GenomeNet

Database: RefSeq
Entry: NP_001175
LinkDB: NP_001175
Original site: NP_001175 
LOCUS       NP_001175               2644 aa            linear   PRI 04-DEC-2023
DEFINITION  serine/threonine-protein kinase ATR isoform 1 [Homo sapiens].
ACCESSION   NP_001175 XP_945854
VERSION     NP_001175.2
DBSOURCE    REFSEQ: accession NM_001184.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 2644)
  AUTHORS   Zhang B, Li Y, Zhang J, Wang Y, Liang C, Lu T, Zhang C, Liu L, Qin
            Y, He J, Zhao X, Yu J, Hao J, Yang J, Li MJ, Yao Z, Ma S, Cheng H,
            Cheng T and Shi L.
  TITLE     ADAR1 links R-loop homeostasis to ATR activation in replication
            stress response
  JOURNAL   Nucleic Acids Res 51 (21), 11668-11687 (2023)
   PUBMED   37831098
  REMARK    GeneRIF: ADAR1 links R-loop homeostasis to ATR activation in
            replication stress response.
REFERENCE   2  (residues 1 to 2644)
  AUTHORS   Zhao JL, Yang J, Li K, Chen Y, Tang M, Zhu HL, Nie CL, Yuan Z and
            Zhao XY.
  TITLE     Abrogation of ATR function preferentially augments
            cisplatin-induced cytotoxicity in PTEN-deficient breast cancer
            cells
  JOURNAL   Chem Biol Interact 385, 110740 (2023)
   PUBMED   37802411
  REMARK    GeneRIF: Abrogation of ATR function preferentially augments
            cisplatin-induced cytotoxicity in PTEN-deficient breast cancer
            cells.
REFERENCE   3  (residues 1 to 2644)
  AUTHORS   Dwivedi D, Harry D and Meraldi P.
  TITLE     Mild replication stress causes premature centriole disengagement
            via a sub-critical Plk1 activity under the control of ATR-Chk1
  JOURNAL   Nat Commun 14 (1), 6088 (2023)
   PUBMED   37773176
  REMARK    GeneRIF: Mild replication stress causes premature centriole
            disengagement via a sub-critical Plk1 activity under the control of
            ATR-Chk1.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 2644)
  AUTHORS   Jiang F, Huang X, Ling L, Tang S, Zhou H, Cai X and Wang Y.
  TITLE     Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression and
            Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis
  JOURNAL   Int J Mol Sci 24 (18), 13925 (2023)
   PUBMED   37762228
  REMARK    GeneRIF: Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression
            and Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 2644)
  AUTHORS   Ahmed-Seghir S, Jalan M, Grimsley HE, Sharma A, Twayana S,
            Kosiyatrakul ST, Thompson C, Schildkraut CL and Powell SN.
  TITLE     A local ATR-dependent checkpoint pathway is activated by a
            site-specific replication fork block in human cells
  JOURNAL   Elife 12, 87357 (2023)
   PUBMED   37647215
  REMARK    GeneRIF: A local ATR-dependent checkpoint pathway is activated by a
            site-specific replication fork block in human cells.
            Publication Status: Online-Only
REFERENCE   6  (residues 1 to 2644)
  AUTHORS   Cliby WA, Roberts CJ, Cimprich KA, Stringer CM, Lamb JR, Schreiber
            SL and Friend SH.
  TITLE     Overexpression of a kinase-inactive ATR protein causes sensitivity
            to DNA-damaging agents and defects in cell cycle checkpoints
  JOURNAL   EMBO J 17 (1), 159-169 (1998)
   PUBMED   9427750
REFERENCE   7  (residues 1 to 2644)
  AUTHORS   Bentley NJ, Holtzman DA, Flaggs G, Keegan KS, DeMaggio A, Ford JC,
            Hoekstra M and Carr AM.
  TITLE     The Schizosaccharomyces pombe rad3 checkpoint gene
  JOURNAL   EMBO J 15 (23), 6641-6651 (1996)
   PUBMED   8978690
REFERENCE   8  (residues 1 to 2644)
  AUTHORS   Keegan KS, Holtzman DA, Plug AW, Christenson ER, Brainerd EE,
            Flaggs G, Bentley NJ, Taylor EM, Meyn MS, Moss SB, Carr AM, Ashley
            T and Hoekstra MF.
  TITLE     The Atr and Atm protein kinases associate with different sites
            along meiotically pairing chromosomes
  JOURNAL   Genes Dev 10 (19), 2423-2437 (1996)
   PUBMED   8843195
REFERENCE   9  (residues 1 to 2644)
  AUTHORS   Cimprich KA, Shin TB, Keith CT and Schreiber SL.
