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O88509 (DNM3B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. 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 3B

Short name=Dnmt3b
EC=2.1.1.37
Alternative name(s):
DNA methyltransferase MmuIIIB
Short name=DNA MTase MmuIIIB
Short name=M.MmuIIIB
Gene names
Name:Dnmt3b
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length859 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing. In association with DNMT1 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. Function as transcriptional corepressor by associating with ZHX1 By similarity. Ref.3 Ref.4 Ref.12 Ref.13 Ref.14 Ref.17

Catalytic activity

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

Enzyme regulation

Activated by binding to the regulatory factor DNMT3L. Ref.11

Subunit structure

Interacts with CBX4, DNMT1, DNMT3A, SETDB1, UBE2I9, UBL1 and ZHX1 By similarity. Interacts with SUV39H1 and BAZ2A/TIP5. Interacts with the PRC2/EED-EZH2 complex. Interacts with UHRF1. Ref.6 Ref.7 Ref.8 Ref.14 Ref.15 Ref.17

Subcellular location

Nucleus. Note: Accumulates in the major satellite repeats at pericentric heterochromatin. Ref.10

Developmental stage

Expressed in almost all blastocysts at embryonic day 3.0 (E3.0). Preferentially expressed in the trophectoderm (TE) in E3.5 and polar TE in E4.0 blastocysts. In E4.5 embryos, expressed in the polar TE and some inner cell mass (ICM) embryonic lineage cells. In post-implantation embryo at E5.5, expressed in the epiblast (embryonic lineage) derived from the ICM. Highly expressed, at E7.5, in the embryonic ectoderm, neural ectoderm, and chorionic ectoderm; a weak expression is also detected in mesodermal and endodermal cells. At later stages, the expression is detected predominantly in the forebrain and eyes but weakly throughout the embryo. Ref.3 Ref.16

Domain

The PWWP domain is essential for targeting to pericentric heterochromatin.

Post-translational modification

Sumoylated By similarity.

Citrullinated by PADI4.

Sequence similarities

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

Contains 1 ADD domain.

Contains 1 GATA-type zinc finger.

Contains 1 PHD-type zinc finger.

Contains 1 PWWP domain.

Contains 1 SAM-dependent MTase C5-type domain.

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
S-adenosyl-L-methionine
Zinc
   Molecular functionActivator
Methyltransferase
Repressor
Transferase
   PTMCitrullination
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processC-5 methylation of cytosine

Inferred from direct assay PubMed 16543361. Source: GOC

DNA methylation

Inferred from mutant phenotype PubMed 22133874. Source: MGI

DNA methylation involved in embryo development

Inferred from expression pattern Ref.16. Source: UniProtKB

cellular response to amino acid stimulus

Inferred from direct assay PubMed 20548288. Source: MGI

methylation-dependent chromatin silencing

Inferred from genetic interaction PubMed 17938196. Source: MGI

negative regulation of gene expression, epigenetic

Inferred from mutant phenotype Ref.13. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 22133874. Source: MGI

protein complex localization

Inferred from direct assay PubMed 16543361. Source: MGI

regulation of gene expression by genetic imprinting

Inferred from mutant phenotype PubMed 11934864. Source: MGI

   Cellular_componentchromosome, centromeric region

Inferred from direct assay Ref.10. Source: UniProtKB

heterochromatin

Inferred from direct assay PubMed 14519686. Source: MGI

nuclear heterochromatin

Inferred from direct assay PubMed 11934864PubMed 16543361. Source: MGI

nucleus

Inferred from direct assay PubMed 16543361PubMed 19796622. Source: MGI

   Molecular_functionDNA (cytosine-5-)-methyltransferase activity

Inferred from direct assay PubMed 16543361. Source: MGI

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

methyltransferase activity

Inferred from direct assay Ref.4. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O88509-1)

Also known as: 5;

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: O88509-2)

Also known as: 6;

The sequence of this isoform differs from the canonical sequence as follows:
     363-382: Missing.
Isoform 3 (identifier: O88509-3)

Also known as: 8;

