[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). PubMed=8978690 [NCBI, ExPASy, EBI, Israel, Japan] Bentley N.J., Holtzman D.A., Flaggs G., Keegan K.S., DeMaggio A., Ford J.C., Hoekstra M., Carr A.M.; "The Schizosaccharomyces pombe rad3 checkpoint gene."; EMBO J. 15:6641-6651(1996).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. TISSUE=T-cell; DOI=10.1073/pnas.93.7.2850; PubMed=8610130 [NCBI, ExPASy, EBI, Israel, Japan] Cimprich K.A., Shin T.B., Keith C.T., Schreiber S.L.; "cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein."; Proc. Natl. Acad. Sci. U.S.A. 93:2850-2855(1996).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 433-526 (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. DOI=10.1016/S0378-1119(01)00543-1; PubMed=11470508 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Evidence for alternate splicing within the mRNA transcript encoding the DNA damage response kinase ATR."; Gene 272:35-43(2001).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2155-2644 (ISOFORM 3). TISSUE=Brain; 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.
[5]	SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. PubMed=8843195 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes."; Genes Dev. 10:2423-2437(1996).
[6]	ENZYME REGULATION. PubMed=9766667 [NCBI, ExPASy, EBI, Israel, Japan] Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E., Abraham R.T.; "Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin."; Cancer Res. 58:4375-4382(1998).
[7]	FUNCTION, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF ASP-2475. DOI=10.1093/emboj/17.1.159; PubMed=9427750 [NCBI, ExPASy, EBI, Israel, Japan] Cliby W.A., Roberts C.J., Cimprich K.A., Stringer C.M., Lamb J.R., Schreiber S.L., Friend S.H.; "Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints."; EMBO J. 17:159-169(1998).
[8]	FUNCTION, AND MUTAGENESIS OF ASP-2494. DOI=10.1073/pnas.95.13.7445; PubMed=9636169 [NCBI, ExPASy, EBI, Israel, Japan] Wright J.A., Keegan K.S., Herendeen D.R., Bentley N.J., Carr A.M., Hoekstra M.F., Concannon P.; "Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control."; Proc. Natl. Acad. Sci. U.S.A. 95:7445-7450(1998).
[9]	INTERACTION WITH HDAC2, AND IDENTIFICATION IN A COMPLEX CONTAINING HDAC2 AND CHD4. DOI=10.1021/bi991614n; PubMed=10545197 [NCBI, ExPASy, EBI, Israel, Japan] Schmidt D.R., Schreiber S.L.; "Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4."; Biochemistry 38:14711-14717(1999).
[10]	FUNCTION, AND MUTAGENESIS OF LYS-2327 AND ASP-2475. PubMed=9925639 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "A role for ATR in the DNA damage-induced phosphorylation of p53."; Genes Dev. 13:152-157(1999).
[11]	COFACTOR, AND FUNCTION. DOI=10.1074/jbc.274.53.37538; PubMed=10608806 [NCBI, ExPASy, EBI, Israel, Japan] Kim S.-T., Lim D.-S., Canman C.E., Kastan M.B.; "Substrate specificities and identification of putative substrates of ATM kinase family members."; J. Biol. Chem. 274:37538-37543(1999).
[12]	FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-2494, AND ENZYME REGULATION. DOI=10.1038/sj.onc.1203077; PubMed=10597277 [NCBI, ExPASy, EBI, Israel, Japan] Hall-Jackson C.A., Cross D.A.E., Morrice N., Smythe C.; "ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK."; Oncogene 18:6707-6713(1999).
[13]	FUNCTION. PubMed=10859164 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint."; Genes Dev. 14:1448-1459(2000).
