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Q13535 (ATR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2644 AA.
Sequence statusComplete.
Protein existenceEvidence 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 p53/TP53, 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. Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.36 Ref.44

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Manganese. Ref.11

Enzyme regulation

Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002. Ref.6 Ref.12 Ref.30

Subunit structure

Interacts with ATRIP By similarity. Forms a 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 and CEP164. Interacts with TELO2 and TTI1. Ref.9 Ref.16 Ref.17 Ref.22 Ref.23 Ref.24 Ref.25 Ref.30 Ref.32 Ref.33 Ref.34 Ref.36 Ref.40 Ref.41 Ref.42

Subcellular location

Nucleus. NucleusPML body By similarity. Chromosome By similarity. 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. Ref.5 Ref.14 Ref.17 Ref.19 Ref.21 Ref.27 Ref.34 Ref.36

Tissue specificity

Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary. Ref.2 Ref.3 Ref.5

Post-translational modification

Phosphorylated; autophosphorylates in vitro. Ref.7 Ref.12 Ref.36 Ref.44

Involvement in 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 mental retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.35

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.47

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 processDNA damage
DNA repair
   Cellular componentChromosome
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Dwarfism
Mental retardation
   DomainRepeat
   LigandATP-binding
DNA-binding
Manganese
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from direct assay Ref.23. Source: UniProtKB

DNA repair

Traceable author statement. Source: Reactome

DNA replication

Traceable author statement. Source: Reactome

cell cycle

Traceable author statement PubMed 9590286. Source: ProtInc

cellular response to DNA damage stimulus

Traceable author statement PubMed 15538388. Source: UniProtKB

cellular response to UV

Inferred from mutant phenotype Ref.10. Source: BHF-UCL

cellular response to gamma radiation

Inferred from direct assay Ref.10. Source: BHF-UCL

multicellular organismal development

Traceable author statement PubMed 9590286. Source: ProtInc

negative regulation of DNA replication

Inferred from mutant phenotype Ref.23. Source: UniProtKB

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 9733515. Source: BHF-UCL

positive regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from mutant phenotype Ref.10. Source: BHF-UCL

protein autophosphorylation

Inferred from direct assay PubMed 9733515. Source: BHF-UCL

regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

replicative senescence

Inferred from mutant phenotype PubMed 15149599. Source: BHF-UCL

response to drug

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentPML body

Inferred from direct assay Ref.21. Source: UniProtKB

XY body

Inferred from electronic annotation. Source: Ensembl

chromosome

Inferred from sequence or structural similarity. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

MutLalpha complex binding

Inferred from direct assay PubMed 16713580. Source: MGI

MutSalpha complex binding

Inferred from direct assay PubMed 16713580. Source: MGI

protein binding

Inferred from physical interaction Ref.23. Source: UniProtKB

protein kinase activity

Inferred from direct assay Ref.23. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay PubMed 9733515Ref.10. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 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.
Isoform 3 (identifier: Q13535-3)

The sequence of this isoform differs from the canonical sequence as follows:
     2588-2610: AKTHVLDIEQRLQGVIKTRNRVT → VSRRYSLIWAVVLISTNELDMQL
     2611-2644: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 26442644Serine/threonine-protein kinase ATR
PRO_0000088844

Regions

Repeat799 – 83537HEAT 1
Repeat1329 – 136537HEAT 2
Domain1640 – 2185546FAT
Domain2322 – 2567246PI3K/PI4K
Domain2612 – 264433FATC

Amino acid modifications

Modified residue4281Phosphoserine Ref.37 Ref.44
Modified residue19891Phosphothreonine Ref.37

Natural variations

Alternative sequence4501E → D in isoform 2.
VSP_013305
Alternative sequence451 – 51464Missing in isoform 2.
VSP_013304
Alternative sequence2588 – 261023AKTHV…RNRVT → VSRRYSLIWAVVLISTNELD MQL in isoform 3.
VSP_036907
Alternative sequence2611 – 264434Missing in isoform 3.
VSP_036908
Natural variant641T → A. Ref.46
Corresponds to variant rs35306038 [ dbSNP | Ensembl ].
VAR_041584
Natural variant901H → Y. Ref.46
Corresponds to variant rs28897763 [ dbSNP | Ensembl ].
VAR_041585
Natural variant2111M → T.
Corresponds to variant rs2227928 [ dbSNP | Ensembl ].
VAR_050532
Natural variant2971K → N. Ref.46
Corresponds to variant rs2229033 [ dbSNP | Ensembl ].
VAR_041586
Natural variant3161V → I. Ref.46
Corresponds to variant rs28897764 [ dbSNP | Ensembl ].
VAR_041587
Natural variant9591V → M. Ref.46
Corresponds to variant rs28910271 [ dbSNP | Ensembl ].
VAR_041588
Natural variant10871Y → H. Ref.46
Corresponds to variant rs34253059 [ dbSNP | Ensembl ].
VAR_041589
Natural variant12131S → G. Ref.46
Corresponds to variant rs34766606 [ dbSNP | Ensembl ].
VAR_041590
Natural variant14881A → P in a lung squamous cell carcinoma sample; somatic mutation. Ref.46
VAR_041591
Natural variant15261I → V.
Corresponds to variant rs34124242 [ dbSNP | Ensembl ].
VAR_050533
Natural variant16071S → N. Ref.46
Corresponds to variant rs55724025 [ dbSNP | Ensembl ].
VAR_041592
Natural variant16121N → S. Ref.46
Corresponds to variant rs55894265 [ dbSNP | Ensembl ].
VAR_041593
Natural variant20021A → G in a lung adenocarcinoma sample; somatic mutation. Ref.46
VAR_041594
Natural variant21201G → A. Ref.46
Corresponds to variant rs35134774 [ dbSNP | Ensembl ].
VAR_041595
Natural variant21321Y → D. Ref.46
Corresponds to variant rs28910273 [ dbSNP | Ensembl ].
VAR_041596
Natural variant21441Q → R in FCTCS. Ref.47
VAR_067919
Natural variant22331S → I in a lung large cell carcinoma sample; somatic mutation. Ref.46
VAR_041597
Natural variant24251R → Q. Ref.46
Corresponds to variant rs2229032 [ dbSNP | Ensembl ].
VAR_041598
Natural variant24341P → A. Ref.46
Corresponds to variant rs33972295 [ dbSNP | Ensembl ].
VAR_041599
Natural variant24381E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.46
VAR_041600
Natural variant25371E → Q in a breast infiltrating ductal carcinoma sample; somatic mutation. Ref.46
VAR_041601

Experimental info

Mutagenesis23271K → R: Abolishes kinase activity. Ref.10 Ref.14 Ref.20
Mutagenesis24751D → A: Abolishes kinase activity; increases sensitivity to IR and impairs translocation to nuclear foci upon DNA damage. Ref.7 Ref.10 Ref.21
Mutagenesis24941D → E: Abolishes kinase activity; reduces cell viability, augments sensitivity to IR and UV. Ref.8 Ref.12
Sequence conflict921A → R in CAA70298. Ref.1
Sequence conflict921A → R in AAC50929. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 3.
Checksum: 11BC22297FB9A802

FASTA2,644301,367
        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 

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Isoform 2 [UniParc].

Checksum: A7C5CED46708FC16
Show »

FASTA2,580294,219
Isoform 3 [UniParc].

Checksum: 44281024A65D73B1
Show »

FASTA2,610297,479

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 433-526 (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
[4]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2155-2644 (ISOFORM 3).
Tissue: Brain.
[5]"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] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"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] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-2475.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-2494.
[9]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC2, IDENTIFICATION IN A COMPLEX CONTAINING HDAC2 AND CHD4.
[10]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-2327 AND ASP-2475.
[11]"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] [Europe PMC] [Abstract]
Cited for: COFACTOR, FUNCTION.
[12]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-2494, ENZYME REGULATION.
[13]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-2327.
[15]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAD17.
[17]"ATR and ATRIP: partners in checkpoint signaling."
Cortez D., Guntuku S., Qin J., Elledge S.J.
Science 294:1713-1716(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATRIP.
[18]"ATR regulates fragile site stability."
Casper A.M., Nghiem P., Arlt M.F., Glover T.W.
Cell 111:779-789(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[20]"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] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, MUTAGENESIS OF LYS-2327.
[21]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-2475.
[22]"Human claspin is required for replication checkpoint control."
Chini C.C.S., Chen J.
J. Biol. Chem. 278:30057-30062(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLSPN.
[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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MSH2, IDENTIFICATION BY MASS SPECTROMETRY.
[24]"Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes."
Zou L., Elledge S.J.
Science 300:1542-1548(2003) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH ATRIP AND RPA1, DNA-BINDING, 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EEF1E1.
[33]"Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage."
Falck J., Coates J., Jackson S.P.
Nature 434:605-611(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATRIP.
[34]"Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1."
Sivasubramaniam S., Sun X., Pan Y.R., Wang S., Lee E.Y.
Genes Dev. 22:587-600(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CEP164, SUBCELLULAR LOCATION.
[35]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SCKL1.
[36]"Protein phosphatase 5 is required for ATR-mediated checkpoint activation."
Zhang J., Bao S., Furumai R., Kucera K.S., Ali A., Dean N.M., Wang X.F.
Mol. Cell. Biol. 25:9910-9919(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA DAMAGE RESPONSE, INTERACTION WITH PPP5C, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION.
[37]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428 AND THR-1989, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[38]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[39]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[40]"A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability."
Hurov K.E., Cotta-Ramusino C., Elledge S.J.
Genes Dev. 24:1939-1950(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TTI1.
[41]"Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes."
Takai H., Xie Y., de Lange T., Pavletich N.P.
Genes Dev. 24:2019-2030(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TELO2.
[42]"Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly."
Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K., Iemura S., Natsume T., Mizushima N.
J. Biol. Chem. 285:20109-20116(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TELO2 AND TTI1.
[43]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[44]"Protein phosphatase 5 is necessary for ATR-mediated DNA repair."
Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y., Jun J.Y., You H.J.
Biochem. Biophys. Res. Commun. 404:476-481(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA REPAIR, PHOSPHORYLATION AT SER-428.
[45]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[46]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ALA-64; TYR-90; ASN-297; ILE-316; MET-959; HIS-1087; GLY-1213; PRO-1488; ASN-1607; SER-1612; GLY-2002; ALA-2120; ASP-2132; ILE-2233; GLN-2425; ALA-2434; LYS-2438 AND GLN-2537.
[47]"Germline mutation in ATR in autosomal- dominant oropharyngeal cancer syndrome."
Tanaka A., Weinel S., Nagy N., O'Driscoll M., Lai-Cheong J.E., Kulp-Shorten C.L., Knable A., Carpenter G., Fisher S.A., Hiragun M., Yanase Y., Hide M., Callen J., McGrath J.A.
Am. J. Hum. Genet. 90:511-517(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FCTCS ARG-2144.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y09077 mRNA. Translation: CAA70298.1.
U76308 mRNA. Translation: AAC50929.1.
U49844 mRNA. Translation: AAC50405.1.
AF325699 Genomic DNA. Translation: AAK26749.1.
AB208847 mRNA. Translation: BAD92084.1.
CCDSCCDS3124.1. [Q13535-1]
RefSeqNP_001175.2. NM_001184.3. [Q13535-1]
UniGeneHs.271791.

3D structure databases

ProteinModelPortalQ13535.
SMRQ13535. Positions 1647-2225, 2302-2544.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107027. 85 interactions.
DIPDIP-35308N.
IntActQ13535. 15 interactions.
MINTMINT-194575.
STRING9606.ENSP00000343741.

Chemistry

BindingDBQ13535.
ChEMBLCHEMBL5024.

PTM databases

PhosphoSiteQ13535.

Polymorphism databases

DMDM62286460.

Proteomic databases

MaxQBQ13535.
PaxDbQ13535.
PRIDEQ13535.

Protocols and materials databases

DNASU545.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000350721; ENSP00000343741; ENSG00000175054. [Q13535-1]
ENST00000383101; ENSP00000372581; ENSG00000175054. [Q13535-2]
GeneID545.
KEGGhsa:545.
UCSCuc003eux.4. human. [Q13535-1]

Organism-specific databases

CTD545.
GeneCardsGC03M142168.
GeneReviewsATR.
H-InvDBHIX0030886.
HGNCHGNC:882. ATR.
HPAHPA028264.
MIM210600. phenotype.
601215. gene.
614564. phenotype.
neXtProtNX_Q13535.
Orphanet313846. Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome.
808. Seckel syndrome.
PharmGKBPA74.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5032.
HOGENOMHOG000034221.
HOVERGENHBG050619.
InParanoidQ13535.
KOK06640.
OMAAIQHENV.
OrthoDBEOG7Z95K8.
PhylomeDBQ13535.
TreeFamTF101183.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_120956. Cellular responses to stress.
REACT_216. DNA Repair.
SignaLinkQ13535.

Gene expression databases

ArrayExpressQ13535.
BgeeQ13535.
CleanExHS_ATR.
GenevestigatorQ13535.

Family and domain databases

Gene3D1.10.1070.11. 2 hits.
1.25.10.10. 4 hits.
1.25.40.10. 3 hits.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR003152. FATC.
IPR021133. HEAT_type_2.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR003151. PIK-rel_kinase_FAT.
IPR014009. PIK_FAT.
IPR011990. TPR-like_helical.
IPR012993. UME.
[Graphical view]
PfamPF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
PF08064. UME. 1 hit.
[Graphical view]
SMARTSM00146. PI3Kc. 1 hit.
SM00802. UME. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 7 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS51189. FAT. 1 hit.
PS51190. FATC. 1 hit.
PS50077. HEAT_REPEAT. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATR. human.
GeneWikiAtaxia_telangiectasia_and_Rad3_related.
GenomeRNAi545.
NextBio2253.
PROQ13535.
SOURCESearch...

Entry information

Entry nameATR_HUMAN
AccessionPrimary (citable) accession number: Q13535
Secondary accession number(s): Q59HB2 expand/collapse secondary AC list , Q7KYL3, Q93051, Q9BXK4
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM