Protein: Serine/threonine-protein kinase ATR (EC 2.7.11.1) (Ataxia telangiectasia and Rad3-related protein) (Q9JKK8)
Organism: Mus musculus (Mouse)
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 [ST]-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 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 (By similarity). Positively regulates the restart of stalled replication forks following activation by the KHDC3-OOEP scaffold complex. Essential for preventing the occurrence of DNA damage during early embryogenesis.
Subcellular location: Nucleus {ECO:0000250|UniProtKB:Q13535}. Chromosome {ECO:0000269|PubMed:22549958, ECO:0000269|PubMed:23039116, ECO:0000269|PubMed:8843195}. Nucleus envelope {ECO:0000250|UniProtKB:Q13535}. Note=Depending on the cell type, it can also be found in PML nuclear bodies. Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling. Relocalizes to the nuclear envelope in response to mechanical stress or DNA damage. Also localizes to the micronuclear envelope in response to response to genome instability. {ECO:0000250|UniProtKB:Q13535}.
Interaction partners:
- Serine-protein kinase ATM
- ATR-interacting protein
- Serine/threonine-protein kinase Chk1
- Serine/threonine-protein kinase Chk2
- Breast cancer type 1 susceptibility protein homolog
- Cell division cycle 7-related protein kinase
- DNA topoisomerase 2-binding protein 1
- Cellular tumor antigen p53
- Telomere length regulation protein TEL2 homolog
- Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
Sequence:
MGDHGLELASMIPALRELGSATPEEYNTVVQKPRQILCQFIDRILTDVNVVALELVKKTDAQPTSVMLLDFIQHIMKSSPLMFVNVNGSQGQNEAKDSCIEFSHWIITRLLRIAATPSCHMLHKKICEVICSLLFLFKSKNPAIFGVLTRELLYLFEDLIYLHKRNAVGEVMEWPVVVSRFLSRLDEHMGCLQPAPLQFMNVQNVEFIEVTLLMVLIHIVPTVFFRRQELLLWQIGCALLEHGSPKIRSLAISLLTELFELGGLPAQPASTFFSLFLELLQHLVGMDADQLKLYEEPLSKLLKTLFPFEAEAYRNIEPVYLNVLLEKLSVMFEDRVLMRLKSDLLKAALCHLLQYFLTFVPAGYESALQVRKVYVTNICRALVDALGVQKHVGYLLGPFYAALKMESKEIIERIQCQAQQENLSGNNDEVSPKRRKLSSSLSSYKKPSRQPEEIIHVDMDKKSILWNVLKQKAESLQISLECGTLKNSVAEALEGITVVLQLTALCTVHCSHQDMDGHNVKDHQHKYKKKPPVVVTWMSLDFYTKVLKSCRSLLESVQKLELELVIDSMVRICDALMYMQVKSSFKDHVLEELCGMLSLPWIYSYSDDNSLKMTTFATNLLPLSQRVWDSYSPQAQSKCVFLLTLFPRRIFLEWRTAVYNWALKSSHEVIRASCVKGFFILLHQQNSCNQIPKMLVDRVKDDSDMVKKEFASVLGQLVCTLHGMFYLSSSVEPCFEHMDLFSKNLKATSQHECSSSQVKASTCKPFLFLLTKNTPSPVKLAFIDNLHHLCKHLDFQEDEREVKAVLGTLLNLMEDPDKDVRIAFSGNIKYILESLNSEDGFVKELFVLRMKEAYTHAQIARNNELKDTLILTTGDIGRAAKGDLIPFALLHLLHCLLSKSASVSGAAYTEIRALVAAKSVKLQNFFSQYKKPICQFLVESLHSSQMTALPSAPCQSSEIRKQDVAHHREMALNTLSEIANVFDFPDLNRFLTRTLQVLLPDLAAKASPAASALIRTLGKQLNVSRREILINNFKYIFSHLVCSCSKDELERALHYLKNETEIELGSLLRQDFQGLHNELLLRIGEHYQQVFNGLSILASFASSDDPYQGPRDITSPELMADYLQPKLLGILAFFNMQLLSSSVGIEDKKMALTSLMSLMKLMGPKHVSSVRVKMMTTLRTGLRFKDDFPELCCRAWDCFVRCLDHAYLGPLLSHVIVALLPLIHMQPKETAAIFHYLIIENRDAVQDFLHEIYFLPDHPELEKIKAVLQEYRKETSETTDLQTTLQLSMKAIQHENVDVRIHALTSLKETLYKNQEKLIKYATDSETVEPVISQLVTVILKGCQDANSQARLLCGECLGELGAIDPGRLDFSTTETQGKDFTFVTGVEDLSFAYGLLMELTRAYLAYADNSRAQDSAAYAIQELLSIYDCREMQSNGPGYQLWKRFPEHVREILEPHLNTRYKSSQKSTDWSGVTKPIYLSKLGNNFAEWSSSWAGYLITKVRDNLASKIFTCCSIMMKHDFKVTIYLLPHILVYVLLGCNQEDQQEVYAEIMAVLKHDEQHAISTQDSASDLCQLSTQTVFSVLDHLTQWARHKFQALNAEKLAQNKPKGVSNVNFEDYQSVTRFLDLIPQDTLAVASFRSKAYTRAVMHFESFITEKKQNIQKHLGFLQKLYAAMHEPDGVAGVSAIRKAEPSLKEQILEHESIGLLRDATACYDRAIQLEPDQIIHYHGVVKSMLGLGQLSTVITQVNGVHANRSEWTDELNTYRVEAAWKLSQWDLVENYLAADGKSTTWSVRLGQLLLSAKKRDTTTFYDTLKLVRAEQIVPLSAASFERGSYQRGYEFIVRLHMLCELEHSLKPLFRKSPGDSCNEDSLNWGARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMVGECWLQSARVARKAGHHQTAYNALLNAGESRLAELYVERAKWLWSKGDVHQALIVLQKGVELCFPENKSPSESKHMLIHGRATLLVGRFMEETANFESNAVMKKYKDVTLFLPEWEDGHFYLAKYYDKLMPMVTDNKMEKQGDLIRYIVLHFGRSLQYGNQFIYQSMPRMLSLWLDFGAKAYEWEKGGRSDRLQMRNDLAKINSVLTEHTNRLAPYQFLTAFSQLISRICHSHDEVFVVLMEIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILTKAIHMKKSLEKFVGDATRLTDKLLELCNKSVDGSNSTLSMSTHFKMLKRLVEDPTFSEILIPLQSVMIPTLPSVLGAHANHDPFPGHWAYLAGFDDVVEILSSLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKSLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKIYKEKGVYMTGKELRQCMLPKSAALSEKLKVFQELLLPRHPPVFHEWFLRTFPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSFTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTLRLMRDQREPLMSVLKTFLHDPLVEGSKPVKGHSKAPLNETGEVVNEKAKTHVLDIEQRLQGVIKTRNRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGWTPYM