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Protein

DNA (cytosine-5)-methyltransferase 1

Gene

DNMT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306).4 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi353 – 3531Zinc
Metal bindingi356 – 3561Zinc
Metal bindingi414 – 4141Zinc
Metal bindingi418 – 4181Zinc
Sitei509 – 5091Important for activityBy similarity
Active sitei1226 – 12261

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri646 – 69247CXXC-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA (cytosine-5-)-methyltransferase activity Source: UniProtKB
  • DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Source: Ensembl
  • DNA binding Source: UniProtKB
  • DNA-methyltransferase activity Source: UniProtKB
  • double-stranded DNA binding Source: Ensembl
  • methyl-CpG binding Source: Ensembl
  • promoter-specific chromatin binding Source: UniProtKB
  • RNA binding Source: Ensembl
  • unmethylated CpG binding Source: Ensembl
  • zinc ion binding Source: Ensembl

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. 2681.
ReactomeiR-HSA-212300. PRC2 methylates histones and DNA.
R-HSA-427413. NoRC negatively regulates rRNA expression.
R-HSA-5334118. DNA methylation.
SIGNORiP26358.

Protein family/group databases

REBASEi1161. M.HsaDnmt1A.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 1 (EC:2.1.1.37)
Short name:
Dnmt1
Alternative name(s):
CXXC-type zinc finger protein 9
DNA methyltransferase HsaI
Short name:
DNA MTase HsaI
Short name:
M.HsaI
MCMT
Gene namesi
Name:DNMT1
Synonyms:AIM, CXXC9, DNMT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:2976. DNMT1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Neuropathy, hereditary sensory, 1E (HSN1E)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.
See also OMIM:614116
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti490 – 4912DP → EY in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase.
Corresponds to variant rs199473691 [ dbSNP | Ensembl ].
VAR_065965
Natural varianti495 – 4951Y → C in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. 1 Publication
Corresponds to variant rs199473690 [ dbSNP | Ensembl ].
VAR_065966
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant (ADCADN)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy, cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression.
See also OMIM:604121
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti554 – 5541A → V in ADCADN. 1 Publication
Corresponds to variant rs397509392 [ dbSNP | Ensembl ].
VAR_070055
Natural varianti589 – 5891G → A in ADCADN. 1 Publication
Corresponds to variant rs397509393 [ dbSNP | Ensembl ].
VAR_070056
Natural varianti590 – 5901V → F in ADCADN. 1 Publication
Corresponds to variant rs397509391 [ dbSNP | Ensembl ].
VAR_070057

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi163 – 1631R → A: Abolishes interaction with PCNA. 1 Publication
Mutagenesisi164 – 1641Q → A: Abolishes interaction with PCNA. 1 Publication
Mutagenesisi166 – 1661T → A: Abolishes interaction with PCNA. 1 Publication
Mutagenesisi167 – 1671I → A: Abolishes interaction with PCNA. 1 Publication
Mutagenesisi169 – 1691S → A: No loss of interaction with PCNA. 1 Publication
Mutagenesisi170 – 1701H → V: Abolishes interaction with PCNA. 1 Publication
Mutagenesisi171 – 1711F → V: Abolishes interaction with PCNA. 1 Publication
Mutagenesisi172 – 1721A → S: No loss of interaction with PCNA. 1 Publication
Mutagenesisi173 – 1731K → A: No loss of interaction with PCNA. 1 Publication
Mutagenesisi653 – 6531C → G: Reduces activity about 10-fold; when associated with G-656; G-659; G-664; G-667 and G-670. 1 Publication
Mutagenesisi656 – 6561C → G: Reduces activity about 10-fold; when associated with G-653; G-659; G-664; G-667 and G-670. 1 Publication
Mutagenesisi659 – 6591C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-664; G-667 and G-670. 1 Publication
Mutagenesisi664 – 6641C → F: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-667 and G-670. 1 Publication
Mutagenesisi667 – 6671C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-670. 1 Publication
Mutagenesisi670 – 6701C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-667. 1 Publication
Mutagenesisi1226 – 12261C → A: Loss of activity. 1 Publication

Keywords - Diseasei

Deafness, Disease mutation, Neuropathy

Organism-specific databases

MalaCardsiDNMT1.
MIMi604121. phenotype.
614116. phenotype.
Orphaneti314404. Autosomal dominant cerebellar ataxia, deafness and narcolepsy.
PharmGKBiPA27443.