[14]	FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-2327. DOI=10.1101/gad.851000; PubMed=11114888 [NCBI, ExPASy, EBI, Israel, Japan] Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D., Elledge S.J., Abraham R.T.; "Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress."; Genes Dev. 14:2989-3002(2000).
[15]	FUNCTION. DOI=10.1074/jbc.C100569200; PubMed=11673449 [NCBI, ExPASy, EBI, Israel, Japan] Ward I.M., Chen J.; "Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress."; J. Biol. Chem. 276:47759-47762(2001).
[16]	FUNCTION, AND INTERACTION WITH RAD17. DOI=10.1038/35082110; PubMed=11418864 [NCBI, ExPASy, EBI, Israel, Japan] Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A., Ali A., Chen S.M., Abraham R.T., Wang X.-F.; "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses."; Nature 411:969-974(2001).
[17]	FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ATRIP. DOI=10.1126/science.1065521; PubMed=11721054 [NCBI, ExPASy, EBI, Israel, Japan] Cortez D., Guntuku S., Qin J., Elledge S.J.; "ATR and ATRIP: partners in checkpoint signaling."; Science 294:1713-1716(2001).
[18]	FUNCTION. DOI=10.1016/S0092-8674(02)01113-3; PubMed=12526805 [NCBI, ExPASy, EBI, Israel, Japan] Casper A.M., Nghiem P., Arlt M.F., Glover T.W.; "ATR regulates fragile site stability."; Cell 111:779-789(2002).
[19]	FUNCTION, AND SUBCELLULAR LOCATION. DOI=10.1128/MCB.22.6.1834-1843.2002; PubMed=11865061 [NCBI, ExPASy, EBI, Israel, Japan] Hammond E.M., Denko N.C., Dorie M.J., Abraham R.T., Giaccia A.J.; "Hypoxia links ATR and p53 through replication arrest."; Mol. Cell. Biol. 22:1834-1843(2002).
[20]	DNA-BINDING, AND MUTAGENESIS OF LYS-2327. DOI=10.1073/pnas.102167799; PubMed=12011431 [NCBI, ExPASy, EBI, Israel, Japan] Uensal-Kacmaz K., Makhov A.M., Griffith J.D., Sancar A.; "Preferential binding of ATR protein to UV-damaged DNA."; Proc. Natl. Acad. Sci. U.S.A. 99:6673-6678(2002).
[21]	FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-2475. DOI=10.1016/S0960-9822(03)00376-2; PubMed=12814551 [NCBI, ExPASy, EBI, Israel, Japan] Barr S.M., Leung C.G., Chang E.E., Cimprich K.A.; "ATR kinase activity regulates the intranuclear translocation of ATR and RPA following ionizing radiation."; Curr. Biol. 13:1047-1051(2003).
[22]	INTERACTION WITH CLSPN. DOI=10.1074/jbc.M301136200; PubMed=12766152 [NCBI, ExPASy, EBI, Israel, Japan] Chini C.C.S., Chen J.; "Human claspin is required for replication checkpoint control."; J. Biol. Chem. 278:30057-30062(2003).
[23]	FUNCTION, INTERACTION WITH MSH2, AND MASS SPECTROMETRY. DOI=10.1073/pnas.2536810100; PubMed=14657349 [NCBI, ExPASy, EBI, Israel, Japan] Wang Y., Qin J.; "MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation."; Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003).
[24]	FUNCTION, DNA-BINDING, AND IDENTIFICATION IN A COMPLEX WITH RPA AND ATRIP. DOI=10.1126/science.1083430; PubMed=12791985 [NCBI, ExPASy, EBI, Israel, Japan] Zou L., Elledge S.J.; "Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes."; Science 300:1542-1548(2003).
[25]	INTERACTION WITH BCR-ABL. DOI=10.1016/S1535-6108(04)00056-X; PubMed=15050919 [NCBI, ExPASy, EBI, Israel, Japan] Dierov J., Dierova R., Carroll M.; "BCR/ABL translocates to the nucleus and disrupts an ATR-dependent intra-S phase checkpoint."; Cancer Cell 5:275-285(2004).
[26]	FUNCTION. DOI=10.1074/jbc.C300554200; PubMed=14742437 [NCBI, ExPASy, EBI, Israel, Japan] Ward I.M., Minn K., Chen J.; "UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress."; J. Biol. Chem. 279:9677-9680(2004).
[27]	DNA-BINDING, AND SUBCELLULAR LOCATION. DOI=10.1074/jbc.M314212200; PubMed=14871897 [NCBI, ExPASy, EBI, Israel, Japan] Dart D.A., Adams K.E., Akerman I., Lakin N.D.; "Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase."; J. Biol. Chem. 279:16433-16440(2004).
[28]	FUNCTION. DOI=10.1101/gad.1196104; PubMed=15314022 [NCBI, ExPASy, EBI, Israel, Japan] Andreassen P.R., D'Andrea A.D., Taniguchi T.; "ATR couples FANCD2 monoubiquitination to the DNA-damage response."; Genes Dev. 18:1958-1963(2004).
[29]	FUNCTION. DOI=10.1093/hmg/ddh335; PubMed=15496423 [NCBI, ExPASy, EBI, Israel, Japan] Alderton G.K., Joenje H., Varon R., Borglum A.D., Jeggo P.A., O'Driscoll M.; "Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway."; Hum. Mol. Genet. 13:3127-3138(2004).
[30]	FUNCTION, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH ATRIP AND RPA1, BINDING TO DNA, AND ENZYME REGULATION. DOI=10.1128/MCB.24.3.1292-1300.2003; PubMed=14729973 [NCBI, ExPASy, EBI, Israel, Japan] Uensal-Kacmaz K., Sancar A.; "Quaternary structure of ATR and effects of ATRIP and replication protein A on its DNA binding and kinase activities."; Mol. Cell. Biol. 24:1292-1300(2004).
[31]	FUNCTION. DOI=10.1073/pnas.0403410101; PubMed=15210935 [NCBI, ExPASy, EBI, Israel, Japan] Cortez D., Glick G., Elledge S.J.; "Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases."; Proc. Natl. Acad. Sci. U.S.A. 101:10078-10083(2004).
[32]	INTERACTION WITH EEF1E1. DOI=10.1016/j.cell.2004.11.054; PubMed=15680327 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR."; Cell 120:209-221(2005).
[33]	INTERACTION WITH ATRIP. DOI=10.1038/nature03442; PubMed=15758953 [NCBI, ExPASy, EBI, Israel, Japan] Falck J., Coates J., Jackson S.P.; "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage."; Nature 434:605-611(2005).
[34]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-919, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1021/pr070152u; PubMed=17924679 [NCBI, ExPASy, EBI, Israel, Japan] Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."; J. Proteome Res. 6:4150-4162(2007).
[35]	INTERACTION WITH CEP164, AND SUBCELLULAR LOCATION. DOI=10.1101/gad.1627708; PubMed=18283122 [NCBI, ExPASy, EBI, Israel, Japan] Sivasubramaniam S., Sun X., Pan Y.R., Wang S., Lee E.Y.; "Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1."; Genes Dev. 22:587-600(2008).
[36]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428; SER-435 AND THR-1989, AND MASS SPECTROMETRY. DOI=10.1016/j.molcel.2008.07.007; PubMed=18691976 [NCBI, ExPASy, EBI, Israel, Japan] Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.; "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."; Mol. Cell 31:438-448(2008).
[37]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1989, AND MASS SPECTROMETRY. DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan] Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.; "A quantitative atlas of mitotic phosphorylation."; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[38]	IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. Colinge J., Superti-Furga G., Bennett K.L.; Submitted (OCT-2008) to UniProtKB.
[39]	INVOLVEMENT IN SCKL1. DOI=10.1038/ng1129; PubMed=12640452 [NCBI, ExPASy, EBI, Israel, Japan] O'Driscoll M., Ruiz-Perez V.L., Woods C.G., Jeggo P.A., Goodship J.A.; "A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome."; Nat. Genet. 33:497-501(2003).
[40]	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. DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan] 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., 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.; "Patterns of somatic mutation in human cancer genomes."; Nature 446:153-158(2007).

