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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)DescriptionActionsGraphical viewLength
Metal bindingi353Zinc1
Metal bindingi356Zinc1
Metal bindingi414Zinc1
Metal bindingi418Zinc1
Sitei509Important for activityBy similarity1
Active sitei12261

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri646 – 692CXXC-typePROSITE-ProRule annotationAdd BLAST47

GO - Molecular functioni

  • DNA (cytosine-5-)-methyltransferase activity Source: UniProtKB
  • DNA binding Source: UniProtKB
  • DNA-methyltransferase activity Source: UniProtKB
  • methyl-CpG binding Source: Ensembl
  • promoter-specific chromatin binding Source: UniProtKB
  • RNA binding Source: Ensembl
  • zinc ion binding Source: Ensembl

GO - Biological processi

  • cellular response to amino acid stimulus Source: Ensembl
  • chromatin modification Source: UniProtKB-KW
  • DNA methylation Source: ProtInc
  • DNA methylation involved in embryo development Source: Ensembl
  • gene silencing Source: Ensembl
  • maintenance of DNA methylation Source: UniProtKB
  • negative regulation of gene expression, epigenetic Source: Reactome
  • negative regulation of histone H3-K9 methylation Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: ProtInc
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of histone H3-K4 methylation Source: UniProtKB
  • positive regulation of methylation-dependent chromatin silencing Source: UniProtKB
  • Ras protein signal transduction Source: UniProtKB
  • regulation of cell proliferation Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
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

BioCyciZFISH:HS05448-MONOMER.
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

  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • pericentric heterochromatin Source: Ensembl
  • replication fork Source: Ensembl
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_065965490 – 491DP → EY in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. Corresponds to variant rs199473691dbSNPEnsembl.2
Natural variantiVAR_065966495Y → C in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. 1 PublicationCorresponds to variant rs199473690dbSNPEnsembl.1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_070055554A → V in ADCADN. 1 PublicationCorresponds to variant rs397509392dbSNPEnsembl.1
Natural variantiVAR_070056589G → A in ADCADN. 1 PublicationCorresponds to variant rs397509393dbSNPEnsembl.1
Natural variantiVAR_070057590V → F in ADCADN. 1 PublicationCorresponds to variant rs397509391dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi163R → A: Abolishes interaction with PCNA. 1 Publication1
Mutagenesisi164Q → A: Abolishes interaction with PCNA. 1 Publication1
Mutagenesisi166T → A: Abolishes interaction with PCNA. 1 Publication1
Mutagenesisi167I → A: Abolishes interaction with PCNA. 1 Publication1
Mutagenesisi169S → A: No loss of interaction with PCNA. 1 Publication1
Mutagenesisi170H → V: Abolishes interaction with PCNA. 1 Publication1
Mutagenesisi171F → V: Abolishes interaction with PCNA. 1 Publication1
Mutagenesisi172A → S: No loss of interaction with PCNA. 1 Publication1
Mutagenesisi173K → A: No loss of interaction with PCNA. 1 Publication1
Mutagenesisi653C → G: Reduces activity about 10-fold; when associated with G-656; G-659; G-664; G-667 and G-670. 1 Publication1
Mutagenesisi656C → G: Reduces activity about 10-fold; when associated with G-653; G-659; G-664; G-667 and G-670. 1 Publication1
Mutagenesisi659C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-664; G-667 and G-670. 1 Publication1
Mutagenesisi664C → F: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-667 and G-670. 1 Publication1
Mutagenesisi667C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-670. 1 Publication1
Mutagenesisi670C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-667. 1 Publication1
Mutagenesisi1226C → A: Loss of activity. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Neuropathy

Organism-specific databases

DisGeNETi1786.
MalaCardsiDNMT1.
MIMi604121. phenotype.
614116. phenotype.
OpenTargetsiENSG00000130816.
Orphaneti314404. Autosomal dominant cerebellar ataxia, deafness and narcolepsy.
PharmGKBiPA27443.

