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Q13535

- ATR_HUMAN

UniProt

Q13535 - ATR_HUMAN

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Protein
Serine/threonine-protein kinase ATR
Gene
ATR, FRP1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.22 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Manganese.1 Publication

Enzyme regulationi

Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002.3 Publications

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. DNA binding Source: UniProtKB-KW
  3. MutLalpha complex binding Source: MGI
  4. MutSalpha complex binding Source: MGI
  5. protein binding Source: UniProtKB
  6. protein kinase activity Source: UniProtKB
  7. protein serine/threonine kinase activity Source: BHF-UCL
Complete GO annotation...

GO - Biological processi

  1. DNA damage checkpoint Source: UniProtKB
  2. DNA repair Source: Reactome
  3. DNA replication Source: Reactome
  4. cell cycle Source: ProtInc
  5. cellular response to DNA damage stimulus Source: UniProtKB
  6. cellular response to UV Source: BHF-UCL
  7. cellular response to gamma radiation Source: BHF-UCL
  8. multicellular organismal development Source: ProtInc
  9. negative regulation of DNA replication Source: UniProtKB
  10. peptidyl-serine phosphorylation Source: BHF-UCL
  11. positive regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
  12. protein autophosphorylation Source: BHF-UCL
  13. regulation of protein binding Source: Ensembl
  14. replicative senescence Source: BHF-UCL
  15. response to drug Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Manganese, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_18265. Regulation of the Fanconi anemia pathway.
REACT_200780. Regulation of HSF1-mediated heat shock response.
REACT_6769. Activation of ATR in response to replication stress.
REACT_75792. Meiotic synapsis.
REACT_897. G2/M DNA damage checkpoint.
SignaLinkiQ13535.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ATR
Synonyms:FRP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:882. ATR.

Subcellular locationi

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.8 Publications

GO - Cellular componenti

  1. PML body Source: UniProtKB
  2. XY body Source: Ensembl
  3. chromosome Source: UniProtKB
  4. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti2144 – 21441Q → R in FCTCS. 1 Publication
VAR_067919

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2327 – 23271K → R: Abolishes kinase activity. 3 Publications
Mutagenesisi2475 – 24751D → A: Abolishes kinase activity; increases sensitivity to IR and impairs translocation to nuclear foci upon DNA damage. 3 Publications
Mutagenesisi2494 – 24941D → E: Abolishes kinase activity; reduces cell viability, augments sensitivity to IR and UV. 2 Publications

Keywords - Diseasei

Disease mutation, Dwarfism, Mental retardation

Organism-specific databases

MIMi210600. phenotype.
614564. phenotype.
Orphaneti313846. Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome.
808. Seckel syndrome.
PharmGKBiPA74.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 26442644Serine/threonine-protein kinase ATR
PRO_0000088844Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei428 – 4281Phosphoserine2 Publications
Modified residuei1989 – 19891Phosphothreonine1 Publication

Post-translational modificationi

Phosphorylated; autophosphorylates in vitro.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ13535.
PaxDbiQ13535.
PRIDEiQ13535.

PTM databases

PhosphoSiteiQ13535.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiQ13535.
BgeeiQ13535.
CleanExiHS_ATR.
GenevestigatoriQ13535.

Organism-specific databases

HPAiHPA028264.

Interactioni

Subunit structurei

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 TTI1.15 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDC5LQ994593EBI-968983,EBI-374880
CDK9P507503EBI-968983,EBI-1383449
IKBKGQ9Y6K92EBI-968983,EBI-81279
TTI1O431562EBI-968983,EBI-1055680

Protein-protein interaction databases

BioGridi107027. 85 interactions.
DIPiDIP-35308N.
IntActiQ13535. 15 interactions.
MINTiMINT-194575.
STRINGi9606.ENSP00000343741.