The sequence of this isoform differs from the canonical sequence as follows:
     363-382: Missing.
     750-812: Missing.
Isoform 4 (identifier: O88509-4)

Also known as: 7;

The sequence of this isoform differs from the canonical sequence as follows:
     750-812: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 859859DNA (cytosine-5)-methyltransferase 3B
PRO_0000088046

Regions

Domain232 – 29059PWWP
Domain428 – 560133ADD
Domain581 – 859279SAM-dependent MTase C5-type
Zinc finger439 – 46931GATA-type; atypical
Zinc finger480 – 53657PHD-type; atypical
Region1 – 305305Interaction with DNMT1 and DNMT3A By similarity
Region440 – 53293Interaction with the PRC2/EED-EZH2 complex
Region588 – 5925S-adenosyl-L-methionine binding By similarity
Region633 – 6353S-adenosyl-L-methionine binding By similarity
Region838 – 8403S-adenosyl-L-methionine binding By similarity
Compositional bias160 – 1656Poly-Arg

Sites

Active site6571 By similarity
Binding site6111S-adenosyl-L-methionine By similarity

Amino acid modifications

Modified residue961Phosphoserine By similarity
Modified residue1121Phosphothreonine By similarity
Modified residue1161Phosphoserine By similarity
Modified residue2161Phosphoserine By similarity
Modified residue4151Citrulline

Natural variations

Alternative sequence363 – 38220Missing in isoform 2 and isoform 3.
VSP_005642
Alternative sequence750 – 81263Missing in isoform 3 and isoform 4.
VSP_005643

Experimental info

Mutagenesis236 – 2372VW → RR: Prevents accumulation in pericentric heterochromatin.
Mutagenesis2771S → P: Prevents accumulation in pericentric heterochromatin. Ref.10
Mutagenesis6091A → T: Significantly reduces activity. Ref.4
Mutagenesis656 – 6572PC → GT: No effect on localization.
Mutagenesis6691G → S: Significantly reduces activity. Ref.4
Mutagenesis6701L → T: Significantly reduces activity. Ref.4
Mutagenesis7251V → G: Loss of activity. Ref.4
Mutagenesis8231D → G: Significantly reduces activity. Ref.4
Mutagenesis8241V → M: Significantly reduces activity. Ref.4
Sequence conflict217 – 2182RD → IY in AAF74515. Ref.2
Sequence conflict217 – 2182RD → IY in AAF74516. Ref.2

Secondary structure

.......................... 859
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (5) [UniParc].

Last modified May 1, 2000. Version 2.
Checksum: 93E334D9FBCC590E

FASTA85997,228
        10         20         30         40         50         60 
MKGDSRHLNE EEGASGYEEC IIVNGNFSDQ SSDTKDAPSP PVLEAICTEP VCTPETRGRR 

        70         80         90        100        110        120 
SSSRLSKREV SSLLNYTQDM TGDGDRDDEV DDGNGSDILM PKLTRETKDT RTRSESPAVR 

       130        140        150        160        170        180 
TRHSNGTSSL ERQRASPRIT RGRQGRHHVQ EYPVEFPATR SRRRRASSSA STPWSSPASV 

       190        200        210        220        230        240 
DFMEEVTPKS VSTPSVDLSQ DGDQEGMDTT QVDAESRDGD STEYQDDKEF GIGDLVWGKI 

       250        260        270        280        290        300 
KGFSWWPAMV VSWKATSKRQ AMPGMRWVQW FGDGKFSEIS ADKLVALGLF SQHFNLATFN 

       310        320        330        340        350        360 
KLVSYRKAMY HTLEKARVRA GKTFSSSPGE SLEDQLKPML EWAHGGFKPT GIEGLKPNKK 

       370        380        390        400        410        420 
QPVVNKSKVR RSDSRNLEPR RRENKSRRRT TNDSAASESP PPKRLKTNSY GGKDRGEDEE 

       430        440        450        460        470        480 
SRERMASEVT NNKGNLEDRC LSCGKKNPVS FHPLFEGGLC QSCRDRFLEL FYMYDEDGYQ 

       490        500        510        520        530        540 
SYCTVCCEGR ELLLCSNTSC CRCFCVECLE VLVGAGTAED AKLQEPWSCY MCLPQRCHGV 

       550        560        570        580        590        600 
LRRRKDWNMR LQDFFTTDPD LEEFEPPKLY PAIPAAKRRP IRVLSLFDGI ATGYLVLKEL 

       610        620        630        640        650        660 
GIKVEKYIAS EVCAESIAVG TVKHEGQIKY VNDVRKITKK NIEEWGPFDL VIGGSPCNDL 

       670        680        690        700        710        720 
SNVNPARKGL YEGTGRLFFE FYHLLNYTRP KEGDNRPFFW MFENVVAMKV NDKKDISRFL 

       730        740        750        760        770        780 
ACNPVMIDAI KVSAAHRARY FWGNLPGMNR PVMASKNDKL ELQDCLEFSR TAKLKKVQTI 

       790        800        810        820        830        840 
TTKSNSIRQG KNQLFPVVMN GKDDVLWCTE LERIFGFPAH YTDVSNMGRG ARQKLLGRSW 

       850 
SVPVIRHLFA PLKDYFACE 

« Hide

Isoform 2 (6) [UniParc].

Checksum: 59BF48AB459A1298
Show »

FASTA83994,793
Isoform 3 (8) [UniParc].

Checksum: 211E2DE8BF06C48E
Show »

FASTA77687,586
Isoform 4 (7) [UniParc].

Checksum: 0B7D93B4D802744E
Show »

FASTA79690,021

References

[1]"Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases."
Okano M., Xie S., Li E.
Nat. Genet. 19:219-220(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[2]"Cloning of full-length Dnmt3b cDNA and its alternative splicing isoforms in mouse embryo."
Yin B., Chen Y., Zhu N., Wu G., Shen Y.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao 21:431-438(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
Strain: KM.
Tissue: Embryo.
[3]"DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development."
Okano M., Bell D.W., Haber D.A., Li E.
Cell 99:247-257(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[4]"Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases."
Gowher H., Jeltsch A.
J. Biol. Chem. 277:20409-20414(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ALA-609; GLY-669; LEU-670; VAL-725; ASP-823 AND VAL-824.
[5]"Citrullination regulates pluripotency and histone H1 binding to chromatin."
Christophorou M.A., Castelo-Branco G., Halley-Stott R.P., Oliveira C.S., Loos R., Radzisheuskaya A., Mowen K.A., Bertone P., Silva J.C., Zernicka-Goetz M., Nielsen M.L., Gurdon J.B., Kouzarides T.
Nature 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: CITRULLINATION AT ARG-415.
[6]"Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin."
Lehnertz B., Ueda Y., Derijck A.A.H.A., Braunschweig U., Perez-Burgos L., Kubicek S., Chen T., Li E., Jenuwein T., Peters A.H.F.M.
Curr. Biol. 13:1192-1200(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUV39H1.
[7]"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.
[8]"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 EED AND EZH2.
[9]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)
[10]"The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin."
Chen T., Tsujimoto N., Li E.
Mol. Cell. Biol. 24:9048-9058(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 236-VAL-TRP-237; SER-277 AND 656-PRO-CYS-657.
[11]"Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L."
Gowher H., Liebert K., Hermann A., Xu G., Jeltsch A.
J. Biol. Chem. 280:13341-13348(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[12]"Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA."
Takeshima H., Suetake I., Shimahara H., Ura K., Tate S., Tajima S.
J. Biochem. 139:503-515(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing."
Linhart H.G., Lin H., Yamada Y., Moran E., Steine E.J., Gokhale S., Lo G., Cantu E., Ehrich M., He T., Meissner A., Jaenisch R.
Genes Dev. 21:3110-3122(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription."
Kim S.-H., Park J., Choi M.-C., Park J.-H., Kim H.-P., Lee J.-H., Oh D.-Y., Im S.-A., Bang Y.-J., Kim T.-Y.
Int. J. Biochem. Cell Biol. 40:2462-2471(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CBX4.
[15]"Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells."
Meilinger D., Fellinger K., Bultmann S., Rothbauer U., Bonapace I.M., Klinkert W.E., Spada F., Leonhardt H.
EMBO Rep. 10:1259-1264(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UHRF1.
[16]"Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation embryos."
Hirasawa R., Sasaki H.
Gene Expr. Patterns 9:27-30(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[17]"The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds."
Qiu C., Sawada K., Zhang X., Cheng X.
Nat. Struct. Biol. 9:217-224(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 219-362, FUNCTION, INTERACTION WITH DNA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF068626 mRNA. Translation: AAC40178.2.
AF068627 mRNA. Translation: AAC40179.2.
AF068628 mRNA. Translation: AAC40180.2.
AF151969 mRNA. Translation: AAF74515.1.
AF151970 mRNA. Translation: AAF74516.1.
AF151971 mRNA. Translation: AAF74517.1.
AF151972 mRNA. Translation: AAF74518.1.
AF151973 mRNA. Translation: AAF74519.1.
AF151974 mRNA. Translation: AAF74520.1.
AF151975 mRNA. Translation: AAF74521.1.
AF151976 mRNA. Translation: AAF74522.1.
RefSeqNP_001003960.2. NM_001003960.4.
NP_001003961.2. NM_001003961.4.
NP_001258673.1. NM_001271744.1.
NP_001258674.1. NM_001271745.1.
NP_001258676.1. NM_001271747.1.
NP_034198.3. NM_010068.5.
UniGeneMm.491804.
Mm.89772.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KHCX-ray1.80A219-362[»]
ProteinModelPortalO88509.
SMRO88509. Positions 223-357, 421-858.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199262. 9 interactions.
DIPDIP-43736N.
IntActO88509. 5 interactions.
MINTMINT-2523761.

