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P26358 (DNMT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA (cytosine-5)-methyltransferase 1

Short name=Dnmt1
EC=2.1.1.37
Alternative name(s):
CXXC-type zinc finger protein 9
DNA methyltransferase HsaI
Short name=DNA MTase HsaI
Short name=M.HsaI
MCMT
Gene names
Name:DNMT1
Synonyms:AIM, CXXC9, DNMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1616 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Ref.15 Ref.18 Ref.19

Catalytic activity

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

Subunit structure

Binds to CSNK1D By similarity. Homodimer. Interacts with HDAC1 and with PCNA. Forms a complex with DMAP1 and HDAC2, with direct interaction. Forms also a stable complex with E2F1, BB1 and HDAC1. Binds MBD2 and MBD3. Component of complexes containing SUV39H1. Interacts with DNMT3A and DNMT3B. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9 and BAZ2A/TIP5. Interacts with UHRF1; promoting its recruitment to hemimethylated DNA. Interacts with USP7, promoting its deubiquitination. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.24 Ref.25 Ref.33

Subcellular location

Nucleus Ref.13.

Tissue specificity

Ubiquitous; highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells, and expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, and skeletal muscle. Isoform 2 is less expressed than isoform 1. Ref.12

Induction

Its abundance is reduced to non detectable levels at the G0 phase of the cell cycle and is dramatically induced upon entrance into the S-phase of the cell cycle.

Domain

The N-terminal part is required for homodimerization and acts as a regulatory domain.

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 (Ref.36).

Post-translational modification

Sumoylated; sumoylation increases activity. Ref.24

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. Ref.31

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.

Methylation at Lys-142 by SETD7 promotes DNMT1 proteasomal degradation. Ref.17 Ref.21 Ref.32

Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome By similarity.

Involvement in disease

Neuropathy, hereditary sensory, 1E (HSN1E) [MIM:614116]: A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37

Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant (ADCADN) [MIM:604121]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.38

Sequence similarities

Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.

Contains 2 BAH domains.

Contains 1 CXXC-type zinc finger.

Contains 1 DMAP-interaction domain.

Contains 1 SAM-dependent MTase C5-type domain.

Sequence caution

The sequence AAD54507.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDeafness
Disease mutation
Neuropathy
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
S-adenosyl-L-methionine
Zinc
   Molecular functionActivator
Chromatin regulator
Methyltransferase
Repressor
Transferase
   PTMAcetylation
Methylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA methylation

Traceable author statement Ref.10. Source: ProtInc

cellular response to amino acid stimulus

Inferred from electronic annotation. Source: Ensembl

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

gene silencing

Inferred from electronic annotation. Source: Ensembl

maintenance of DNA methylation

Inferred from direct assay Ref.18Ref.33. Source: UniProtKB

negative regulation of histone H3-K9 methylation

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.10. Source: ProtInc

positive regulation of gene expression

Inferred from mutant phenotype Ref.19. Source: UniProtKB

positive regulation of histone H3-K4 methylation

Inferred from mutant phenotype Ref.19. Source: UniProtKB

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcentromeric heterochromatin

Inferred from electronic annotation. Source: Ensembl

nucleus

Traceable author statement Ref.2. Source: ProtInc

replication fork

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA (cytosine-5-)-methyltransferase activity

Inferred from direct assay Ref.33. Source: UniProtKB

DNA binding

Inferred from direct assay Ref.18. Source: UniProtKB

DNA-methyltransferase activity

Inferred from direct assay Ref.18. Source: UniProtKB

RNA binding

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from electronic annotation. Source: InterPro

methyl-CpG binding

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 16161616DNA (cytosine-5)-methyltransferase 1
PRO_0000088034

Regions

Domain18 – 10386DMAP-interaction
Domain755 – 880126BAH 1
Domain972 – 1100129BAH 2
Repeat1109 – 111021
Repeat1111 – 111222
Repeat1113 – 111423
Repeat1115 – 111624
Repeat1117 – 111825
Repeat1119 – 112026; approximate
Domain1139 – 1599461SAM-dependent MTase C5-type
Zinc finger646 – 69247CXXC-type
Region1 – 336336Interaction with the PRC2/EED-EZH2 complex By similarity
Region1 – 148148Interaction with DNMT3A
Region1 – 120120Interaction with DMAP1
Region149 – 21769Interaction with DNMT3B
Region163 – 17412Interaction with PCNA
Region308 – 606299Interaction with the PRC2/EED-EZH2 complex By similarity
Region310 – 502193Homodimerization
Region331 – 550220DNA replication foci-targeting sequence By similarity
Region651 – 69747Required for activity
Region693 – 75462Autoinhibitory linker
Region1109 – 1120126 X 2 AA tandem repeats of K-G
Region1121 – 1616496Interaction with the PRC2/EED-EZH2 complex By similarity
Region1139 – 1616478Catalytic
Motif177 – 20529Nuclear localization signal Potential

Sites

Active site12261
Metal binding3531Zinc
Metal binding3561Zinc
Metal binding4141Zinc
Metal binding4181Zinc
Site5091Important for activity By similarity

Amino acid modifications

Modified residue701N6,N6-dimethyllysine Ref.21
Modified residue1271Phosphoserine Ref.14 Ref.22 Ref.26 Ref.34
Modified residue1331Phosphoserine Ref.34
Modified residue1421N6-methyllysine; by SETD7 Ref.32
Modified residue1431Phosphoserine; by PKB/AKT1 Ref.22 Ref.32
Modified residue1521Phosphoserine Ref.22
Modified residue1541Phosphoserine Ref.22 Ref.30
Modified residue1601N6-acetyllysine Ref.31
Modified residue1731N6-acetyllysine Ref.27
Modified residue1881N6-acetyllysine Ref.31
Modified residue2591N6-acetyllysine Ref.31
Modified residue3661N6-acetyllysine Ref.31
Modified residue3941Phosphoserine Ref.22 Ref.28
Modified residue5091Phosphoserine By similarity
Modified residue7141Phosphoserine Ref.14 Ref.28 Ref.34
Modified residue7321Phosphoserine Ref.20
Modified residue7491N6-acetyllysine Ref.31
Modified residue8911N6-acetyllysine Ref.31
Modified residue9571N6-acetyllysine Ref.31
Modified residue9611N6-acetyllysine Ref.31
Modified residue9751N6-acetyllysine Ref.31
Modified residue10541N6-acetyllysine Ref.31
Modified residue11111N6-acetyllysine Ref.27 Ref.31
Modified residue11131N6-acetyllysine Ref.27 Ref.31
Modified residue11151N6-acetyllysine Ref.27 Ref.31
Modified residue11171N6-acetyllysine; by EHMT2 Ref.31
Modified residue11191N6-acetyllysine By similarity
Modified residue11211N6-acetyllysine By similarity
Modified residue13491N6-acetyllysine Ref.31
Modified residue14151N6-acetyllysine Ref.31

Natural variations

Alternative sequence1 – 336336Missing in isoform 3.
VSP_005617
Alternative sequence1491P → RSRDPPASASQVTGIRA in isoform 2.
VSP_005618
Natural variant971H → R.
Corresponds to variant rs16999593 [ dbSNP | Ensembl ].
VAR_024605
Natural variant3111I → V.
Corresponds to variant rs2228612 [ dbSNP | Ensembl ].
VAR_051960
Natural variant490 – 4912DP → EY in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase.
VAR_065965
Natural variant4951Y → C in HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase. Ref.37
VAR_065966
Natural variant5541A → V in ADCADN. Ref.38
VAR_070055
Natural variant5891G → A in ADCADN. Ref.38
VAR_070056
Natural variant5901V → F in ADCADN. Ref.38
VAR_070057

Experimental info

Mutagenesis1631R → A: Abolishes interaction with PCNA.
Mutagenesis1641Q → A: Abolishes interaction with PCNA.
Mutagenesis1661T → A: Abolishes interaction with PCNA.
Mutagenesis1671I → A: Abolishes interaction with PCNA.
Mutagenesis1691S → A: No loss of interaction with PCNA.
Mutagenesis1701H → V: Abolishes interaction with PCNA.
Mutagenesis1711F → V: Abolishes interaction with PCNA.
Mutagenesis1721A → S: No loss of interaction with PCNA.
Mutagenesis1731K → A: No loss of interaction with PCNA.
Mutagenesis6531C → G: Reduces activity about 10-fold; when associated with G-656; G-659; G-664; G-667 and G-670. Ref.18
Mutagenesis6561C → G: Reduces activity about 10-fold; when associated with G-653; G-659; G-664; G-667 and G-670. Ref.18
Mutagenesis6591C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-664; G-667 and G-670. Ref.18
Mutagenesis6641C → F: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-667 and G-670. Ref.18
Mutagenesis6671C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-670. Ref.18
Mutagenesis6701C → G: Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-667. Ref.18
Mutagenesis12261C → A: Loss of activity. Ref.24

Secondary structure

...................................................................................................................................................................................................... 1616
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 11, 2001. Version 2.
Checksum: 1E833192D22AFA5B

FASTA1,616183,165
        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 

« Hide

Isoform 2 (Dnmt1b) [UniParc].

