ATR
entrez
545
canonical
uniprot
Q13535
canonical
ensembl
ENSG00000175054
resolver
ensp
ENSP00000343741
resolver
ensp
ENSP00000499589
resolver
genesymbol
ATR
resolver
genesymbol_syn
FRP1
resolver
hgnc
HGNC:882
resolver
uniprot
Q59HB2
resolver
uniprot
Q7KYL3
resolver
uniprot
Q93051
resolver
uniprot
Q9BXK4
resolver
uniprot_entry
ATR_HUMAN
resolver
uniprot_sec
Q59HB2
resolver
uniprot_sec
Q7KYL3
resolver
uniprot_sec
Q93051
resolver
uniprot_sec
Q9BXK4
resolver
activity_regulation
ACTIVITY REGULATION: Serine/threonine-protein kinase activity is directly stimulated by TOPBP1 (PubMed:16530042, PubMed:21777809). ATR kinase activity is also directly activated by ETAA1, independently of TOPBP1 (PubMed:27723717, PubMed:27723720, PubMed:30139873). Activated by DNA and inhibited by BCR-ABL oncogene (PubMed:10597277). Slightly activated by ATRIP (PubMed:14729973). Inhibited by caffeine, wortmannin and LY294002 (PubMed:9766667). {ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:14729973, ECO:0000269|PubMed:16530042, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:9766667}.
uniprot
proteins
amino_acid_sequence
MGEHGLELASMIPALRELGSATPEEYNTVVQKPRQILCQFIDRILTDVNVVAVELVKKTDSQPTSVMLLDFIQHIMKSSPLMFVNVSGSHEAKGSCIEFSNWIITRLLRIAATPSCHLLHKKICEVICSLLFLFKSKSPAIFGVLTKELLQLFEDLVYLHRRNVMGHAVEWPVVMSRFLSQLDEHMGYLQSAPLQLMSMQNLEFIEVTLLMVLTRIIAIVFFRRQELLLWQIGCVLLEYGSPKIKSLAISFLTELFQLGGLPAQPASTFFSSFLELLKHLVEMDTDQLKLYEEPLSKLIKTLFPFEAEAYRNIEPVYLNMLLEKLCVMFEDGVLMRLKSDLLKAALCHLLQYFLKFVPAGYESALQVRKVYVRNICKALLDVLGIEVDAEYLLGPLYAALKMESMEIIEEIQCQTQQENLSSNSDGISPKRRRLSSSLNPSKRAPKQTEEIKHVDMNQKSILWSALKQKAESLQISLEYSGLKNPVIEMLEGIAVVLQLTALCTVHCSHQNMNCRTFKDCQHKSKKKPSVVITWMSLDFYTKVLKSCRSLLESVQKLDLEATIDKVVKIYDALIYMQVNSSFEDHILEDLCGMLSLPWIYSHSDDGCLKLTTFAANLLTLSCRISDSYSPQAQSRCVFLLTLFPRRIFLEWRTAVYNWALQSSHEVIRASCVSGFFILLQQQNSCNRVPKILIDKVKDDSDIVKKEFASILGQLVCTLHGMFYLTSSLTEPFSEHGHVDLFCRNLKATSQHECSSSQLKASVCKPFLFLLKKKIPSPVKLAFIDNLHHLCKHLDFREDETDVKAVLGTLLNLMEDPDKDVRVAFSGNIKHILESLDSEDGFIKELFVLRMKEAYTHAQISRNNELKDTLILTTGDIGRAAKGDLVPFALLHLLHCLLSKSASVSGAAYTEIRALVAAKSVKLQSFFSQYKKPICQFLVESLHSSQMTALPNTPCQNADVRKQDVAHQREMALNTLSEIANVFDFPDLNRFLTRTLQVLLPDLAAKASPAASALIRTLGKQLNVNRREILINNFKYIFSHLVCSCSKDELERALHYLKNETEIELGSLLRQDFQGLHNELLLRIGEHYQQVFNGLSILASFASSDDPYQGPRDIISPELMADYLQPKLLGILAFFNMQLLSSSVGIEDKKMALNSLMSLMKLMGPKHVSSVRVKMMTTLRTGLRFKDDFPELCCRAWDCFVRCLDHACLGSLLSHVIVALLPLIHIQPKETAAIFHYLIIENRDAVQDFLHEIYFLPDHPELKKIKAVLQEYRKETSESTDLQTTLQLSMKAIQHENVDVRIHALTSLKETLYKNQEKLIKYATDSETVEPIISQLVTVLLKGCQDANSQARLLCGECLGELGAIDPGRLDFSTTETQGKDFTFVTGVEDSSFAYGLLMELTRAYLAYADNSRAQDSAAYAIQELLSIYDCREMETNGPGHQLWRRFPEHVREILEPHLNTRYKSSQKSTDWSGVKKPIYLSKLGSNFAEWSASWAGYLITKVRHDLASKIFTCCSIMMKHDFKVTIYLLPHILVYVLLGCNQEDQQEVYAEIMAVLKHDDQHTINTQDIASDLCQLSTQTVFSMLDHLTQWARHKFQALKAEKCPHSKSNRNKVDSMVSTVDYEDYQSVTRFLDLIPQDTLAVASFRSKAYTRAVMHFESFITEKKQNIQEHLGFLQKLYAAMHEPDGVAGVSAIRKAEPSLKEQILEHESLGLLRDATACYDRAIQLEPDQIIHYHGVVKSMLGLGQLSTVITQVNGVHANRSEWTDELNTYRVEAAWKLSQWDLVENYLAADGKSTTWSVRLGQLLLSAKKRDITAFYDSLKLVRAEQIVPLSAASFERGSYQRGYEYIVRLHMLCELEHSIKPLFQHSPGDSSQEDSLNWVARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMVGECWLQSARVARKAGHHQTAYNALLNAGESRLAELYVERAKWLWSKGDVHQALIVLQKGVELCFPENETPPEGKNMLIHGRAMLLVGRFMEETANFESNAIMKKYKDVTACLPEWEDGHFYLAKYYDKLMPMVTDNKMEKQGDLIRYIVLHFGRSLQYGNQFIYQSMPRMLTLWLDYGTKAYEWEKAGRSDRVQMRNDLGKINKVITEHTNYLAPYQFLTAFSQLISRICHSHDEVFVVLMEIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILNKAIHMKKSLEKFVGDATRLTDKLLELCNKPVDGSSSTLSMSTHFKMLKKLVEEATFSEILIPLQSVMIPTLPSILGTHANHASHEPFPGHWAYIAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTGKELRQCMLPKSAALSEKLKVFREFLLPRHPPIFHEWFLRTFPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSKPVKGHSKAPLNETGEVVNEKAKTHVLDIEQRLQGVIKTRNRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGWTPYM
uniprot
proteins
disease_involvement
DISEASE: Seckel syndrome 1 (SCKL1) [MIM:210600]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability. {ECO:0000269|PubMed:12640452}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cutaneous telangiectasia and cancer syndrome, familial (FCTCS) [MIM:614564]: A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well. {ECO:0000269|PubMed:22341969}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:27723717, PubMed:27723720, PubMed:30139873, PubMed:33848395, PubMed:37788673, PubMed:37832547, PubMed:9427750, PubMed:9636169). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:23273981, PubMed:27723717, PubMed:27723720, PubMed:33848395, PubMed:9427750, PubMed:9636169). 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:11114888, PubMed:11418864, PubMed:11865061, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:9925639). Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism (PubMed:11673449). Required for FANCD2 ubiquitination (PubMed:15314022). Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication (PubMed:12526805). Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2 (PubMed:30139873). Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress (PubMed:25083873, PubMed:37788673, PubMed:37832547). 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 (PubMed:25083873). Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly (PubMed:37832547). 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 (PubMed:37788673). The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity (PubMed:37788673). Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity). {ECO:0000250|UniProtKB:Q9JKK8, ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:10608806, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:11721054, ECO:0000269|PubMed:11865061, ECO:0000269|PubMed:12526805, ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14729973, ECO:0000269|PubMed:14742437, ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15496423, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:33848395, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547, ECO:0000269|PubMed:9427750, ECO:0000269|PubMed:9636169, ECO:0000269|PubMed:9925639}.
