ATR_CAEEL
ID ATR_CAEEL Reviewed; 2531 AA.
AC Q22258; Q9Y061;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Serine/threonine-protein kinase ATR;
DE EC=2.7.11.1;
DE AltName: Full=ATM-like protein 1;
DE AltName: Full=Ataxia telangiectasia and Rad3-related protein homolog;
DE Short=ATR homolog;
DE AltName: Full=Ce-atl-1;
GN Name=atl-1 {ECO:0000312|WormBase:T06E4.3a};
GN ORFNames=T06E4.3 {ECO:0000312|WormBase:T06E4.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND DEVELOPMENTAL STAGE.
RX PubMed=11016841; DOI=10.1007/s004380000291;
RA Aoki H., Sato S., Takanami T., Ishihara T., Katsura I., Takahashi H.,
RA Higashitani A.;
RT "Characterization of Ce-atl-1, an ATM-like gene from Caenorhabditis
RT elegans.";
RL Mol. Gen. Genet. 264:119-126(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION.
RX PubMed=12747829; DOI=10.1016/s0960-9822(03)00295-1;
RA Brauchle M., Baumer K., Goenczy P.;
RT "Differential activation of the DNA replication checkpoint contributes to
RT asynchrony of cell division in C. elegans embryos.";
RL Curr. Biol. 13:819-827(2003).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16319925; DOI=10.1038/sj.emboj.7600896;
RA Garcia-Muse T., Boulton S.J.;
RT "Distinct modes of ATR activation after replication stress and DNA double-
RT strand breaks in Caenorhabditis elegans.";
RL EMBO J. 24:4345-4355(2005).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16628214; DOI=10.1038/sj.emboj.7601102;
RA Polanowska J., Martin J.S., Garcia-Muse T., Petalcorin M.I.R.,
RA Boulton S.J.;
RT "A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA
RT damage sites.";
RL EMBO J. 25:2178-2188(2006).
CC -!- FUNCTION: Serine/threonine protein kinase which activates checkpoint
CC signaling upon genotoxic stresses such as ionizing radiation (IR),
CC ultraviolet light (UV), or DNA replication stalling, thereby acting as
CC a DNA damage sensor (By similarity). Recognizes the substrate consensus
CC sequence [ST]-Q (By similarity). Phosphorylates various proteins, which
CC collectively inhibits DNA replication and mitosis and promotes DNA
CC repair and recombination (By similarity). Prevents mitotic catastrophe
CC by functioning in the S-phase checkpoint and cooperating with atm-1 in
CC the checkpoint response to double-strand breaks (DSBs) after ionizing
CC radiation (IR) to induce cell cycle arrest or apoptosis via the cep-
CC 1/p53 pathway (PubMed:12747829, PubMed:16319925). In response to
CC ionizing radiation, probably required for the association between the
CC brc-1-brd-1 heterodimer and rad-51 and let-70 in order to activate E3-
CC ubiquitin ligase activity of the heterodimer and induce ubiquitination
CC at DNA damage sites (PubMed:16628214). {ECO:0000250|UniProtKB:Q13535,
CC ECO:0000269|PubMed:16319925, ECO:0000269|PubMed:16628214,
CC ECO:0000305|PubMed:12747829}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16319925}.
CC Note=Recruited to stalled replication forks by rpa-1-coated single-
CC stranded DNA. Recruited to processed double-strand breaks in a rpa-1
CC and mre-11-dependent manner.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q22258-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q22258-2; Sequence=VSP_017390;
CC -!- DEVELOPMENTAL STAGE: Expressed at all larval stages and is expressed at
CC higher level in the adult. {ECO:0000269|PubMed:11016841}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in DNA damage
CC repair defects following ionizing radiation with reduced ubiquitination
CC at DNA damage sites. {ECO:0000269|PubMed:16628214}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC {ECO:0000305}.
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DR EMBL; AB018598; BAA33886.1; -; mRNA.
DR EMBL; Z70756; CAA94790.2; -; Genomic_DNA.
DR EMBL; Z70756; CAC42337.1; -; Genomic_DNA.
DR PIR; T24588; T24588.
DR PIR; T37320; T37320.
DR RefSeq; NP_001024110.1; NM_001028939.2.