  TITLE     cDNA cloning and gene mapping of a candidate human cell cycle
            checkpoint protein
  JOURNAL   Proc Natl Acad Sci U S A 93 (7), 2850-2855 (1996)
   PUBMED   8610130
REFERENCE   10 (residues 1 to 2644)
  AUTHORS   Verloes,A., Drunat,S., Gressens,P. and Passemard,S.
  TITLE     Primary Autosomal Recessive Microcephalies and Seckel Syndrome
            Spectrum Disorders - RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH,
            Gripp KW and Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301772
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from U49844.1, U76308.1 and
            BE859077.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Sep 14, 2007 this sequence version replaced NP_001175.1.
            
            Summary: The protein encoded by this gene is a serine/threonine
            kinase and DNA damage sensor, activating cell cycle checkpoint
            signaling upon DNA stress. The encoded protein can phosphorylate
            and activate several proteins involved in the inhibition of DNA
            replication and mitosis, and can promote DNA repair, recombination,
            and apoptosis. This protein is also important for fragile site
            stability and centrosome duplication. Defects in this gene are a
            cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: U76308.1, Y09077.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000350721.9/ ENSP00000343741.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..2644
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q23"
     Protein         1..2644
                     /product="serine/threonine-protein kinase ATR isoform 1"
                     /EC_number="2.7.11.1"
                     /note="MEC1, mitosis entry checkpoint 1, homolog;
                     FRAP-related protein-1; ataxia telangiectasia and
                     Rad3-related protein"
                     /calculated_mol_wt=301237
     Region          418..450
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13535.3)"
     Site            428
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:21144835,
                     ECO:0007744|PubMed:18691976; propagated from
                     UniProtKB/Swiss-Prot (Q13535.3)"
     Site            435
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q13535.3)"
     Site            436
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q13535.3)"
     Region          799..835
                     /region_name="HEAT 1"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13535.3)"
     Region          1119..1224
                     /region_name="UME"
                     /note="Domain in UVSB PI-3 kinase, MEI-41 and ESR-1;
                     smart00802"
                     /db_xref="CDD:214825"
     Region          1329..1365
                     /region_name="HEAT 2"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13535.3)"
     Region          1771..2092
                     /region_name="FAT"
                     /note="FAT domain; pfam02259"
                     /db_xref="CDD:396714"
     Site            1989
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q13535.3)"
     Region          <2133..2644
                     /region_name="TEL1"
                     /note="Phosphatidylinositol kinase or protein kinase, PI-3
                     family [Signal transduction mechanisms]; COG5032"
                     /db_xref="CDD:227365"
     Region          2293..2567
                     /region_name="PIKKc_ATR"
                     /note="Catalytic domain of Ataxia telangiectasia and
                     Rad3-related proteins; cd00892"
                     /db_xref="CDD:270625"
     Region          2302..2308
                     /region_name="G-loop.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00269"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13535.3)"
     Site            order(2303,2305..2307,2309,2325,2327,2330,2365,2377..2380,
                     2385,2480,2482,2493..2494)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:270625"
     Region          2472..2480
                     /region_name="Catalytic loop.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00269"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13535.3)"