Structurei

3D structure databases

ProteinModelPortaliQ13535.
SMRiQ13535. Positions 1647-2225, 2302-2544.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati799 – 83537HEAT 1
Add
BLAST
Repeati1329 – 136537HEAT 2
Add
BLAST
Domaini1640 – 2185546FAT
Add
BLAST
Domaini2322 – 2567246PI3K/PI4K
Add
BLAST
Domaini2612 – 264433FATC
Add
BLAST

Sequence similaritiesi

Contains 1 FAT domain.
Contains 1 FATC domain.
Contains 2 HEAT repeats.
Contains 1 PI3K/PI4K domain.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG5032.
HOGENOMiHOG000034221.
HOVERGENiHBG050619.
InParanoidiQ13535.
KOiK06640.
OMAiAIQHENV.
OrthoDBiEOG7Z95K8.
PhylomeDBiQ13535.
TreeFamiTF101183.

Family and domain databases

Gene3Di1.10.1070.11. 2 hits.
1.25.10.10. 4 hits.
1.25.40.10. 3 hits.
InterProiIPR011989. 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]
PfamiPF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
PF08064. UME. 1 hit.
[Graphical view]
SMARTiSM00146. PI3Kc. 1 hit.
SM00802. UME. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 7 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS51189. 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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q13535-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MGEHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV     50
VAVELVKKTD SQPTSVMLLD FIQHIMKSSP LMFVNVSGSH EAKGSCIEFS 100
NWIITRLLRI AATPSCHLLH KKICEVICSL LFLFKSKSPA IFGVLTKELL 150
QLFEDLVYLH RRNVMGHAVE WPVVMSRFLS QLDEHMGYLQ SAPLQLMSMQ 200
NLEFIEVTLL MVLTRIIAIV FFRRQELLLW QIGCVLLEYG SPKIKSLAIS 250
FLTELFQLGG LPAQPASTFF SSFLELLKHL VEMDTDQLKL YEEPLSKLIK 300
TLFPFEAEAY RNIEPVYLNM LLEKLCVMFE DGVLMRLKSD LLKAALCHLL 350
QYFLKFVPAG YESALQVRKV YVRNICKALL DVLGIEVDAE YLLGPLYAAL 400
KMESMEIIEE IQCQTQQENL SSNSDGISPK RRRLSSSLNP SKRAPKQTEE 450
IKHVDMNQKS ILWSALKQKA ESLQISLEYS GLKNPVIEML EGIAVVLQLT 500
ALCTVHCSHQ NMNCRTFKDC QHKSKKKPSV VITWMSLDFY TKVLKSCRSL 550
LESVQKLDLE ATIDKVVKIY DALIYMQVNS SFEDHILEDL CGMLSLPWIY 600
SHSDDGCLKL TTFAANLLTL SCRISDSYSP QAQSRCVFLL TLFPRRIFLE 650
WRTAVYNWAL QSSHEVIRAS CVSGFFILLQ QQNSCNRVPK ILIDKVKDDS 700
DIVKKEFASI LGQLVCTLHG MFYLTSSLTE PFSEHGHVDL FCRNLKATSQ 750
HECSSSQLKA SVCKPFLFLL KKKIPSPVKL AFIDNLHHLC KHLDFREDET 800
DVKAVLGTLL NLMEDPDKDV RVAFSGNIKH ILESLDSEDG FIKELFVLRM 850
KEAYTHAQIS RNNELKDTLI LTTGDIGRAA KGDLVPFALL HLLHCLLSKS 900
ASVSGAAYTE IRALVAAKSV KLQSFFSQYK KPICQFLVES LHSSQMTALP 950
NTPCQNADVR KQDVAHQREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP 1000
DLAAKASPAA SALIRTLGKQ LNVNRREILI NNFKYIFSHL VCSCSKDELE 1050
RALHYLKNET EIELGSLLRQ DFQGLHNELL LRIGEHYQQV FNGLSILASF 1100
ASSDDPYQGP RDIISPELMA DYLQPKLLGI LAFFNMQLLS SSVGIEDKKM 1150
ALNSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV 1200
RCLDHACLGS LLSHVIVALL PLIHIQPKET AAIFHYLIIE NRDAVQDFLH 1250
EIYFLPDHPE LKKIKAVLQE YRKETSESTD LQTTLQLSMK AIQHENVDVR 1300
IHALTSLKET LYKNQEKLIK YATDSETVEP IISQLVTVLL KGCQDANSQA 1350
RLLCGECLGE LGAIDPGRLD FSTTETQGKD FTFVTGVEDS SFAYGLLMEL 1400
TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMETNGPGH QLWRRFPEHV 1450
REILEPHLNT RYKSSQKSTD WSGVKKPIYL SKLGSNFAEW SASWAGYLIT 1500
KVRHDLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA 1550
EIMAVLKHDD QHTINTQDIA SDLCQLSTQT VFSMLDHLTQ WARHKFQALK 1600
AEKCPHSKSN RNKVDSMVST VDYEDYQSVT RFLDLIPQDT LAVASFRSKA 1650
YTRAVMHFES FITEKKQNIQ EHLGFLQKLY AAMHEPDGVA GVSAIRKAEP 1700
SLKEQILEHE SLGLLRDATA CYDRAIQLEP DQIIHYHGVV KSMLGLGQLS 1750
TVITQVNGVH ANRSEWTDEL NTYRVEAAWK LSQWDLVENY LAADGKSTTW 1800
SVRLGQLLLS AKKRDITAFY DSLKLVRAEQ IVPLSAASFE RGSYQRGYEY 1850
IVRLHMLCEL EHSIKPLFQH SPGDSSQEDS LNWVARLEMT QNSYRAKEPI 1900
LALRRALLSL NKRPDYNEMV GECWLQSARV ARKAGHHQTA YNALLNAGES 1950
RLAELYVERA KWLWSKGDVH QALIVLQKGV ELCFPENETP PEGKNMLIHG 2000
RAMLLVGRFM EETANFESNA IMKKYKDVTA CLPEWEDGHF YLAKYYDKLM 2050
PMVTDNKMEK QGDLIRYIVL HFGRSLQYGN QFIYQSMPRM LTLWLDYGTK 2100
AYEWEKAGRS DRVQMRNDLG KINKVITEHT NYLAPYQFLT AFSQLISRIC 2150
HSHDEVFVVL MEIIAKVFLA YPQQAMWMMT AVSKSSYPMR VNRCKEILNK 2200
AIHMKKSLEK FVGDATRLTD KLLELCNKPV DGSSSTLSMS THFKMLKKLV 2250
EEATFSEILI PLQSVMIPTL PSILGTHANH ASHEPFPGHW AYIAGFDDMV 2300
EILASLQKPK KISLKGSDGK FYIMMCKPKD DLRKDCRLME FNSLINKCLR 2350
KDAESRRREL HIRTYAVIPL NDECGIIEWV NNTAGLRPIL TKLYKEKGVY 2400
MTGKELRQCM LPKSAALSEK LKVFREFLLP RHPPIFHEWF LRTFPDPTSW 2450
YSSRSAYCRS TAVMSMVGYI LGLGDRHGEN ILFDSLTGEC VHVDFNCLFN 2500
KGETFEVPEI VPFRLTHNMV NGMGPMGTEG LFRRACEVTM RLMRDQREPL 2550
MSVLKTFLHD PLVEWSKPVK GHSKAPLNET GEVVNEKAKT HVLDIEQRLQ 2600
GVIKTRNRVT GLPLSIEGHV HYLIQEATDE NLLCQMYLGW TPYM 2644
Length:2,644
Mass (Da):301,367
Last modified:July 5, 2004 - v3
Checksum:i11BC22297FB9A802
GO
Isoform 2 (identifier: Q13535-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:2,580
Mass (Da):294,219
Checksum:iA7C5CED46708FC16
GO
Isoform 3 (identifier: Q13535-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     2588-2610: AKTHVLDIEQRLQGVIKTRNRVT → VSRRYSLIWAVVLISTNELDMQL
     2611-2644: Missing.

Note: No experimental confirmation available.

Show »
Length:2,610
Mass (Da):297,479
Checksum:i44281024A65D73B1
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti64 – 641T → A.1 Publication
Corresponds to variant rs35306038 [ dbSNP | Ensembl ].
VAR_041584
Natural varianti90 – 901H → Y.1 Publication
Corresponds to variant rs28897763 [ dbSNP | Ensembl ].
VAR_041585
Natural varianti211 – 2111M → T.
Corresponds to variant rs2227928 [ dbSNP | Ensembl ].
VAR_050532
Natural varianti297 – 2971K → N.1 Publication
Corresponds to variant rs2229033 [ dbSNP | Ensembl ].
VAR_041586
Natural varianti316 – 3161V → I.1 Publication
Corresponds to variant rs28897764 [ dbSNP | Ensembl ].
VAR_041587
Natural varianti959 – 9591V → M.1 Publication
Corresponds to variant rs28910271 [ dbSNP | Ensembl ].
VAR_041588
Natural varianti1087 – 10871Y → H.1 Publication
Corresponds to variant rs34253059 [ dbSNP | Ensembl ].
VAR_041589
Natural varianti1213 – 12131S → G.1 Publication
Corresponds to variant rs34766606 [ dbSNP | Ensembl ].
VAR_041590
Natural varianti1488 – 14881A → P in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
VAR_041591
Natural varianti1526 – 15261I → V.
Corresponds to variant rs34124242 [ dbSNP | Ensembl ].
VAR_050533
Natural varianti1607 – 16071S → N.1 Publication
Corresponds to variant rs55724025 [ dbSNP | Ensembl ].
VAR_041592
Natural varianti1612 – 16121N → S.1 Publication
Corresponds to variant rs55894265 [ dbSNP | Ensembl ].
VAR_041593
Natural varianti2002 – 20021A → G in a lung adenocarcinoma sample; somatic mutation. 1 Publication
VAR_041594
Natural varianti2120 – 21201G → A.1 Publication
Corresponds to variant rs35134774 [ dbSNP | Ensembl ].
VAR_041595
Natural varianti2132 – 21321Y → D.1 Publication
Corresponds to variant rs28910273 [ dbSNP | Ensembl ].
VAR_041596
Natural varianti2144 – 21441Q → R in FCTCS. 1 Publication
VAR_067919
Natural varianti2233 – 22331S → I in a lung large cell carcinoma sample; somatic mutation. 1 Publication
VAR_041597
Natural varianti2425 – 24251R → Q.1 Publication
Corresponds to variant rs2229032 [ dbSNP | Ensembl ].
VAR_041598
Natural varianti2434 – 24341P → A.1 Publication
Corresponds to variant rs33972295 [ dbSNP | Ensembl ].
VAR_041599
Natural varianti2438 – 24381E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication
VAR_041600
Natural varianti2537 – 25371E → Q in a breast infiltrating ductal carcinoma sample; somatic mutation. 1 Publication
VAR_041601

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei450 – 4501E → D in isoform 2.
VSP_013305
Alternative sequencei451 – 51464Missing in isoform 2.
VSP_013304Add
BLAST
Alternative sequencei2588 – 261023AKTHV…RNRVT → VSRRYSLIWAVVLISTNELD MQL in isoform 3.
VSP_036907Add
BLAST
Alternative sequencei2611 – 264434Missing in isoform 3.
VSP_036908Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti92 – 921A → R in CAA70298. 1 Publication
Sequence conflicti92 – 921A → R in AAC50929. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS3124.1. [Q13535-1]
RefSeqiNP_001175.2. NM_001184.3. [Q13535-1]
UniGeneiHs.271791.

