CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005496
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA (cytosine-5)-methyltransferase 1 
Protein Synonyms/Alias
 Dnmt1; CXXC-type zinc finger protein 9; DNA methyltransferase HsaI; DNA MTase HsaI; M.HsaI; MCMT 
Gene Name
 DNMT1 
Gene Synonyms/Alias
 AIM; CXXC9; DNMT 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
70DLETKLRKEELSEEGmethylation[1, 2]
88KVKSLLNKDLSLENGubiquitination[3, 4]
134SPPKPLSKPRTPRRSubiquitination[3, 4]
142PRTPRRSKSDGEAKPmethylation[5]
160PSPRITRKSTRQTTIacetylation[6]
173TITSHFAKGPAKRKPacetylation[7]
188QEESERAKSDESIKEacetylation[6]
259PTPKQKLKEEPDREAacetylation[6]
366YLDDPDLKYGQHPPDacetylation[6]
385PQMLTNEKLSIFDANubiquitination[8]
586PCMRDLIKLAGVTLGubiquitination[3, 4, 8]
749GKKSYYKKVCIDAETacetylation[6]
891PTEDNKFKFCVSCARacetylation[6]
928VLYYSATKNGILYRVubiquitination[3, 4]
957IKLSSPVKRPRKEPVacetylation[6]
961SPVKRPRKEPVDEDLacetylation[6]
961SPVKRPRKEPVDEDLubiquitination[8]
975LYPEHYRKYSDYIKGacetylation[6]
981RKYSDYIKGSNLDAPubiquitination[3, 4, 8, 9]
997PYRIGRIKEIFCPKKubiquitination[3, 4, 9]
1054EEAVVDFKAVQGRCTacetylation[6]
1092FLEAYNAKSKSFEDPubiquitination[3, 4, 8]
1111RSPGNKGKGKGKGKGacetylation[6, 7, 10]
1113PGNKGKGKGKGKGKPacetylation[6, 7, 10, 11]
1115NKGKGKGKGKGKPKSacetylation[6, 7, 10, 11]
1117GKGKGKGKGKPKSQAacetylation[11]
1323LAAAPGEKLPLFPEPubiquitination[8]
1348LSVVVDDKKFVSNITubiquitination[9]
1349SVVVDDKKFVSNITRacetylation[6]
1415ILRDHICKDMSALVAacetylation[6]
1415ILRDHICKDMSALVAubiquitination[9]
1483CSCVEAGKACDPAARubiquitination[9]
1535TNPEPMGKQGRVLHPubiquitination[8]
1572LFGNILDKHRQVGNAubiquitination[3, 4]
1586AVPPPLAKAIGLEIKubiquitination[8]
Reference
 [1] Protein lysine methyltransferase G9a acts on non-histone targets.
 Rathert P, Dhayalan A, Murakami M, Zhang X, Tamas R, Jurkowska R, Komatsu Y, Shinkai Y, Cheng X, Jeltsch A.
 Nat Chem Biol. 2008 Jun;4(6):344-6. [PMID: 18438403]
 [2] Update on activities at the Universal Protein Resource (UniProt) in 2013.
 e="String">UniProt Consortium.
 Nucleic Acids Res. 2013 Jan;41(Database issue):D43-7. [PMID: 23161681]
 [3] 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]
 [4] 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]
 [5] Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.
 Estève PO, Chin HG, Benner J, Feehery GR, Samaranayake M, Horwitz GA, Jacobsen SE, Pradhan S.
 Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5076-81. [PMID: 19282482]
 [6] SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities.
 Peng L, Yuan Z, Ling H, Fukasawa K, Robertson K, Olashaw N, Koomen J, Chen J, Lane WS, Seto E.
 Mol Cell Biol. 2011 Dec;31(23):4720-34. [PMID: 21947282]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [8] 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]
 [9] 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]
 [10] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [11] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 
Functional Description
 Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. 
Sequence Annotation
 DOMAIN 755 880 BAH 1.
 DOMAIN 972 1100 BAH 2.
 REPEAT 1109 1110 1.
 REPEAT 1111 1112 2.
 REPEAT 1113 1114 3.
 REPEAT 1115 1116 4.
 REPEAT 1117 1118 5.
 REPEAT 1119 1120 6; approximate.
 ZN_FING 646 692 CXXC-type.
