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Q13535

- ATR_HUMAN

UniProt

Q13535 - ATR_HUMAN

Protein

Serine/threonine-protein kinase ATR

Gene

ATR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 3 (05 Jul 2004)
      Previous versions | rss
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    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

    GO - Biological processi

    1. cell cycle Source: ProtInc
    2. cellular response to DNA damage stimulus Source: UniProtKB
    3. cellular response to gamma radiation Source: BHF-UCL
    4. cellular response to UV Source: BHF-UCL
    5. DNA damage checkpoint Source: UniProtKB
    6. DNA repair Source: Reactome
    7. DNA replication Source: Reactome
    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

    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 8 Publications. 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.

    GO - Cellular componenti

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

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 ATRPRO_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.2 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.By similarity15 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati799 – 83537HEAT 1Add
    BLAST
    Repeati1329 – 136537HEAT 2Add
    BLAST
    Domaini1640 – 2185546FATPROSITE-ProRule annotationAdd
    BLAST
    Domaini2322 – 2567246PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST
    Domaini2612 – 264433FATCPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the PI3/PI4-kinase family. ATM subfamily.Curated
    Contains 1 FAT domain.PROSITE-ProRule annotation
    Contains 1 FATC domain.PROSITE-ProRule annotation
    Contains 2 HEAT repeats.PROSITE-ProRule annotation
    Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti92 – 921A → R in CAA70298. (PubMed:8978690)Curated
    Sequence conflicti92 – 921A → R in AAC50929. (PubMed:8978690)Curated

    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. 1 PublicationVSP_013305
    Alternative sequencei451 – 51464Missing in isoform 2. 1 PublicationVSP_013304Add
    BLAST
    Alternative sequencei2588 – 261023AKTHV…RNRVT → VSRRYSLIWAVVLISTNELD MQL in isoform 3. 1 PublicationVSP_036907Add
    BLAST
    Alternative sequencei2611 – 264434Missing in isoform 3. 1 PublicationVSP_036908Add
    BLAST

    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]
    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...
    MobiDBi 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 ]
    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

    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: October 1, 2014
    This is version 138 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