CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012136
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase ATR 
Protein Synonyms/Alias
 Ataxia telangiectasia and Rad3-related protein; FRAP-related protein 1 
Gene Name
 ATR 
Gene Synonyms/Alias
 FRP1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
32EYNTVVQKPRQILCQubiquitination[1, 2]
58VAVELVKKTDSQPTSubiquitination[2]
442SSSLNPSKRAPKQTEubiquitination[1]
746DLFCRNLKATSQHECubiquitination[2, 3, 4]
764QLKASVCKPFLFLLKubiquitination[2]
791DNLHHLCKHLDFREDubiquitination[2]
851ELFVLRMKEAYTHAQubiquitination[4]
866ISRNNELKDTLILTTubiquitination[1, 2, 3, 4]
921LVAAKSVKLQSFFSQubiquitination[5]
1005LLPDLAAKASPAASAubiquitination[1, 2, 3, 4]
1057ERALHYLKNETEIELubiquitination[6]
1173HVSSVRVKMMTTLRTubiquitination[2]
1185LRTGLRFKDDFPELCubiquitination[2, 4]
1262LPDHPELKKIKAVLQubiquitination[3]
1308IHALTSLKETLYKNQubiquitination[2, 3]
1313SLKETLYKNQEKLIKubiquitination[2]
1467TRYKSSQKSTDWSGVubiquitination[1, 3]
1475STDWSGVKKPIYLSKubiquitination[2]
1476TDWSGVKKPIYLSKLubiquitination[2]
1613HSKSNRNKVDSMVSTubiquitination[1, 2]
1697AGVSAIRKAEPSLKEubiquitination[2]
1703RKAEPSLKEQILEHEubiquitination[1, 2, 3, 4]
1796NYLAADGKSTTWSVRubiquitination[3]
1812GQLLLSAKKRDITAFubiquitination[1]
1824TAFYDSLKLVRAEQIubiquitination[1, 2, 3, 4]
1897TQNSYRAKEPILALRubiquitination[2, 4]
1912RALLSLNKRPDYNEMubiquitination[2]
1933QSARVARKAGHHQTAubiquitination[2]
1994NETPPEGKNMLIHGRubiquitination[2]
2026NAIMKKYKDVTACLPubiquitination[2]
2057MPMVTDNKMEKQGDLubiquitination[2]
2106TKAYEWEKAGRSDRVubiquitination[2]
2210HMKKSLEKFVGDATRubiquitination[2]
2221DATRLTDKLLELCNKubiquitination[2]
2228KLLELCNKPVDGSSSubiquitination[2]
2347EFNSLINKCLRKDAEubiquitination[2]
2397LTKLYKEKGVYMTGKubiquitination[2]
2404KGVYMTGKELRQCMLubiquitination[2]
2420KSAALSEKLKVFREFubiquitination[2]
2567DPLVEWSKPVKGHSKubiquitination[2]
2574KPVKGHSKAPLNETGubiquitination[2, 3]
2587TGEVVNEKAKTHVLDubiquitination[1, 2, 3, 4, 7]
2589EVVNEKAKTHVLDIEubiquitination[2]
2604QRLQGVIKTRNRVTGubiquitination[2, 4, 8, 9]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [8] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [9] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 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. 
Sequence Annotation
 REPEAT 799 835 HEAT 1.
 REPEAT 1329 1365 HEAT 2.
 DOMAIN 1640 2185 FAT.
 DOMAIN 2322 2567 PI3K/PI4K.
 DOMAIN 2612 2644 FATC.
 MOD_RES 428 428 Phosphoserine.
 MOD_RES 1989 1989 Phosphothreonine.  
