Search Results

Overview

Uniprot IDQ13535
Protein NameSerine/threonine-protein kinase ATR
Gene NameATR
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
2574 KPVKGHSKAPLNETG

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)

Protein Sequence

10 MGEHGLELAS 20 MIPALRELGS 30 ATPEEYNTVV 40 QKPRQILCQF 50 IDRILTDVNV 60 VAVELVKKTD 70 SQPTSVMLLD 80 FIQHIMKSSP 90 LMFVNVSGSH 100 EAKGSCIEFS 110 NWIITRLLRI 120 AATPSCHLLH 130 KKICEVICSL 140 LFLFKSKSPA 150 IFGVLTKELL 160 QLFEDLVYLH 170 RRNVMGHAVE 180 WPVVMSRFLS 190 QLDEHMGYLQ 200 SAPLQLMSMQ 210 NLEFIEVTLL 220 MVLTRIIAIV 230 FFRRQELLLW 240 QIGCVLLEYG 250 SPKIKSLAIS 260 FLTELFQLGG 270 LPAQPASTFF 280 SSFLELLKHL 290 VEMDTDQLKL 300 YEEPLSKLIK 310 TLFPFEAEAY 320 RNIEPVYLNM 330 LLEKLCVMFE 340 DGVLMRLKSD 350 LLKAALCHLL 360 QYFLKFVPAG 370 YESALQVRKV 380 YVRNICKALL 390 DVLGIEVDAE 400 YLLGPLYAAL 410 KMESMEIIEE 420 IQCQTQQENL 430 SSNSDGISPK 440 RRRLSSSLNP 450 SKRAPKQTEE 460 IKHVDMNQKS 470 ILWSALKQKA 480 ESLQISLEYS 490 GLKNPVIEML 500 EGIAVVLQLT 510 ALCTVHCSHQ 520 NMNCRTFKDC 530 QHKSKKKPSV 540 VITWMSLDFY 550 TKVLKSCRSL 560 LESVQKLDLE 570 ATIDKVVKIY 580 DALIYMQVNS 590 SFEDHILEDL 600 CGMLSLPWIY 610 SHSDDGCLKL 620 TTFAANLLTL 630 SCRISDSYSP 640 QAQSRCVFLL 650 TLFPRRIFLE 660 WRTAVYNWAL 670 QSSHEVIRAS 680 CVSGFFILLQ 690 QQNSCNRVPK 700 ILIDKVKDDS 710 DIVKKEFASI 720 LGQLVCTLHG 730 MFYLTSSLTE 740 PFSEHGHVDL 750 FCRNLKATSQ 760 HECSSSQLKA 770 SVCKPFLFLL 780 KKKIPSPVKL 790 AFIDNLHHLC 800 KHLDFREDET 810 DVKAVLGTLL 820 NLMEDPDKDV 830 RVAFSGNIKH 840 ILESLDSEDG 850 FIKELFVLRM 860 KEAYTHAQIS 870 RNNELKDTLI 880 LTTGDIGRAA 890 KGDLVPFALL 900 HLLHCLLSKS 910 ASVSGAAYTE 920 IRALVAAKSV 930 KLQSFFSQYK 940 KPICQFLVES 950 LHSSQMTALP 960 NTPCQNADVR 970 KQDVAHQREM 980 ALNTLSEIAN 990 VFDFPDLNRF 1000 LTRTLQVLLP 1010 DLAAKASPAA 1020 SALIRTLGKQ 1030 LNVNRREILI 1040 NNFKYIFSHL 1050 VCSCSKDELE 1060 RALHYLKNET 1070 EIELGSLLRQ 1080 DFQGLHNELL 1090 LRIGEHYQQV 1100 FNGLSILASF 1110 ASSDDPYQGP 1120 RDIISPELMA 1130 DYLQPKLLGI 1140 LAFFNMQLLS 1150 SSVGIEDKKM 1160 ALNSLMSLMK 1170 LMGPKHVSSV 1180 RVKMMTTLRT 1190 GLRFKDDFPE 1200 LCCRAWDCFV 1210 RCLDHACLGS 1220 LLSHVIVALL 1230 PLIHIQPKET 1240 AAIFHYLIIE 1250 NRDAVQDFLH 1260 EIYFLPDHPE 1270 LKKIKAVLQE 1280 YRKETSESTD 1290 LQTTLQLSMK 1300 AIQHENVDVR 1310 IHALTSLKET 1320 LYKNQEKLIK 1330 YATDSETVEP 1340 IISQLVTVLL 1350 KGCQDANSQA 1360 RLLCGECLGE 1370 LGAIDPGRLD 1380 FSTTETQGKD 1390 FTFVTGVEDS 1400 SFAYGLLMEL 1410 TRAYLAYADN 1420 SRAQDSAAYA 1430 IQELLSIYDC 1440 REMETNGPGH 1450 QLWRRFPEHV 1460 REILEPHLNT 1470 RYKSSQKSTD 1480 WSGVKKPIYL 1490 SKLGSNFAEW 1500 SASWAGYLIT 1510 KVRHDLASKI 1520 FTCCSIMMKH 1530 DFKVTIYLLP 1540 HILVYVLLGC 1550 NQEDQQEVYA 1560 EIMAVLKHDD 1570 QHTINTQDIA 1580 SDLCQLSTQT 1590 VFSMLDHLTQ 1600 WARHKFQALK 1610 AEKCPHSKSN 1620 RNKVDSMVST 1630 VDYEDYQSVT 1640 RFLDLIPQDT 1650 LAVASFRSKA 1660 YTRAVMHFES 1670 FITEKKQNIQ 1680 EHLGFLQKLY 1690 AAMHEPDGVA 1700 GVSAIRKAEP 1710 SLKEQILEHE 1720 SLGLLRDATA 1730 CYDRAIQLEP 1740 DQIIHYHGVV 1750 KSMLGLGQLS 1760 TVITQVNGVH 1770 ANRSEWTDEL 1780 NTYRVEAAWK 1790 LSQWDLVENY 1800 LAADGKSTTW 1810 SVRLGQLLLS 1820 AKKRDITAFY 1830 DSLKLVRAEQ 1840 IVPLSAASFE 1850 RGSYQRGYEY 1860 IVRLHMLCEL 1870 EHSIKPLFQH 1880 SPGDSSQEDS 1890 LNWVARLEMT 1900 QNSYRAKEPI 1910 LALRRALLSL 1920 NKRPDYNEMV 1930 GECWLQSARV 1940 ARKAGHHQTA 1950 YNALLNAGES 1960 RLAELYVERA 1970 KWLWSKGDVH 1980 QALIVLQKGV 1990 ELCFPENETP 2000 PEGKNMLIHG 2010 RAMLLVGRFM 2020 EETANFESNA 2030 IMKKYKDVTA 2040 CLPEWEDGHF 2050 YLAKYYDKLM 2060 PMVTDNKMEK 2070 QGDLIRYIVL 2080 HFGRSLQYGN 2090 QFIYQSMPRM 2100 LTLWLDYGTK 2110 AYEWEKAGRS 2120 DRVQMRNDLG 2130 KINKVITEHT 2140 NYLAPYQFLT 2150 AFSQLISRIC 2160 HSHDEVFVVL 2170 MEIIAKVFLA 2180 YPQQAMWMMT 2190 AVSKSSYPMR 2200 VNRCKEILNK 2210 AIHMKKSLEK 2220 FVGDATRLTD 2230 KLLELCNKPV 2240 DGSSSTLSMS 2250 THFKMLKKLV 2260 EEATFSEILI 2270 PLQSVMIPTL 2280 PSILGTHANH 2290 ASHEPFPGHW 2300 AYIAGFDDMV 2310 EILASLQKPK 2320 KISLKGSDGK 2330 FYIMMCKPKD 2340 DLRKDCRLME 2350 FNSLINKCLR 2360 KDAESRRREL 2370 HIRTYAVIPL 2380 NDECGIIEWV 2390 NNTAGLRPIL 2400 TKLYKEKGVY 2410 MTGKELRQCM 2420 LPKSAALSEK 2430 LKVFREFLLP 2440 RHPPIFHEWF 2450 LRTFPDPTSW 2460 YSSRSAYCRS 2470 TAVMSMVGYI 2480 LGLGDRHGEN 2490 ILFDSLTGEC 2500 VHVDFNCLFN 2510 KGETFEVPEI 2520 VPFRLTHNMV 2530 NGMGPMGTEG 2540 LFRRACEVTM 2550 RLMRDQREPL 2560 MSVLKTFLHD 2570 PLVEWSKPVK 2580 GHSKAPLNET 2590 GEVVNEKAKT 2600 HVLDIEQRLQ 2610 GVIKTRNRVT 2620 GLPLSIEGHV 2630 HYLIQEATDE 2640 NLLCQMYLGW TPYM

Gene Ontology

Classification GO ID Description
Cellular Component GO:0070310 ATR-ATRIP complex
Cellular Component GO:0005694 chromosome
Cellular Component GO:0005635 nuclear envelope
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0016605 PML body
Cellular Component GO:0090734 site of DNA damage
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0035979 histone H2AXS139 kinase activity
Molecular Function GO:0032405 MutLalpha complex binding
Molecular Function GO:0032407 MutSalpha complex binding
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Biological Process GO:0071480 cellular response to gamma radiation
Biological Process GO:0034644 cellular response to UV
Biological Process GO:0000077 DNA damage checkpoint signaling
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0006260 DNA replication
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0097695 establishment of protein-containing complex localization to telomere
Biological Process GO:0097694 establishment of RNA localization to telomere
Biological Process GO:0036297 interstrand cross-link repair
Biological Process GO:0044818 mitotic G2/M transition checkpoint
Biological Process GO:0008156 negative regulation of DNA replication
Biological Process GO:0051081 nuclear membrane disassembly
Biological Process GO:0006139 nucleobase-containing compound metabolic process
Biological Process GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator
Biological Process GO:1904884 positive regulation of telomerase catalytic core complex assembly
Biological Process GO:0032212 positive regulation of telomere maintenance via telomerase
Biological Process GO:0070198 protein localization to chromosome, telomeric region
Biological Process GO:1900034 regulation of cellular response to heat
Biological Process GO:2000779 regulation of double-strand break repair
Biological Process GO:0031297 replication fork processing
Biological Process GO:0090399 replicative senescence
Biological Process GO:0046685 response to arsenic-containing substance
Biological Process GO:0009612 response to mechanical stimulus
Biological Process GO:0009410 response to xenobiotic stimulus
Biological Process GO:0000723 telomere maintenance

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.