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: 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 and CEP164.
INTERACTION:
Q9NY61:AATF; NbExp=1; IntAct=EBI-968983, EBI-372428;
P16220:CREB1; NbExp=1; IntAct=EBI-968983, EBI-711855;
P04637:TP53; NbExp=1; IntAct=EBI-968983, EBI-366083;
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.

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	Q13535-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	Q13535-2
Features which should be applied to build the isoform sequence: VSP_013305, VSP_013304.

Name	3
Isoform ID	Q13535-3
Note: No experimental confirmation available.
Features which should be applied to build the isoform sequence: VSP_036907, VSP_036908.

TISSUE SPECIFICITY: Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary.
PTM: Phosphorylated; autophosphorylates in vitro.
DISEASE: Defects in ATR are a cause of Seckel syndrome type 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.
SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
SIMILARITY: Contains 1 FAT domain.
SIMILARITY: Contains 1 FATC domain.
SIMILARITY: Contains 2 HEAT repeats.
SIMILARITY: Contains 1 PI3K/PI4K domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=ATR";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

Y09077; CAA70298.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U76308; AAC50929.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U49844; AAC50405.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF325699; AAK26749.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB208847; BAD92084.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00412298; -.
IPI00554573; -.
IPI00926461; -.

RefSeq

NP_001175.2; -.

UniGene

Hs.271791

3D structure databases

ModBase

Q13535.

Protein-protein interaction databases

IntAct

Q13535; 10.

PTM databases

PhosphoSite

Q13535; -.

Enzyme and pathway databases

BRENDA

2.7.11.1; 247.

Pathway_Interaction_DB

bard1pathway; BARD1 signaling events.
circadianpathway; Circadian rhythm pathway.

Reactome

REACT_1538; Cell Cycle Checkpoints.

Organism-specific databases

GeneCards

GC03M143650; -.
GC03M143651; -.
GC03M143652; -.

HGNC

HGNC:882; ATR.

GenAtlas

ATR.

MIM

210600; phenotype. [NCBI / EBI]
601215; gene. [NCBI / EBI]

Orphanet

808; Seckel syndrome.

PharmGKB

PA74; -.

Gene expression databases

Q13535; -.

Q13535; -.

HS_ATR; -.

ENSG00000175054; Homo sapiens.

Ontologies

GO:0005654;	Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0005524;	Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0003677;	Molecular function: DNA binding (inferred from electronic annotation from UniProtKB-KW).
GO:0030145;	Molecular function: manganese ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0032405;	Molecular function: MutLalpha complex binding (inferred from direct assay from MGI).
GO:0032407;	Molecular function: MutSalpha complex binding (inferred from direct assay from MGI).
GO:0004674;	Molecular function: protein serine/threonine kinase activity (inferred from electronic annotation from UniProtKB-KW).
GO:0007049;	Biological process: cell cycle (traceable author statement from ProtInc).
GO:0000077;	Biological process: DNA damage checkpoint (inferred from direct assay from UniProtKB).
GO:0006281;	Biological process: DNA repair (traceable author statement from ProtInc).
GO:0006260;	Biological process: DNA replication (inferred from experiment from Reactome).
GO:0007275;	Biological process: multicellular organismal development (traceable author statement from ProtInc).
GO:0008156;	Biological process: negative regulation of DNA replication (inferred from mutant phenotype from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR003152; FATC.
IPR000357; HEAT.
IPR000403; PI3/4_kinase_cat.
IPR018936; PI3/4_kinase_CS.
IPR003151; PIK-rel_kinase_FAT.
IPR014009; PIK_FAT.
IPR012993; UME.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.1070.11; PI3/4_kinase_cat; 1.

Pfam

PF02259; FAT; 1.
PF02260; FATC; 1.
PF02985; HEAT; 2.
PF00454; PI3_PI4_kinase; 1.
PF08064; UME; 1.
Pfam graphical view of domain structure.

SMART

SM00146; PI3Kc; 1.
SM00802; UME; 1.
SMART graphical view of domain structure.

PROSITE

PS51189; FAT; 1.
PS51190; FATC; 1.
PS50077; HEAT_REPEAT; 1.
PS00915; PI3_4_KINASE_1; FALSE_NEG.
PS00916; PI3_4_KINASE_2; 1.
PS50290; PI3_4_KINASE_3; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

Q13535; -.

Genome annotation databases

Ensembl

ENSG00000175054; Homo sapiens. [Contig view]

GeneID

545; -.

KEGG

hsa:545; -.

Phylogenomic databases

HOVERGEN

Q13535; -.

OMA

Q13535; EWSASWA.

Other

2253; -.

ATR; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; ATP-binding; Chromosomal protein; DNA damage; DNA repair; DNA-binding; Dwarfism; Kinase; Manganese; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Repeat; Serine/threonine-protein kinase; Transferase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 2644`	`2644`	`Serine/threonine-protein kinase ATR.`	`PRO_0000088844`
`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.`
`MOD_RES`	`428 428`		`Phosphoserine.`
`MOD_RES`	`435 435`		`Phosphoserine.`
`MOD_RES`	`919 919`		`Phosphoserine.`
`MOD_RES`	`1989 1989`		`Phosphothreonine.`
`VAR_SEQ`	`450 450`		`E -> D (in isoform 2).`	`VSP_013305`
`VAR_SEQ`	`451 514`		`Missing (in isoform 2).`	`VSP_013304`
`VAR_SEQ`	`2588 2610`		`AKTHVLDIEQRLQGVIKTRNRVT -> VSRRYSLIWAVVLISTNELDMQL (in isoform 3).`	`VSP_036907`
`VAR_SEQ`	`2611 2644`		`Missing (in isoform 3).`	`VSP_036908`
`VARIANT`	`64 64`	`1`	`T -> A.`	`VAR_041584`
`VARIANT`	`90 90`	`1`	`H -> Y.`	`VAR_041585`
`VARIANT`	`211 211`	`1`	`M -> T (in dbSNP:rs2227928 [NCBI]).`	`VAR_050532`
`VARIANT`	`297 297`	`1`	`K -> N (in dbSNP:rs2229033 [NCBI]).`	`VAR_041586`
`VARIANT`	`316 316`	`1`	`V -> I (in dbSNP:rs28897764 [NCBI]).`	`VAR_041587`
`VARIANT`	`959 959`	`1`	`V -> M (in dbSNP:rs28910271 [NCBI]).`	`VAR_041588`
`VARIANT`	`1087 1087`	`1`	`Y -> H.`	`VAR_041589`
`VARIANT`	`1213 1213`	`1`	`S -> G.`	`VAR_041590`
`VARIANT`	`1488 1488`	`1`	`A -> P (in a lung squamous cell carcinoma sample; somatic mutation).`	`VAR_041591`
`VARIANT`	`1526 1526`	`1`	`I -> V (in dbSNP:rs34124242 [NCBI]).`	`VAR_050533`
`VARIANT`	`1607 1607`	`1`	`S -> N.`	`VAR_041592`
`VARIANT`	`1612 1612`	`1`	`N -> S.`	`VAR_041593`
`VARIANT`	`2002 2002`	`1`	`A -> G (in a lung adenocarcinoma sample; somatic mutation).`	`VAR_041594`
`VARIANT`	`2120 2120`	`1`	`G -> A.`	`VAR_041595`
`VARIANT`	`2132 2132`	`1`	`Y -> D (in dbSNP:rs28910273 [NCBI]).`	`VAR_041596`
`VARIANT`	`2233 2233`	`1`	`S -> I (in a lung large cell carcinoma sample; somatic mutation).`	`VAR_041597`
`VARIANT`	`2425 2425`	`1`	`R -> Q (in dbSNP:rs2229032 [NCBI]).`	`VAR_041598`
`VARIANT`	`2434 2434`	`1`	`P -> A (in dbSNP:rs33972295 [NCBI]).`	`VAR_041599`
`VARIANT`	`2438 2438`	`1`	`E -> K (in a breast pleomorphic lobular carcinoma sample; somatic mutation).`	`VAR_041600`
`VARIANT`	`2537 2537`	`1`	`E -> Q (in a breast infiltrating ductal carcinoma sample; somatic mutation).`	`VAR_041601`
`MUTAGEN`	`2327 2327`		`K->R: Abolishes kinase activity.`
`MUTAGEN`	`2475 2475`		`D->A: Abolishes kinase activity; increases sensitivity to IR and impairs translocation to nuclear foci upon DNA damage.`
`MUTAGEN`	`2494 2494`		`D->E: Abolishes kinase activity; reduces cell viability, augments sensitivity to IR and UV.`
`CONFLICT`	`92 92`		`A -> R (in Ref. 1; CAA70298/AAC50929).`

Sequence information

Length: 2644 AA [This is the length of the unprocessed precursor]

Molecular weight: 301367 Da [This is the MW of the unprocessed precursor]

CRC64: 11BC22297FB9A802 [This is a checksum on the sequence]

        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

Q13535 in FASTA format

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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools