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Q9Z330 (DNMT1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
EC=2.1.1.37
Alternative name(s):
DNA MTase RnoIP
Short name=M.RnoIP
DNA methyltransferase I
MCMT
Gene names
Name:Dnmt1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1622 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 By similarity.

Catalytic activity

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

Subunit structure

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 By similarity. Binds annexin V Potential. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9 and BAZ2A/TIP5 By similarity. Binds to CSNK1D. Interacts with BAZ2A/TIP5. Binds to CSNK1D. Interacts with UHRF1; promoting its recruitment to hemimethylated DNA. Interacts with USP7, promoting its deubiquitination By similarity.

Subcellular location

Nucleus.

Tissue specificity

Isoforms 0 and 8 are highly expressed in placenta, brain, lung, spleen, kidney, heart, and at much lower levels in liver. Isoform 1 is expressed in cerebellum, isoform 2 in muscle and testis, isoform 3 in lung, isoform 4 in spleen and brain, and isoform 5 in brain.

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 By similarity.

Post-translational modification

Sumoylated By similarity.

Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G2/M transition. Deacetylation of Lys-1116 and Lys-1354 by SIRT1 increases methyltransferase activity By similarity.

Phosphorylation of Ser-151 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 By similarity.

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.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA methylation

Traceable author statement Ref.1. Source: RGD

DNA methylation on cytosine within a CG sequence

Inferred from direct assay PubMed 11844796PubMed 3856245. Source: RGD

S-adenosylhomocysteine metabolic process

Inferred from direct assay PubMed 11844796PubMed 3856245. Source: RGD

S-adenosylmethioninamine metabolic process

Inferred from direct assay PubMed 11844796. Source: RGD

S-adenosylmethionine metabolic process

Inferred from direct assay PubMed 3856245. Source: RGD

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

maintenance of DNA methylation

Inferred from direct assay PubMed 12473678. Source: RGD

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay PubMed 12473678PubMed 3856245. Source: RGD

protein complex

Inferred from direct assay PubMed 12473678. Source: RGD

   Molecular_functionDNA (cytosine-5-)-methyltransferase activity

Inferred from direct assay PubMed 12473678. Source: RGD

DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates

Inferred from direct assay PubMed 11844796PubMed 3856245. Source: RGD

S-adenosylmethionine-dependent methyltransferase activity

Traceable author statement PubMed 12473678. Source: RGD

chromatin binding

Inferred from electronic annotation. Source: InterPro

double-stranded DNA binding

Inferred from direct assay PubMed 11844796. Source: RGD

histone deacetylase binding

Inferred from physical interaction PubMed 12473678. Source: RGD

methyl-CpG binding

Inferred from direct assay PubMed 3856245. Source: RGD

protein domain specific binding

Inferred from physical interaction PubMed 12473678. Source: RGD

unmethylated CpG binding

Inferred from direct assay PubMed 3856245. Source: RGD

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9Z330-1)

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: Q9Z330-2)

Also known as: SF1;

The sequence of this isoform differs from the canonical sequence as follows:
     1323-1403: Missing.
Isoform 3 (identifier: Q9Z330-3)

Also known as: SF2;

The sequence of this isoform differs from the canonical sequence as follows:
     1252-1482: Missing.
Isoform 4 (identifier: Q9Z330-4)

Also known as: SF3;

The sequence of this isoform differs from the canonical sequence as follows:
     1226-1477: Missing.
Isoform 5 (identifier: Q9Z330-5)

Also known as: SF4;

The sequence of this isoform differs from the canonical sequence as follows:
     1218-1430: QKGDVEMLCG...VHERAGGCRM → VC
Isoform 6 (identifier: Q9Z330-6)

Also known as: SF5;

The sequence of this isoform differs from the canonical sequence as follows:
     1202-1410: Missing.
Isoform 7 (identifier: Q9Z330-7)

Also known as: SF6;

The sequence of this isoform differs from the canonical sequence as follows:
     1259-1481: Missing.
Isoform 8 (identifier: Q9Z330-8)

Also known as: SF7;

The sequence of this isoform differs from the canonical sequence as follows:
     1216-1504: Missing.
Isoform 9 (identifier: Q9Z330-9)

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 – 16221622DNA (cytosine-5)-methyltransferase 1
PRO_0000088036

