P26358 (DNMT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA (cytosine-5)-methyltransferase 1
Short name=Dnmt1
EC=2.1.1.37

Alternative name(s):
CXXC-type zinc finger protein 9
DNA methyltransferase HsaI
Short name=DNA MTase HsaI
Short name=M.HsaI
MCMT

Gene names

Name:	DNMT1
Synonyms:	AIM, CXXC9, DNMT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1616 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.17 Ref.22 Ref.23
Catalytic activity	S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.
Subunit structure	Binds to CSNK1D By similarity. Homodimer. Interacts with HDAC1 and with PCNA. Forms a complex with DMAP1 and HDAC2, with direct interaction. Forms also a stable complex with E2F1, BB1 and HDAC1. Binds MBD2 and MBD3. Component of complexes containing SUV39H1. Interacts with DNMT3A and DNMT3B. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9 and BAZ2A/TIP5. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.17 Ref.28 Ref.29
Subcellular location	Nucleus Ref.13.
Tissue specificity	Ubiquitous; highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells, and expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, and skeletal muscle. Isoform 2 is less expressed than isoform 1. Ref.12
Induction	Its abundance is reduced to non detectable levels at the G0 phase of the cell cycle and is dramatically induced upon entrance into the S-phase of the cell cycle.
Domain	The N-terminal part is required for homodimerization and acts as a regulatory domain.
Post-translational modification	Sumoylated; sumoylation increases activity. Ref.28
Involvement in disease	Defects in DNMT1 are the cause of hereditary sensory neuropathy type 1E (HSN1E) [MIM:614116]. A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia. Ref.34
Sequence similarities	Belongs to the C5-methyltransferase family. Contains 2 BAH domains. Contains 1 CXXC-type zinc finger.
Sequence caution	The sequence AAD54507.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Neuropathy
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Activator Chromatin regulator Methyltransferase Repressor Transferase
PTM	Acetylation Methylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW maintenance of DNA methylation Inferred from direct assay Ref.22. Source: UniProtKB negative regulation of histone H3-K9 methylation Inferred from mutant phenotype Ref.23. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc positive regulation of gene expression Inferred from mutant phenotype Ref.23. Source: UniProtKB positive regulation of histone H3-K4 methylation Inferred from mutant phenotype Ref.23. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Traceable author statement. Source: ProtInc
Molecular function	DNA (cytosine-5-)-methyltransferase activity Traceable author statement. Source: ProtInc DNA binding Inferred from direct assay Ref.22. Source: UniProtKB transcription factor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EED	O75530	2	EBI-719459,EBI-923794
EZH2	Q15910	4	EBI-719459,EBI-530054
SIRT1	Q96EB6	6	EBI-719459,EBI-1802965
UHRF1	Q96T88	10	EBI-719459,EBI-1548946

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P26358-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P26358-2)

Also known as: Dnmt1b;

The sequence of this isoform differs from the canonical sequence as follows:
     149-149: P → RSRDPPASASQVTGIRA

Isoform 3 (identifier: P26358-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-336: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1616

1616

DNA (cytosine-5)-methyltransferase 1

PRO_0000088034

Regions

Domain

755 – 880

126

BAH 1

Domain

972 – 1100

129

BAH 2

Repeat

1109 – 1110

2

1

Repeat

1111 – 1112

2

2

Repeat

1113 – 1114

2

3

Repeat

1115 – 1116

2

4

Repeat

1117 – 1118

2

5

Repeat

1119 – 1120

2

6; approximate

Zinc finger

646 – 692

47

CXXC-type

Region

1 – 336

336

Interaction with the PRC2/EED-EZH2 complex By similarity

Region

1 – 148

148

Interaction with DNMT3A

Region

1 – 120

120

Interaction with DMAP1

Region

149 – 217

69

Interaction with DNMT3B

Region

163 – 174

12

Interaction with PCNA

Region

308 – 606

299

Interaction with the PRC2/EED-EZH2 complex By similarity

Region

310 – 502

193

Homodimerization

Region

331 – 550

220

DNA replication foci-targeting sequence By similarity

Region

651 – 697

47

Required for activity

Region

1109 – 1120

12

6 X 2 AA tandem repeats of K-G

Region

1121 – 1616

496

Interaction with the PRC2/EED-EZH2 complex By similarity

Region

1139 – 1616

478

Catalytic

Motif

177 – 205

29

Nuclear localization signal Potential

Sites

Active site

1226

1

Metal binding

353

1

Zinc

Metal binding

356

1

Zinc

Metal binding

414

1

Zinc

Metal binding

418

1

Zinc

Site

509

1

Important for activity By similarity

Amino acid modifications

Modified residue

70

1

N6,N6-dimethyllysine Ref.25

Modified residue

127

1

Phosphoserine Ref.15 Ref.26 Ref.30

Modified residue

137

1

Phosphothreonine Ref.26

Modified residue

152

1

Phosphoserine Ref.26

Modified residue

154

1

Phosphoserine Ref.21 Ref.26

Modified residue

173

1

N6-acetyllysine Ref.31

Modified residue

288

1

Phosphoserine By similarity

Modified residue

394

1

Phosphoserine Ref.26

Modified residue

509

1

Phosphoserine By similarity

Modified residue

714

1

Phosphoserine Ref.14 Ref.15 Ref.26 Ref.27 Ref.30

Modified residue

732

1

Phosphoserine Ref.24

Modified residue

954

1

Phosphoserine Ref.14

Modified residue

969

1

Phosphotyrosine Ref.19

Modified residue

1105

1

Phosphoserine Ref.15

Modified residue

1113

1

N6-acetyllysine Ref.16 Ref.31

Modified residue

1115

1

N6-acetyllysine Ref.16 Ref.31

Modified residue

1117

1

N6-acetyllysine; by EHMT2 Ref.16 Ref.31

Natural variations

Alternative sequence

1 – 336

336

Missing in isoform 3.

VSP_005617

Alternative sequence

149

1

P → RSRDPPASASQVTGIRA in isoform 2.

VSP_005618

Natural variant

97

1

H → R.
Corresponds to variant rs16999593 [ dbSNP | Ensembl ].

VAR_024605

Natural variant

311

1

I → V.
Corresponds to variant rs2228612 [ dbSNP | Ensembl ].

VAR_051960

Natural variant

490 – 491

2

DP → EY in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase.

VAR_065965

Natural variant

495

1

Y → C in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. Ref.34

VAR_065966

Experimental info

Mutagenesis

163

1

R → A: Abolishes interaction with PCNA.

Mutagenesis

164

1

Q → A: Abolishes interaction with PCNA.

Mutagenesis

166

1

T → A: Abolishes interaction with PCNA.

Mutagenesis

167

1

I → A: Abolishes interaction with PCNA.

Mutagenesis

169

1

S → A: No loss of interaction with PCNA.

Mutagenesis

170

1

H → V: Abolishes interaction with PCNA.

Mutagenesis

171

1

F → V: Abolishes interaction with PCNA.

Mutagenesis

172

1

A → S: No loss of interaction with PCNA.

Mutagenesis

173

1

K → A: No loss of interaction with PCNA.

Mutagenesis

653

1

C → G: Reduces activity about 10-fold; when associated with G-656; G-659; G-664; G-667 and G-670. Ref.22

Mutagenesis

656

1

C → G: Reduces activity about 10-fold; when associated with G-653; G-659; G-664; G-667 and G-670. Ref.22

Mutagenesis

659

1

C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-664; G-667 and G-670. Ref.22

Mutagenesis

664

1

C → F: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-667 and G-670. Ref.22

Mutagenesis

667

1

C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-670. Ref.22

Mutagenesis

670

1

C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-667. Ref.22

Mutagenesis

1226

1

C → A: Loss of activity. Ref.28

Secondary structure

1

.

.

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.

.

.

.

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.

.

.

.

.

.

.

.

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.

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.

.

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1616

Helix Strand Turn

Details...