Chemistry

ChEMBLiCHEMBL1993.
DrugBankiDB00928. Azacitidine.
DB01262. Decitabine.
DB01099. Flucytosine.
DB01035. Procainamide.
GuidetoPHARMACOLOGYi2605.

Polymorphism and mutation databases

BioMutaiDNMT1.
DMDMi12231019.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 16161616DNA (cytosine-5)-methyltransferase 1PRO_0000088034Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei70 – 701N6,N6-dimethyllysine1 Publication
Modified residuei127 – 1271PhosphoserineCombined sources
Modified residuei133 – 1331PhosphoserineCombined sources
Modified residuei137 – 1371PhosphothreonineCombined sources
Modified residuei141 – 1411PhosphoserineBy similarity
Modified residuei142 – 1421N6-methyllysine; by SETD71 Publication
Modified residuei143 – 1431Phosphoserine; by PKB/AKT1Combined sources1 Publication
Modified residuei152 – 1521PhosphoserineCombined sources
Modified residuei154 – 1541PhosphoserineCombined sources1 Publication
Modified residuei160 – 1601N6-acetyllysine1 Publication
Modified residuei166 – 1661PhosphothreonineCombined sources
Modified residuei173 – 1731N6-acetyllysineCombined sources
Modified residuei188 – 1881N6-acetyllysine1 Publication
Modified residuei259 – 2591N6-acetyllysine1 Publication
Modified residuei312 – 3121PhosphoserineCombined sources
Modified residuei366 – 3661N6-acetyllysine1 Publication
Modified residuei394 – 3941PhosphoserineCombined sources
Modified residuei398 – 3981PhosphoserineCombined sources
Modified residuei509 – 5091PhosphoserineBy similarity
Modified residuei549 – 5491PhosphoserineCombined sources
Modified residuei714 – 7141PhosphoserineCombined sources
Modified residuei732 – 7321PhosphoserineCombined sources
Modified residuei749 – 7491N6-acetyllysine1 Publication
Modified residuei878 – 8781PhosphoserineCombined sources
Modified residuei891 – 8911N6-acetyllysine1 Publication
Modified residuei957 – 9571N6-acetyllysine1 Publication
Modified residuei961 – 9611N6-acetyllysine1 Publication
Modified residuei975 – 9751N6-acetyllysine1 Publication
Modified residuei1054 – 10541N6-acetyllysine1 Publication
Modified residuei1111 – 11111N6-acetyllysineCombined sources1 Publication
Modified residuei1113 – 11131N6-acetyllysineCombined sources1 Publication
Modified residuei1115 – 11151N6-acetyllysineCombined sources1 Publication
Modified residuei1117 – 11171N6-acetyllysine; by EHMT21 Publication
Modified residuei1119 – 11191N6-acetyllysineBy similarity
Modified residuei1121 – 11211N6-acetyllysineBy similarity
Modified residuei1349 – 13491N6-acetyllysine1 Publication
Modified residuei1415 – 14151N6-acetyllysine1 Publication
Cross-linki1609 – 1609Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Sumoylated; sumoylation increases activity.1 Publication
Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G2/M transition. Deacetylation of Lys-1349 and Lys-1415 by SIRT1 increases methyltransferase activity.1 Publication
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.2 Publications
Methylation at Lys-142 by SETD7 promotes DNMT1 proteasomal degradation.2 Publications
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

EPDiP26358.
MaxQBiP26358.
PaxDbiP26358.
PeptideAtlasiP26358.
PRIDEiP26358.

PTM databases

iPTMnetiP26358.
PhosphoSiteiP26358.

Expressioni

Tissue specificityi

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 1.1 Publication

Inductioni

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.

Gene expression databases

BgeeiENSG00000130816.
CleanExiHS_DNMT1.
ExpressionAtlasiP26358. baseline and differential.
GenevisibleiP26358. HS.