Regions

Domain18 – 10588DMAP-interaction
Domain759 – 884126BAH 1
Domain977 – 1105129BAH 2
Repeat1114 – 111521
Repeat1116 – 111722
Repeat1118 – 111923
Repeat1120 – 112124
Repeat1122 – 112325
Repeat1124 – 112526
Repeat1126 – 112727; approximate
Domain1144 – 1603460SAM-dependent MTase C5-type
Zinc finger650 – 69647CXXC-type
Region1 – 342342Interaction with the PRC2/EED-EZH2 complex By similarity
Region1 – 145145Interaction with DNMT3A By similarity
Region146 – 21368Interaction with DNMT3B By similarity
Region304 – 610307Interaction with the PRC2/EED-EZH2 complex By similarity
Region327 – 556230DNA replication foci-targeting sequence
Region697 – 75862Autoinhibitory linker
Region1114 – 1127147 X 2 AA tandem repeats of K-G
Region1126 – 1622497Interaction with the PRC2/EED-EZH2 complex By similarity
Region1144 – 1622479Catalytic
Motif173 – 20028Nuclear localization signal Potential
Compositional bias149 – 1524Poly-Ser
Compositional bias269 – 2746Poly-Asp
Compositional bias726 – 7294Poly-Lys

Sites

Active site12311 By similarity
Metal binding3591Zinc By similarity
Metal binding3621Zinc By similarity
Metal binding4201Zinc By similarity
Metal binding4241Zinc By similarity
Site5151Important for activity 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 residue1491Phosphoserine By similarity
Modified residue1511Phosphoserine By similarity
Modified residue1691N6-acetyllysine By similarity
Modified residue3721N6-acetyllysine By similarity
Modified residue4001Phosphoserine By similarity
Modified residue5151Phosphoserine By similarity
Modified residue7181Phosphoserine By similarity
Modified residue7361Phosphoserine By similarity
Modified residue7531N6-acetyllysine By similarity
Modified residue8951N6-acetyllysine By similarity
Modified residue9611N6-acetyllysine By similarity
Modified residue9801N6-acetyllysine By similarity
Modified residue11161N6-acetyllysine By similarity
Modified residue11181N6-acetyllysine By similarity
Modified residue11201N6-acetyllysine By similarity
Modified residue11221N6-acetyllysine By similarity
Modified residue11241N6-acetyllysine By similarity
Modified residue11261N6-acetyllysine By similarity
Modified residue13541N6-acetyllysine By similarity

Natural variations

Alternative sequence1 – 118118Missing in isoform 9.
VSP_005620
Alternative sequence1202 – 1410209Missing in isoform 6.
VSP_005622
Alternative sequence1216 – 1504289Missing in isoform 8.
VSP_005623
Alternative sequence1218 – 1430213QKGDV…GGCRM → VC in isoform 5.
VSP_005621
Alternative sequence1226 – 1477252Missing in isoform 4.
VSP_005624
Alternative sequence1252 – 1482231Missing in isoform 3.
VSP_005625
Alternative sequence1259 – 1481223Missing in isoform 7.
VSP_005626
Alternative sequence1323 – 140381Missing in isoform 2.
VSP_005627

Experimental info

Sequence conflict17 – 259AGSLPDHVR → RQARPRPCP in BAA20854. Ref.3
Sequence conflict1891A → V in BAA20854. Ref.3
Sequence conflict12761F → S in BAA37118. Ref.1
Sequence conflict13001T → I in AAD28102. Ref.4
Sequence conflict13721M → V in BAA37118. Ref.1
Sequence conflict1394 – 142835KWRAT…RAGGC → NGEPQSWFQRQLRGSHYQPI LRDHICKDMSALVAA in BAA37118. Ref.1

Sequences

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

Last modified February 21, 2002. Version 2.
Checksum: FCFA4AAA69E234BA

FASTA1,622182,774
        10         20         30         40         50         60 
MPARTAPARV PALASPAGSL PDHVRRRLKD LERDGLTEKE CVKEKLNLLH EFLQTEIKSQ 

        70         80         90        100        110        120 
LCDLETKLHK EELSEEGYLA KVKTLLNKDL CLENGTLSLT QKANGCPANG SRPTWKAEMA 