DR RefSeq; NP_505487.3; NM_073086.4. [Q22258-1]
DR AlphaFoldDB; Q22258; -.
DR BioGRID; 44389; 4.
DR IntAct; Q22258; 4.
DR MINT; Q22258; -.
DR STRING; 6239.T06E4.3a; -.
DR EPD; Q22258; -.
DR PaxDb; Q22258; -.
DR PeptideAtlas; Q22258; -.
DR PRIDE; Q22258; -.
DR EnsemblMetazoa; T06E4.3a.1; T06E4.3a.1; WBGene00000226. [Q22258-1]
DR EnsemblMetazoa; T06E4.3a.2; T06E4.3a.2; WBGene00000226. [Q22258-1]
DR GeneID; 179352; -.
DR KEGG; cel:CELE_T06E4.3; -.
DR UCSC; T06E4.3b; c. elegans. [Q22258-1]
DR CTD; 179352; -.
DR WormBase; T06E4.3a; CE25103; WBGene00000226; atl-1. [Q22258-1]
DR WormBase; T06E4.3b; CE28250; WBGene00000226; atl-1. [Q22258-2]
DR eggNOG; KOG0890; Eukaryota.
DR HOGENOM; CLU_228436_0_0_1; -.
DR InParanoid; Q22258; -.
DR OMA; RISHMIK; -.
DR OrthoDB; 80538at2759; -.
DR SignaLink; Q22258; -.
DR PRO; PR:Q22258; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000226; Expressed in germ line (C elegans) and 5 other tissues.
DR ExpressionAtlas; Q22258; baseline and differential.
DR GO; GO:0000794; C:condensed nuclear chromosome; TAS:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; ISS:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:WormBase.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0045132; P:meiotic chromosome segregation; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR Gene3D; 1.10.1070.11; -; 1.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR014009; PIK_FAT.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; DNA damage; DNA repair; DNA-binding;
KW Kinase; Manganese; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..2531
FT /note="Serine/threonine-protein kinase ATR"
FT /id="PRO_0000225629"
FT DOMAIN 1490..2067
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 2192..2512
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 2499..2531
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 2198..2204
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2368..2376
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2387..2411
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT VAR_SEQ 1630..1646
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:11016841"
FT /id="VSP_017390"
SQ SEQUENCE 2531 AA; 292612 MW; E12332B3F6319560 CRC64;
MNIDKDVSAL LCTAKKYVTQ KEFNRQKMKF LLDDITKLLS KSFVSRIEQL DENEFMEKIM
ILQSITFTLH LITEKQELSS EEKIRLFQSV IASMCAFEDE ELAKCFDRIL SVLMISVTKQ
DPRETIYFLQ GLLEVVKYCD VEPSSSLPQL ITPEIASAIS LGASGFFRYH LKWNIISTLF
GENAGECVHF DELVLFWPHC RSQLEDKLKN DCSMTENCLR AGLTILKYKK LHNSILDQAL