Helix

377 – 389

13

Beta strand

405 – 413

9

Turn

427 – 430

4

Beta strand

434 – 436

3

Beta strand

438 – 441

4

Beta strand

485 – 488

4

Turn

493 – 498

6

Helix

504 – 518

15

Helix

524 – 533

10

Helix

547 – 551

5

Helix

554 – 566

13

Helix

575 – 577

3

Helix

579 – 587

9

Helix

595 – 598

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 1E833192D22AFA5B	FASTA	1,616	183,165
	10 20 30 40 50 60 MPARTAPARV PTLAVPAISL PDDVRRRLKD LERDSLTEKE CVKEKLNLLH EFLQTEIKNQ 70 80 90 100 110 120 LCDLETKLRK EELSEEGYLA KVKSLLNKDL SLENGAHAYN REVNGRLENG NQARSEARRV 130 140 150 160 170 180 GMADANSPPK PLSKPRTPRR SKSDGEAKPE PSPSPRITRK STRQTTITSH FAKGPAKRKP 190 200 210 220 230 240 QEESERAKSD ESIKEEDKDQ DEKRRRVTSR ERVARPLPAE EPERAKSGTR TEKEEERDEK 250 260 270 280 290 300 EEKRLRSQTK EPTPKQKLKE EPDREARAGV QADEDEDGDE KDEKKHRSQP KDLAAKRRPE 310 320 330 340 350 360 EKEPEKVNPQ ISDEKDEDEK EEKRRKTTPK EPTEKKMARA KTVMNSKTHP PKCIQCGQYL 370 380 390 400 410 420 DDPDLKYGQH PPDAVDEPQM LTNEKLSIFD ANESGFESYE ALPQHKLTCF SVYCKHGHLC 430 440 450 460 470 480 PIDTGLIEKN IELFFSGSAK PIYDDDPSLE GGVNGKNLGP INEWWITGFD GGEKALIGFS 490 500 510 520 530 540 TSFAEYILMD PSPEYAPIFG LMQEKIYISK IVVEFLQSNS DSTYEDLINK IETTVPPSGL 550 560 570 580 590 600 NLNRFTEDSL LRHAQFVVEQ VESYDEAGDS DEQPIFLTPC MRDLIKLAGV TLGQRRAQAR 610 620 630 640 650 660 RQTIRHSTRE KDRGPTKATT TKLVYQIFDT FFAEQIEKDD REDKENAFKR RRCGVCEVCQ 670 680 690 700 710 720 QPECGKCKAC KDMVKFGGSG RSKQACQERR CPNMAMKEAD DDEEVDDNIP EMPSPKKMHQ 730 740 750 760 770 780 GKKKKQNKNR ISWVGEAVKT DGKKSYYKKV CIDAETLEVG DCVSVIPDDS SKPLYLARVT 790 800 810 820 830 840 ALWEDSSNGQ MFHAHWFCAG TDTVLGATSD PLELFLVDEC EDMQLSYIHS KVKVIYKAPS 850 860 870 880 890 900 ENWAMEGGMD PESLLEGDDG KTYFYQLWYD QDYARFESPP KTQPTEDNKF KFCVSCARLA 910 920 930 940 950 960 EMRQKEIPRV LEQLEDLDSR VLYYSATKNG ILYRVGDGVY LPPEAFTFNI KLSSPVKRPR 970 980 990 1000 1010 1020 KEPVDEDLYP EHYRKYSDYI KGSNLDAPEP YRIGRIKEIF CPKKSNGRPN ETDIKIRVNK 1030 1040 1050 1060 1070 1080 FYRPENTHKS TPASYHADIN LLYWSDEEAV VDFKAVQGRC TVEYGEDLPE CVQVYSMGGP 1090 1100 1110 1120 1130 1140 NRFYFLEAYN AKSKSFEDPP NHARSPGNKG KGKGKGKGKP KSQACEPSEP EIEIKLPKLR 1150 1160 1170 1180 1190 1200 TLDVFSGCGG LSEGFHQAGI SDTLWAIEMW DPAAQAFRLN NPGSTVFTED CNILLKLVMA 1210 1220 1230 1240 1250 1260 GETTNSRGQR LPQKGDVEML CGGPPCQGFS GMNRFNSRTY SKFKNSLVVS FLSYCDYYRP 1270 1280 1290 1300 1310 1320 RFFLLENVRN FVSFKRSMVL KLTLRCLVRM GYQCTFGVLQ AGQYGVAQTR RRAIILAAAP 1330 1340 1350 1360 1370 1380 GEKLPLFPEP LHVFAPRACQ LSVVVDDKKF VSNITRLSSG PFRTITVRDT MSDLPEVRNG 1390 1400 1410 1420 1430 1440 ASALEISYNG EPQSWFQRQL RGAQYQPILR DHICKDMSAL VAARMRHIPL APGSDWRDLP 1450 1460 1470 1480 1490 1500 NIEVRLSDGT MARKLRYTHH DRKNGRSSSG ALRGVCSCVE AGKACDPAAR QFNTLIPWCL 1510 1520 1530 1540 1550 1560 PHTGNRHNHW AGLYGRLEWD GFFSTTVTNP EPMGKQGRVL HPEQHRVVSV RECARSQGFP 1570 1580 1590 1600 1610 DTYRLFGNIL DKHRQVGNAV PPPLAKAIGL EIKLCMLAKA RESASAKIKE EEAAKD
	Isoform 2 (Dnmt1b) [UniParc]. Checksum: 650AA14F73A75649	FASTA	1,632	184,819
	10 20 30 40 50 60 MPARTAPARV PTLAVPAISL PDDVRRRLKD LERDSLTEKE CVKEKLNLLH EFLQTEIKNQ 70 80 90 100 110 120 LCDLETKLRK EELSEEGYLA KVKSLLNKDL SLENGAHAYN REVNGRLENG NQARSEARRV 130 140 150 160 170 180 GMADANSPPK PLSKPRTPRR SKSDGEAKRS RDPPASASQV TGIRAEPSPS PRITRKSTRQ 190 200 210 220 230 240 TTITSHFAKG PAKRKPQEES ERAKSDESIK EEDKDQDEKR RRVTSRERVA RPLPAEEPER 250 260 270 280 290 300 AKSGTRTEKE EERDEKEEKR LRSQTKEPTP KQKLKEEPDR EARAGVQADE DEDGDEKDEK 310 320 330 340 350 360 KHRSQPKDLA AKRRPEEKEP EKVNPQISDE KDEDEKEEKR RKTTPKEPTE KKMARAKTVM 370 380 390 400 410 420 NSKTHPPKCI QCGQYLDDPD LKYGQHPPDA VDEPQMLTNE KLSIFDANES GFESYEALPQ 430 440 450 460 470 480 HKLTCFSVYC KHGHLCPIDT GLIEKNIELF FSGSAKPIYD DDPSLEGGVN GKNLGPINEW 490 500 510 520 530 540 WITGFDGGEK ALIGFSTSFA EYILMDPSPE YAPIFGLMQE KIYISKIVVE FLQSNSDSTY 550 560 570 580 590 600 EDLINKIETT VPPSGLNLNR FTEDSLLRHA QFVVEQVESY DEAGDSDEQP IFLTPCMRDL 610 620 630 640 650 660 IKLAGVTLGQ RRAQARRQTI RHSTREKDRG PTKATTTKLV YQIFDTFFAE QIEKDDREDK 670 680 690 700 710 720 ENAFKRRRCG VCEVCQQPEC GKCKACKDMV KFGGSGRSKQ ACQERRCPNM AMKEADDDEE 730 740 750 760 770 780 VDDNIPEMPS PKKMHQGKKK KQNKNRISWV GEAVKTDGKK SYYKKVCIDA ETLEVGDCVS 790 800 810 820 830 840 VIPDDSSKPL YLARVTALWE DSSNGQMFHA HWFCAGTDTV LGATSDPLEL FLVDECEDMQ 850 860 870 880 890 900 LSYIHSKVKV IYKAPSENWA MEGGMDPESL LEGDDGKTYF YQLWYDQDYA RFESPPKTQP 910 920 930 940 950 960 TEDNKFKFCV SCARLAEMRQ KEIPRVLEQL EDLDSRVLYY SATKNGILYR VGDGVYLPPE 970 980 990 1000 1010 1020 AFTFNIKLSS PVKRPRKEPV DEDLYPEHYR KYSDYIKGSN LDAPEPYRIG RIKEIFCPKK 1030 1040 1050 1060 1070 1080 SNGRPNETDI KIRVNKFYRP ENTHKSTPAS YHADINLLYW SDEEAVVDFK AVQGRCTVEY 1090 1100 1110 1120 1130 1140 GEDLPECVQV YSMGGPNRFY FLEAYNAKSK SFEDPPNHAR SPGNKGKGKG KGKGKPKSQA 1150 1160 1170 1180 1190 1200 CEPSEPEIEI KLPKLRTLDV FSGCGGLSEG FHQAGISDTL WAIEMWDPAA QAFRLNNPGS 1210 1220 1230 1240 1250 1260 TVFTEDCNIL LKLVMAGETT NSRGQRLPQK GDVEMLCGGP PCQGFSGMNR FNSRTYSKFK 1270 1280 1290 1300 1310 1320 NSLVVSFLSY CDYYRPRFFL LENVRNFVSF KRSMVLKLTL RCLVRMGYQC TFGVLQAGQY 1330 1340 1350 1360 1370 1380 GVAQTRRRAI ILAAAPGEKL PLFPEPLHVF APRACQLSVV VDDKKFVSNI TRLSSGPFRT 1390 1400 1410 1420 1430 1440 ITVRDTMSDL PEVRNGASAL EISYNGEPQS WFQRQLRGAQ YQPILRDHIC KDMSALVAAR 1450 1460 1470 1480 1490 1500 MRHIPLAPGS DWRDLPNIEV RLSDGTMARK LRYTHHDRKN GRSSSGALRG VCSCVEAGKA 1510 1520 1530 1540 1550 1560 CDPAARQFNT LIPWCLPHTG NRHNHWAGLY GRLEWDGFFS TTVTNPEPMG KQGRVLHPEQ 1570 1580 1590 1600 1610 1620 HRVVSVRECA RSQGFPDTYR LFGNILDKHR QVGNAVPPPL AKAIGLEIKL CMLAKARESA 1630 SAKIKEEEAA KD
	Isoform 3 [UniParc]. Checksum: 70ECEE72AE313EE9	FASTA	1,280	144,465
	10 20 30 40 50 60 MARAKTVMNS KTHPPKCIQC GQYLDDPDLK YGQHPPDAVD EPQMLTNEKL SIFDANESGF 70 80 90 100 110 120 ESYEALPQHK LTCFSVYCKH GHLCPIDTGL IEKNIELFFS GSAKPIYDDD PSLEGGVNGK 130 140 150 160 170 180 NLGPINEWWI TGFDGGEKAL IGFSTSFAEY ILMDPSPEYA PIFGLMQEKI YISKIVVEFL 190 200 210 220 230 240 QSNSDSTYED LINKIETTVP PSGLNLNRFT EDSLLRHAQF VVEQVESYDE AGDSDEQPIF 250 260 270 280 290 300 LTPCMRDLIK LAGVTLGQRR AQARRQTIRH STREKDRGPT KATTTKLVYQ IFDTFFAEQI 310 320 330 340 350 360 EKDDREDKEN AFKRRRCGVC EVCQQPECGK CKACKDMVKF GGSGRSKQAC QERRCPNMAM 370 380 390 400 410 420 KEADDDEEVD DNIPEMPSPK KMHQGKKKKQ NKNRISWVGE AVKTDGKKSY YKKVCIDAET 430 440 450 460 470 480 LEVGDCVSVI PDDSSKPLYL ARVTALWEDS SNGQMFHAHW FCAGTDTVLG ATSDPLELFL 490 500 510 520 530 540 VDECEDMQLS YIHSKVKVIY KAPSENWAME GGMDPESLLE GDDGKTYFYQ LWYDQDYARF 550 560 570 580 590 600 ESPPKTQPTE DNKFKFCVSC ARLAEMRQKE IPRVLEQLED LDSRVLYYSA TKNGILYRVG 610 620 630 640 650 660 DGVYLPPEAF TFNIKLSSPV KRPRKEPVDE DLYPEHYRKY SDYIKGSNLD APEPYRIGRI 670 680 690 700 710 720 KEIFCPKKSN GRPNETDIKI RVNKFYRPEN THKSTPASYH ADINLLYWSD EEAVVDFKAV 730 740 750 760 770 780 QGRCTVEYGE DLPECVQVYS MGGPNRFYFL EAYNAKSKSF EDPPNHARSP GNKGKGKGKG 790 800 810 820 830 840 KGKPKSQACE PSEPEIEIKL PKLRTLDVFS GCGGLSEGFH QAGISDTLWA IEMWDPAAQA 850 860 870 880 890 900 FRLNNPGSTV FTEDCNILLK LVMAGETTNS RGQRLPQKGD VEMLCGGPPC QGFSGMNRFN 910 920 930 940 950 960 SRTYSKFKNS LVVSFLSYCD YYRPRFFLLE NVRNFVSFKR SMVLKLTLRC LVRMGYQCTF 970 980 990 1000 1010 1020 GVLQAGQYGV AQTRRRAIIL AAAPGEKLPL FPEPLHVFAP RACQLSVVVD DKKFVSNITR 1030 1040 1050 1060 1070 1080 LSSGPFRTIT VRDTMSDLPE VRNGASALEI SYNGEPQSWF QRQLRGAQYQ PILRDHICKD 1090 1100 1110 1120 1130 1140 MSALVAARMR HIPLAPGSDW RDLPNIEVRL SDGTMARKLR YTHHDRKNGR SSSGALRGVC 1150 1160 1170 1180 1190 1200 SCVEAGKACD PAARQFNTLI PWCLPHTGNR HNHWAGLYGR LEWDGFFSTT VTNPEPMGKQ 1210 1220 1230 1240 1250 1260 GRVLHPEQHR VVSVRECARS QGFPDTYRLF GNILDKHRQV GNAVPPPLAK AIGLEIKLCM 1270 1280 LAKARESASA KIKEEEAAKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the cDNA encoding human DNA methyltransferase." Yen R.-W.C., Vertino P.M., Nelkin B.D., Yu J.J., Deiry W.E., Cumaraswamy A., Lennon G.G., Trask B.J., Celano P., Baylin S.B. Nucleic Acids Res. 20:2287-2291(1992) [PubMed: 1594447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"New 5' regions of the murine and human genes for DNA (cytosine-5)-methyltransferase." Yoder J.A., Yen R.-W.C., Vertino P.M., Bestor T.H., Baylin S.B. J. Biol. Chem. 271:31092-31097(1996) [PubMed: 8940105] [Abstract] Cited for: SEQUENCE REVISION TO N-TERMINUS.
[3]	"Human DNA methyltransferase (DNMT1) is alternatively spliced." Li L.C., Au H., Chui R., Dahiya R. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Prostatic carcinoma.
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	"Two major forms of DNA (cytosine-5) methyltransferase in human somatic tissues." Hsu D.-W., Lin M.-J., Lee T.-L., Wen S.-C., Chen X., Shen C.-K.J. Proc. Natl. Acad. Sci. U.S.A. 96:9751-9756(1999) [PubMed: 10449766] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
[7]	"Characterization of the human DNA methyltransferase splice variant Dnmt1b." Bonfils C., Beaulieu N., Chan E., Cotton-Montpetit J., MacLeod A.R. J. Biol. Chem. 275:10754-10760(2000) [PubMed: 10753866] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
[8]	"Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1." Chuang L.S.-H., Ian H.-I., Koh T.-W., Ng H.-H., Xu G., Li B.F.L. Science 277:1996-2000(1997) [PubMed: 9302295] [Abstract] Cited for: INTERACTION WITH PCNA, MUTAGENESIS.
[9]	"MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase." Tatematsu K., Yamazaki T., Ishikawa F. Genes Cells 5:677-688(2000) [PubMed: 10947852] [Abstract] Cited for: INTERACTION WITH MBD2 AND MBD3.
[10]	"DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci." Rountree M.R., Bachman K.E., Baylin S.B. Nat. Genet. 25:269-277(2000) [PubMed: 10888872] [Abstract] Cited for: INTERACTION WITH HDAC2 AND DMAP1.
[11]	"DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters." Robertson K.D., Ait-Si-Ali S., Yokochi T., Wade P.A., Jones P.L., Wolffe A.P. Nat. Genet. 25:338-342(2000) [PubMed: 10888886] [Abstract] Cited for: INTERACTION WITH RB1; E2F1 AND HDAC1.
[12]	"The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors." Robertson K.D., Uzvolgyi E., Liang G., Talmadge C., Sumegi J., Gonzales F.A., Jones P.A. Nucleic Acids Res. 27:2291-2298(1999) [PubMed: 10325416] [Abstract] Cited for: TISSUE SPECIFICITY.
[13]	"Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases." Kim G.-D., Ni J., Kelesoglu N., Roberts R.J., Pradhan S. EMBO J. 21:4183-4195(2002) [PubMed: 12145218] [Abstract] Cited for: INTERACTION WITH DNMT3A AND DNMT3B, SUBCELLULAR LOCATION.
[14]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-714 AND SER-954, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; SER-714 AND SER-1105, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1113; LYS-1115 AND LYS-1117, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"The Polycomb group protein EZH2 directly controls DNA methylation." Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 439:871-874(2006) [PubMed: 16357870] [Abstract] Cited for: FUNCTION, INTERACTION WITH EED AND EZH2.
[18]	Erratum Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 446:824-824(2006)
[19]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-969, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[20]	"Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer." Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M., Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E., Bergman Y., Simon I., Cedar H. Nat. Genet. 39:232-236(2007) [PubMed: 17200670] [Abstract] Cited for: DE NOVO DNA METHYLATION OF TARGET GENES.
[21]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[22]	"CXXC domain of human DNMT1 is essential for enzymatic activity." Pradhan M., Esteve P.-O., Chin H.G., Samaranayke M., Kim G.-D., Pradhan S. Biochemistry 47:10000-10009(2008) [PubMed: 18754681] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-653; CYS-656; CYS-659; CYS-664; CYS-667 AND CYS-670.
[23]	"DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation." Sun L., Huang L., Nguyen P., Bisht K.S., Bar-Sela G., Ho A.S., Bradbury C.M., Yu W., Cui H., Lee S., Trepel J.B., Feinberg A.P., Gius D. Cancer Res. 68:2726-2735(2008) [PubMed: 18413740] [Abstract] Cited for: FUNCTION.
[24]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-732, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"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. 4:344-346(2008) [PubMed: 18438403] [Abstract] Cited for: METHYLATION AT LYS-70, MASS SPECTROMETRY.
[26]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; THR-137; SER-152; SER-154; SER-394 AND SER-714, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-714, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[28]	"SUMOylation enhances DNA methyltransferase 1 activity." Lee B., Muller M.T. Biochem. J. 421:449-461(2009) [PubMed: 19450230] [Abstract] Cited for: SUMOYLATION, INTERACTION WITH UBC9, MUTAGENESIS OF CYS-1226.
[29]	"Dimerization of DNA methyltransferase 1 is mediated by its regulatory domain." Fellinger K., Rothbauer U., Felle M., Laengst G., Leonhardt H. J. Cell. Biochem. 106:521-528(2009) [PubMed: 19173286] [Abstract] Cited for: HOMODIMERIZATION.
[30]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127 AND SER-714, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[31]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173; LYS-1113; LYS-1115 AND LYS-1117, MASS SPECTROMETRY.
[32]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]	"Replication foci-targeting sequence of human DNMT1." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 351-600 IN COMPLEX WITH ZINC IONS.
[34]	"Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss." Klein C.J., Botuyan M.V., Wu Y., Ward C.J., Nicholson G.A., Hammans S., Hojo K., Yamanishi H., Karpf A.R., Wallace D.C., Simon M., Lander C., Boardman L.A., Cunningham J.M., Smith G.E., Litchy W.J., Boes B., Atkinson E.J. , Middha S., Dyck P.J.B., Parisi J.E., Mer G., Smith D.I., Dyck P.J. Nat. Genet. 43:595-600(2011) [PubMed: 21532572] [Abstract] Cited for: VARIANTS HSN1E 490-GLU-TYR-491 AND CYS-495, CHARACTERIZATION OF VARIANTS HSN1E 490-GLU-TYR-491 AND CYS-495.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X63692 mRNA. Translation: CAA45219.1.
AF180682 mRNA. Translation: AAF23609.1.
AC010077 Genomic DNA. Translation: AAD54507.1. Sequence problems.
AC011511 Genomic DNA. No translation available.
AC020931 Genomic DNA. No translation available.
BC126227 mRNA. Translation: AAI26228.1.
BC144093 mRNA. Translation: AAI44094.1.
AF169120 Genomic DNA. Translation: AAD51619.1.

IPI

IPI00031519.
IPI00220918.
IPI00220919.

PIR

S22610.

RefSeq

NP_001124295.1. NM_001130823.1.
NP_001370.1. NM_001379.2.

UniGene

Hs.202672.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EPZ	X-ray	2.31	A/B	351-600	[»]
3PTA	X-ray	3.60	A	646-1600	[»]
3SWR	X-ray	2.49	A	601-1600	[»]

ProteinModelPortal

P26358.

SMR

P26358. Positions 351-599, 601-1600.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39693N.

IntAct

P26358. 13 interactions.

MINT

MINT-232346.

STRING

P26358.

Protein family/group databases

REBASE

1161. M.HsaDnmt1A.
4240. M.HsaDnmt1B.

PTM databases

PhosphoSite

P26358.

Polymorphism databases

DMDM

12231019.

Proteomic databases

PRIDE

P26358.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340748; ENSP00000345739; ENSG00000130816.
ENST00000359526; ENSP00000352516; ENSG00000130816.

GeneID

1786.

KEGG

hsa:1786.

UCSC

uc002mng.1. human.

Organism-specific databases

CTD

1786.

GeneCards

GC19M010244.

H-InvDB

HIX0202861.

HGNC

HGNC:2976. DNMT1.

HPA

CAB005876.
HPA002694.

MIM

126375. gene.
614116. phenotype.

neXtProt

NX_P26358.

Orphanet

36386. Hereditary sensory and autonomic neuropathy type 1.

PharmGKB

PA27443.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04806.

GeneTree

ENSGT00390000005100.

HOVERGEN

HBG051384.

OMA

KNRISWV.

OrthoDB

EOG4T1HKN.

PhylomeDB

P26358.

Enzyme and pathway databases

BRENDA

2.1.1.37. 2681.

Gene expression databases

ArrayExpress

P26358.

Bgee

P26358.

CleanEx

HS_DNMT1.

Genevestigator

P26358.

GermOnline

ENSG00000130816. Homo sapiens.

Family and domain databases

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.
[Graphical view]

KO

K00558.

PANTHER

PTHR10629. C5_DNA_meth. 1 hit.

Pfam

PF01426. BAH. 2 hits.
PF06464. DMAP_binding. 1 hit.
PF00145. DNA_methylase. 1 hit.
PF12047. DNMT1-RFD. 1 hit.
PF02008. zf-CXXC. 1 hit.
[Graphical view]

PIRSF

PIRSF037404. DNMT1. 1 hit.

PRINTS

PR00105. C5METTRFRASE.

SMART

SM00439. BAH. 2 hits.
[Graphical view]

PROSITE

PS51038. BAH. 2 hits.
PS00094. C5_MTASE_1. 1 hit.
PS00095. C5_MTASE_2. 1 hit.
PS51058. ZF_CXXC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00928. Azacitidine.
DB01262. Decitabine.
DB01099. Flucytosine.
DB01181. Ifosfamide.
DB01035. Procainamide.

NextBio

7267.

SOURCE

Search...

Entry information

Entry name

DNMT1_HUMAN

Accession

Primary (citable) accession number: P26358
Secondary accession number(s): A0AV63 , B7ZLW6, Q9UHG5, Q9ULA2, Q9UMZ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	January 11, 2001
Last modified:	January 25, 2012
This is version 139 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.