Chemistry databases

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

Polymorphism and mutation databases

BioMutaiDNMT1.
DMDMi12231019.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880341 – 1616DNA (cytosine-5)-methyltransferase 1Add BLAST1616

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei70N6,N6-dimethyllysine1 Publication1
Modified residuei127PhosphoserineCombined sources1
Modified residuei133PhosphoserineCombined sources1
Modified residuei137PhosphothreonineCombined sources1
Modified residuei141PhosphoserineBy similarity1
Modified residuei142N6-methyllysine; by SETD71 Publication1
Modified residuei143Phosphoserine; by PKB/AKT1Combined sources1 Publication1
Modified residuei152PhosphoserineCombined sources1
Modified residuei154PhosphoserineCombined sources1 Publication1
Modified residuei160N6-acetyllysine1 Publication1
Modified residuei166PhosphothreonineCombined sources1
Modified residuei173N6-acetyllysineCombined sources1
Modified residuei188N6-acetyllysine1 Publication1
Modified residuei259N6-acetyllysine1 Publication1
Modified residuei312PhosphoserineCombined sources1
Modified residuei366N6-acetyllysine1 Publication1
Modified residuei394PhosphoserineCombined sources1
Modified residuei398PhosphoserineCombined sources1
Modified residuei509PhosphoserineBy similarity1
Modified residuei549PhosphoserineCombined sources1
Modified residuei714PhosphoserineCombined sources1
Modified residuei732PhosphoserineCombined sources1
Modified residuei749N6-acetyllysine1 Publication1
Modified residuei878PhosphoserineCombined sources1
Modified residuei891N6-acetyllysine1 Publication1
Modified residuei957N6-acetyllysine1 Publication1
Modified residuei961N6-acetyllysine1 Publication1
Modified residuei975N6-acetyllysine1 Publication1
Modified residuei1054N6-acetyllysine1 Publication1
Modified residuei1111N6-acetyllysineCombined sources1 Publication1
Modified residuei1113N6-acetyllysineCombined sources1 Publication1
Modified residuei1115N6-acetyllysineCombined sources1 Publication1
Modified residuei1117N6-acetyllysine; by EHMT21 Publication1
Modified residuei1119N6-acetyllysineBy similarity1
Modified residuei1121N6-acetyllysineBy similarity1
Modified residuei1349N6-acetyllysine1 Publication1
Modified residuei1415N6-acetyllysine1 Publication1
Cross-linki1609Glycyl 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.
PhosphoSitePlusiP26358.

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 interactors.
DIPiDIP-39693N.
IntActiP26358. 26 interactors.
MINTiMINT-232346.
STRINGi9606.ENSP00000352516.

Chemistry databases

BindingDBiP26358.

