CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012280
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Werner syndrome ATP-dependent helicase 
Protein Synonyms/Alias
 DNA helicase, RecQ-like type 3; RecQ3; Exonuclease WRN; RecQ protein-like 2 
Gene Name
 WRN 
Gene Synonyms/Alias
 RECQ3; RECQL2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
131LKMLLENKAVKKAGVubiquitination[1]
146GIEGDQWKLLRDFDIubiquitination[1]
154LLRDFDIKLKNFVELubiquitination[1]
167ELTDVANKKLKCTETubiquitination[1]
168LTDVANKKLKCTETWubiquitination[1]
202IRCSNWSKFPLTEDQubiquitination[1]
241VQRFAINKEEEILLSubiquitination[1, 2]
274HLPHAFSKLENPRRVubiquitination[3]
286RRVSILLKDISENLYubiquitination[1]
366GEDVLGNKVERKEDGacetylation[4]
366GEDVLGNKVERKEDGubiquitination[1, 2, 5]
382EDGVEDNKLKENMERubiquitination[2]
493TVEPTHSKCLKMERNacetylation[5]
496PTHSKCLKMERNLGLsumoylation[6]
496PTHSKCLKMERNLGLubiquitination[1]
775IIYCPSRKMTQQVTGubiquitination[1]
887LTEIRNEKFRLYKLKacetylation[4]
924FEDKQVQKASLGIMGubiquitination[1]
934LGIMGTEKCCDNCRSubiquitination[1]
1103VELSTEKKSNLEKLYubiquitination[1]
1117YSYKPCDKISSGSNIacetylation[4]
1127SGSNISKKSIMVQSPacetylation[4]
1314GLTPEVQKIIADVIRubiquitination[1]
1331PVNSDMSKISLIRMLubiquitination[1]
1371QPSCDVNKRRCFPGSubiquitination[1]
1389CSSSKRSKEEVGINTacetylation[4]
1389CSSSKRSKEEVGINTubiquitination[1]
1413RLPVWFAKGSDTSKKacetylation[4]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] Acetylation of WRN protein regulates its stability by inhibiting ubiquitination.
 Li K, Wang R, Lozada E, Fan W, Orren DK, Luo J.
 PLoS One. 2010 Apr 23;5(4):e10341. [PMID: 20428248]
 [5] 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]
 [6] p14 Arf promotes small ubiquitin-like modifier conjugation of Werners helicase.
 Woods YL, Xirodimas DP, Prescott AR, Sparks A, Lane DP, Saville MK.
 J Biol Chem. 2004 Nov 26;279(48):50157-66. [PMID: 15355988] 
Functional Description
 Multifunctional enzyme that has both magnesium and ATP- dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double- stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation. 
Sequence Annotation
 DOMAIN 60 228 3'-5' exonuclease.
 REPEAT 424 450 1.
 REPEAT 451 477 2.
 DOMAIN 558 724 Helicase ATP-binding.
 DOMAIN 749 899 Helicase C-terminal.
 DOMAIN 1150 1229 HRDC.
 NP_BIND 571 578 ATP (By similarity).
 REGION 1 277 Interaction with WRNIP1 (By similarity).
 REGION 424 477 2 X 27 AA tandem repeats of H-L-S-P-N-D-
 REGION 987 993 Interaction with DNA.
 MOTIF 668 671 DEAH box.
 METAL 82 82 Magnesium 1; catalytic.
 METAL 82 82 Magnesium 2; catalytic.
 METAL 84 84 Magnesium 1; catalytic.
 METAL 216 216 Magnesium 1; catalytic.
 MOD_RES 426 426 Phosphoserine.
 MOD_RES 440 440 Phosphoserine.
 MOD_RES 453 453 Phosphoserine.
 MOD_RES 467 467 Phosphoserine.
 MOD_RES 1133 1133 Phosphoserine.  