     Site            2472..2480
                     /site_type="active"
                     /note="catalytic loop [active]"
                     /db_xref="CDD:270625"
     Region          2492..2516
                     /region_name="Activation loop.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00269"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13535.3)"
     Site            2494..2516
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:270625"
     CDS             1..2644
                     /gene="ATR"
                     /gene_synonym="FCTCS; FRP1; MEC1; SCKL; SCKL1"
                     /coded_by="NM_001184.4:30..7964"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS3124.1"
                     /db_xref="GeneID:545"
                     /db_xref="HGNC:HGNC:882"
                     /db_xref="MIM:601215"
ORIGIN      
        1 mgehglelas mipalrelgs atpeeyntvv qkprqilcqf idriltdvnv vavelvkktd
       61 sqptsvmlld fiqhimkssp lmfvnvsgsh eakgsciefs nwiitrllri aatpschllh
      121 kkicevicsl lflfkskspa ifgvltkell qlfedlvylh rrnvmghave wpvvmsrfls
      181 qldehmgylq saplqlmsmq nlefievtll mvltriiaiv ffrrqelllw qigcvlleyg
      241 spkikslais fltelfqlgg lpaqpastff ssflellkhl vemdtdqlkl yeeplsklik
      301 tlfpfeaeay rniepvylnm lleklcvmfe dgvlmrlksd llkaalchll qyflkfvpag
      361 yesalqvrkv yvrnickall dvlgievdae yllgplyaal kmesmeiiee iqcqtqqenl
      421 ssnsdgispk rrrlssslnp skrapkqtee ikhvdmnqks ilwsalkqka eslqisleys
      481 glknpvieml egiavvlqlt alctvhcshq nmncrtfkdc qhkskkkpsv vitwmsldfy
      541 tkvlkscrsl lesvqkldle atidkvvkiy daliymqvns sfedhiledl cgmlslpwiy
      601 shsddgclkl ttfaanlltl scrisdsysp qaqsrcvfll tlfprrifle wrtavynwal
      661 qssheviras cvsgffillq qqnscnrvpk ilidkvkdds divkkefasi lgqlvctlhg
      721 mfyltsslte pfsehghvdl fcrnlkatsq hecsssqlka svckpflfll kkkipspvkl
      781 afidnlhhlc khldfredet dvkavlgtll nlmedpdkdv rvafsgnikh ilesldsedg
      841 fikelfvlrm keaythaqis rnnelkdtli lttgdigraa kgdlvpfall hllhcllsks
      901 asvsgaayte iralvaaksv klqsffsqyk kpicqflves lhssqmtalp ntpcqnadvr
      961 kqdvahqrem alntlseian vfdfpdlnrf ltrtlqvllp dlaakaspaa salirtlgkq
     1021 lnvnrreili nnfkyifshl vcscskdele ralhylknet eielgsllrq dfqglhnell
     1081 lrigehyqqv fnglsilasf assddpyqgp rdiispelma dylqpkllgi laffnmqlls
     1141 ssvgiedkkm alnslmslmk lmgpkhvssv rvkmmttlrt glrfkddfpe lccrawdcfv
     1201 rcldhaclgs llshvivall plihiqpket aaifhyliie nrdavqdflh eiyflpdhpe
     1261 lkkikavlqe yrketsestd lqttlqlsmk aiqhenvdvr ihaltslket lyknqeklik
     1321 yatdsetvep iisqlvtvll kgcqdansqa rllcgeclge lgaidpgrld fsttetqgkd
     1381 ftfvtgveds sfaygllmel traylayadn sraqdsaaya iqellsiydc remetngpgh
     1441 qlwrrfpehv reilephlnt rykssqkstd wsgvkkpiyl sklgsnfaew saswagylit
     1501 kvrhdlaski ftccsimmkh dfkvtiyllp hilvyvllgc nqedqqevya eimavlkhdd
     1561 qhtintqdia sdlcqlstqt vfsmldhltq warhkfqalk aekcphsksn rnkvdsmvst
     1621 vdyedyqsvt rfldlipqdt lavasfrska ytravmhfes fitekkqniq ehlgflqkly
     1681 aamhepdgva gvsairkaep slkeqilehe slgllrdata cydraiqlep dqiihyhgvv
     1741 ksmlglgqls tvitqvngvh anrsewtdel ntyrveaawk lsqwdlveny laadgksttw
     1801 svrlgqllls akkrditafy dslklvraeq ivplsaasfe rgsyqrgyey ivrlhmlcel
     1861 ehsikplfqh spgdssqeds lnwvarlemt qnsyrakepi lalrrallsl nkrpdynemv
     1921 gecwlqsarv arkaghhqta ynallnages rlaelyvera kwlwskgdvh qalivlqkgv
     1981 elcfpenetp pegknmlihg ramllvgrfm eetanfesna imkkykdvta clpewedghf
     2041 ylakyydklm pmvtdnkmek qgdliryivl hfgrslqygn qfiyqsmprm ltlwldygtk
     2101 ayewekagrs drvqmrndlg kinkviteht nylapyqflt afsqlisric hshdevfvvl
     2161 meiiakvfla ypqqamwmmt avskssypmr vnrckeilnk aihmkkslek fvgdatrltd
     2221 kllelcnkpv dgssstlsms thfkmlkklv eeatfseili plqsvmiptl psilgthanh
     2281 ashepfpghw ayiagfddmv eilaslqkpk kislkgsdgk fyimmckpkd dlrkdcrlme
     2341 fnslinkclr kdaesrrrel hirtyavipl ndecgiiewv nntaglrpil tklykekgvy
     2401 mtgkelrqcm lpksaalsek lkvfrefllp rhppifhewf lrtfpdptsw yssrsaycrs
     2461 tavmsmvgyi lglgdrhgen ilfdsltgec vhvdfnclfn kgetfevpei vpfrlthnmv
     2521 ngmgpmgteg lfrracevtm rlmrdqrepl msvlktflhd plvewskpvk ghskaplnet
     2581 gevvnekakt hvldieqrlq gviktrnrvt glplsieghv hyliqeatde nllcqmylgw
     2641 tpym
//
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