Reviewed, UniProtKB/Swiss-Prot P26358 (DNMT1_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA (cytosine-5)-methyltransferase 1
      Short name=Dnmt1
    EC=2.1.1.37
Alternative name(s):
    MCMT
    DNA methyltransferase HsaI
      Short name=DNA MTase HsaI
      Short name=M.HsaI
    CXXC-type zinc finger protein 9

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.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Methylates CpG residues. Preferentially methylates hemimethylated DNA. 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. Ref.17
Catalytic activity	S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.
Subunit structure	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. Ref.17 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
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.
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
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Methyltransferase Repressor Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA methylation Ref.10 Traceable author statement. Source: ProtInc negative regulation of transcription from RNA polymerase II promoter Ref.10 Traceable author statement. Source: ProtInc transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.2 Traceable author statement. Source: ProtInc
Molecular function	DNA (cytosine-5-)-methyltransferase activity Ref.2 Traceable author statement. Source: ProtInc DNA binding Inferred from electronic annotation. Source: UniProtKB-KW transcription factor binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EED	O75530	1	EBI-719459,EBI-923794
EZH2	Q15910	3	EBI-719459,EBI-530054
UHRF1	Q96T88	1	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	331 – 550	220	DNA replication foci-targeting sequence By similarity
	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	By similarity
Amino acid modifications
	Modified residue	127	1	Phosphoserine Ref.15 Ref.23
	Modified residue	137	1	Phosphothreonine Ref.23
	Modified residue	152	1	Phosphoserine Ref.23
	Modified residue	154	1	Phosphoserine Ref.23 Ref.21
	Modified residue	394	1	Phosphoserine Ref.23
	Modified residue	509	1	Phosphoserine By similarity
	Modified residue	714	1	Phosphoserine Ref.15 Ref.23 Ref.14
	Modified residue	732	1	Phosphoserine Ref.22
	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
	Modified residue	1115	1	N6-acetyllysine Ref.16
	Modified residue	1117	1	N6-acetyllysine Ref.16
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: dbSNP rs16999593.		VAR_024605
	Natural variant	311	1	I → V: dbSNP rs2228612.		VAR_051960
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.

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). 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. 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: Epithelium.
[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: Epithelium.
[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: Epithelium.
[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.
[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.
[22]	"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.
[23]	"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.
[24]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
AF169120 Genomic DNA. Translation: AAD51619.1.

IPI

IPI00031519.
IPI00220918.
IPI00220919.

PIR

S22610.

RefSeq

NP_001124295.1.
NP_001370.1.

UniGene

Hs.202672

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EPZ	X-ray	2.31	A/B	351-600	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P26358. 6 interactions.

Protein family/group databases

REBASE

1161. M.HsaDnmt1A.

PTM databases

PhosphoSite

P26358.

Proteomic databases

PRIDE

P26358.

Genome annotation databases

Ensembl

ENSG00000130816. Homo sapiens. [Contig view]

GeneID

1786.

Organism-specific databases

GeneCards

GC19M010105.

H-InvDB

HIX0027457.

HGNC

HGNC:2976. DNMT1.

HPA

CAB005876.
HPA002694.

MIM

126375. gene.

PharmGKB

PA27443.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P26358.

OMA

P26358. GQRLPQK.

Enzyme and pathway databases

BRENDA

2.1.1.37. 247.

Gene expression databases

ArrayExpress

P26358.

Bgee

P26358.

CleanEx

HS_DNMT1.

GermOnline

ENSG00000130816. Homo sapiens.

Family and domain databases

InterPro

IPR001025. BAH.
IPR001525. C5_DNA_meth.
IPR018117. C5_DNA_meth_AS.
IPR010506. DMAP1_bd.
IPR017198. DNA_C5-MeTrfase_1.
IPR002857. Znf_CXXC.
[Graphical view]

PANTHER

PTHR10629. C5_DNA_meth. 1 hit.

Pfam

PF01426. BAH. 2 hits.
PF06464. DMAP_binding. 1 hit.
PF00145. DNA_methylase. 3 hits.
PF02008. zf-CXXC. 1 hit.
[Graphical view]

PIRSF

PIRSF037404. DNMT1. 1 hit.

PRINTS

PR00105. C5METTRFRASE.

SMART

SM00439. BAH. 2 hits.
[Graphical view]

TIGRFAMs

TIGR00675. dcm. 1 hit.

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 Resources

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 , Q9UHG5, Q9ULA2, Q9UMZ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	January 11, 2001
Last modified:	June 16, 2009
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)