Keyword
 Alternative splicing; ATP-binding; Chromosome; Complete proteome; Disease mutation; DNA damage; DNA repair; DNA-binding; Dwarfism; Kinase; Manganese; Mental retardation; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 2644 AA 
Protein Sequence
MGEHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VAVELVKKTD 60
SQPTSVMLLD FIQHIMKSSP LMFVNVSGSH EAKGSCIEFS NWIITRLLRI AATPSCHLLH 120
KKICEVICSL LFLFKSKSPA IFGVLTKELL QLFEDLVYLH RRNVMGHAVE WPVVMSRFLS 180
QLDEHMGYLQ SAPLQLMSMQ NLEFIEVTLL MVLTRIIAIV FFRRQELLLW QIGCVLLEYG 240
SPKIKSLAIS FLTELFQLGG LPAQPASTFF SSFLELLKHL VEMDTDQLKL YEEPLSKLIK 300
TLFPFEAEAY RNIEPVYLNM LLEKLCVMFE DGVLMRLKSD LLKAALCHLL QYFLKFVPAG 360
YESALQVRKV YVRNICKALL DVLGIEVDAE YLLGPLYAAL KMESMEIIEE IQCQTQQENL 420
SSNSDGISPK RRRLSSSLNP SKRAPKQTEE IKHVDMNQKS ILWSALKQKA ESLQISLEYS 480
GLKNPVIEML EGIAVVLQLT ALCTVHCSHQ NMNCRTFKDC QHKSKKKPSV VITWMSLDFY 540
TKVLKSCRSL LESVQKLDLE ATIDKVVKIY DALIYMQVNS SFEDHILEDL CGMLSLPWIY 600
SHSDDGCLKL TTFAANLLTL SCRISDSYSP QAQSRCVFLL TLFPRRIFLE WRTAVYNWAL 660
QSSHEVIRAS CVSGFFILLQ QQNSCNRVPK ILIDKVKDDS DIVKKEFASI LGQLVCTLHG 720
MFYLTSSLTE PFSEHGHVDL FCRNLKATSQ HECSSSQLKA SVCKPFLFLL KKKIPSPVKL 780
AFIDNLHHLC KHLDFREDET DVKAVLGTLL NLMEDPDKDV RVAFSGNIKH ILESLDSEDG 840
FIKELFVLRM KEAYTHAQIS RNNELKDTLI LTTGDIGRAA KGDLVPFALL HLLHCLLSKS 900
ASVSGAAYTE IRALVAAKSV KLQSFFSQYK KPICQFLVES LHSSQMTALP NTPCQNADVR 960
KQDVAHQREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP DLAAKASPAA SALIRTLGKQ 1020
LNVNRREILI NNFKYIFSHL VCSCSKDELE RALHYLKNET EIELGSLLRQ DFQGLHNELL 1080
LRIGEHYQQV FNGLSILASF ASSDDPYQGP RDIISPELMA DYLQPKLLGI LAFFNMQLLS 1140
SSVGIEDKKM ALNSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV 1200
RCLDHACLGS LLSHVIVALL PLIHIQPKET AAIFHYLIIE NRDAVQDFLH EIYFLPDHPE 1260
LKKIKAVLQE YRKETSESTD LQTTLQLSMK AIQHENVDVR IHALTSLKET LYKNQEKLIK 1320
YATDSETVEP IISQLVTVLL KGCQDANSQA RLLCGECLGE LGAIDPGRLD FSTTETQGKD 1380
FTFVTGVEDS SFAYGLLMEL TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMETNGPGH 1440
QLWRRFPEHV REILEPHLNT RYKSSQKSTD WSGVKKPIYL SKLGSNFAEW SASWAGYLIT 1500
KVRHDLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA EIMAVLKHDD 1560
QHTINTQDIA SDLCQLSTQT VFSMLDHLTQ WARHKFQALK AEKCPHSKSN RNKVDSMVST 1620
VDYEDYQSVT RFLDLIPQDT LAVASFRSKA YTRAVMHFES FITEKKQNIQ EHLGFLQKLY 1680
AAMHEPDGVA GVSAIRKAEP SLKEQILEHE SLGLLRDATA CYDRAIQLEP DQIIHYHGVV 1740
KSMLGLGQLS TVITQVNGVH ANRSEWTDEL NTYRVEAAWK LSQWDLVENY LAADGKSTTW 1800
SVRLGQLLLS AKKRDITAFY DSLKLVRAEQ IVPLSAASFE RGSYQRGYEY IVRLHMLCEL 1860
EHSIKPLFQH SPGDSSQEDS LNWVARLEMT QNSYRAKEPI LALRRALLSL NKRPDYNEMV 1920
GECWLQSARV ARKAGHHQTA YNALLNAGES RLAELYVERA KWLWSKGDVH QALIVLQKGV 1980
ELCFPENETP PEGKNMLIHG RAMLLVGRFM EETANFESNA IMKKYKDVTA CLPEWEDGHF 2040
YLAKYYDKLM PMVTDNKMEK QGDLIRYIVL HFGRSLQYGN QFIYQSMPRM LTLWLDYGTK 2100
AYEWEKAGRS DRVQMRNDLG KINKVITEHT NYLAPYQFLT AFSQLISRIC HSHDEVFVVL 2160
MEIIAKVFLA YPQQAMWMMT AVSKSSYPMR VNRCKEILNK AIHMKKSLEK FVGDATRLTD 2220
KLLELCNKPV DGSSSTLSMS THFKMLKKLV EEATFSEILI PLQSVMIPTL PSILGTHANH 2280
ASHEPFPGHW AYIAGFDDMV EILASLQKPK KISLKGSDGK FYIMMCKPKD DLRKDCRLME 2340
FNSLINKCLR KDAESRRREL HIRTYAVIPL NDECGIIEWV NNTAGLRPIL TKLYKEKGVY 2400
MTGKELRQCM LPKSAALSEK LKVFREFLLP RHPPIFHEWF LRTFPDPTSW YSSRSAYCRS 2460
TAVMSMVGYI LGLGDRHGEN ILFDSLTGEC VHVDFNCLFN KGETFEVPEI VPFRLTHNMV 2520
NGMGPMGTEG LFRRACEVTM RLMRDQREPL MSVLKTFLHD PLVEWSKPVK GHSKAPLNET 2580
GEVVNEKAKT HVLDIEQRLQ GVIKTRNRVT GLPLSIEGHV HYLIQEATDE NLLCQMYLGW 2640
TPYM 2644 
Gene Ontology
 GO:0005694; C:chromosome; ISS:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0001741; C:XY body; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0032405; F:MutLalpha complex binding; IDA:MGI.
 GO:0032407; F:MutSalpha complex binding; IDA:MGI.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0007049; P:cell cycle; TAS:ProtInc.
 GO:0071480; P:cellular response to gamma radiation; IDA:BHF-UCL.
 GO:0034644; P:cellular response to UV; IMP:BHF-UCL.
 GO:0000077; P:DNA damage checkpoint; IDA:UniProtKB.
 GO:0006281; P:DNA repair; TAS:Reactome.
 GO:0006260; P:DNA replication; TAS:Reactome.
 GO:0007275; P:multicellular organismal development; TAS:ProtInc.
 GO:0008156; P:negative regulation of DNA replication; IMP:UniProtKB.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IMP:BHF-UCL.
 GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
 GO:0043393; P:regulation of protein binding; IEA:Compara.
 GO:0090399; P:replicative senescence; IMP:BHF-UCL. 
Interpro
 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. 
Pfam
 PF02259; FAT
 PF02260; FATC
 PF00454; PI3_PI4_kinase
 PF08064; UME 
SMART
 SM00146; PI3Kc
 SM00802; UME 
PROSITE
 PS51189; FAT
 PS51190; FATC
 PS50077; HEAT_REPEAT
 PS00915; PI3_4_KINASE_1
 PS00916; PI3_4_KINASE_2
 PS50290; PI3_4_KINASE_3 
PRINTS