Genome annotation databases

EnsembliENST00000350721; ENSP00000343741; ENSG00000175054. [Q13535-1]
ENST00000383101; ENSP00000372581; ENSG00000175054. [Q13535-2]
GeneIDi545.
KEGGihsa:545.
UCSCiuc003eux.4. human. [Q13535-1]

Polymorphism databases

DMDMi62286460.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS3124.1. [Q13535-1 ]
RefSeqi NP_001175.2. NM_001184.3. [Q13535-1 ]
UniGenei Hs.271791.

3D structure databases

ProteinModelPortali Q13535.
SMRi Q13535. Positions 1647-2225, 2302-2544.
ModBasei Search...

Protein-protein interaction databases

BioGridi 107027. 85 interactions.
DIPi DIP-35308N.
IntActi Q13535. 15 interactions.
MINTi MINT-194575.
STRINGi 9606.ENSP00000343741.

Chemistry

BindingDBi Q13535.
ChEMBLi CHEMBL5024.

PTM databases

PhosphoSitei Q13535.

Polymorphism databases

DMDMi 62286460.

Proteomic databases

MaxQBi Q13535.
PaxDbi Q13535.
PRIDEi Q13535.

Protocols and materials databases

DNASUi 545.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000350721 ; ENSP00000343741 ; ENSG00000175054 . [Q13535-1 ]
ENST00000383101 ; ENSP00000372581 ; ENSG00000175054 . [Q13535-2 ]
GeneIDi 545.
KEGGi hsa:545.
UCSCi uc003eux.4. human. [Q13535-1 ]

Organism-specific databases

CTDi 545.
GeneCardsi GC03M142168.
GeneReviewsi ATR.
H-InvDB HIX0030886.
HGNCi HGNC:882. ATR.
HPAi HPA028264.
MIMi 210600. phenotype.
601215. gene.
614564. phenotype.
neXtProti NX_Q13535.
Orphaneti 313846. Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome.
808. Seckel syndrome.
PharmGKBi PA74.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5032.
HOGENOMi HOG000034221.
HOVERGENi HBG050619.
InParanoidi Q13535.
KOi K06640.
OMAi AIQHENV.
OrthoDBi EOG7Z95K8.
PhylomeDBi Q13535.
TreeFami TF101183.

Enzyme and pathway databases

Reactomei REACT_18265. Regulation of the Fanconi anemia pathway.
REACT_200780. Regulation of HSF1-mediated heat shock response.
REACT_6769. Activation of ATR in response to replication stress.
REACT_75792. Meiotic synapsis.
REACT_897. G2/M DNA damage checkpoint.
SignaLinki Q13535.

Miscellaneous databases

ChiTaRSi ATR. human.
GeneWikii Ataxia_telangiectasia_and_Rad3_related.
GenomeRNAii 545.
NextBioi 2253.
PROi Q13535.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q13535.
Bgeei Q13535.
CleanExi HS_ATR.
Genevestigatori Q13535.

Family and domain databases

Gene3Di 1.10.1070.11. 2 hits.
1.25.10.10. 4 hits.
1.25.40.10. 3 hits.
InterProi IPR011989. 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 ]
Pfami PF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
PF08064. UME. 1 hit.
[Graphical view ]
SMARTi SM00146. PI3Kc. 1 hit.
SM00802. UME. 1 hit.
[Graphical view ]
SUPFAMi SSF48371. SSF48371. 7 hits.
SSF56112. SSF56112. 2 hits.
PROSITEi PS51189. 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 ]
ProtoNeti Search...

Publicationsi

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  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. 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. Cited for: FUNCTION.
  19. Cited for: FUNCTION, SUBCELLULAR LOCATION.
  20. 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  44. 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.
    , 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. Cited for: VARIANT FCTCS ARG-2144.

Entry informationi

Entry nameiATR_HUMAN
AccessioniPrimary (citable) accession number: Q13535
Secondary accession number(s): Q59HB2
, Q7KYL3, Q93051, Q9BXK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: July 5, 2004
Last modified: September 3, 2014
This is version 137 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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