Organism-specific databases

HPAiCAB005876.
HPA002694.

Interactioni

Subunit structurei

Homodimer (PubMed:19173286). Forms a stable complex with E2F1, BB1 and HDAC1 (PubMed:10888886). Forms a complex with DMAP1 and HDAC2, with direct interaction (PubMed:10888872). Interacts with the PRC2/EED-EZH2 complex (PubMed:16357870). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1 (PubMed:24623306). Interacts with UHRF1; promoting its recruitment to hemimethylated DNA (PubMed:21745816). Interacts with USP7, promoting its deubiquitination (PubMed:21745816). Interacts with PCNA (PubMed:9302295). Interacts with MBD2 and MBD3 (PubMed:10947852). Interacts with DNMT3A and DNMT3B (PubMed:12145218). Interacts with UBC9 (PubMed:19450230). Interacts with CSNK1D (By similarity). Interacts with HDAC1 (By similarity). Interacts with BAZ2A/TIP5 (By similarity).By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EEDO755303EBI-719459,EBI-923794
EZH2Q159108EBI-719459,EBI-530054
NRIP1P485523EBI-719459,EBI-746484
SIRT1Q96EB611EBI-719459,EBI-1802965
UHRF1Q96T8812EBI-719459,EBI-1548946

Protein-protein interaction databases

BioGridi108123. 90 interactions.
DIPiDIP-39693N.
IntActiP26358. 26 interactions.
MINTiMINT-232346.
STRINGi9606.ENSP00000352516.

Chemistry

BindingDBiP26358.

Structurei

Secondary structure

1
1616
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni354 – 3563Combined sources
Beta strandi359 – 3646Combined sources
Helixi377 – 38913Combined sources
Beta strandi405 – 4139Combined sources
Beta strandi422 – 4254Combined sources
Turni426 – 4305Combined sources
Beta strandi434 – 4418Combined sources
Beta strandi453 – 4586Combined sources
Beta strandi462 – 4676Combined sources
Beta strandi476 – 4805Combined sources
Beta strandi485 – 4884Combined sources
Turni493 – 4953Combined sources
Helixi496 – 4994Combined sources
Helixi504 – 51815Combined sources
Helixi524 – 53310Combined sources
Helixi538 – 5403Combined sources
Helixi547 – 5515Combined sources
Helixi554 – 56714Combined sources
Helixi575 – 5773Combined sources
Helixi579 – 5879Combined sources
Helixi592 – 5987Combined sources
Helixi622 – 6298Combined sources
Turni657 – 6593Combined sources
Helixi670 – 6723Combined sources
Turni674 – 6774Combined sources
Helixi687 – 6893Combined sources
Helixi692 – 70312Combined sources
Beta strandi731 – 7355Combined sources
Beta strandi738 – 7403Combined sources
Beta strandi744 – 7463Combined sources
Beta strandi748 – 7525Combined sources
Beta strandi755 – 7584Combined sources
Beta strandi762 – 7654Combined sources
Beta strandi767 – 7693Combined sources
Beta strandi775 – 78511Combined sources
Turni786 – 7883Combined sources
Beta strandi789 – 79911Combined sources
Helixi800 – 8023Combined sources
Beta strandi803 – 8053Combined sources
Helixi806 – 8083Combined sources
Beta strandi813 – 82412Combined sources
Helixi825 – 8273Combined sources
Beta strandi828 – 8325Combined sources
Beta strandi834 – 8363Combined sources
Helixi843 – 8453Combined sources
Turni851 – 8533Combined sources
Helixi856 – 8605Combined sources
Beta strandi862 – 8709Combined sources
Turni871 – 8744Combined sources
Beta strandi875 – 8773Combined sources
Beta strandi886 – 8883Combined sources
Turni889 – 8913Combined sources
Helixi894 – 90512Combined sources
Beta strandi912 – 9165Combined sources
Beta strandi921 – 9288Combined sources
Beta strandi931 – 9344Combined sources
Beta strandi938 – 9414Combined sources
Turni966 – 9683Combined sources
Helixi973 – 9753Combined sources
Helixi976 – 9805Combined sources
Beta strandi992 – 100110Combined sources
Beta strandi1005 – 10084Combined sources
Beta strandi1015 – 10206Combined sources
Helixi1024 – 10263Combined sources
Helixi1031 – 10344Combined sources
Beta strandi1035 – 10373Combined sources
Beta strandi1041 – 10444Combined sources
Beta strandi1048 – 10525Combined sources
Helixi1053 – 10553Combined sources
Beta strandi1058 – 10647Combined sources
Helixi1065 – 10673Combined sources
Helixi1072 – 10776Combined sources
Beta strandi1079 – 109012Combined sources
Turni1091 – 10944Combined sources
Beta strandi1095 – 10973Combined sources
Helixi1101 – 11033Combined sources
Beta strandi1139 – 11457Combined sources
Helixi1150 – 11589Combined sources
Beta strandi1160 – 11678Combined sources
Helixi1171 – 118010Combined sources
Beta strandi1184 – 11874Combined sources
Helixi1191 – 120010Combined sources
Turni1214 – 12163Combined sources
Beta strandi1218 – 12225Combined sources
Beta strandi1231 – 12333Combined sources
Helixi1237 – 12437Combined sources
Helixi1247 – 125812Combined sources
Beta strandi1261 – 12688Combined sources
Helixi1269 – 12724Combined sources
Helixi1275 – 12773Combined sources
Helixi1278 – 128912Combined sources
Beta strandi1293 – 13008Combined sources
Helixi1301 – 13044Combined sources
Beta strandi1311 – 13188Combined sources
Helixi1336 – 13383Combined sources
Beta strandi1343 – 13453Combined sources
Beta strandi1348 – 13503Combined sources
Helixi1367 – 13715Combined sources
Beta strandi1384 – 13863Combined sources
Helixi1395 – 14017Combined sources
Helixi1419 – 14268Combined sources
Helixi1436 – 14383Combined sources
Beta strandi1451 – 14533Combined sources
Turni1462 – 14643Combined sources
Beta strandi1474 – 14763Combined sources
Helixi1477 – 14793Combined sources
Beta strandi1480 – 14823Combined sources
Helixi1487 – 14893Combined sources
Beta strandi1493 – 14964Combined sources
Helixi1499 – 15035Combined sources
Helixi1504 – 15063Combined sources
Helixi1508 – 15103Combined sources
Turni1511 – 15144Combined sources
Beta strandi1523 – 15253Combined sources
Beta strandi1534 – 15363Combined sources
Beta strandi1542 – 15476Combined sources
Helixi1550 – 15567Combined sources
Helixi1569 – 157810Combined sources
Helixi1582 – 159817Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EPZX-ray2.31A/B351-600[»]
3PTAX-ray3.60A646-1600[»]
3SWRX-ray2.49A601-1600[»]
4WXXX-ray2.62A/B351-1600[»]
4YOCX-ray2.92A600-1600[»]
ProteinModelPortaliP26358.
SMRiP26358. Positions 351-599, 601-1600.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26358.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 10386DMAP-interactionAdd
BLAST
Domaini755 – 880126BAH 1PROSITE-ProRule annotationAdd
BLAST
Domaini972 – 1100129BAH 2PROSITE-ProRule annotationAdd
BLAST
Repeati1109 – 111021
Repeati1111 – 111222
Repeati1113 – 111423
Repeati1115 – 111624
Repeati1117 – 111825
Repeati1119 – 112026; approximate
Domaini1139 – 1599461SAM-dependent MTase C5-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 336336Interaction with the PRC2/EED-EZH2 complexBy similarityAdd
BLAST
Regioni1 – 148148Interaction with DNMT3AAdd
BLAST
Regioni1 – 120120Interaction with DMAP1Add
BLAST
Regioni149 – 21769Interaction with DNMT3BAdd
BLAST
Regioni163 – 17412Interaction with PCNAAdd
BLAST
Regioni308 – 606299Interaction with the PRC2/EED-EZH2 complexBy similarityAdd
BLAST
Regioni310 – 502193HomodimerizationAdd
BLAST
Regioni331 – 550220DNA replication foci-targeting sequenceBy similarityAdd
BLAST
Regioni651 – 69747Required for activityAdd
BLAST
Regioni693 – 75462Autoinhibitory linkerAdd
BLAST
Regioni1109 – 1120126 X 2 AA tandem repeats of K-GAdd
BLAST
Regioni1121 – 1616496Interaction with the PRC2/EED-EZH2 complexBy similarityAdd
BLAST
Regioni1139 – 1616478CatalyticAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi177 – 20529Nuclear localization signalSequence analysisAdd
BLAST