       130        140        150        160        170        180 
DSNRSPRSRP KPRGPRRSKS DSETMIEASS SSVATRRTTR QTTITSHFKG PAKRKPKEDS 

       190        200        210        220        230        240 
EKGNANESAA EERDQDKKRR VAGTESRASR AGESVEKPER VRPGTQLCQE EQGEQEDDRR 

       250        260        270        280        290        300 
PRRQTRELAS RRKSREDPDR EARPGTHLDV DDDDEKDKRS SRPRSQPRDL ATKRRPKEEV 

       310        320        330        340        350        360 
EQITPEPPEG KDEDEREEKR RKTTRKKPEP LSIPVQSRVE RKASQGKASA IPKLNPPQCP 

       370        380        390        400        410        420 
ECGQYLDDPD LKYQQHPVDA VDEPQMLTNE ALSVFDSNSS WFETYDSSPM HKFTFFSVYC 

       430        440        450        460        470        480 
SRGHLCPVDT GLIEKNVELY FSGVAKAIHE ENPSVEGGVN GKNLGPINQW WISGFDGGEK 

       490        500        510        520        530        540 
ALIGFSTAFA EYFLMEPSPE YAPIFGLMQE KIYISKIVVE FLQSNPDAVY EDLINKIETT 

       550        560        570        580        590        600 
VPPSAINVNR FTEDSLLRHA QFVVSQVESY DDAKDDDETP IFLSPCMRSL IHLAGVSLGQ 

       610        620        630        640        650        660 
RRATRRTVIN SAKVKRKGPT KATTTKLVYQ IFDTFFSEQI EKDDKEDKEN TMKRRRCGVC 

       670        680        690        700        710        720 
EVCQQPECGK CKACKDMVKF GGTGRSKQAC LKRRCPNLAV KEADEDEEAD DDIPELPSPK 

       730        740        750        760        770        780 
KLHQGKKKKQ NKDRISWLGE PVKIEENRTY YWKVSIDEET LEVGDCVSVI PDDPSKPLYL 

       790        800        810        820        830        840 
ARVTALWEDK NGQMFHAHWF CAGTDTVLGA TSDPLELFLV GECENMQLSY IHSKVKVIYR 

       850        860        870        880        890        900 
GPSPNWAMEG GMDPEAMLPG AEDGKTYFYQ FWYSQDYARF ESPPKTQPAE DNKHKFCLSC 

       910        920        930        940        950        960 
IRLAELRQKE MPKVLEQLEE VDGRVYCSSI TKNGVVYRLG DSVYLPPEAF TFNIKMASPM 

       970        980        990       1000       1010       1020 
KRSKRDPVNE NPVPRDTYRK YSDYIKGSNL DAPEPYRIGR IKEIYCGKKK GGKVNEADIK 

      1030       1040       1050       1060       1070       1080 
IRLYKFYRPE NTHKSIQATY HADINLLYWS DEEAVVDFSD VQGRCTVEYG EDLLESIQDY 

      1090       1100       1110       1120       1130       1140 
SQGGPDRFYF LEAYNSKTKS FEDPPNHARS PGNKGKGKGK GKGKGKPQVS EPKEPEAAIK 

      1150       1160       1170       1180       1190       1200 
LPKLRTLDVF SGCGGLTEGF HQAGISETLW AIEMWEPAAQ AFRLNNPGTT VFTEDCNVLL 

      1210       1220       1230       1240       1250       1260 
KLVMAGEVTN SLGQRLPQKG DVEMLCGGPP CQGFSGMNRF NSRTYSKFKN SLVVSFLSYC 

      1270       1280       1290       1300       1310       1320 
DYYRPRFFLL ENVRNFVSFR RSMVLKLTLR CLVRMGYQCT FGVLQAGQYG VAQTRRRAII 

      1330       1340       1350       1360       1370       1380 
LAAAPGEKLP LFPEPLHVFA PRACQLSVVV DDKKFVSNIT RLSSGPFRTI TMRDTMSDLP 

      1390       1400       1410       1420       1430       1440 
EIQNGASAPE ISYKWRATVL VPEAAARVAL PAHPQGPYPQ VHERAGGCRM RHIPLSPGSD 

      1450       1460       1470       1480       1490       1500 
WRDLPNIQVR LRDGVITNKL RYTFHDTKNG CSSTGALRGV CSCAEGKTCD PASRQFNTLI 

      1510       1520       1530       1540       1550       1560 
PWCLPHTGNR HNHWAGLYGR LEWDGFFSTT VTNPEPMGKQ GRVLHPEQHR VVSVRECARS 

      1570       1580       1590       1600       1610       1620 
QGFPDTYRLF GNILDRHRQV GNAVPPPLAK AIGLEIKLCL LASAQESASA AVKGKEETTT 


ED 

« Hide

Isoform 2 (SF1) [UniParc].