uniprot
proteins
mass_dalton
301367
uniprot
proteins
mutagenesis
MUTAGEN 1989; /note="T->A: Impaired autophosphorylation, leading to decreased activation of ATR."; /evidence="ECO:0000269|PubMed:21705319"; MUTAGEN 2327; /note="K->R: Abolishes kinase activity."; /evidence="ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:12011431, ECO:0000269|PubMed:9925639"; MUTAGEN 2475; /note="D->A: Abolishes kinase activity; increases sensitivity to IR and impairs translocation to nuclear foci upon DNA damage."; /evidence="ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:9427750, ECO:0000269|PubMed:9925639"; MUTAGEN 2494; /note="D->E: Abolishes kinase activity; reduces cell viability, augments sensitivity to IR and UV."; /evidence="ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:9636169
uniprot
proteins
post_translational_modification
PTM: Phosphorylated (PubMed:21144835). Autophosphorylation at Thr-1989 in response to DNA damage promotes interaction with TOPBP1 and activation of ATR (PubMed:21705319, PubMed:21777809). {ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:21705319, ECO:0000269|PubMed:21777809}.
uniprot
proteins
protein_family
ATM subfamily
uniprot
proteins
protein_family
PI3/PI4-kinase family
uniprot
proteins
pubmed
10545197
uniprot
proteins
pubmed
10597277
uniprot
proteins
pubmed
10608806
uniprot
proteins
pubmed
10859164
uniprot
proteins
pubmed
11114888
uniprot
proteins
pubmed
11418864
uniprot
proteins
pubmed
11470508
uniprot
proteins
pubmed
11673449
uniprot
proteins
pubmed
11721054
uniprot
proteins
pubmed
11865061
uniprot
proteins
pubmed
12011431
uniprot
proteins
pubmed
12526805
uniprot
proteins
pubmed
12640452
uniprot
proteins
pubmed
12766152
uniprot
proteins
pubmed
12791985
uniprot
proteins
pubmed
12814551
uniprot
proteins
pubmed
14657349
uniprot
proteins
pubmed
14729973
uniprot
proteins
pubmed
14742437
uniprot
proteins
pubmed
14871897
uniprot
proteins
pubmed
15050919
uniprot
proteins
pubmed
15210935
uniprot
proteins
pubmed
15314022
uniprot
proteins
pubmed
15496423
uniprot
proteins
pubmed
15680327
uniprot
proteins
pubmed
15758953
uniprot
proteins
pubmed
16260606
uniprot
proteins
pubmed
16530042
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18283122
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20427287
uniprot
proteins
pubmed
20801936
uniprot
proteins
pubmed
20810650
uniprot
proteins
pubmed
21144835
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21705319
uniprot
proteins
pubmed
21777809
uniprot
proteins
pubmed
22341969
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23273981
uniprot
proteins
pubmed
25083873
uniprot
proteins
pubmed
27723717
uniprot
proteins
pubmed
27723720
uniprot
proteins
pubmed
30139873
uniprot
proteins
pubmed
33848395
uniprot
proteins
pubmed
37788673
uniprot
proteins
pubmed
37832547
uniprot
proteins
pubmed
8610130
uniprot
proteins
pubmed
8843195
uniprot
proteins
pubmed
8978690
uniprot
proteins
pubmed
9427750
uniprot
proteins
pubmed
9636169
uniprot
proteins
pubmed
9766667
uniprot
proteins
pubmed
9925639
uniprot
proteins
sequence_length
2644
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11721054, ECO:0000269|PubMed:11865061, ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:14871897, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:18283122, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:8843195}. Chromosome {ECO:0000269|PubMed:11673449}. Nucleus envelope {ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}. Note=Depending on the cell type, it can also be found in PML nuclear bodies (PubMed:12814551). Recruited to chromatin during S-phase (PubMed:14871897). Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling (PubMed:27723720). Relocalizes to the nuclear envelope in response to mechanical stress or DNA damage (PubMed:25083873, PubMed:37832547). Also localizes to the micronuclear envelope in response to response to genome instability (PubMed:37788673). {ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.
uniprot
proteins