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Protein

DNA (cytosine-5)-methyltransferase 1

Gene

DNMT1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. Promotes tumor growth.By similarity

Catalytic activityi

S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi351ZincBy similarity1
Metal bindingi354ZincBy similarity1
Metal bindingi412ZincBy similarity1
Metal bindingi416ZincBy similarity1
Sitei507Important for activityBy similarity1
Active sitei1223PROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri643 – 689CXXC-typePROSITE-ProRule annotationAdd BLAST47

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

BRENDAi2.1.1.37. 908.
ReactomeiR-BTA-212300. PRC2 methylates histones and DNA.

Protein family/group databases

REBASEi7406. M.BtaDnmt1AP.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 1 (EC:2.1.1.37)
Short name:
Dnmt1
Gene namesi
Name:DNMT1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 7

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002398451 – 1611DNA (cytosine-5)-methyltransferase 1Add BLAST1611

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei15PhosphoserineBy similarity1
Modified residuei70N6,N6-dimethyllysine; by EHMT2By similarity1
Modified residuei133PhosphoserineBy similarity1
Modified residuei137PhosphothreonineBy similarity1
Modified residuei141PhosphoserineBy similarity1
Modified residuei142N6-methyllysine; by SETD7By similarity1
Modified residuei143Phosphoserine; by PKB/AKT1By similarity1
Modified residuei152PhosphoserineBy similarity1
Modified residuei154PhosphoserineBy similarity1
Modified residuei160N6-acetyllysineBy similarity1
Modified residuei166PhosphothreonineBy similarity1
Modified residuei188N6-acetyllysineBy similarity1
Modified residuei257N6-acetyllysineBy similarity1
Modified residuei310PhosphoserineBy similarity1
Modified residuei392PhosphoserineBy similarity1
Modified residuei396PhosphoserineBy similarity1
Modified residuei507PhosphoserineBy similarity1
Modified residuei547PhosphoserineBy similarity1
Modified residuei711PhosphoserineBy similarity1
Modified residuei729PhosphoserineBy similarity1
Modified residuei746N6-acetyllysineBy similarity1
Modified residuei875PhosphoserineBy similarity1
Modified residuei888N6-acetyllysineBy similarity1
Modified residuei954N6-acetyllysineBy similarity1
Modified residuei958N6-acetyllysineBy similarity1
Modified residuei972N6-acetyllysineBy similarity1
Modified residuei1051N6-acetyllysineBy similarity1
Modified residuei1108N6-acetyllysineBy similarity1
Modified residuei1110N6-acetyllysineBy similarity1
Modified residuei1112N6-acetyllysineBy similarity1
Modified residuei1114N6-acetyllysineBy similarity1
Modified residuei1118N6-acetyllysineBy similarity1
Modified residuei1346N6-acetyllysineBy similarity1
Modified residuei1412N6-acetyllysineBy similarity1
Cross-linki1605Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

Sumoylated.By similarity
Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G2/M transition. Deacetylation of Lys-1346 and Lys-1412 by SIRT1 increases methyltransferase activity (By similarity).By similarity
Phosphorylation of Ser-154 by CDKs is important for enzymatic activity and protein stability. Phosphorylation of Ser-143 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability (By similarity).By similarity
Methylation at Lys-142 by SETD7 promotes DNMT1 proteasomal degradation.By similarity
Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ24K09.
PRIDEiQ24K09.

Expressioni

Gene expression databases

BgeeiENSBTAG00000002736.

Interactioni

Subunit structurei

Homodimer. Forms a stable complex with E2F1, BB1 and HDAC1. Forms a complex with DMAP1 and HDAC2, with direct interaction. Interacts with the PRC2/EED-EZH2 complex. Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1. Interacts with UHRF1; promoting its recruitment to hemimethylated DNA. Interacts with USP7, promoting its deubiquitination. Interacts with BAZ2A/TIP5. Interacts with PCNA. Interacts with MBD2 and MBD3. Interacts with DNMT3A and DNMT3B. Interacts with UBC9. Interacts with HDAC1. Interacts with CSNK1D.By similarity

Protein-protein interaction databases

BioGridi158481. 1 interactor.
STRINGi9913.ENSBTAP00000003549.

Structurei

3D structure databases

ProteinModelPortaliQ24K09.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 106DMAP-interactionAdd BLAST89
Domaini752 – 877BAH 1PROSITE-ProRule annotationAdd BLAST126
Domaini969 – 1097BAH 2PROSITE-ProRule annotationAdd BLAST129
Repeati1106 – 110712
Repeati1108 – 110922
Repeati1110 – 111132
Repeati1112 – 111342
Repeati1114 – 11155; approximate2
Domaini1136 – 1595SAM-dependent MTase C5-typePROSITE-ProRule annotationAdd BLAST460

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 334Interaction with the PRC2/EED-EZH2 complexBy similarityAdd BLAST334
Regioni1 – 148Interaction with DNMT3ABy similarityAdd BLAST148
Regioni1 – 120Interaction with DMAP1By similarityAdd BLAST120
Regioni149 – 216Interaction with DNMT3BBy similarityAdd BLAST68
Regioni163 – 174Interaction with PCNABy similarityAdd BLAST12
Regioni306 – 603Interaction with the PRC2/EED-EZH2 complexBy similarityAdd BLAST298
Regioni329 – 548DNA replication foci-targeting sequenceBy similarityAdd BLAST220
Regioni690 – 751Autoinhibitory linkerAdd BLAST62
Regioni1106 – 11155 X 2 AA tandem repeats of K-G10
Regioni1118 – 1611Interaction with the PRC2/EED-EZH2 complexBy similarityAdd BLAST494
Regioni1136 – 1611CatalyticBy similarityAdd BLAST476

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi177 – 204Nuclear localization signalSequence analysisAdd BLAST28

Domaini

The N-terminal part is required for homodimerization and acts as a regulatory domain.
The CXXC-type zinc finger specifically binds to unmethylated CpG dinucleotides, positioning the autoinhibitory linker between the DNA and the active site, thus providing a mechanism to ensure that only hemimethylated CpG dinucleotides undergo methylation.By similarity

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.PROSITE-ProRule annotation
Contains 2 BAH domains.PROSITE-ProRule annotation
Contains 1 CXXC-type zinc finger.PROSITE-ProRule annotation
Contains 1 DMAP-interaction domain.Curated
Contains 1 SAM-dependent MTase C5-type domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri643 – 689CXXC-typePROSITE-ProRule annotationAdd BLAST47

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IF68. Eukaryota.
COG0270. LUCA.
GeneTreeiENSGT00390000005100.
HOGENOMiHOG000082497.
HOVERGENiHBG051384.
InParanoidiQ24K09.
KOiK00558.
OMAiTQYQPIL.
OrthoDBiEOG091G02YU.
TreeFamiTF328926.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR001025. BAH_dom.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR031303. C5_meth_CS.
IPR022702. Cytosine_MeTrfase1_RFD.
IPR010506. DMAP1-bd.
IPR017198. DNMT1_meta.
IPR029063. SAM-dependent_MTases.
IPR002857. Znf_CXXC.
[Graphical view]
PfamiPF01426. 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]
PIRSFiPIRSF037404. DNMT1. 1 hit.
PRINTSiPR00105. C5METTRFRASE.
SMARTiSM00439. BAH. 2 hits.
SM01137. DMAP_binding. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 2 hits.
PROSITEiPS51038. BAH. 2 hits.
PS00094. C5_MTASE_1. 1 hit.
PS00095. C5_MTASE_2. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
PS51058. ZF_CXXC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q24K09-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPARTAPARV PALASRAFSL PDDVRRRLKD LERDSLTEKE CVKEKLNLLH
60 70 80 90 100
EFLRTEIKNQ LCDLETKLHK EELSEEGYLA KVKSLLNKDL SLENGAHAFS
110 120 130 140 150
REANGCLENG SQTSGEDCRV VMAEKGKPPK PVSRLYTPRR SKSDGETKSE
160 170 180 190 200
VSSSPRITRK TTRQTTITSH FPRGPAKRKP EEEPEKVKSD DSVDEEKDQE
210 220 230 240 250
EKRRRVTSRE RVAGLLPAEE PGRVRPGTHM EEEGRDDKEE KRLRSQTKEP
260 270 280 290 300
TPKHKAKEEP DRDVRPGGAQ AEMNEGEDKD EKRHRSQPKD LASKRRPEEK
310 320 330 340 350
EPERVKPQVS DEKDEDEKEE KRRRTTYREL TEKKMTRTKI AVVSKTNPPK
360 370 380 390 400
CTECLQYLDD PELRYEQHPP DAVEEIQILT NERLSIFDAN ESGFESYEDL
410 420 430 440 450
PQHKLTCFSV YCKRGHLCPI DTGLIEKDVE LLFSGSAKPI YEDDPSPEGG
460 470 480 490 500
INGKNFGPIN EWWIAGFDGG EKALLGFSTS FAEYILMDPS PEYAPLFSVM
510 520 530 540 550
QEKIYISKIV VEFLQSNPDS TYEDLINKIE TTVPPCMLNL NRFTEDSLLR
560 570 580 590 600
HAQFVVEQVE SYDRAGDSDE QPIFLSPCMR DLIKLAGVTL GKRRAERRQT
610 620 630 640 650
IRQPAKEKDK GPTKATTTKL VYQIFDTFFA EQIEKDDKED KENAFKRRRC
660 670 680 690 700
GVCEICQQPE CGKCKACKDM VKFGGSGRSK QACQKRRCPN MAMKEADDDE
710 720 730 740 750
EVDDNIPEMP SPKKMHQGKK KKQNKNRISW VGDAVKTDGK KSYYKKVCID
760 770 780 790 800
SETLEVGDCV SVIPDDSSKP LYLARVTALW EDSSNGQMFH AHWFCAGTDT
810 820 830 840 850
VLGATSDPLE LFLVDECEDM QLSYIHSKVQ VIYKAPSENW AMEGGVDPEA
860 870 880 890 900
LMSEDDGKTY FYQLWYDQDY ARFESPPKTQ PTEDNKYKFC ASCARLAEMR
910 920 930 940 950
QKEIPRVVEQ LQDLEGRVLY SLATKNGVQY RVGDGVYLPP EAFTFNIKLS
960 970 980 990 1000
SPVKRPRKEP VDEALYPEHY RKYSDYIKGS NLDAPEPYRI GRIKEIFCSK
1010 1020 1030 1040 1050
KSNGRPNETD IKIRVNKFYR PENTHKSTPA SYHADINLLY WSDEEAVVDF
1060 1070 1080 1090 1100
KAVQGRCTVE YGEDLPQCLQ DFSAGGPDRF YFLEAYNAKS KSFEDPPNHA
1110 1120 1130 1140 1150
RSTGNKGKGK GKGKNRTKSQ TCEPSELETE IKLPKLRTLD VFSGCGGLSE
1160 1170 1180 1190 1200
GFHQAGISET LWAIEMWDPA AQAFRLNNPG STVFTEDCNV LLKLVMAGEV
1210 1220 1230 1240 1250
TNSRGQKLPQ KGDVEMLCGG PPCQGFSGMN RFNSRTYSKF KNSLVVSFLS
1260 1270 1280 1290 1300
YCDYYRPRYF LLENVRNFVS FKRSMVLKLT LRCLVRMGYQ CTFGVLQAGQ
1310 1320 1330 1340 1350
YGVAQTRRRA IILAAAPGEP LPLFPEPLHV FAPRACQLSV VVDDKKFVSN
1360 1370 1380 1390 1400
ITRLSSGPFR TITVRDTMSD LPEIRNGASA LEISYNGEPQ SWFQRQLRGS
1410 1420 1430 1440 1450
QYQPILRDHI CKDMSALVAA RMRHIPLAPG SDWRDLPNIE VRLSDGTLAR
1460 1470 1480 1490 1500
KLRYNYHDKK NGCSSSGALR GVCSCVEGKP CEPAARQFNT LIPWCLPHTG
1510 1520 1530 1540 1550
NRHNHWAGLY GRLEWDGFFS TTVTNPEPMG KQGRVLHPEQ HRVVSVRECA
1560 1570 1580 1590 1600
RSQGFPDTYR LFGNILDKHR QVGNAVPPPL AKAIGLEIKR CMLAKARESA
1610
SAKIKEEAAK D
Length:1,611
Mass (Da):182,842
Last modified:April 18, 2006 - v1
Checksum:iA7F0D9B24A18771C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti655I → V in AAO44952 (Ref. 2) Curated1
Sequence conflicti716H → R in AAO44952 (Ref. 2) Curated1
Sequence conflicti777T → A in AAO44952 (Ref. 2) Curated1
Sequence conflicti1176L → F in AAP20551 (PubMed:12971987).Curated1
Sequence conflicti1186E → K in AAP20551 (PubMed:12971987).Curated1
Sequence conflicti1192L → V in AAP20551 (PubMed:12971987).Curated1
Sequence conflicti1209P → L in AAP20551 (PubMed:12971987).Curated1
Sequence conflicti1287M → R in AAP20551 (PubMed:12971987).Curated1
Sequence conflicti1387G → R in AAP20551 (PubMed:12971987).Curated1
Sequence conflicti1405I → T in AAO44952 (Ref. 2) Curated1
Sequence conflicti1466S → T in AAO44952 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY244709 mRNA. Translation: AAP20551.1.
AY173048 mRNA. Translation: AAO44952.1.
BC114063 mRNA. Translation: AAI14064.1.
RefSeqiNP_872592.2. NM_182651.2.
UniGeneiBt.108052.
Bt.48560.

Genome annotation databases

EnsembliENSBTAT00000003549; ENSBTAP00000003549; ENSBTAG00000002736.
GeneIDi281119.
KEGGibta:281119.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY244709 mRNA. Translation: AAP20551.1.
AY173048 mRNA. Translation: AAO44952.1.
BC114063 mRNA. Translation: AAI14064.1.
RefSeqiNP_872592.2. NM_182651.2.
UniGeneiBt.108052.
Bt.48560.

3D structure databases

ProteinModelPortaliQ24K09.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi158481. 1 interactor.
STRINGi9913.ENSBTAP00000003549.

Protein family/group databases

REBASEi7406. M.BtaDnmt1AP.

Proteomic databases

PaxDbiQ24K09.
PRIDEiQ24K09.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000003549; ENSBTAP00000003549; ENSBTAG00000002736.
GeneIDi281119.
KEGGibta:281119.

Organism-specific databases

CTDi1786.

Phylogenomic databases

eggNOGiENOG410IF68. Eukaryota.
COG0270. LUCA.
GeneTreeiENSGT00390000005100.
HOGENOMiHOG000082497.
HOVERGENiHBG051384.
InParanoidiQ24K09.
KOiK00558.
OMAiTQYQPIL.
OrthoDBiEOG091G02YU.
TreeFamiTF328926.

Enzyme and pathway databases

BRENDAi2.1.1.37. 908.
ReactomeiR-BTA-212300. PRC2 methylates histones and DNA.

Gene expression databases

BgeeiENSBTAG00000002736.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR001025. BAH_dom.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR031303. C5_meth_CS.
IPR022702. Cytosine_MeTrfase1_RFD.
IPR010506. DMAP1-bd.
IPR017198. DNMT1_meta.
IPR029063. SAM-dependent_MTases.
IPR002857. Znf_CXXC.
[Graphical view]
PfamiPF01426. 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]
PIRSFiPIRSF037404. DNMT1. 1 hit.
PRINTSiPR00105. C5METTRFRASE.
SMARTiSM00439. BAH. 2 hits.
SM01137. DMAP_binding. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 2 hits.
PROSITEiPS51038. BAH. 2 hits.
PS00094. C5_MTASE_1. 1 hit.
PS00095. C5_MTASE_2. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
PS51058. ZF_CXXC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDNMT1_BOVIN
AccessioniPrimary (citable) accession number: Q24K09
Secondary accession number(s): Q6Y856, Q7YS60
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: April 18, 2006
Last modified: November 30, 2016
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.