ATR_XENLA
ID ATR_XENLA Reviewed; 2654 AA.
AC Q9DE14; Q5EGL8; Q9DDK7;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Serine/threonine-protein kinase atr;
DE Short=Xatr;
DE EC=2.7.11.1;
DE AltName: Full=Ataxia telangiectasia and Rad3-related protein;
GN Name=atr;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=11137007; DOI=10.1016/s0960-9822(00)00855-1;
RA Hekmat-Nejad M., You Z., Yee M.-C., Newport J., Cimprich K.A.;
RT "Xenopus ATR is a replication-dependent chromatin binding protein required
RT for the DNA replication checkpoint.";
RL Curr. Biol. 10:1565-1573(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11069891; DOI=10.1101/gad.842500;
RA Guo Z., Kumagai A., Wang S.X., Dunphy W.G.;
RT "Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation
RT in response to DNA replication blocks and UV-damaged DNA in Xenopus egg
RT extracts.";
RL Genes Dev. 14:2745-2756(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA McSherry T.D., Mueller P.R.;
RT "Characterization of Xenopus ATR.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH ATRIP, AND INTERACTION WITH
RP TOPBP1.
RX PubMed=16530042; DOI=10.1016/j.cell.2005.12.041;
RA Kumagai A., Lee J., Yoo H.Y., Dunphy W.G.;
RT "TopBP1 activates the ATR-ATRIP complex.";
RL Cell 124:943-955(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. Recognizes the substrate consensus sequence [ST]-
CC Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53,
CC which collectively inhibit DNA replication and mitosis and promote DNA
CC repair, recombination and apoptosis. Phosphorylates 'Ser-139' of
CC histone variant H2AX at sites of DNA damage, thereby regulating DNA
CC damage response mechanism. {ECO:0000269|PubMed:11069891,
CC ECO:0000269|PubMed:11137007, ECO:0000269|PubMed:16530042}.
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 -!- ACTIVITY REGULATION: Kinase activity is activated by topbp1.
CC {ECO:0000269|PubMed:16530042}.
CC -!- SUBUNIT: Forms a heterodimer with atrip. Interacts with topbp1 in the
CC presence of atrip. {ECO:0000269|PubMed:16530042}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11069891}. Chromosome
CC {ECO:0000250|UniProtKB:Q9JKK8}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC {ECO:0000305}.
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DR EMBL; AF320125; AAG40002.1; -; mRNA.
DR EMBL; AF223644; AAG34794.1; -; mRNA.
DR EMBL; AY882989; AAW78662.1; -; mRNA.
DR RefSeq; NP_001082049.1; NM_001088580.1.
DR AlphaFoldDB; Q9DE14; -.
DR SMR; Q9DE14; -.
DR BioGRID; 99532; 4.
DR IntAct; Q9DE14; 2.
DR iPTMnet; Q9DE14; -.
DR GeneID; 398197; -.
DR KEGG; xla:398197; -.
DR CTD; 398197; -.
DR Xenbase; XB-GENE-1012725; atr.L.
DR OMA; YTVYSQM; -.
DR OrthoDB; 80538at2759; -.
DR Proteomes; UP000186698; Chromosome 5L.
