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
//