Checksum: 650AA14F73A75649
Show »

FASTA1,632184,819
Isoform 3 [UniParc].

Checksum: 70ECEE72AE313EE9
Show »

FASTA1,280144,465

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNMT3A AND DNMT3B, SUBCELLULAR LOCATION.
[14]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127 AND SER-714, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EED AND EZH2.
[16]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)
[17]"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] [Europe PMC] [Abstract]
Cited for: DE NOVO DNA METHYLATION OF TARGET GENES.
[18]"CXXC domain of human DNMT1 is essential for enzymatic activity."
Pradhan M., Esteve P.-O., Chin H.G., Samaranayke M., Kim G.-D., Pradhan S.
Biochemistry 47:10000-10009(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-653; CYS-656; CYS-659; CYS-664; CYS-667 AND CYS-670.
[19]"DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation."
Sun L., Huang L., Nguyen P., Bisht K.S., Bar-Sela G., Ho A.S., Bradbury C.M., Yu W., Cui H., Lee S., Trepel J.B., Feinberg A.P., Gius D.
Cancer Res. 68:2726-2735(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-732, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"Protein lysine methyltransferase G9a acts on non-histone targets."
Rathert P., Dhayalan A., Murakami M., Zhang X., Tamas R., Jurkowska R., Komatsu Y., Shinkai Y., Cheng X., Jeltsch A.
Nat. Chem. Biol. 4:344-346(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: METHYLATION AT LYS-70, IDENTIFICATION BY MASS SPECTROMETRY.
[22]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; SER-143; SER-152; SER-154 AND SER-394, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"SUMOylation enhances DNA methyltransferase 1 activity."
Lee B., Muller M.T.
Biochem. J. 421:449-461(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION, INTERACTION WITH UBC9, MUTAGENESIS OF CYS-1226.
[25]"Dimerization of DNA methyltransferase 1 is mediated by its regulatory domain."
Fellinger K., Rothbauer U., Felle M., Laengst G., Leonhardt H.
J. Cell. Biochem. 106:521-528(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: HOMODIMERIZATION.
[26]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[27]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173; LYS-1111; LYS-1113 AND LYS-1115, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394 AND SER-714, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[29]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"Phosphorylation of human DNMT1: implication of cyclin-dependent kinases."
Lavoie G., St-Pierre Y.
Biochem. Biophys. Res. Commun. 409:187-192(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-154.
[31]"SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities."
Peng L., Yuan Z., Ling H., Fukasawa K., Robertson K., Olashaw N., Koomen J., Chen J., Lane W.S., Seto E.
Mol. Cell. Biol. 31:4720-4734(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-160; LYS-188; LYS-259; LYS-366; LYS-749; LYS-891; LYS-957; LYS-961; LYS-975; LYS-1054; LYS-1111; LYS-1113; LYS-1115; LYS-1117; LYS-1349 AND LYS-1415, DEACETYLATION BY SIRT1.
[32]"A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability."
Esteve P.O., Chang Y., Samaranayake M., Upadhyay A.K., Horton J.R., Feehery G.R., Cheng X., Pradhan S.
Nat. Struct. Mol. Biol. 18:42-48(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: METHYLATION AT LYS-142, PHOSPHORYLATION AT SER-143.
[33]"The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1."
Felle M., Joppien S., Nemeth A., Diermeier S., Thalhammer V., Dobner T., Kremmer E., Kappler R., Langst G.
Nucleic Acids Res. 39:8355-8365(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP7 AND UHRF1.
[34]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; SER-133 AND SER-714, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1."
Syeda F., Fagan R.L., Wean M., Avvakumov G.V., Walker J.R., Xue S., Dhe-Paganon S., Brenner C.
J. Biol. Chem. 286:15344-15351(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 351-600 IN COMPLEX WITH ZINC IONS.
[36]"Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation."
Song J., Rechkoblit O., Bestor T.H., Patel D.J.
Science 331:1036-1040(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 646-1600 IN COMPLEX WITH SAH AND DNA, AUTOINHIBITORY LINKER.
[37]"Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss."
Klein C.J., Botuyan M.V., Wu Y., Ward C.J., Nicholson G.A., Hammans S., Hojo K., Yamanishi H., Karpf A.R., Wallace D.C., Simon M., Lander C., Boardman L.A., Cunningham J.M., Smith G.E., Litchy W.J., Boes B., Atkinson E.J. expand/collapse author list , Middha S., Dyck P.J.B., Parisi J.E., Mer G., Smith D.I., Dyck P.J.
Nat. Genet. 43:595-600(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSN1E 490-GLU-TYR-491 AND CYS-495, CHARACTERIZATION OF VARIANTS HSN1E 490-GLU-TYR-491 AND CYS-495.
[38]"Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy."
Winkelmann J., Lin L., Schormair B., Kornum B.R., Faraco J., Plazzi G., Melberg A., Cornelio F., Urban A.E., Pizza F., Poli F., Grubert F., Wieland T., Graf E., Hallmayer J., Strom T.M., Mignot E.
Hum. Mol. Genet. 21:2205-2210(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ADCADN VAL-554; ALA-589 AND PHE-590.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X63692 mRNA. Translation: CAA45219.1.
AF180682 mRNA. Translation: AAF23609.1.
AC010077 Genomic DNA. Translation: AAD54507.1. Sequence problems.
AC011511 Genomic DNA. No translation available.
AC020931 Genomic DNA. No translation available.
BC126227 mRNA. Translation: AAI26228.1.
BC144093 mRNA. Translation: AAI44094.1.
AH008119 Genomic DNA. Translation: AAD51619.1.
PIRS22610.
RefSeqNP_001124295.1. NM_001130823.1.
NP_001370.1. NM_001379.2.
UniGeneHs.202672.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EPZX-ray2.31A/B351-600[»]
3PTAX-ray3.60A646-1600[»]
3SWRX-ray2.49A601-1600[»]
ProteinModelPortalP26358.
SMRP26358. Positions 351-599, 601-1600.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108123. 75 interactions.
DIPDIP-39693N.
IntActP26358. 21 interactions.
MINTMINT-232346.
STRING9606.ENSP00000352516.