Structurei

Secondary structure

11616
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni354 – 356Combined sources3
Beta strandi359 – 364Combined sources6
Helixi377 – 389Combined sources13
Beta strandi405 – 413Combined sources9
Beta strandi422 – 425Combined sources4
Turni426 – 430Combined sources5
Beta strandi434 – 441Combined sources8
Beta strandi453 – 458Combined sources6
Beta strandi462 – 467Combined sources6
Beta strandi476 – 480Combined sources5
Beta strandi485 – 488Combined sources4
Turni493 – 495Combined sources3
Helixi496 – 499Combined sources4
Helixi504 – 518Combined sources15
Helixi524 – 533Combined sources10
Helixi538 – 540Combined sources3
Helixi547 – 551Combined sources5
Helixi554 – 567Combined sources14
Helixi575 – 577Combined sources3
Helixi579 – 587Combined sources9
Helixi592 – 598Combined sources7
Helixi622 – 629Combined sources8
Turni657 – 659Combined sources3
Helixi670 – 672Combined sources3
Turni674 – 677Combined sources4
Helixi687 – 689Combined sources3
Helixi692 – 703Combined sources12
Beta strandi731 – 735Combined sources5
Beta strandi738 – 740Combined sources3
Beta strandi744 – 746Combined sources3
Beta strandi748 – 752Combined sources5
Beta strandi755 – 758Combined sources4
Beta strandi762 – 765Combined sources4
Beta strandi767 – 769Combined sources3
Beta strandi775 – 785Combined sources11
Turni786 – 788Combined sources3
Beta strandi789 – 799Combined sources11
Helixi800 – 802Combined sources3
Beta strandi803 – 805Combined sources3
Helixi806 – 808Combined sources3
Beta strandi813 – 824Combined sources12
Helixi825 – 827Combined sources3
Beta strandi828 – 832Combined sources5
Beta strandi834 – 836Combined sources3
Helixi843 – 845Combined sources3
Turni851 – 853Combined sources3
Helixi856 – 860Combined sources5
Beta strandi862 – 870Combined sources9
Turni871 – 874Combined sources4
Beta strandi875 – 877Combined sources3
Beta strandi886 – 888Combined sources3
Turni889 – 891Combined sources3
Helixi894 – 905Combined sources12
Beta strandi912 – 916Combined sources5
Beta strandi921 – 928Combined sources8
Beta strandi931 – 934Combined sources4
Beta strandi938 – 941Combined sources4
Turni966 – 968Combined sources3
Helixi973 – 975Combined sources3
Helixi976 – 980Combined sources5
Beta strandi992 – 1001Combined sources10
Beta strandi1005 – 1008Combined sources4
Beta strandi1015 – 1020Combined sources6
Helixi1024 – 1026Combined sources3
Helixi1031 – 1034Combined sources4
Beta strandi1035 – 1037Combined sources3
Beta strandi1041 – 1044Combined sources4
Beta strandi1048 – 1052Combined sources5
Helixi1053 – 1055Combined sources3
Beta strandi1058 – 1064Combined sources7
Helixi1065 – 1067Combined sources3
Helixi1072 – 1077Combined sources6
Beta strandi1079 – 1090Combined sources12
Turni1091 – 1094Combined sources4
Beta strandi1095 – 1097Combined sources3
Helixi1101 – 1103Combined sources3
Beta strandi1139 – 1145Combined sources7
Helixi1150 – 1158Combined sources9
Beta strandi1160 – 1167Combined sources8
Helixi1171 – 1180Combined sources10
Beta strandi1184 – 1187Combined sources4
Helixi1191 – 1200Combined sources10
Turni1214 – 1216Combined sources3
Beta strandi1218 – 1222Combined sources5
Beta strandi1231 – 1233Combined sources3
Helixi1237 – 1243Combined sources7
Helixi1247 – 1258Combined sources12
Beta strandi1261 – 1268Combined sources8
Helixi1269 – 1272Combined sources4
Helixi1275 – 1277Combined sources3
Helixi1278 – 1289Combined sources12
Beta strandi1293 – 1300Combined sources8
Helixi1301 – 1304Combined sources4
Beta strandi1311 – 1318Combined sources8
Helixi1336 – 1338Combined sources3
Beta strandi1343 – 1345Combined sources3
Beta strandi1348 – 1350Combined sources3
Helixi1367 – 1371Combined sources5
Beta strandi1384 – 1386Combined sources3
Helixi1395 – 1401Combined sources7
Helixi1419 – 1426Combined sources8
Helixi1436 – 1438Combined sources3
Beta strandi1451 – 1453Combined sources3
Turni1462 – 1464Combined sources3
Beta strandi1474 – 1476Combined sources3
Helixi1477 – 1479Combined sources3
Beta strandi1480 – 1482Combined sources3
Helixi1487 – 1489Combined sources3
Beta strandi1493 – 1496Combined sources4
Helixi1499 – 1503Combined sources5
Helixi1504 – 1506Combined sources3
Helixi1508 – 1510Combined sources3
Turni1511 – 1514Combined sources4
Beta strandi1523 – 1525Combined sources3
Beta strandi1534 – 1536Combined sources3
Beta strandi1542 – 1547Combined sources6
Helixi1550 – 1556Combined sources7
Helixi1569 – 1578Combined sources10
Helixi1582 – 1598Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4Z96X-ray2.85C1098-1129[»]
ProteinModelPortaliP26358.
SMRiP26358.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26358.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 103DMAP-interactionAdd BLAST86
Domaini755 – 880BAH 1PROSITE-ProRule annotationAdd BLAST126
Domaini972 – 1100BAH 2PROSITE-ProRule annotationAdd BLAST129
Repeati1109 – 111012
Repeati1111 – 111222
Repeati1113 – 111432
Repeati1115 – 111642
Repeati1117 – 111852
Repeati1119 – 11206; approximate2
Domaini1139 – 1599SAM-dependent MTase C5-typePROSITE-ProRule annotationAdd BLAST461