Checksum: 9F1B86D1D13B45AB
Show »

FASTA1,541173,853
Isoform 3 (SF2) [UniParc].

Checksum: 7F92F4E446BBD358
Show »

FASTA1,391156,880
Isoform 4 (SF3) [UniParc].

Checksum: 9137E151ED3EED0B
Show »

FASTA1,370154,529
Isoform 5 (SF4) [UniParc].

Checksum: 961F53E307E2447E
Show »

FASTA1,411159,119
Isoform 6 (SF5) [UniParc].

Checksum: AE3F0037058D8167
Show »

FASTA1,413159,421
Isoform 7 (SF6) [UniParc].

Checksum: 28C6F61C3085A7ED
Show »

FASTA1,399157,713
Isoform 8 (SF7) [UniParc].

Checksum: D8713CC5B748BFC2
Show »

FASTA1,333150,479
Isoform 9 (short) [UniParc].

Checksum: C880386135929522
Show »

FASTA1,504169,645

References

[1]"Expression of rat DNA (cytosine-5) methyltransferase (DNA MTase) in rodent trophoblast giant cells: molecular cloning and characterization of rat DNA MTase."
Kimura H., Takeda T., Tanaka S., Ogawa T., Shiota K.
Biochem. Biophys. Res. Commun. 253:495-501(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: Sprague-Dawley.
Tissue: Brain and Placenta.
[2]"Multiple N-terminal isoforms of DNA (cytosine-5-)-methyltransferase in vivo."
Deng J., Szyf M.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE OF 1-144 (ISOFORMS 1 AND 9).
Tissue: Brain.
[3]"Molecular cloning and characterization of annexin V-binding proteins with highly hydrophilic peptide structure."
Ohsawa K., Imai Y., Ito D., Kohsaka S.
J. Neurochem. 67:89-97(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-356, IN VITRO BINDING TO ANNEXIN V.
Strain: Wistar.
Tissue: Brain.
[4]"Multiple isoforms of DNA methyltransferase are encoded by the vertebrate cytosine DNA methyltransferase gene."
Deng J., Szyf M.
J. Biol. Chem. 273:22869-22872(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1169-1517 (ISOFORMS 1; 2; 3; 4; 5; 6; 7 AND 8).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB012214 mRNA. Translation: BAA37118.1.
AF116344 mRNA. Translation: AAD32541.1.
AF116345 Genomic DNA. Translation: AAD32542.1.
D64060 mRNA. Translation: BAA20854.1.
AH007612 Genomic DNA. Translation: AAD28102.1.
PIRJE0378.
UniGeneRn.6955.

3D structure databases

ProteinModelPortalQ9Z330.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9Z330. 2 interactions.
STRING10116.ENSRNOP00000063029.

Protein family/group databases

REBASE3019. M.RnoDnmt1.

PTM databases

PhosphoSiteQ9Z330.

Proteomic databases

PaxDbQ9Z330.
PRIDEQ9Z330.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:620979. rat. [Q9Z330-1]

Organism-specific databases

RGD620979. Dnmt1.

Phylogenomic databases

eggNOGCOG0270.
HOGENOMHOG000082497.
HOVERGENHBG051384.
PhylomeDBQ9Z330.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-8581.

Gene expression databases

GenevestigatorQ9Z330.

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

PROQ9Z330.

Entry information

Entry nameDNMT1_RAT
AccessionPrimary (citable) accession number: Q9Z330
Secondary accession number(s): P70487 expand/collapse secondary AC list , Q9R252, Q9WTX3, Q9WU57
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2002
Last sequence update: February 21, 2002
Last modified: April 16, 2014
This is version 123 of the entry and version 2 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