrand cross-link repair
multicellular organism development
negative regulation of DNA replication
peptidyl-serine phosphorylation
positive regulation of DNA damage response, signal transduction by p53 class mediator
positive regulation of telomerase catalytic core complex assembly
positive regulation of telomere maintenance via telomerase
protein autophosphorylation
protein localization to chromosome, telomeric region
regulation of cellular response to heat
replicative senescence
response to drug
Gene Ontology Molecular Function:
ATP binding
DNA binding
MutLalpha complex binding
MutSalpha complex binding
protein kinase activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:
chromosome
Golgi apparatus
nucleoplasm
PML body
Keywords:
ATP-binding
Alternative splicing
Chromosome
Complete proteome
DNA damage
DNA repair
DNA-binding
Disease mutation
Dwarfism
Kinase
Manganese
Mental retardation
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Interacts With:
Q99459; P50750; Q9Y6K9; O43156

Publication

PubMed ID:
8978690 8610130 11470508 8843195 9766667 9427750 9636169 10545197 9925639 10608806 10597277 10859164 11114888 11673449 11418864 11721054 12526805 11865061 12011431 12814551 12766152 14657349 12791985 15050919 14742437 14871897 15314022 15496423 14729973 15210935 15680327 15758953 18283122 12640452 16260606 18691976 18669648 19413330 20810650 20801936 20427287 21269460 21144835 21406692 17344846 22341969