Chemistry

ChEMBLCHEMBL2189115.

Protein family/group databases

REBASE3748. M.MmuDnmt3B.

PTM databases

PhosphoSiteO88509.

Proteomic databases

PaxDbO88509.
PRIDEO88509.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000072997; ENSMUSP00000072761; ENSMUSG00000027478. [O88509-1]
ENSMUST00000081628; ENSMUSP00000080334; ENSMUSG00000027478. [O88509-2]
ENSMUST00000088976; ENSMUSP00000086370; ENSMUSG00000027478. [O88509-4]
ENSMUST00000103150; ENSMUSP00000099439; ENSMUSG00000027478. [O88509-3]
ENSMUST00000103151; ENSMUSP00000099440; ENSMUSG00000027478. [O88509-3]
ENSMUST00000109772; ENSMUSP00000105394; ENSMUSG00000027478. [O88509-4]
ENSMUST00000109773; ENSMUSP00000105395; ENSMUSG00000027478. [O88509-2]
ENSMUST00000109774; ENSMUSP00000105396; ENSMUSG00000027478. [O88509-1]
GeneID13436.
KEGGmmu:13436.
UCSCuc008nib.2. mouse. [O88509-1]

Organism-specific databases

CTD1789.
MGIMGI:1261819. Dnmt3b.

Phylogenomic databases

eggNOGNOG70699.
GeneTreeENSGT00390000008341.
HOGENOMHOG000230875.
HOVERGENHBG051381.
KOK17399.
OrthoDBEOG7MWGW6.
TreeFamTF329039.

Enzyme and pathway databases

BRENDA2.1.1.37. 3474.

Gene expression databases

ArrayExpressO88509.
BgeeO88509.
CleanExMM_DNMT3B.
GenevestigatorO88509.

Family and domain databases

InterProIPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR025811. C5_MeTrfase_3.
IPR000313. PWWP_dom.
IPR011011. Znf_FYVE_PHD.
[Graphical view]
PfamPF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTSM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMSSF57903. SSF57903. 1 hit.
PROSITEPS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDNMT3B. mouse.
EvolutionaryTraceO88509.
NextBio283873.
PROO88509.
SOURCESearch...

Entry information

Entry nameDNM3B_MOUSE
AccessionPrimary (citable) accession number: O88509
Secondary accession number(s): O88510, O88511
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 126 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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