Q9JKK8
uniprot
Q9JKK8
canonical
activity_regulation
ACTIVITY REGULATION: Serine/threonine-protein kinase activity is directly stimulated by TOPBP1. ATR kinase activity is also directly activated by ETAA1, independently of TOPBP1. Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. {ECO:0000250|UniProtKB:Q13535}.
uniprot
proteins
amino_acid_sequence
MGDHGLELASMIPALRELGSATPEEYNTVVQKPRQILCQFIDRILTDVNVVALELVKKTDAQPTSVMLLDFIQHIMKSSPLMFVNVNGSQGQNEAKDSCIEFSHWIITRLLRIAATPSCHMLHKKICEVICSLLFLFKSKNPAIFGVLTRELLYLFEDLIYLHKRNAVGEVMEWPVVVSRFLSRLDEHMGCLQPAPLQFMNVQNVEFIEVTLLMVLIHIVPTVFFRRQELLLWQIGCALLEHGSPKIRSLAISLLTELFELGGLPAQPASTFFSLFLELLQHLVGMDADQLKLYEEPLSKLLKTLFPFEAEAYRNIEPVYLNVLLEKLSVMFEDRVLMRLKSDLLKAALCHLLQYFLTFVPAGYESALQVRKVYVTNICRALVDALGVQKHVGYLLGPFYAALKMESKEIIERIQCQAQQENLSGNNDEVSPKRRKLSSSLSSYKKPSRQPEEIIHVDMDKKSILWNVLKQKAESLQISLECGTLKNSVAEALEGITVVLQLTALCTVHCSHQDMDGHNVKDHQHKYKKKPPVVVTWMSLDFYTKVLKSCRSLLESVQKLELELVIDSMVRICDALMYMQVKSSFKDHVLEELCGMLSLPWIYSYSDDNSLKMTTFATNLLPLSQRVWDSYSPQAQSKCVFLLTLFPRRIFLEWRTAVYNWALKSSHEVIRASCVKGFFILLHQQNSCNQIPKMLVDRVKDDSDMVKKEFASVLGQLVCTLHGMFYLSSSVEPCFEHMDLFSKNLKATSQHECSSSQVKASTCKPFLFLLTKNTPSPVKLAFIDNLHHLCKHLDFQEDEREVKAVLGTLLNLMEDPDKDVRIAFSGNIKYILESLNSEDGFVKELFVLRMKEAYTHAQIARNNELKDTLILTTGDIGRAAKGDLIPFALLHLLHCLLSKSASVSGAAYTEIRALVAAKSVKLQNFFSQYKKPICQFLVESLHSSQMTALPSAPCQSSEIRKQDVAHHREMALNTLSEIANVFDFPDLNRFLTRTLQVLLPDLAAKASPAASALIRTLGKQLNVSRREILINNFKYIFSHLVCSCSKDELERALHYLKNETEIELGSLLRQDFQGLHNELLLRIGEHYQQVFNGLSILASFASSDDPYQGPRDITSPELMADYLQPKLLGILAFFNMQLLSSSVGIEDKKMALTSLMSLMKLMGPKHVSSVRVKMMTTLRTGLRFKDDFPELCCRAWDCFVRCLDHAYLGPLLSHVIVALLPLIHMQPKETAAIFHYLIIENRDAVQDFLHEIYFLPDHPELEKIKAVLQEYRKETSETTDLQTTLQLSMKAIQHENVDVRIHALTSLKETLYKNQEKLIKYATDSETVEPVISQLVTVILKGCQDANSQARLLCGECLGELGAIDPGRLDFSTTETQGKDFTFVTGVEDLSFAYGLLMELTRAYLAYADNSRAQDSAAYAIQELLSIYDCREMQSNGPGYQLWKRFPEHVREILEPHLNTRYKSSQKSTDWSGVTKPIYLSKLGNNFAEWSSSWAGYLITKVRDNLASKIFTCCSIMMKHDFKVTIYLLPHILVYVLLGCNQEDQQEVYAEIMAVLKHDEQHAISTQDSASDLCQLSTQTVFSVLDHLTQWARHKFQALNAEKLAQNKPKGVSNVNFEDYQSVTRFLDLIPQDTLAVASFRSKAYTRAVMHFESFITEKKQNIQKHLGFLQKLYAAMHEPDGVAGVSAIRKAEPSLKEQILEHESIGLLRDATACYDRAIQLEPDQIIHYHGVVKSMLGLGQLSTVITQVNGVHANRSEWTDELNTYRVEAAWKLSQWDLVENYLAADGKSTTWSVRLGQLLLSAKKRDTTTFYDTLKLVRAEQIVPLSAASFERGSYQRGYEFIVRLHMLCELEHSLKPLFRKSPGDSCNEDSLNWGARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMVGECWLQSARVARKAGHHQTAYNALLNAGESRLAELYVERAKWLWSKGDVHQALIVLQKGVELCFPENKSPSESKHMLIHGRATLLVGRFMEETANFESNAVMKKYKDVTLFLPEWEDGHFYLAKYYDKLMPMVTDNKMEKQGDLIRYIVLHFGRSLQYGNQFIYQSMPRMLSLWLDFGAKAYEWEKGGRSDRLQMRNDLAKINSVLTEHTNRLAPYQFLTAFSQLISRICHSHDEVFVVLMEIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILTKAIHMKKSLEKFVGDATRLTDKLLELCNKSVDGSNSTLSMSTHFKMLKRLVEDPTFSEILIPLQSVMIPTLPSVLGAHANHDPFPGHWAYLAGFDDVVEILSSLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKSLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKIYKEKGVYMTGKELRQCMLPKSAALSEKLKVFQELLLPRHPPVFHEWFLRTFPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSFTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTLRLMRDQREPLMSVLKTFLHDPLVEGSKPVKGHSKAPLNETGEVVNEKAKTHVLDIEQRLQGVIKTRNRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGWTPYM
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
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 (PubMed:12629044, PubMed:8843195). Recognizes the substrate consensus sequence [ST]-Q (By similarity). Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RBBP8, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis (PubMed:12629044, PubMed:8843195). Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism (By similarity). Required for FANCD2 ubiquitination (By similarity). Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication (By similarity). Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2 (By similarity). Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress (By similarity). Acts as a mechanical stress sensor at the nuclear envelope: relocalizes to the nuclear envelope in response to mechanical stress and mediates a checkpoint via phosphorylation of CHEK1 (By similarity). Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly (By similarity). Involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability and catalyzing phosphorylation of LMNA at 'Ser-395', priming LMNA for subsequent phosphorylation by CDK1 and micronuclei envelope rupture (By similarity). The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity (By similarity). Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (PubMed:29125140). Essential for preventing the occurrence of DNA damage during early embryogenesis (PubMed:10691732, PubMed:10801416). {ECO:0000250|UniProtKB:Q13535, ECO:0000269|PubMed:10691732, ECO:0000269|PubMed:10801416, ECO:0000269|PubMed:12629044, ECO:0000269|PubMed:29125140, ECO:0000269|PubMed:8843195}.
uniprot
proteins
mass_dalton
300224
uniprot
proteins
post_translational_modification
PTM: Phosphorylated; autophosphorylates in vitro. {ECO:0000250|UniProtKB:Q13535}.
uniprot
proteins
protein_family
ATM subfamily
uniprot
proteins
protein_family
PI3/PI4-kinase family
uniprot
proteins
pubmed
10691732
uniprot
proteins
pubmed
10801416
uniprot
proteins
pubmed
12629044
uniprot
proteins
pubmed
15449545
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20801936
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22549958
uniprot
proteins
pubmed
23039116
uniprot
proteins
pubmed
29125140
uniprot
proteins
pubmed
8843195
uniprot
proteins
sequence_length
2635
uniprot
proteins
subcellular_location
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}.
uniprot
proteins