DR Bgee; 398197; Expressed in egg cell and 19 other tissues.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.10.10; -; 2.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
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; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR003151; PIK-rel_kinase_FAT.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR012993; UME.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF08064; UME; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SMART; SM00802; UME; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chromosome; DNA damage; DNA repair; DNA-binding; Kinase;
KW Manganese; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..2654
FT /note="Serine/threonine-protein kinase atr"
FT /id="PRO_0000225628"
FT REPEAT 814..850
FT /note="HEAT 1"
FT REPEAT 1344..1380
FT /note="HEAT 2"
FT DOMAIN 1654..2196
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 2306..2614
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 2622..2654
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 421..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2312..2318
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2482..2490
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2502..2526
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT CONFLICT 191
FT /note="Y -> C (in Ref. 2; AAG34794)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="P -> S (in Ref. 2; AAG34794)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="S -> SS (in Ref. 3; AAW78662)"
FT /evidence="ECO:0000305"
FT CONFLICT 520
FT /note="D -> N (in Ref. 3; AAW78662)"
FT /evidence="ECO:0000305"
FT CONFLICT 1047
FT /note="N -> S (in Ref. 3; AAW78662)"
FT /evidence="ECO:0000305"
FT CONFLICT 1543
FT /note="L -> P (in Ref. 3; AAW78662)"
FT /evidence="ECO:0000305"
FT CONFLICT 1785
FT /note="N -> S (in Ref. 1; AAG40002)"
FT /evidence="ECO:0000305"
FT CONFLICT 1952
FT /note="T -> A (in Ref. 3; AAW78662)"
FT /evidence="ECO:0000305"
FT CONFLICT 2082
FT /note="H -> P (in Ref. 2; AAG34794)"
FT /evidence="ECO:0000305"
FT CONFLICT 2215
FT /note="M -> T (in Ref. 3; AAW78662)"
FT /evidence="ECO:0000305"
FT CONFLICT 2362
FT /note="D -> G (in Ref. 2; AAG34794)"
FT /evidence="ECO:0000305"
FT CONFLICT 2424
FT /note="S -> N (in Ref. 1; AAG40002)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2654 AA; 301459 MW; F88E8A6541E6DD13 CRC64;
MATDPGLEMA SMIPALRELA SAGAEEYNTT VQKPRQILCQ FIDRILTDVD VVAVELSKNT
DSQPSSVMLL DFIQHIMKST PLMFLSANNG DQSAETNQNC VAFSNWIISR LLRIGATPSC
KALHRKIAEV IRSLLFLFKN KSSFLFGVFT KDLLHLFEDL IYIHEQNMEK SVVWPVTISR
FLSNASENQT YLRCTQFQLL NMQNIEPLES TLLMVLMDNE HDISPVFFQR QNLLLWGIGC
SLLDYGSTPL KIQALHFLRQ LIKLGGPPEQ GAYFFFIVFF GILTCIKDMD LEEVSLYEMP
LLKLVKVLFP FESKSYLNIE PVYLNMLLEK LAALFDGGIL SNIQSAPLKE ALCYMVHYFL
SIVPPGYESA KEVREAHVRC ICRAFVDVLG LQSKQEYLVC PLHEALRIEN LVFMQQQRMQ
PLSTDSEGGG SSSSDEVQEK RPRLSLTAKP LRRNTPSVPA PVDMKTKSIL WKAVSAKFSS
ILCKLEGDEV TDEEMVSLLE GLNTTVRVAA LNTVHIFTND STDTDQLVSD LSNTSGIQSV
EIVPHVFWLS PEDILKILKI CRKVLDSAHQ RANINDILMK IIKIFDAILY IHAGNRLNDQ
TLKDLCSMIS LPWLQNHSNH ASFKVASFDP TLMTISERIG QHYSPEIQSQ LVFLLCLFPK
MLCPEWRLAV YQWALDSPHE IVRARCIKGF PVLLCNVSQQ GYGPIPKILI DCLNDASELV
KKELANSVGM FASGLACGFE LQYSPTAPTA AESEFLCSSL TVTALPSSKL SRMTASALKP
FLALLNRNMP SSVKMAFIEN MPMLFAHLSL EKDDLDSRTV IESLLNLMED PDKDVRTAFS
GNIKHLLACA DCEDGYLKEI VVSRMKKAYT DAKMSRDNEM KDTLILTTGD IGRAAKGELV
PFALLHLLHC LLSKSPCVAG ASYTEIRSLA AAKSTSLHIF FSQYKKPICQ FLIESLHSSQ
AALLTNTPGR SSEMQKQEAT HHREAALDIL SEIANVFDFP DLNRFLTRTL QLLLPYLAAK
ASPTASTLIR TIAKQLNVNR REILINNFKY IFSHLVCSCT KDELEKSLHY LKNETEIELG
SLLRQDYQGL HNELLLRLGE HYQQVFSGLS ILATYASNDD PYQGPRNFAK PEIMADYLQP
KLLGILAFFN MHLLSSSIGI EDKKMALNSL VSLMKLMGPK HISSVRVKMM TTLRTGLRYK
EEFPGLCCSA WDLFVRCLDQ AYLGPLLSHV IVALLPLLHI QPKETVAVFR YLIVENRDAV
QDFLHEIYFL PDHPELKEIQ KVLQEYRKET TKSTDLQTAM QLSIRAIQHE NVDVRMHALT
SLKETLYKNQ AKLLQYSTDS ETVEPVISQL VTVLLIGCQD ANPQARLFCG ECLGQLGAID
PGRLDFSPSE TQGKGFTFVS GVEDSDFAYE LLTEQTRAFL AYADNVRAQD SAAYAIQELL
SIFECKEGRT DCPGRRLWRR FPEHVQEILE PHLNTRYKSS RKAVNWSRVK KPIYLSKLGN
NFADWSATWA GYLITKVRHE LARRVFSCCS IMMKHDFKVT IYLLPHILVY VLLGCNKEDQ
QEVYAEIMAV LKHEDPLMRR LQDSASDLSQ LSTQTVFSML DHLTQWAREK FQALNAEKTN
PKPGTRGEPK AVSNEDYGEY QNVTRFLDLI PQDTLAVASF RSKAYTRALM HFESFIMEKK
QEIQEHLGFL QKLYAAMHEP DGVAGVSAIR KKEASLKEQI LEHESIGLLR DATACYDRAI
QLKPEEIIHY HGVVKSMLGL GQLSTVITQV NGILNSRSEW TAELNTYRVE AAWKLSQWDL
VEEYLSADRK STTWSIRLGQ LLLSAKKGER DMFYETLKVV RAEQIVPLSA ASFERGSYQR
GYEYIVRLHM LCELEHSVKM FLQKPSVEPA VDSLNLPARL EMTQNSYRAR EPILAVRRAL
QTINKRPNHA DMIGECWLQS ARVARKAGHH QTAYNALLNA GESRLSELNV ERAKWLWSKG
DVHQALIVLQ KGAELFLSST SAPPEQQLIH GRAMLLVGRL MEETANFESN AVMKKYKDVT
ALLPEWEDGH FYLAKYYDKL MPMVTDNKME KQGDLIRYIV LHFGRSLQFG NQYIYQSMPR
MLSLWLDFGA KVYEWEKAGR ADRLQMKNEL MKINKVISDH KNQLAPYQFL TAFSQLISRI
CHSHDEVFAV LMEIVAKVFV AYPQQAMWMM TAVSKSSYPM RVNRCKEILE KAIHMKPSLG
KFIGDATRLT DKLLELCNKP VDGNTSTLSM NIHFKMLKKL VEETTFSEIL IPLQSVMIPT
LPSTAGKRDH ADHDPFPGHW AYLSGFDDAV EILPSLQKPK KISLKGSDGK SYIMMCKPKD
DLRKDCRLME FNSLINKCLR KDAESRRREL HIRTYAVIPL NDECGIIEWV NNTAGFRNIL
IKLYKEKGIY MGGKELRQCM LPKSAPLQEK LKVFKEALLP RHPPLFHEWF LRTFPDPTSW
YNSRSAYCRS TAVMSMVGYI LGLGDRHGEN ILFDSLTGEC VHVDFNCLFN KGETFEVPEI
VPFRLTHNMV NGMGPMGTEG LFRRACEVIM RLMREQRESL MSVLKPFLHD PLVEWSKPAR
GSSKGQVNET GEVMNEKAKT HVLDIEQRLQ GVIKTRNRVK GLPLSIEGHV HYLIQEATDE
NLLSQMYLGW APYM