Keyword
 3D-structure; ATP-binding; Complete proteome; Direct protein sequencing; Disease mutation; DNA damage; DNA repair; DNA-binding; Exonuclease; Helicase; Hydrolase; Magnesium; Metal-binding; Multifunctional enzyme; Nuclease; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1432 AA 
Protein Sequence
MSEKKLETTA QQRKCPEWMN VQNKRCAVEE RKACVRKSVF EDDLPFLEFT GSIVYSYDAS 60
DCSFLSEDIS MSLSDGDVVG FDMEWPPLYN RGKLGKVALI QLCVSESKCY LFHVSSMSVF 120
PQGLKMLLEN KAVKKAGVGI EGDQWKLLRD FDIKLKNFVE LTDVANKKLK CTETWSLNSL 180
VKHLLGKQLL KDKSIRCSNW SKFPLTEDQK LYAATDAYAG FIIYRNLEIL DDTVQRFAIN 240
KEEEILLSDM NKQLTSISEE VMDLAKHLPH AFSKLENPRR VSILLKDISE NLYSLRRMII 300
GSTNIETELR PSNNLNLLSF EDSTTGGVQQ KQIREHEVLI HVEDETWDPT LDHLAKHDGE 360
DVLGNKVERK EDGFEDGVED NKLKENMERA CLMSLDITEH ELQILEQQSQ EEYLSDIAYK 420
STEHLSPNDN ENDTSYVIES DEDLEMEMLK HLSPNDNEND TSYVIESDED LEMEMLKSLE 480
NLNSGTVEPT HSKCLKMERN LGLPTKEEEE DDENEANEGE EDDDKDFLWP APNEEQVTCL 540
KMYFGHSSFK PVQWKVIHSV LEERRDNVAV MATGYGKSLC FQYPPVYVGK IGLVISPLIS 600
LMEDQVLQLK MSNIPACFLG SAQSENVLTD IKLGKYRIVY VTPEYCSGNM GLLQQLEADI 660
GITLIAVDEA HCISEWGHDF RDSFRKLGSL KTALPMVPIV ALTATASSSI REDIVRCLNL 720
RNPQITCTGF DRPNLYLEVR RKTGNILQDL QPFLVKTSSH WEFEGPTIIY CPSRKMTQQV 780
TGELRKLNLS CGTYHAGMSF STRKDIHHRF VRDEIQCVIA TIAFGMGINK ADIRQVIHYG 840
APKDMESYYQ EIGRAGRDGL QSSCHVLWAP ADINLNRHLL TEIRNEKFRL YKLKMMAKME 900
KYLHSSRCRR QIILSHFEDK QVQKASLGIM GTEKCCDNCR SRLDHCYSMD DSEDTSWDFG 960
PQAFKLLSAV DILGEKFGIG LPILFLRGSN SQRLADQYRR HSLFGTGKDQ TESWWKAFSR 1020
QLITEGFLVE VSRYNKFMKI CALTKKGRNW LHKANTESQS LILQANEELC PKKLLLPSSK 1080
TVSSGTKEHC YNQVPVELST EKKSNLEKLY SYKPCDKISS GSNISKKSIM VQSPEKAYSS 1140
SQPVISAQEQ ETQIVLYGKL VEARQKHANK MDVPPAILAT NKILVDMAKM RPTTVENVKR 1200
IDGVSEGKAA MLAPLLEVIK HFCQTNSVQT DLFSSTKPQE EQKTSLVAKN KICTLSQSMA 1260
ITYSLFQEKK MPLKSIAESR ILPLMTIGMH LSQAVKAGCP LDLERAGLTP EVQKIIADVI 1320
RNPPVNSDMS KISLIRMLVP ENIDTYLIHM AIEILKHGPD SGLQPSCDVN KRRCFPGSEE 1380
ICSSSKRSKE EVGINTETSS AERKRRLPVW FAKGSDTSKK LMDKTKRGGL FS 1432 
Gene Ontology
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; IDA:UniProtKB.
 GO:0043138; F:3'-5' DNA helicase activity; IDA:UniProtKB.
 GO:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0043140; F:ATP-dependent 3'-5' DNA helicase activity; IEA:InterPro.
 GO:0004003; F:ATP-dependent DNA helicase activity; IDA:UniProtKB.
 GO:0000405; F:bubble DNA binding; IDA:UniProtKB.
 GO:0009378; F:four-way junction helicase activity; IDA:UniProtKB.
 GO:0051880; F:G-quadruplex DNA binding; IDA:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0030145; F:manganese ion binding; IDA:UniProtKB.
 GO:0032403; F:protein complex binding; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0000403; F:Y-form DNA binding; IDA:UniProtKB.
 GO:0006284; P:base-excision repair; IDA:UniProtKB.
 GO:0007569; P:cell aging; IMP:UniProtKB.
 GO:0071480; P:cellular response to gamma radiation; IDA:UniProtKB.
 GO:0009267; P:cellular response to starvation; IDA:MGI.
 GO:0006310; P:DNA recombination; IEA:InterPro.
 GO:0000731; P:DNA synthesis involved in DNA repair; IDA:UniProtKB.
 GO:0006302; P:double-strand break repair; IMP:UniProtKB.
 GO:0010259; P:multicellular organismal aging; IMP:UniProtKB.
 GO:0032066; P:nucleolus to nucleoplasm transport; IDA:MGI.
 GO:0051345; P:positive regulation of hydrolase activity; IDA:UniProtKB.
 GO:0042981; P:regulation of apoptotic process; IGI:MGI.
 GO:0040009; P:regulation of growth rate; IEA:Compara.
 GO:0031297; P:replication fork processing; IDA:UniProtKB.
 GO:0001302; P:replicative cell aging; IEA:Compara.
 GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
 GO:0010225; P:response to UV-C; IDA:UniProtKB.
 GO:0000723; P:telomere maintenance; IMP:UniProtKB. 
Interpro
 IPR002562; 3'-5'_exonuclease_dom.
 IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
 IPR004589; DNA_helicase_ATP-dep_RecQ.
 IPR014001; Helicase_ATP-bd.
 IPR001650; Helicase_C.
 IPR010997; HRDC-like.
 IPR002121; HRDC_dom.
 IPR027417; P-loop_NTPase.
 IPR012337; RNaseH-like_dom.
 IPR018982; RQC_domain.
 IPR011991; WHTH_DNA-bd_dom. 
Pfam
 PF00270; DEAD
 PF01612; DNA_pol_A_exo1
 PF00271; Helicase_C
 PF00570; HRDC
 PF09382; RQC 
SMART
 SM00474; 35EXOc
 SM00487; DEXDc
 SM00490; HELICc
 SM00341; HRDC
 SM00956; RQC 
PROSITE
 PS00690; DEAH_ATP_HELICASE
 PS51192; HELICASE_ATP_BIND_1
 PS51194; HELICASE_CTER
 PS50967; HRDC 
PRINTS