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.1 Publication

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri646 – 69247CXXC-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IF68. Eukaryota.
COG0270. LUCA.
GeneTreeiENSGT00390000005100.
HOGENOMiHOG000082497.
HOVERGENiHBG051384.
InParanoidiP26358.
KOiK00558.
OrthoDBiEOG091G02YU.
PhylomeDBiP26358.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P26358-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPARTAPARV PTLAVPAISL PDDVRRRLKD LERDSLTEKE CVKEKLNLLH
60 70 80 90 100
EFLQTEIKNQ LCDLETKLRK EELSEEGYLA KVKSLLNKDL SLENGAHAYN
110 120 130 140 150
REVNGRLENG NQARSEARRV GMADANSPPK PLSKPRTPRR SKSDGEAKPE
160 170 180 190 200
PSPSPRITRK STRQTTITSH FAKGPAKRKP QEESERAKSD ESIKEEDKDQ
210 220 230 240 250
DEKRRRVTSR ERVARPLPAE EPERAKSGTR TEKEEERDEK EEKRLRSQTK
260 270 280 290 300
EPTPKQKLKE EPDREARAGV QADEDEDGDE KDEKKHRSQP KDLAAKRRPE
310 320 330 340 350
EKEPEKVNPQ ISDEKDEDEK EEKRRKTTPK EPTEKKMARA KTVMNSKTHP
360 370 380 390 400
PKCIQCGQYL DDPDLKYGQH PPDAVDEPQM LTNEKLSIFD ANESGFESYE
410 420 430 440 450
ALPQHKLTCF SVYCKHGHLC PIDTGLIEKN IELFFSGSAK PIYDDDPSLE
460 470 480 490 500
GGVNGKNLGP INEWWITGFD GGEKALIGFS TSFAEYILMD PSPEYAPIFG
510 520 530 540 550
LMQEKIYISK IVVEFLQSNS DSTYEDLINK IETTVPPSGL NLNRFTEDSL
560 570 580 590 600
LRHAQFVVEQ VESYDEAGDS DEQPIFLTPC MRDLIKLAGV TLGQRRAQAR
610 620 630 640 650
RQTIRHSTRE KDRGPTKATT TKLVYQIFDT FFAEQIEKDD REDKENAFKR
660 670 680 690 700
RRCGVCEVCQ QPECGKCKAC KDMVKFGGSG RSKQACQERR CPNMAMKEAD
710 720 730 740 750
DDEEVDDNIP EMPSPKKMHQ GKKKKQNKNR ISWVGEAVKT DGKKSYYKKV
760 770 780 790 800
CIDAETLEVG DCVSVIPDDS SKPLYLARVT ALWEDSSNGQ MFHAHWFCAG
810 820 830 840 850
TDTVLGATSD PLELFLVDEC EDMQLSYIHS KVKVIYKAPS ENWAMEGGMD
860 870 880 890 900
PESLLEGDDG KTYFYQLWYD QDYARFESPP KTQPTEDNKF KFCVSCARLA
910 920 930 940 950
EMRQKEIPRV LEQLEDLDSR VLYYSATKNG ILYRVGDGVY LPPEAFTFNI
960 970 980 990 1000
KLSSPVKRPR KEPVDEDLYP EHYRKYSDYI KGSNLDAPEP YRIGRIKEIF
1010 1020 1030 1040 1050
CPKKSNGRPN ETDIKIRVNK FYRPENTHKS TPASYHADIN LLYWSDEEAV
1060 1070 1080 1090 1100
VDFKAVQGRC TVEYGEDLPE CVQVYSMGGP NRFYFLEAYN AKSKSFEDPP
1110 1120 1130 1140 1150
NHARSPGNKG KGKGKGKGKP KSQACEPSEP EIEIKLPKLR TLDVFSGCGG
1160 1170 1180 1190 1200
LSEGFHQAGI SDTLWAIEMW DPAAQAFRLN NPGSTVFTED CNILLKLVMA
1210 1220 1230 1240 1250
GETTNSRGQR LPQKGDVEML CGGPPCQGFS GMNRFNSRTY SKFKNSLVVS
1260 1270 1280 1290 1300
FLSYCDYYRP RFFLLENVRN FVSFKRSMVL KLTLRCLVRM GYQCTFGVLQ
1310 1320 1330 1340 1350
AGQYGVAQTR RRAIILAAAP GEKLPLFPEP LHVFAPRACQ LSVVVDDKKF
1360 1370 1380 1390 1400
VSNITRLSSG PFRTITVRDT MSDLPEVRNG ASALEISYNG EPQSWFQRQL
1410 1420 1430 1440 1450
RGAQYQPILR DHICKDMSAL VAARMRHIPL APGSDWRDLP NIEVRLSDGT
1460 1470 1480 1490 1500
MARKLRYTHH DRKNGRSSSG ALRGVCSCVE AGKACDPAAR QFNTLIPWCL
1510 1520 1530 1540 1550
PHTGNRHNHW AGLYGRLEWD GFFSTTVTNP EPMGKQGRVL HPEQHRVVSV
1560 1570 1580 1590 1600
RECARSQGFP DTYRLFGNIL DKHRQVGNAV PPPLAKAIGL EIKLCMLAKA
1610
RESASAKIKE EEAAKD
Length:1,616
Mass (Da):183,165
Last modified:January 11, 2001 - v2
Checksum:i1E833192D22AFA5B
GO
Isoform 2 (identifier: P26358-2) [UniParc]FASTAAdd to basket
Also known as: Dnmt1b

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

Show »
Length:1,632
Mass (Da):184,819
Checksum:i650AA14F73A75649
GO
Isoform 3 (identifier: P26358-3) [UniParc]FASTAAdd to basket

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

Show »
Length:1,280
Mass (Da):144,465
Checksum:i70ECEE72AE313EE9
GO

Sequence cautioni

The sequence AAD54507 differs from that shown. Reason: Erroneous gene model prediction. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti97 – 971H → R.
Corresponds to variant rs16999593 [ dbSNP | Ensembl ].
VAR_024605
Natural varianti311 – 3111I → V.
Corresponds to variant rs2228612 [ dbSNP | Ensembl ].
VAR_051960
Natural varianti490 – 4912DP → EY in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase.
Corresponds to variant rs199473691 [ dbSNP | Ensembl ].
VAR_065965
Natural varianti495 – 4951Y → C in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. 1 Publication
Corresponds to variant rs199473690 [ dbSNP | Ensembl ].
VAR_065966
Natural varianti554 – 5541A → V in ADCADN. 1 Publication
Corresponds to variant rs397509392 [ dbSNP | Ensembl ].
VAR_070055
Natural varianti589 – 5891G → A in ADCADN. 1 Publication
Corresponds to variant rs397509393 [ dbSNP | Ensembl ].
VAR_070056
Natural varianti590 – 5901V → F in ADCADN. 1 Publication
Corresponds to variant rs397509391 [ dbSNP | Ensembl ].
VAR_070057

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 336336Missing in isoform 3. 1 PublicationVSP_005617Add
BLAST
Alternative sequencei149 – 1491P → RSRDPPASASQVTGIRA in isoform 2. 1 PublicationVSP_005618

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AH008119 Genomic DNA. Translation: AAD51619.1.
CCDSiCCDS12228.1. [P26358-1]
CCDS45958.1. [P26358-2]
PIRiS22610.
RefSeqiNP_001124295.1. NM_001130823.2. [P26358-2]
NP_001305659.1. NM_001318730.1.
NP_001305660.1. NM_001318731.1.
NP_001370.1. NM_001379.3. [P26358-1]
UniGeneiHs.202672.

Genome annotation databases

EnsembliENST00000340748; ENSP00000345739; ENSG00000130816. [P26358-1]
ENST00000359526; ENSP00000352516; ENSG00000130816. [P26358-2]
ENST00000540357; ENSP00000440457; ENSG00000130816. [P26358-3]
GeneIDi1786.
KEGGihsa:1786.
UCSCiuc002mng.4. human. [P26358-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AH008119 Genomic DNA. Translation: AAD51619.1.
CCDSiCCDS12228.1. [P26358-1]
CCDS45958.1. [P26358-2]
PIRiS22610.
RefSeqiNP_001124295.1. NM_001130823.2. [P26358-2]
NP_001305659.1. NM_001318730.1.
NP_001305660.1. NM_001318731.1.
NP_001370.1. NM_001379.3. [P26358-1]
UniGeneiHs.202672.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EPZX-ray2.31A/B351-600[»]
3PTAX-ray3.60A646-1600[»]
3SWRX-ray2.49A601-1600[»]
4WXXX-ray2.62A/B351-1600[»]
4YOCX-ray2.92A600-1600[»]
ProteinModelPortaliP26358.
SMRiP26358. Positions 351-599, 601-1600.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108123. 90 interactions.
DIPiDIP-39693N.
IntActiP26358. 26 interactions.
MINTiMINT-232346.
STRINGi9606.ENSP00000352516.

Chemistry

BindingDBiP26358.
ChEMBLiCHEMBL1993.
DrugBankiDB00928. Azacitidine.
DB01262. Decitabine.
DB01099. Flucytosine.
DB01035. Procainamide.
GuidetoPHARMACOLOGYi2605.

Protein family/group databases

REBASEi1161. M.HsaDnmt1A.

PTM databases

iPTMnetiP26358.
PhosphoSiteiP26358.

Polymorphism and mutation databases

BioMutaiDNMT1.
DMDMi12231019.

Proteomic databases

EPDiP26358.
MaxQBiP26358.
PaxDbiP26358.
PeptideAtlasiP26358.
PRIDEiP26358.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340748; ENSP00000345739; ENSG00000130816. [P26358-1]
ENST00000359526; ENSP00000352516; ENSG00000130816. [P26358-2]
ENST00000540357; ENSP00000440457; ENSG00000130816. [P26358-3]
GeneIDi1786.
KEGGihsa:1786.
UCSCiuc002mng.4. human. [P26358-1]

Organism-specific databases

CTDi1786.
GeneCardsiDNMT1.
GeneReviewsiDNMT1.
HGNCiHGNC:2976. DNMT1.
HPAiCAB005876.
HPA002694.
MalaCardsiDNMT1.
MIMi126375. gene.
604121. phenotype.
614116. phenotype.
neXtProtiNX_P26358.
Orphaneti314404. Autosomal dominant cerebellar ataxia, deafness and narcolepsy.
PharmGKBiPA27443.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF68. Eukaryota.
COG0270. LUCA.
GeneTreeiENSGT00390000005100.
HOGENOMiHOG000082497.
HOVERGENiHBG051384.
InParanoidiP26358.
KOiK00558.
OrthoDBiEOG091G02YU.
PhylomeDBiP26358.
TreeFamiTF328926.

Enzyme and pathway databases

BRENDAi2.1.1.37. 2681.
ReactomeiR-HSA-212300. PRC2 methylates histones and DNA.
R-HSA-427413. NoRC negatively regulates rRNA expression.
R-HSA-5334118. DNA methylation.
SIGNORiP26358.

Miscellaneous databases

ChiTaRSiDNMT1. human.
EvolutionaryTraceiP26358.
GeneWikiiDNMT1.
GenomeRNAii1786.
PROiP26358.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130816.
CleanExiHS_DNMT1.
ExpressionAtlasiP26358. baseline and differential.
GenevisibleiP26358. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P26358
Secondary accession number(s): A0AV63
, B7ZLW6, Q9UHG5, Q9ULA2, Q9UMZ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: January 11, 2001
Last modified: September 7, 2016
This is version 189 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.