Reviewed, UniProtKB/Swiss-Prot Q13535 (ATR_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase ATR
    EC=2.7.11.1
Alternative name(s):
    Ataxia telangiectasia and Rad3-related protein
    FRAP-related protein 1

Gene names

Name:	ATR
Synonyms:	FRP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2644 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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 TP53/p53, 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	Manganese.
Enzyme regulation	Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002.
Subunit structure	Forms an heterodimer with ATRIP. Binds to DNA, and to UV-damaged DNA with higher affinity. Interacts with RAD17, MSH2 and HDAC2. Present in a complex containing ATRIP and RPA-coated single-stranded DNA. Present in a complex containing CHD4 and HDAC2. Interacts with BCR-ABL after genotoxic stress. Interacts with EEF1E1. This interaction is enhanced by UV irradiation. Interacts with CLSPN.
Subcellular location	Nucleus. 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.
Tissue specificity	Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary.
Post-translational modification	Phosphorylated; autophosphorylates in vitro.
Involvement in disease	Defects in ATR are a cause of Seckel syndrome 1 (SCKL1) [MIM:210600]. SCKL1 is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance.
Sequence similarities	Belongs to the PI3/PI4-kinase family. ATM subfamily. Contains 1 FAT domain. Contains 1 FATC domain. Contains 2 HEAT repeats. Contains 1 PI3K/PI4K domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Chromosomal protein Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Dwarfism
Domain	Repeat
Ligand	DNA-binding Manganese
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA damage checkpoint Ref.23 Inferred from direct assay. Source: UniProtKB DNA repair Ref.2 Traceable author statement. Source: ProtInc multicellular organismal development Traceable author statement. Source: ProtInc negative regulation of DNA replication Ref.23 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	protein binding Ref.23 Inferred from physical interaction. Source: UniProtKB protein kinase activity Ref.2 Ref.23 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AATF	Q9NY61	1	EBI-968983,EBI-372428
CREB1	P16220	1	EBI-968983,EBI-711855
TP53	P04637	1	EBI-968983,EBI-366083

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13535-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q13535-2)

The sequence of this isoform differs from the canonical sequence as follows:
     450-450: E → D
     451-514: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 2644	2644	Serine/threonine-protein kinase ATR
Regions
	Repeat	799 – 835	37	HEAT 1
	Repeat	1329 – 1365	37	HEAT 2
	Domain	1640 – 2185	546	FAT
	Domain	2322 – 2567	246	PI3K/PI4K
	Domain	2612 – 2644	33	FATC
Amino acid modifications
	Modified residue	919	1	Phosphoserine
Natural variations
	Alternative sequence	450	1	E → D in isoform 2.
	Alternative sequence	451 – 514	64	Missing in isoform 2.
	Natural variant	64	1	T → A
	Natural variant	90	1	H → Y
	Natural variant	297	1	K → N
	Natural variant	316	1	V → I
	Natural variant	959	1	V → M
	Natural variant	1087	1	Y → H
	Natural variant	1213	1	S → G
	Natural variant	1488	1	A → P in a lung squamous cell carcinoma sample; somatic mutation.
	Natural variant	1607	1	S → N
	Natural variant	1612	1	N → S
	Natural variant	2002	1	A → G in a lung adenocarcinoma sample; somatic mutation.
	Natural variant	2120	1	G → A
	Natural variant	2132	1	Y → D
	Natural variant	2233	1	S → I in a lung large cell carcinoma sample; somatic mutation.
	Natural variant	2425	1	R → Q
	Natural variant	2434	1	P → A
	Natural variant	2438	1	E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation.
	Natural variant	2537	1	E → Q in a breast infiltrating ductal carcinoma sample; somatic mutation.
Experimental info
	Mutagenesis	2327	1	K → R: Abolishes kinase activity
	Mutagenesis	2475	1	D → A: Abolishes kinase activity; increases sensitivity to IR and impairs translocation to nuclear foci upon DNA damage
	Mutagenesis	2494	1	D → E: Abolishes kinase activity; reduces cell viability, augments sensitivity to IR and UV
	Sequence conflict	92	1	A → R in CAA70298 and AAC50929. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 3. Checksum: 11BC22297FB9A802	FASTA	2,644	301,367
	10 20 30 40 50 60 MGEHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VAVELVKKTD 70 80 90 100 110 120 SQPTSVMLLD FIQHIMKSSP LMFVNVSGSH EAKGSCIEFS NWIITRLLRI AATPSCHLLH 130 140 150 160 170 180 KKICEVICSL LFLFKSKSPA IFGVLTKELL QLFEDLVYLH RRNVMGHAVE WPVVMSRFLS 190 200 210 220 230 240 QLDEHMGYLQ SAPLQLMSMQ NLEFIEVTLL MVLTRIIAIV FFRRQELLLW QIGCVLLEYG 250 260 270 280 290 300 SPKIKSLAIS FLTELFQLGG LPAQPASTFF SSFLELLKHL VEMDTDQLKL YEEPLSKLIK 310 320 330 340 350 360 TLFPFEAEAY RNIEPVYLNM LLEKLCVMFE DGVLMRLKSD LLKAALCHLL QYFLKFVPAG 370 380 390 400 410 420 YESALQVRKV YVRNICKALL DVLGIEVDAE YLLGPLYAAL KMESMEIIEE IQCQTQQENL 430 440 450 460 470 480 SSNSDGISPK RRRLSSSLNP SKRAPKQTEE IKHVDMNQKS ILWSALKQKA ESLQISLEYS 490 500 510 520 530 540 GLKNPVIEML EGIAVVLQLT ALCTVHCSHQ NMNCRTFKDC QHKSKKKPSV VITWMSLDFY 550 560 570 580 590 600 TKVLKSCRSL LESVQKLDLE ATIDKVVKIY DALIYMQVNS SFEDHILEDL CGMLSLPWIY 610 620 630 640 650 660 SHSDDGCLKL TTFAANLLTL SCRISDSYSP QAQSRCVFLL TLFPRRIFLE WRTAVYNWAL 670 680 690 700 710 720 QSSHEVIRAS CVSGFFILLQ QQNSCNRVPK ILIDKVKDDS DIVKKEFASI LGQLVCTLHG 730 740 750 760 770 780 MFYLTSSLTE PFSEHGHVDL FCRNLKATSQ HECSSSQLKA SVCKPFLFLL KKKIPSPVKL 790 800 810 820 830 840 AFIDNLHHLC KHLDFREDET DVKAVLGTLL NLMEDPDKDV RVAFSGNIKH ILESLDSEDG 850 860 870 880 890 900 FIKELFVLRM KEAYTHAQIS RNNELKDTLI LTTGDIGRAA KGDLVPFALL HLLHCLLSKS 910 920 930 940 950 960 ASVSGAAYTE IRALVAAKSV KLQSFFSQYK KPICQFLVES LHSSQMTALP NTPCQNADVR 970 980 990 1000 1010 1020 KQDVAHQREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP DLAAKASPAA SALIRTLGKQ 1030 1040 1050 1060 1070 1080 LNVNRREILI NNFKYIFSHL VCSCSKDELE RALHYLKNET EIELGSLLRQ DFQGLHNELL 1090 1100 1110 1120 1130 1140 LRIGEHYQQV FNGLSILASF ASSDDPYQGP RDIISPELMA DYLQPKLLGI LAFFNMQLLS 1150 1160 1170 1180 1190 1200 SSVGIEDKKM ALNSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV 1210 1220 1230 1240 1250 1260 RCLDHACLGS LLSHVIVALL PLIHIQPKET AAIFHYLIIE NRDAVQDFLH EIYFLPDHPE 1270 1280 1290 1300 1310 1320 LKKIKAVLQE YRKETSESTD LQTTLQLSMK AIQHENVDVR IHALTSLKET LYKNQEKLIK 1330 1340 1350 1360 1370 1380 YATDSETVEP IISQLVTVLL KGCQDANSQA RLLCGECLGE LGAIDPGRLD FSTTETQGKD 1390 1400 1410 1420 1430 1440 FTFVTGVEDS SFAYGLLMEL TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMETNGPGH 1450 1460 1470 1480 1490 1500 QLWRRFPEHV REILEPHLNT RYKSSQKSTD WSGVKKPIYL SKLGSNFAEW SASWAGYLIT 1510 1520 1530 1540 1550 1560 KVRHDLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA EIMAVLKHDD 1570 1580 1590 1600 1610 1620 QHTINTQDIA SDLCQLSTQT VFSMLDHLTQ WARHKFQALK AEKCPHSKSN RNKVDSMVST 1630 1640 1650 1660 1670 1680 VDYEDYQSVT RFLDLIPQDT LAVASFRSKA YTRAVMHFES FITEKKQNIQ EHLGFLQKLY 1690 1700 1710 1720 1730 1740 AAMHEPDGVA GVSAIRKAEP SLKEQILEHE SLGLLRDATA CYDRAIQLEP DQIIHYHGVV 1750 1760 1770 1780 1790 1800 KSMLGLGQLS TVITQVNGVH ANRSEWTDEL NTYRVEAAWK LSQWDLVENY LAADGKSTTW 1810 1820 1830 1840 1850 1860 SVRLGQLLLS AKKRDITAFY DSLKLVRAEQ IVPLSAASFE RGSYQRGYEY IVRLHMLCEL 1870 1880 1890 1900 1910 1920 EHSIKPLFQH SPGDSSQEDS LNWVARLEMT QNSYRAKEPI LALRRALLSL NKRPDYNEMV 1930 1940 1950 1960 1970 1980 GECWLQSARV ARKAGHHQTA YNALLNAGES RLAELYVERA KWLWSKGDVH QALIVLQKGV 1990 2000 2010 2020 2030 2040 ELCFPENETP PEGKNMLIHG RAMLLVGRFM EETANFESNA IMKKYKDVTA CLPEWEDGHF 2050 2060 2070 2080 2090 2100 YLAKYYDKLM PMVTDNKMEK QGDLIRYIVL HFGRSLQYGN QFIYQSMPRM LTLWLDYGTK 2110 2120 2130 2140 2150 2160 AYEWEKAGRS DRVQMRNDLG KINKVITEHT NYLAPYQFLT AFSQLISRIC HSHDEVFVVL 2170 2180 2190 2200 2210 2220 MEIIAKVFLA YPQQAMWMMT AVSKSSYPMR VNRCKEILNK AIHMKKSLEK FVGDATRLTD 2230 2240 2250 2260 2270 2280 KLLELCNKPV DGSSSTLSMS THFKMLKKLV EEATFSEILI PLQSVMIPTL PSILGTHANH 2290 2300 2310 2320 2330 2340 ASHEPFPGHW AYIAGFDDMV EILASLQKPK KISLKGSDGK FYIMMCKPKD DLRKDCRLME 2350 2360 2370 2380 2390 2400 FNSLINKCLR KDAESRRREL HIRTYAVIPL NDECGIIEWV NNTAGLRPIL TKLYKEKGVY 2410 2420 2430 2440 2450 2460 MTGKELRQCM LPKSAALSEK LKVFREFLLP RHPPIFHEWF LRTFPDPTSW YSSRSAYCRS 2470 2480 2490 2500 2510 2520 TAVMSMVGYI LGLGDRHGEN ILFDSLTGEC VHVDFNCLFN KGETFEVPEI VPFRLTHNMV 2530 2540 2550 2560 2570 2580 NGMGPMGTEG LFRRACEVTM RLMRDQREPL MSVLKTFLHD PLVEWSKPVK GHSKAPLNET 2590 2600 2610 2620 2630 2640 GEVVNEKAKT HVLDIEQRLQ GVIKTRNRVT GLPLSIEGHV HYLIQEATDE NLLCQMYLGW TPYM
	Isoform 2 [UniParc]. Checksum: A7C5CED46708FC16		2,580	294,219
	10 20 30 40 50 60 MGEHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VAVELVKKTD 70 80 90 100 110 120 SQPTSVMLLD FIQHIMKSSP LMFVNVSGSH EAKGSCIEFS NWIITRLLRI AATPSCHLLH 130 140 150 160 170 180 KKICEVICSL LFLFKSKSPA IFGVLTKELL QLFEDLVYLH RRNVMGHAVE WPVVMSRFLS 190 200 210 220 230 240 QLDEHMGYLQ SAPLQLMSMQ NLEFIEVTLL MVLTRIIAIV FFRRQELLLW QIGCVLLEYG 250 260 270 280 290 300 SPKIKSLAIS FLTELFQLGG LPAQPASTFF SSFLELLKHL VEMDTDQLKL YEEPLSKLIK 310 320 330 340 350 360 TLFPFEAEAY RNIEPVYLNM LLEKLCVMFE DGVLMRLKSD LLKAALCHLL QYFLKFVPAG 370 380 390 400 410 420 YESALQVRKV YVRNICKALL DVLGIEVDAE YLLGPLYAAL KMESMEIIEE IQCQTQQENL 430 440 450 460 470 480 SSNSDGISPK RRRLSSSLNP SKRAPKQTED RTFKDCQHKS KKKPSVVITW MSLDFYTKVL 490 500 510 520 530 540 KSCRSLLESV QKLDLEATID KVVKIYDALI YMQVNSSFED HILEDLCGML SLPWIYSHSD 550 560 570 580 590 600 DGCLKLTTFA ANLLTLSCRI SDSYSPQAQS RCVFLLTLFP RRIFLEWRTA VYNWALQSSH 610 620 630 640 650 660 EVIRASCVSG FFILLQQQNS CNRVPKILID KVKDDSDIVK KEFASILGQL VCTLHGMFYL 670 680 690 700 710 720 TSSLTEPFSE HGHVDLFCRN LKATSQHECS SSQLKASVCK PFLFLLKKKI PSPVKLAFID 730 740 750 760 770 780 NLHHLCKHLD FREDETDVKA VLGTLLNLME DPDKDVRVAF SGNIKHILES LDSEDGFIKE 790 800 810 820 830 840 LFVLRMKEAY THAQISRNNE LKDTLILTTG DIGRAAKGDL VPFALLHLLH CLLSKSASVS 850 860 870 880 890 900 GAAYTEIRAL VAAKSVKLQS FFSQYKKPIC QFLVESLHSS QMTALPNTPC QNADVRKQDV 910 920 930 940 950 960 AHQREMALNT LSEIANVFDF PDLNRFLTRT LQVLLPDLAA KASPAASALI RTLGKQLNVN 970 980 990 1000 1010 1020 RREILINNFK YIFSHLVCSC SKDELERALH YLKNETEIEL GSLLRQDFQG LHNELLLRIG 1030 1040 1050 1060 1070 1080 EHYQQVFNGL SILASFASSD DPYQGPRDII SPELMADYLQ PKLLGILAFF NMQLLSSSVG 1090 1100 1110 1120 1130 1140 IEDKKMALNS LMSLMKLMGP KHVSSVRVKM MTTLRTGLRF KDDFPELCCR AWDCFVRCLD 1150 1160 1170 1180 1190 1200 HACLGSLLSH VIVALLPLIH IQPKETAAIF HYLIIENRDA VQDFLHEIYF LPDHPELKKI 1210 1220 1230 1240 1250 1260 KAVLQEYRKE TSESTDLQTT LQLSMKAIQH ENVDVRIHAL TSLKETLYKN QEKLIKYATD 1270 1280 1290 1300 1310 1320 SETVEPIISQ LVTVLLKGCQ DANSQARLLC GECLGELGAI DPGRLDFSTT ETQGKDFTFV 1330 1340 1350 1360 1370 1380 TGVEDSSFAY GLLMELTRAY LAYADNSRAQ DSAAYAIQEL LSIYDCREME TNGPGHQLWR 1390 1400 1410 1420 1430 1440 RFPEHVREIL EPHLNTRYKS SQKSTDWSGV KKPIYLSKLG SNFAEWSASW AGYLITKVRH 1450 1460 1470 1480 1490 1500 DLASKIFTCC SIMMKHDFKV TIYLLPHILV YVLLGCNQED QQEVYAEIMA VLKHDDQHTI 1510 1520 1530 1540 1550 1560 NTQDIASDLC QLSTQTVFSM LDHLTQWARH KFQALKAEKC PHSKSNRNKV DSMVSTVDYE 1570 1580 1590 1600 1610 1620 DYQSVTRFLD LIPQDTLAVA SFRSKAYTRA VMHFESFITE KKQNIQEHLG FLQKLYAAMH 1630 1640 1650 1660 1670 1680 EPDGVAGVSA IRKAEPSLKE QILEHESLGL LRDATACYDR AIQLEPDQII HYHGVVKSML 1690 1700 1710 1720 1730 1740 GLGQLSTVIT QVNGVHANRS EWTDELNTYR VEAAWKLSQW DLVENYLAAD GKSTTWSVRL 1750 1760 1770 1780 1790 1800 GQLLLSAKKR DITAFYDSLK LVRAEQIVPL SAASFERGSY QRGYEYIVRL HMLCELEHSI 1810 1820 1830 1840 1850 1860 KPLFQHSPGD SSQEDSLNWV ARLEMTQNSY RAKEPILALR RALLSLNKRP DYNEMVGECW 1870 1880 1890 1900 1910 1920 LQSARVARKA GHHQTAYNAL LNAGESRLAE LYVERAKWLW SKGDVHQALI VLQKGVELCF 1930 1940 1950 1960 1970 1980 PENETPPEGK NMLIHGRAML LVGRFMEETA NFESNAIMKK YKDVTACLPE WEDGHFYLAK 1990 2000 2010 2020 2030 2040 YYDKLMPMVT DNKMEKQGDL IRYIVLHFGR SLQYGNQFIY QSMPRMLTLW LDYGTKAYEW 2050 2060 2070 2080 2090 2100 EKAGRSDRVQ MRNDLGKINK VITEHTNYLA PYQFLTAFSQ LISRICHSHD EVFVVLMEII 2110 2120 2130 2140 2150 2160 AKVFLAYPQQ AMWMMTAVSK SSYPMRVNRC KEILNKAIHM KKSLEKFVGD ATRLTDKLLE 2170 2180 2190 2200 2210 2220 LCNKPVDGSS STLSMSTHFK MLKKLVEEAT FSEILIPLQS VMIPTLPSIL GTHANHASHE 2230 2240 2250 2260 2270 2280 PFPGHWAYIA GFDDMVEILA SLQKPKKISL KGSDGKFYIM MCKPKDDLRK DCRLMEFNSL 2290 2300 2310 2320 2330 2340 INKCLRKDAE SRRRELHIRT YAVIPLNDEC GIIEWVNNTA GLRPILTKLY KEKGVYMTGK 2350 2360 2370 2380 2390 2400 ELRQCMLPKS AALSEKLKVF REFLLPRHPP IFHEWFLRTF PDPTSWYSSR SAYCRSTAVM 2410 2420 2430 2440 2450 2460 SMVGYILGLG DRHGENILFD SLTGECVHVD FNCLFNKGET FEVPEIVPFR LTHNMVNGMG 2470 2480 2490 2500 2510 2520 PMGTEGLFRR ACEVTMRLMR DQREPLMSVL KTFLHDPLVE WSKPVKGHSK APLNETGEVV 2530 2540 2550 2560 2570 2580 NEKAKTHVLD IEQRLQGVIK TRNRVTGLPL SIEGHVHYLI QEATDENLLC QMYLGWTPYM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Schizosaccharomyces pombe rad3 checkpoint gene." Bentley N.J., Holtzman D.A., Flaggs G., Keegan K.S., DeMaggio A., Ford J.C., Hoekstra M., Carr A.M. EMBO J. 15:6641-6651(1996) [PubMed: 8978690] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein." Cimprich K.A., Shin T.B., Keith C.T., Schreiber S.L. Proc. Natl. Acad. Sci. U.S.A. 93:2850-2855(1996) [PubMed: 8610130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: T-cell.
[3]	"Evidence for alternate splicing within the mRNA transcript encoding the DNA damage response kinase ATR." Mannino J.L., Kim W.-J., Wernick M., Nguyen S.V., Braquet R., Adamson A.W., Den Z., Batzer M.A., Collins C.C., Brown K.D. Gene 272:35-43(2001) [PubMed: 11470508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 433-526 (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
[4]	"The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes." Keegan K.S., Holtzman D.A., Plug A.W., Christenson E.R., Brainerd E.E., Flaggs G., Bentley N.J., Taylor E.M., Meyn M.S., Moss S.B., Carr A.M., Ashley T., Hoekstra M.F. Genes Dev. 10:2423-2437(1996) [PubMed: 8843195] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]	"Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin." Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E., Abraham R.T. Cancer Res. 58:4375-4382(1998) [PubMed: 9766667] [Abstract] Cited for: ENZYME REGULATION.
[6]	"Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints." Cliby W.A., Roberts C.J., Cimprich K.A., Stringer C.M., Lamb J.R., Schreiber S.L., Friend S.H. EMBO J. 17:159-169(1998) [PubMed: 9427750] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-2475.
[7]	"Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control." Wright J.A., Keegan K.S., Herendeen D.R., Bentley N.J., Carr A.M., Hoekstra M.F., Concannon P. Proc. Natl. Acad. Sci. U.S.A. 95:7445-7450(1998) [PubMed: 9636169] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-2494.
[8]	"Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4." Schmidt D.R., Schreiber S.L. Biochemistry 38:14711-14717(1999) [PubMed: 10545197] [Abstract] Cited for: INTERACTION WITH HDAC2, IDENTIFICATION IN A COMPLEX CONTAINING HDAC2 AND CHD4.
[9]	"A role for ATR in the DNA damage-induced phosphorylation of p53." Tibbetts R.S., Brumbaugh K.M., Williams J.M., Sarkaria J.N., Cliby W.A., Shieh S.-Y., Taya Y., Prives C., Abraham R.T. Genes Dev. 13:152-157(1999) [PubMed: 9925639] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-2327 AND ASP-2475.
[10]	"Substrate specificities and identification of putative substrates of ATM kinase family members." Kim S.-T., Lim D.-S., Canman C.E., Kastan M.B. J. Biol. Chem. 274:37538-37543(1999) [PubMed: 10608806] [Abstract] Cited for: COFACTOR, FUNCTION.
[11]	"ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK." Hall-Jackson C.A., Cross D.A.E., Morrice N., Smythe C. Oncogene 18:6707-6713(1999) [PubMed: 10597277] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-2494, ENZYME REGULATION.
[12]	"Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint." Liu Q., Guntuku S., Cui X.-S., Matsuoka S., Cortez D., Tamai K., Luo G., Carattini-Rivera S., DeMayo F., Bradley A., Donehower L.A., Elledge S.J. Genes Dev. 14:1448-1459(2000) [PubMed: 10859164] [Abstract] Cited for: FUNCTION.
[13]	"Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress." Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D., Elledge S.J., Abraham R.T. Genes Dev. 14:2989-3002(2000) [PubMed: 11114888] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-2327.
[14]	"Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress." Ward I.M., Chen J. J. Biol. Chem. 276:47759-47762(2001) [PubMed: 11673449] [Abstract] Cited for: FUNCTION.
[15]	"ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses." Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A., Ali A., Chen S.M., Abraham R.T., Wang X.-F. Nature 411:969-974(2001) [PubMed: 11418864] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAD17.
[16]	"ATR and ATRIP: partners in checkpoint signaling." Cortez D., Guntuku S., Qin J., Elledge S.J. Science 294:1713-1716(2001) [PubMed: 11721054] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATRIP.
[17]	"ATR regulates fragile site stability." Casper A.M., Nghiem P., Arlt M.F., Glover T.W. Cell 111:779-789(2002) [PubMed: 12526805] [Abstract] Cited for: FUNCTION.
[18]	"Hypoxia links ATR and p53 through replication arrest." Hammond E.M., Denko N.C., Dorie M.J., Abraham R.T., Giaccia A.J. Mol. Cell. Biol. 22:1834-1843(2002) [PubMed: 11865061] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[19]	"Preferential binding of ATR protein to UV-damaged DNA." Uensal-Kacmaz K., Makhov A.M., Griffith J.D., Sancar A. Proc. Natl. Acad. Sci. U.S.A. 99:6673-6678(2002) [PubMed: 12011431] [Abstract] Cited for: DNA-BINDING, MUTAGENESIS OF LYS-2327.
[20]	"ATR kinase activity regulates the intranuclear translocation of ATR and RPA following ionizing radiation." Barr S.M., Leung C.G., Chang E.E., Cimprich K.A. Curr. Biol. 13:1047-1051(2003) [PubMed: 12814551] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-2475.
[21]	"Human claspin is required for replication checkpoint control." Chini C.C.S., Chen J. J. Biol. Chem. 278:30057-30062(2003) [PubMed: 12766152] [Abstract] Cited for: INTERACTION WITH CLSPN.
[22]	"A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome." O'Driscoll M., Ruiz-Perez V.L., Woods C.G., Jeggo P.A., Goodship J.A. Nat. Genet. 33:497-501(2003) [PubMed: 12640452] [Abstract] Cited for: DISEASE.
[23]	"MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation." Wang Y., Qin J. Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003) [PubMed: 14657349] [Abstract] Cited for: FUNCTION, INTERACTION WITH MSH2, MASS SPECTROMETRY.
[24]	"Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes." Zou L., Elledge S.J. Science 300:1542-1548(2003) [PubMed: 12791985] [Abstract] Cited for: FUNCTION, DNA-BINDING, IDENTIFICATION IN A COMPLEX WITH RPA AND ATRIP.
[25]	"BCR/ABL translocates to the nucleus and disrupts an ATR-dependent intra-S phase checkpoint." Dierov J., Dierova R., Carroll M. Cancer Cell 5:275-285(2004) [PubMed: 15050919] [Abstract] Cited for: INTERACTION WITH BCR-ABL.
[26]	"UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress." Ward I.M., Minn K., Chen J. J. Biol. Chem. 279:9677-9680(2004) [PubMed: 14742437] [Abstract] Cited for: FUNCTION.
[27]	"Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase." Dart D.A., Adams K.E., Akerman I., Lakin N.D. J. Biol. Chem. 279:16433-16440(2004) [PubMed: 14871897] [Abstract] Cited for: DNA-BINDING, SUBCELLULAR LOCATION.
[28]	"ATR couples FANCD2 monoubiquitination to the DNA-damage response." Andreassen P.R., D'Andrea A.D., Taniguchi T. Genes Dev. 18:1958-1963(2004) [PubMed: 15314022] [Abstract] Cited for: FUNCTION.
[29]	"Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway." Alderton G.K., Joenje H., Varon R., Borglum A.D., Jeggo P.A., O'Driscoll M. Hum. Mol. Genet. 13:3127-3138(2004) [PubMed: 15496423] [Abstract] Cited for: FUNCTION.
[30]	"Quaternary structure of ATR and effects of ATRIP and replication protein A on its DNA binding and kinase activities." Uensal-Kacmaz K., Sancar A. Mol. Cell. Biol. 24:1292-1300(2004) [PubMed: 14729973] [Abstract] Cited for: FUNCTION, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH ATRIP AND RPA1, BINDING TO DNA, ENZYME REGULATION.
[31]	"Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases." Cortez D., Glick G., Elledge S.J. Proc. Natl. Acad. Sci. U.S.A. 101:10078-10083(2004) [PubMed: 15210935] [Abstract] Cited for: FUNCTION.
[32]	"The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR." Park B.-J., Kang J.W., Lee S.W., Choi S.-J., Shin Y.K., Ahn Y.H., Choi Y.H., Choi D., Lee K.S., Kim S. Cell 120:209-221(2005) [PubMed: 15680327] [Abstract] Cited for: INTERACTION WITH EEF1E1.