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 336Interaction with the PRC2/EED-EZH2 complexBy similarityAdd BLAST336
Regioni1 – 148Interaction with DNMT3A1 PublicationAdd BLAST148
Regioni1 – 120Interaction with DMAP11 PublicationAdd BLAST120
Regioni149 – 217Interaction with DNMT3B1 PublicationAdd BLAST69
Regioni163 – 174Interaction with PCNA1 PublicationAdd BLAST12
Regioni308 – 606Interaction with the PRC2/EED-EZH2 complexBy similarityAdd BLAST299
Regioni310 – 502HomodimerizationAdd BLAST193
Regioni331 – 550DNA replication foci-targeting sequenceBy similarityAdd BLAST220
Regioni651 – 697Required for activityAdd BLAST47
Regioni693 – 754Autoinhibitory linkerAdd BLAST62
Regioni1109 – 11206 X 2 AA tandem repeats of K-GAdd BLAST12
Regioni1121 – 1616Interaction with the PRC2/EED-EZH2 complexBy similarityAdd BLAST496
Regioni1139 – 1616CatalyticAdd BLAST478

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi177 – 205Nuclear localization signalSequence analysisAdd BLAST29

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)DescriptionActionsGraphical viewLength
Zinc fingeri646 – 692CXXC-typePROSITE-ProRule annotationAdd BLAST47

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_02460597H → R.Corresponds to variant rs16999593dbSNPEnsembl.1
Natural variantiVAR_051960311I → V.Corresponds to variant rs2228612dbSNPEnsembl.1
Natural variantiVAR_065965490 – 491DP → EY in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. Corresponds to variant rs199473691dbSNPEnsembl.2
Natural variantiVAR_065966495Y → C in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. 1 PublicationCorresponds to variant rs199473690dbSNPEnsembl.1
Natural variantiVAR_070055554A → V in ADCADN. 1 PublicationCorresponds to variant rs397509392dbSNPEnsembl.1
Natural variantiVAR_070056589G → A in ADCADN. 1 PublicationCorresponds to variant rs397509393dbSNPEnsembl.1
Natural variantiVAR_070057590V → F in ADCADN. 1 PublicationCorresponds to variant rs397509391dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0056171 – 336Missing in isoform 3. 1 PublicationAdd BLAST336
Alternative sequenceiVSP_005618149P → RSRDPPASASQVTGIRA in isoform 2. 1 Publication1

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
PDB 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[»]
4Z96X-ray2.85C1098-1129[»]
ProteinModelPortaliP26358.
SMRiP26358.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

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

Protein family/group databases

REBASEi1161. M.HsaDnmt1A.

PTM databases

iPTMnetiP26358.
PhosphoSitePlusiP26358.

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.
DisGeNETi1786.
GeneCardsiDNMT1.
GeneReviewsiDNMT1.
HGNCiHGNC:2976. DNMT1.
HPAiCAB005876.
HPA002694.
MalaCardsiDNMT1.
MIMi126375. gene.
604121. phenotype.
614116. phenotype.
neXtProtiNX_P26358.
OpenTargetsiENSG00000130816.
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

BioCyciZFISH:HS05448-MONOMER.
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: November 30, 2016
This is version 192 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.