FIDELFATFN SLTAKKSTNH MTFPKLLNEI QHFLQDHGKV LIMHKELRQK PVQWLIIYLE
LIDDANDKFG LLENFSLLLL DLSTNHDIHE FPARLCMTAS EICMRRIKHS IQSTHTDCLA
DYLDILASLL KLARIQKLDI FQCFATEIEA HHSLNNPLWP RILRSLLSVQ NPHCQQFCKK
FVPSIDKLWI TLLNGESSRA TLNSLVIVTA SCPFANNNDE GVKQIIPFLL IPCFQDFRDR
VGSKWDNFRF IGLPKSEPSE LINLERFTTV LERSTSESTK LRAVNCALQL EKKTGKYINL
VAEMSLAVFS KSQTDRIANS FEPLILFLTD NLQLINDFIT ILIAKLCEKQ EFYSELTILK
YFKTLQKLFC LAANGRNSCK KCGEECFVDP DSKENVKIDY ESLSGLIKGI VARRNTFSQE
LIREFLQTSR VMLLHVDSKG IASSFTSIIK ALDIGFSENA NAYFRVWELV CCRSEATVEK
KLQMYIPLIG RSFALLGDDA ALKVHGFLSN VLSARLSSTV KATLFASSFA HSVLKNCEID
WNVSYTWKTQ FSQCLIKAPV GTCEEALQIM FKRYSTIFTR CFLNRLFFDA SSAGAQKPSY
DEHRIREITR CYLSHVLSDF NFPNQKITFN MIRPSLLYWS LLSSARGINS KLTLSVIDFI
CQEMSAASVS MSSISPNPSD IRIVMIQRKS LITETFAQLV QFLAFENNRN TTSFWKFCSD
HCDFKDEDIR TVISSYRKQV FMHLLLVSAR EFLNPRNPSM IVEQLRATYE NIKKGEKFMI
STAIETRNEG IEFLFIFRTY FTNDQYFLTR EATAESFRIL LQNMKQDFFD TNWYIILMTL
RQIPLNLDST QSSWISFIEQ INYSILRSNI WRILTDISRI ENNDILIEKV WNRLSYDMVI
DKISTDAMIK RVFWLIPLEV EKRIDLKFEI SKSRQIEDVL EFIRMFPQYP SVQFADNLAS
KIERKTVYKE ELPKLIGSLS RILPQCHSKR EQNKIIKILQ KLPIICSDLP DHNFIRWDTR
FKFFCEPRQL TQAVLEDCAG IVEVMTGTSK IEYVDRTMCE IYKFFNPNEA SPEMKSTLDG
IKNMYAKMIC SQKPEPSMIE QKTIDELSLG GSRRESFSRW LTVIILKCAE MSEDAPLSSL
ASIAHVDDTR FLSKLAMRFI LTVIHMERDS VTQWILSTFE EALTNTNHRR LTNSDRGPAS
FVFYVFDFIY SYSSSEELRK KKKIWEKVIS FWKSMMSWTF KDENGHGQPL IVKVAETFGM
EKRCILWLEM FMEQKRKTST EIESETEAAY YFTLMNLYGR IHELNGVRGA YARLSRIQID
HVYGKISMRE AFGDFNSAAC FARMTGKGKP FNSTEAIQKL IDELNCLEYS QIERNEQEDY
LNSLKTLSQW VNIDNDIGPS PHIFSRNIEY WATESTILKM IRNDERDEIV NNAIENAKSK
VIERLSECAI GGSCSYEIAT PFLVELQKLN EIVELKNVSN DELSAFNSDF WKNIQKRTDD
SEQKISILEP ILRVRRSMLD IRMQSMTGRD KENIRSRIVE VHLQSARIAR LTGCFERAQL
SLINAKKVLP FENKIVLEEA KLQLQTSDEL NGMSLLDSII SKNFGDLHTI YTDTQQSVNL
DVQKSAKLKI EHYQEETKNL FSSVQMLRIS HMIKAGNTIG FDKVYHETTQ LLQCFAHSGV
MYEAAWLLDY LSNYKERSKH VLPLLKAYKE VAKYEKNQVL QARAVERMTS LWLSNTRKIS
THISSVPKLP EGQISDLRQN IKSMNREIQT ALEHIGWRAF YPAYAVLARH IDHQDEEVTR
TIKQIMKQLI LRMPHQCMWQ SAYLLRQNIA SVKEKYMEVL TEVKRKAPCY VTLIDQYDYA
SGVFNTVSGK VESDDCKLSE KVDGLKTMFR DKKYDPKELV MNRRVDCDCK ILSGIMVPVR
SVIDESVHDT EIRDDGFEES CHLPDRYLIH DFSDKVKVLH SNTKPVIIKL TTKTGRIVRL
ICKKDDDLSK DYHFTKMVEM CNDLLMKDEQ TRIQKMTATT YSVIPLGKQG GIIEFMEGVT
SFYETLDKLM GMTSGEWLEK LKFWNTHMKP MGKEERTKYF REVACKNTPV VMGKWFRIQY
PEAGQWFASR KLFAKSTAVM SVIGYIFGLG DRHTKNLMVH TTGKCIHVDF DMIFNKGETL
GTPELVPFRL TQNMINGMGE VALDGEFRTV CEQALRVFRE NSYEIEKYIA DLPNLVADFP
SNKRAPKDFD MSEAKRLVSG RLRGQIMTAK LYRSNPISHP MQVSQLASSL IELATSEEKL
SEMYLGWMAT L