 REGION 1 336 Interaction with the PRC2/EED-EZH2
 REGION 1 148 Interaction with DNMT3A.
 REGION 1 120 Interaction with DMAP1.
 REGION 149 217 Interaction with DNMT3B.
 REGION 163 174 Interaction with PCNA.
 REGION 308 606 Interaction with the PRC2/EED-EZH2
 REGION 310 502 Homodimerization.
 REGION 331 550 DNA replication foci-targeting sequence
 REGION 651 697 Required for activity.
 REGION 693 754 Autoinhibitory linker.
 REGION 1109 1120 6 X 2 AA tandem repeats of K-G.
 REGION 1121 1616 Interaction with the PRC2/EED-EZH2
 REGION 1139 1616 Catalytic.
 MOTIF 177 205 Nuclear localization signal (Potential).
 ACT_SITE 1226 1226
 METAL 353 353 Zinc.
 METAL 356 356 Zinc.
 METAL 414 414 Zinc.
 METAL 418 418 Zinc.
 MOD_RES 70 70 N6,N6-dimethyllysine.
 MOD_RES 127 127 Phosphoserine.
 MOD_RES 133 133 Phosphoserine.
 MOD_RES 142 142 N6-methyllysine; by SETD7.
 MOD_RES 143 143 Phosphoserine; by PKB/AKT1.
 MOD_RES 152 152 Phosphoserine.
 MOD_RES 154 154 Phosphoserine.
 MOD_RES 160 160 N6-acetyllysine.
 MOD_RES 173 173 N6-acetyllysine.
 MOD_RES 188 188 N6-acetyllysine.
 MOD_RES 259 259 N6-acetyllysine.
 MOD_RES 288 288 Phosphoserine (By similarity).
 MOD_RES 366 366 N6-acetyllysine.
 MOD_RES 394 394 Phosphoserine.
 MOD_RES 509 509 Phosphoserine (By similarity).
 MOD_RES 714 714 Phosphoserine.
 MOD_RES 732 732 Phosphoserine.
 MOD_RES 749 749 N6-acetyllysine.
 MOD_RES 891 891 N6-acetyllysine.
 MOD_RES 957 957 N6-acetyllysine.
 MOD_RES 961 961 N6-acetyllysine.
 MOD_RES 975 975 N6-acetyllysine.
 MOD_RES 1054 1054 N6-acetyllysine.
 MOD_RES 1111 1111 N6-acetyllysine.
 MOD_RES 1113 1113 N6-acetyllysine.
 MOD_RES 1115 1115 N6-acetyllysine.
 MOD_RES 1117 1117 N6-acetyllysine; by EHMT2.
 MOD_RES 1349 1349 N6-acetyllysine.
 MOD_RES 1415 1415 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Activator; Alternative splicing; Chromatin regulator; Complete proteome; Disease mutation; DNA-binding; Metal-binding; Methylation; Methyltransferase; Neuropathy; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1616 AA 
Protein Sequence
MPARTAPARV PTLAVPAISL PDDVRRRLKD LERDSLTEKE CVKEKLNLLH EFLQTEIKNQ 60
LCDLETKLRK EELSEEGYLA KVKSLLNKDL SLENGAHAYN REVNGRLENG NQARSEARRV 120
GMADANSPPK PLSKPRTPRR SKSDGEAKPE PSPSPRITRK STRQTTITSH FAKGPAKRKP 180
QEESERAKSD ESIKEEDKDQ DEKRRRVTSR ERVARPLPAE EPERAKSGTR TEKEEERDEK 240
EEKRLRSQTK EPTPKQKLKE EPDREARAGV QADEDEDGDE KDEKKHRSQP KDLAAKRRPE 300
EKEPEKVNPQ ISDEKDEDEK EEKRRKTTPK EPTEKKMARA KTVMNSKTHP PKCIQCGQYL 360
DDPDLKYGQH PPDAVDEPQM LTNEKLSIFD ANESGFESYE ALPQHKLTCF SVYCKHGHLC 420
PIDTGLIEKN IELFFSGSAK PIYDDDPSLE GGVNGKNLGP INEWWITGFD GGEKALIGFS 480
TSFAEYILMD PSPEYAPIFG LMQEKIYISK IVVEFLQSNS DSTYEDLINK IETTVPPSGL 540
NLNRFTEDSL LRHAQFVVEQ VESYDEAGDS DEQPIFLTPC MRDLIKLAGV TLGQRRAQAR 600
RQTIRHSTRE KDRGPTKATT TKLVYQIFDT FFAEQIEKDD REDKENAFKR RRCGVCEVCQ 660
QPECGKCKAC KDMVKFGGSG RSKQACQERR CPNMAMKEAD DDEEVDDNIP EMPSPKKMHQ 720
GKKKKQNKNR ISWVGEAVKT DGKKSYYKKV CIDAETLEVG DCVSVIPDDS SKPLYLARVT 780
ALWEDSSNGQ MFHAHWFCAG TDTVLGATSD PLELFLVDEC EDMQLSYIHS KVKVIYKAPS 840
ENWAMEGGMD PESLLEGDDG KTYFYQLWYD QDYARFESPP KTQPTEDNKF KFCVSCARLA 900
EMRQKEIPRV LEQLEDLDSR VLYYSATKNG ILYRVGDGVY LPPEAFTFNI KLSSPVKRPR 960
KEPVDEDLYP EHYRKYSDYI KGSNLDAPEP YRIGRIKEIF CPKKSNGRPN ETDIKIRVNK 1020
FYRPENTHKS TPASYHADIN LLYWSDEEAV VDFKAVQGRC TVEYGEDLPE CVQVYSMGGP 1080
NRFYFLEAYN AKSKSFEDPP NHARSPGNKG KGKGKGKGKP KSQACEPSEP EIEIKLPKLR 1140
TLDVFSGCGG LSEGFHQAGI SDTLWAIEMW DPAAQAFRLN NPGSTVFTED CNILLKLVMA 1200
GETTNSRGQR LPQKGDVEML CGGPPCQGFS GMNRFNSRTY SKFKNSLVVS FLSYCDYYRP 1260
RFFLLENVRN FVSFKRSMVL KLTLRCLVRM GYQCTFGVLQ AGQYGVAQTR RRAIILAAAP 1320
GEKLPLFPEP LHVFAPRACQ LSVVVDDKKF VSNITRLSSG PFRTITVRDT MSDLPEVRNG 1380
ASALEISYNG EPQSWFQRQL RGAQYQPILR DHICKDMSAL VAARMRHIPL APGSDWRDLP 1440
NIEVRLSDGT MARKLRYTHH DRKNGRSSSG ALRGVCSCVE AGKACDPAAR QFNTLIPWCL 1500
PHTGNRHNHW AGLYGRLEWD GFFSTTVTNP EPMGKQGRVL HPEQHRVVSV RECARSQGFP 1560
DTYRLFGNIL DKHRQVGNAV PPPLAKAIGL EIKLCMLAKA RESASAKIKE EEAAKD 1616 
Gene Ontology
 GO:0005721; C:centromeric heterochromatin; IEA:Compara.
 GO:0005634; C:nucleus; TAS:ProtInc.
 GO:0005657; C:replication fork; IEA:Compara.
 GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0008327; F:methyl-CpG binding; IEA:Compara.
 GO:0003723; F:RNA binding; IEA:Compara.
 GO:0008270; F:zinc ion binding; IEA:Compara.
 GO:0071230; P:cellular response to amino acid stimulus; IEA:Compara.
 GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
 GO:0016458; P:gene silencing; IEA:Compara.
 GO:0010216; P:maintenance of DNA methylation; IDA:UniProtKB.
 GO:0051573; P:negative regulation of histone H3-K9 methylation; IMP:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
 GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
 GO:0051571; P:positive regulation of histone H3-K4 methylation; IMP:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR001025; BAH_dom.
 IPR018117; C5_DNA_meth_AS.
 IPR001525; C5_MeTfrase.
 IPR022702; Cytosine_MeTrfase1_RFD.
 IPR010506; DMAP1-bd.
 IPR017198; DNA_C5-MeTrfase_1_euk.
 IPR002857; Znf_CXXC. 
Pfam
 PF01426; BAH
 PF06464; DMAP_binding
 PF00145; DNA_methylase
 PF12047; DNMT1-RFD
 PF02008; zf-CXXC 
SMART
 SM00439; BAH 
PROSITE
 PS51038; BAH
 PS00094; C5_MTASE_1
 PS00095; C5_MTASE_2
 PS51058; ZF_CXXC 
PRINTS
 PR00105; C5METTRFRASE.