Chemistry

BindingDBP26358.
ChEMBLCHEMBL1993.
DrugBankDB00928. Azacitidine.
DB01262. Decitabine.
DB01099. Flucytosine.
DB01181. Ifosfamide.
DB01035. Procainamide.

Protein family/group databases

REBASE1161. M.HsaDnmt1A.

PTM databases

PhosphoSiteP26358.

Polymorphism databases

DMDM12231019.

Proteomic databases

PaxDbP26358.
PRIDEP26358.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340748; ENSP00000345739; ENSG00000130816. [P26358-1]
ENST00000359526; ENSP00000352516; ENSG00000130816. [P26358-2]
GeneID1786.
KEGGhsa:1786.
UCSCuc002mng.3. human. [P26358-1]
uc010xlc.2. human. [P26358-2]

Organism-specific databases

CTD1786.
GeneCardsGC19M010244.
HGNCHGNC:2976. DNMT1.
HPACAB005876.
HPA002694.
MIM126375. gene.
604121. phenotype.
614116. phenotype.
neXtProtNX_P26358.
Orphanet314404. Cerebellar ataxia-deafness-narcolepsy syndrome.
PharmGKBPA27443.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0270.
HOGENOMHOG000082497.
HOVERGENHBG051384.
KOK00558.
OMACPNLAVK.
OrthoDBEOG77WWBH.
PhylomeDBP26358.
TreeFamTF328926.

Enzyme and pathway databases

BRENDA2.1.1.37. 2681.

Gene expression databases

ArrayExpressP26358.
BgeeP26358.
CleanExHS_DNMT1.
GenevestigatorP26358.

Family and domain databases

InterProIPR001025. BAH_dom.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR022702. Cytosine_MeTrfase1_RFD.
IPR010506. DMAP1-bd.
IPR017198. DNA_C5-MeTrfase_1_euk.
IPR002857. Znf_CXXC.
[Graphical view]
PANTHERPTHR10629. PTHR10629. 1 hit.
PfamPF01426. 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]
PIRSFPIRSF037404. DNMT1. 1 hit.
PRINTSPR00105. C5METTRFRASE.
SMARTSM00439. BAH. 2 hits.
[Graphical view]
PROSITEPS51038. 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]
ProtoNetSearch...

Other

ChiTaRSDNMT1. human.
EvolutionaryTraceP26358.
GeneWikiDNMT1.
GenomeRNAi1786.
NextBio7267.
PROP26358.
SOURCESearch...

Entry information

Entry nameDNMT1_HUMAN
AccessionPrimary (citable) accession number: P26358
Secondary accession number(s): A0AV63 expand/collapse secondary AC list , B7ZLW6, Q9UHG5, Q9ULA2, Q9UMZ6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: January 11, 2001
Last modified: April 16, 2014
This is version 163 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM