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P13864 (DNMT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

Short name=Dnmt1
Short name=Met-1
EC=2.1.1.37
Alternative name(s):
DNA methyltransferase MmuI
Short name=DNA MTase MmuI
Short name=M.MmuI
MCMT
Gene names
Name:Dnmt1
Synonyms:Dnmt, Met1, Uim
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1620 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.14 Ref.16 Ref.21

Catalytic activity

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

Enzyme regulation

Allosterically regulated. The binding of 5-methylcytosine-containing DNA to the N-terminal parts of DNMT1 causes an allosteric activation of the catalytic domain by a direct interaction of its Zn-binding domain with the catalytic domain. Ref.10

Subunit structure

Homodimer. Interacts with HDAC1 and with PCNA. Binds MBD2 and MBD3. Component of complexes containing SUV39H1. Interacts with DNMT3A and DNMT3B By similarity. Forms a complex with DMAP1 and HDAC2, with direct interaction. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9 By similarity. Interacts with BAZ2A/TIP5. Binds to CSNK1D. Interacts with UHRF1; promoting its recruitment to hemimethylated DNA. Interacts with USP7, promoting its deubiquitination. Ref.12 Ref.13 Ref.17 Ref.18 Ref.24 Ref.25

Subcellular location

Nucleus. Cytoplasm. Note: It is nucleoplasmic through most of the cell cycle and associates with replication foci during S-phase. In germ cells, spermatogonia, preleptotene and leptotene spermatocytes all express high levels of nuclear protein, while the protein is not detected in pachytene spermatocytes, despite the fact they expressed high levels of mRNA. In females, the protein is not detected in non-growing oocytes, in contrast to the growing oocytes. During the growing, the protein is no longer detectable in nuclei but accumulates to very high levels first throughout the cytoplasm. At the time of ovulation, all the protein is cytoplasmic and is actively associated with the oocyte cortex. After fecondation, in the preimplantation embryo, the protein remains cytoplasmic and after implantation, it is exclusively nuclear in all tissue types. Isoform 2 is sequestered in the cytoplasm of maturing oocytes and of preimplantation embryos, except for the 8-cell stage, while isoform 1 is exclusively nuclear. Ref.14

Tissue specificity

Isoform 1 is expressed in embryonic stem cells and in somatic tissues. Isoform 2 is expressed in oocytes, preimplantation embryos, testis and in skeletal muscle during myogenesis.

Developmental stage

In germ cells, it is present at high levels in spermatogonia and spermatocytes until the pachytene stage, where it falls to undetectable levels. The transient drop at the pachytene stage coincides with the disappearance of the 5.2 kb mRNA and the accumulation of a larger 6.0 kb mRNA. Oocytes accumulate very large amounts of Dnmt1 protein during the growth phase.

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.27).

Post-translational modification

Sumoylated By similarity.

Phosphorylation at Ser-146 by CK1 reduces DNA-binding activity.

Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G2/M transition. Deacetylation of Lys-1352 and Lys-1418 by SIRT1 increases methyltransferase activity By similarity.

Phosphorylation of Ser-152 by CDKs is important for enzymatic activity and protein stability. Phosphorylation of Ser-140 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability By similarity.

Methylation at Lys-139 by SETD7 promotes DNMT1 proteasomal degradation By similarity.

Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome. Ref.24

Miscellaneous

There are three 5' exons, one specific to the oocyte (1c), one specific to the pachytene spermatocyte and also found in skeletal muscle (1b) and one found in somatic cells (1a). Three differents mRNAs can be produced which give rise to two different translation products: isoform 1 (mRNAs-1a) and isoform 2 (mRNA-1b or -1c). Association of DNMT1 with the replication machinery is not strictly required for maintaining global methylation but still enhances methylation efficiency by 2-fold. Pre-existing cytosine methylation at CpG and non-CpG sites enhances methylation activity.

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 AAC52900.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   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
Allosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA methylation

Inferred from direct assay Ref.15. Source: MGI

cellular response to amino acid stimulus

Inferred from direct assay PubMed 20548288. Source: MGI

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

gene silencing

Inferred from direct assay Ref.12. Source: UniProtKB

maintenance of DNA methylation

Inferred from mutant phenotype Ref.21. Source: UniProtKB

negative regulation of histone H3-K9 methylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 16887828. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.13. Source: MGI

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of histone H3-K4 methylation

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from genetic interaction PubMed 10919675. Source: MGI

regulation of gene expression

Inferred from mutant phenotype PubMed 16491076PubMed 23028046. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcentromeric heterochromatin

Inferred from direct assay Ref.21. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

heterochromatin

Inferred from direct assay PubMed 14519686. Source: MGI

nucleus

Inferred from direct assay PubMed 11942627PubMed 15063176PubMed 16424344PubMed 17931718. Source: MGI

replication fork

Inferred from direct assay Ref.13. Source: MGI

   Molecular_functionDNA (cytosine-5-)-methyltransferase activity

Inferred from direct assay Ref.15. Source: MGI

DNA binding

Inferred from direct assay Ref.15. Source: MGI

RNA binding

Inferred from direct assay PubMed 20573698. Source: MGI

chromatin binding

Inferred from electronic annotation. Source: InterPro

methyl-CpG binding

Inferred from direct assay PubMed 20573698. Source: MGI

methyltransferase activity

Inferred from direct assay Ref.12. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.15. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Hdac1O091063EBI-301927,EBI-301912

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P13864-1)

Also known as: Long;

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: P13864-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 16201620DNA (cytosine-5)-methyltransferase 1
PRO_0000088035

Regions

Domain18 – 10689DMAP-interaction
Domain758 – 884127BAH 1
Domain976 – 1103128BAH 2
Repeat1112 – 111321
Repeat1114 – 111522
Repeat1116 – 111723
Repeat1118 – 111924
Repeat1120 – 112125
Repeat1122 – 112326
Repeat1124 – 112527; approximate
Domain1142 – 1601460SAM-dependent MTase C5-type
Zinc finger649 – 69547CXXC-type
Region1 – 343343Interaction with the PRC2/EED-EZH2 complex
Region1 – 145145Interaction with DNMT3A By similarity
Region1 – 120120Interaction with DMAP1
Region147 – 21771Interaction with DNMT3B By similarity
Region161 – 17212Interaction with PCNA
Region305 – 609305Interaction with the PRC2/EED-EZH2 complex
Region328 – 556229DNA replication foci-targeting sequence By similarity
Region696 – 813118Interaction with HDAC1
Region696 – 75762Autoinhibitory linker
Region1112 – 1125147 X 2 AA tandem repeats of K-G
Region1124 – 1620497Interaction with the PRC2/EED-EZH2 complex
Region1142 – 1620479Catalytic
Motif175 – 20228Nuclear localization signal Potential

Sites

Active site12291
Metal binding3591Zinc By similarity
Metal binding3621Zinc By similarity
Metal binding4201Zinc By similarity
Metal binding4241Zinc By similarity

Amino acid modifications

Modified residue701N6,N6-dimethyllysine; by EHMT2 By similarity
Modified residue1391N6-methyllysine; by SETD7 By similarity
Modified residue1401Phosphoserine; by PKB/AKT1 By similarity
Modified residue1461Phosphoserine; by CK1 Ref.25
Modified residue1501Phosphoserine By similarity
Modified residue1521Phosphoserine Ref.22
Modified residue1711N6-acetyllysine By similarity
Modified residue2551N6-acetyllysine By similarity
Modified residue3721N6-acetyllysine By similarity
Modified residue5151Phosphoserine Ref.11 Ref.20
Modified residue7171Phosphoserine Ref.22 Ref.23
Modified residue7351Phosphoserine By similarity
Modified residue7521N6-acetyllysine By similarity
Modified residue8951N6-acetyllysine By similarity
Modified residue9611N6-acetyllysine By similarity
Modified residue9651N6-acetyllysine By similarity
Modified residue9791N6-acetyllysine By similarity
Modified residue11141N6-acetyllysine By similarity
Modified residue11161N6-acetyllysine By similarity
Modified residue11181N6-acetyllysine By similarity
Modified residue11201N6-acetyllysine By similarity
Modified residue11221N6-acetyllysine Ref.26
Modified residue11241N6-acetyllysine Ref.26
Modified residue13521N6-acetyllysine By similarity
Modified residue14181N6-acetyllysine By similarity

Natural variations

Alternative sequence1 – 118118Missing in isoform 2.
VSP_005619

Experimental info

Mutagenesis1621Q → E: Abolishes interaction with PCNA. No effect on activity. Ref.21
Mutagenesis1691F → S: Abolishes interaction with PCNA. No effect on activity. Ref.21
Mutagenesis5151S → A: Loss of activity. No effect on DNA-binding capacity. Ref.20
Mutagenesis5151S → E: Slightly reduces activity. Ref.20
Mutagenesis12291C → W: Loss of activity. Ref.21
Sequence conflict146 – 1472SV → F in CAA32910. Ref.1
Sequence conflict146 – 1472SV → F in AAC40061. Ref.6
Sequence conflict299 – 30911AEPEQVAPETP → VRARAGSSRDS in CAA32910. Ref.1
Sequence conflict299 – 30911AEPEQVAPETP → VRARAGSSRDS in AAC40061. Ref.6
Sequence conflict9361V → C in CAA32910. Ref.1
Sequence conflict9361V → C in AAC40061. Ref.6
Sequence conflict9471P → R in CAA32910. Ref.1
Sequence conflict9471P → R in AAC40061. Ref.6
Sequence conflict969 – 9768NETLYPEH → KENPVPRDT in CAA32910. Ref.1
Sequence conflict969 – 9768NETLYPEH → KENPVPRDT in AAC40061. Ref.6
Sequence conflict9871S → R in CAA32910. Ref.1
Sequence conflict9871S → R in AAC40061. Ref.6
Sequence conflict10461Y → C in CAA32910. Ref.1
Sequence conflict10461Y → C in AAC40061. Ref.6
Sequence conflict10681G → R in CAA32910. Ref.1
Sequence conflict10681G → R in AAC40061. Ref.6
Sequence conflict14291R → P in CAA32910. Ref.1
Sequence conflict14291R → P in AAC40061. Ref.6
Sequence conflict14561H → D in CAA32910. Ref.1
Sequence conflict14561H → D in AAC40061. Ref.6

Secondary structure

..................................................................................................................................................................................................................... 1620
Helix Strand Turn

Details...

Sequences

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

Last modified February 21, 2002. Version 5.
Checksum: 4F9A98CEAF09F037

FASTA1,620183,189
        10         20         30         40         50         60 
MPARTAPARV PALASPAGSL PDHVRRRLKD LERDGLTEKE CVREKLNLLH EFLQTEIKSQ 

        70         80         90        100        110        120 
LCDLETKLHK EELSEEGYLA KVKSLLNKDL SLENGTHTLT QKANGCPANG SRPTWRAEMA 

       130        140        150        160        170        180 
DSNRSPRSRP KPRGPRRSKS DSDTLSVETS PSSVATRRTT RQTTITAHFT KGPTKRKPKE 

       190        200        210        220        230        240 
ESEEGNSAES AAEERDQDKK RRVVDTESGA AAAVEKLEEV TAGTQLGPEE PCEQEDDNRS 

       250        260        270        280        290        300 
LRRHTRELSL RRKSKEDPDR EARPETHLDE DEDGKKDKRS SRPRSQPRDP AAKRRPKEAE 

       310        320        330        340        350        360 
PEQVAPETPE DRDEDEREEK RRKTTRKKLE SHTVPVQSRS ERKAAQSKSV IPKINSPKCP 

       370        380        390        400        410        420 
ECGQHLDDPN LKYQQHPEDA VDEPQMLTSE KLSIYDSTST WFDTYEDSPM HRFTSFSVYC 

       430        440        450        460        470        480 
SRGHLCPVDT GLIEKNVELY FSGCAKAIHD ENPSMEGGIN GKNLGPINQW WLSGFDGGEK 

       490        500        510        520        530        540 
VLIGFSTAFA EYILMEPSKE YEPIFGLMQE KIYISKIVVE FLQNNPDAVY EDLINKIETT 

       550        560        570        580        590        600 
VPPSTINVNR FTEDSLLRHA QFVVSQVESY DEAKDDDETP IFLSPCMRAL IHLAGVSLGQ 

       610        620        630        640        650        660 
RRATRRVMGA TKEKDKAPTK ATTTKLVYQI FDTFFSEQIE KYDKEDKENA MKRRRCGVCE 

       670        680        690        700        710        720 
VCQQPECGKC KACKDMVKFG GTGRSKQACL KRRCPNLAVK EADDDEEADD DVSEMPSPKK 

       730        740        750        760        770        780 
LHQGKKKKQN KDRISWLGQP MKIEENRTYY QKVSIDEEML EVGDCVSVIP DDSSKPLYLA 

       790        800        810        820        830        840 
RVTALWEDKN GQMMFHAHWF CAGTDTVLGA TSDPLELFLV GECENMQLSY IHSKVKVIYK 

       850        860        870        880        890        900 
APSENWAMEG GTDPETTLPG AEDGKTYFFQ LWYNQEYARF ESPPKTQPTE DNKHKFCLSC 

       910        920        930        940        950        960 
IRLAELRQKE MPKVLEQIEE VDGRVYCSSI TKNGVVYRLG DSVYLPPEAF TFNIKVASPV 

       970        980        990       1000       1010       1020 
KRPKKDPVNE TLYPEHYRKY SDYIKGSNLD APEPYRIGRI KEIHCGKKKG KVNEADIKLR 

      1030       1040       1050       1060       1070       1080 
LYKFYRPENT HRSYNGSYHT DINMLYWSDE EAVVNFSDVQ GRCTVEYGED LLESIQDYSQ 

      1090       1100       1110       1120       1130       1140 
GGPDRFYFLE AYNSKTKNFE DPPNHARSPG NKGKGKGKGK GKGKHQVSEP KEPEAAIKLP 

      1150       1160       1170       1180       1190       1200 
KLRTLDVFSG CGGLSEGFHQ AGISETLWAI EMWDPAAQAF RLNNPGTTVF TEDCNVLLKL 

      1210       1220       1230       1240       1250       1260 
VMAGEVTNSL GQRLPQKGDV EMLCGGPPCQ GFSGMNRFNS RTYSKFKNSL VVSFLSYCDY 

      1270       1280       1290       1300       1310       1320 
YRPRFFLLEN VRNFVSYRRS MVLKLTLRCL VRMGYQCTFG VLQAGQYGVA QTRRRAIILA 

      1330       1340       1350       1360       1370       1380 
AAPGEKLPLF PEPLHVFAPR ACQLSVVVDD KKFVSNITRL SSGPFRTITV RDTMSDLPEI 

      1390       1400       1410       1420       1430       1440 
QNGASNSEIP YNGEPLSWFQ RQLRGSHYQP ILRDHICKDM SPLVAARMRH IPLFPGSDWR 

      1450       1460       1470       1480       1490       1500 
DLPNIQVRLG DGVIAHKLQY TFHDVKNGYS STGALRGVCS CAEGKACDPE SRQFSTLIPW 

      1510       1520       1530       1540       1550       1560 
CLPHTGNRHN HWAGLYGRLE WDGFFSTTVT NPEPMGKQGR VLHPEQHRVV SVRECARSQG 

      1570       1580       1590       1600       1610       1620 
FPDSYRFFGN ILDRHRQVGN AVPPPLAKAI GLEIKLCLLS SARESASAAV KAKEEAATKD 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 4364F6D494EA67E4
Show »

FASTA1,502169,996

References

« Hide 'large scale' references
[1]"Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases."
Bestor T.H., Laudano A., Mattaliano R., Ingram V.
J. Mol. Biol. 203:971-983(1988) [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.
Tissue: Embryo.
[3]"Expression of an alternative Dnmt1 isoform during muscle differentiation."
Aguirre-Arteta A.M., Grunewald I., Cardoso M.C., Leonhardt H.
Cell Growth Differ. 11:551-559(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: C57BL/6.
Tissue: Skeletal muscle.
[4]"Structure and function of the mouse DNA methyltransferase gene: Dnmt1 shows a tripartite structure."
Margot J.B., Aguirre-Arteta A.M., Di Giacco B.V., Pradhan S., Roberts R.J., Cardoso M.C., Leonhardt H.
J. Mol. Biol. 297:293-300(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6.
[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 1).
Strain: C57BL/6.
Tissue: Brain.
[6]"Sex-specific exons control DNA methyltransferase in mammalian germ cells."
Mertineit C., Yoder J.A., Taketo T., Laird D.W., Trasler J.M., Bestor T.H.
Development 125:889-897(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-27 AND 119-1619 (ISOFORMS 1 AND 2).
[7]"A short DNA methyltransferase isoform restores methylation in vivo."
Gaudet F., Talbot D., Leonhardt H., Jaenisch R.
J. Biol. Chem. 273:32725-32729(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 1-144 (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 3-6.
Strain: 129/Sv and BALB/c.
Tissue: Embryonic stem cell.
[8]"Complementation of methylation deficiency in embryonic stem cells by a DNA methyltransferase minigene."
Tucker K.L., Talbot D., Lee M.A., Leonhardt H., Jaenisch R.
Proc. Natl. Acad. Sci. U.S.A. 93:12920-12925(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-119 (ISOFORM 1).
Strain: 129/Sv.
Tissue: Embryonic stem cell and Kidney.
[9]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-272 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Embryo.
[10]"Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain."
Bestor T.H.
EMBO J. 11:2611-2617(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1108-1154, ENZYME REGULATION.
[11]"Peptide mapping of the murine DNA methyltransferase reveals a major phosphorylation site and the start of translation."
Glickman J.F., Pavlovich J.G., Reich N.O.
J. Biol. Chem. 272:17851-17857(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-515, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Erythroleukemia.
[12]"DNA methyltransferase Dnmt1 associates with histone deacetylase activity."
Fuks F., Burgers W.A., Brehm A., Hughes-Davies L., Kouzarides T.
Nat. Genet. 24:88-91(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC1.
[13]"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.
[14]"Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene."
Howell C.Y., Bestor T.H., Ding F., Latham K.E., Mertineit C., Trasler J.M., Chaillet J.R.
Cell 104:829-838(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[15]"The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA."
Fatemi M., Hermann A., Pradhan S., Jeltsch A.
J. Mol. Biol. 309:1189-1199(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ALLOSTERIC REGULATION.
[16]"Replication-independent chromatin loading of Dnmt1 during G2 and M phases."
Easwaran H.P., Schermelleh L., Leonhardt H., Cardoso M.C.
EMBO Rep. 5:1181-1186(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is sufficient for rDNA silencing."
Zhou Y., Grummt I.
Curr. Biol. 15:1434-1438(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAZ2A.
[18]"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: INTERACTION WITH THE PRC2 COMPLEX.
[19]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)
[20]"Phosphorylation of serine-515 activates the mammalian maintenance methyltransferase Dnmt1."
Goyal R., Rathert P., Laser H., Gowher H., Jeltsch A.
Epigenetics 2:155-160(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-515, MUTAGENESIS OF SER-515.
[21]"Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation."
Schermelleh L., Haemmer A., Spada F., Roesing N., Meilinger D., Rothbauer U., Cardoso M.C., Leonhardt H.
Nucleic Acids Res. 35:4301-4312(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLN-162; PHE-169 AND CYS-1229.
[22]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152 AND SER-717, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[23]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-717, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1."
Qin W., Leonhardt H., Spada F.
J. Cell. Biochem. 112:439-444(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP7, INTERACTION WITH USP7 AND UHRF1.
[25]"The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/epsilon."
Sugiyama Y., Hatano N., Sueyoshi N., Suetake I., Tajima S., Kinoshita E., Kinoshita-Kikuta E., Koike T., Kameshita I.
Biochem. J. 427:489-497(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-146 BY CSNK1D/CK1, INTERACTION WITH CSNK1D.
[26]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1122 AND LYS-1124, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[27]"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 (2.5 ANGSTROMS) OF 731-1602 IN COMPLEX WITH SAH AND DNA, AUTOINHIBITORY LINKER.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14805 mRNA. Translation: CAA32910.1.
AF175432 mRNA. Translation: AAF97695.1.
AF162282 mRNA. Translation: AAF19352.1.
AF175431 expand/collapse EMBL AC list , AF175412, AF175413, AF175414, AF244089, AF244090, AF175416, AF175417, AF175418, AF175419, AF175420, AF175421, AF175422, AF175423, AF234317, AF175424, AF175425, AF175426, AF234318, AF175427, AF175428, AF175429, AF175430 Genomic DNA. Translation: AAF60965.1.
BC048148 mRNA. Translation: AAH48148.2.
AF036007 mRNA. Translation: AAC40061.1.
AF036008 Genomic DNA. Translation: AAC53551.1.
U70051 mRNA. Translation: AAC52900.1. Different initiation.
AK013247 mRNA. Translation: BAB28743.1.
PIRS01845.
RefSeqNP_001186360.2. NM_001199431.1.
NP_001186361.1. NM_001199432.1.
NP_001186362.1. NM_001199433.1.
NP_034196.5. NM_010066.4.
UniGeneMm.128580.
Mm.485562.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3AV4X-ray2.75A291-1620[»]
3AV5X-ray3.25A291-1620[»]
3AV6X-ray3.09A291-1620[»]
3PT6X-ray3.00A/B650-1602[»]
3PT9X-ray2.50A731-1602[»]
4DA4X-ray2.60A/B731-1602[»]
ProteinModelPortalP13864.
SMRP13864. Positions 357-603, 651-1600.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199259. 30 interactions.
IntActP13864. 4 interactions.
MINTMINT-4093291.

Chemistry

GuidetoPHARMACOLOGY2605.

Protein family/group databases

REBASE2844. M.MmuDnmt1.

PTM databases

PhosphoSiteP13864.

Proteomic databases

PaxDbP13864.
PRIDEP13864.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000004202; ENSMUSP00000004202; ENSMUSG00000004099. [P13864-1]
ENSMUST00000178110; ENSMUSP00000136669; ENSMUSG00000004099. [P13864-2]
GeneID13433.
KEGGmmu:13433.
UCSCuc009ojo.2. mouse. [P13864-1]

Organism-specific databases

CTD1786.
MGIMGI:94912. Dnmt1.

Phylogenomic databases

eggNOGCOG0270.
GeneTreeENSGT00390000005100.
HOVERGENHBG051384.
InParanoidP13864.
KOK00558.
OMACPNLAVK.
OrthoDBEOG77WWBH.
PhylomeDBP13864.
TreeFamTF328926.

Enzyme and pathway databases

BRENDA2.1.1.37. 3474.

Gene expression databases

ArrayExpressP13864.
BgeeP13864.
CleanExMM_DNMT1.
GenevestigatorP13864.

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. mouse.
EvolutionaryTraceP13864.
NextBio283859.
PROP13864.
SOURCESearch...

Entry information

Entry nameDNMT1_MOUSE
AccessionPrimary (citable) accession number: P13864
Secondary accession number(s): P97413 expand/collapse secondary AC list , Q80ZU3, Q9CSC6, Q9QXX6
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: February 21, 2002
Last modified: April 16, 2014
This is version 164 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot