Reviewed,
UniProtKB/Swiss-Prot O88508 (DNM3A_MOUSE)
Last modified
November 3, 2009.
Version 95.
History...
Clusters with 100%,
90%,
50% identity |
Documents (2) |
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Names and origin
| Protein names | Recommended name: DNA (cytosine-5)-methyltransferase 3A Short name=Dnmt3a EC=2.1.1.37 Alternative name(s): DNA methyltransferase MmuIIIA Short name=DNA MTase MmuIIIA Short name=M.MmuIIIA | ||
| Gene names |
| ||
| Organism | Mus musculus (Mouse) | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 908 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence 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. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZNF238. Can actively repress transcription through the recruitment of HDAC activity. Ref.5 Ref.6 Ref.8 Ref.9 Ref.12 Ref.15 Ref.19 Ref.20 |
| 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.19 Ref.14 |
| Subunit structure | Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with DNMT1 and DNMT3B By similarity. Binds the ZNF238 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD-type zinc-finger. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9, PIAS1 and PIAS2. |
| Subcellular location | Nucleus. Cytoplasm By similarity. Note: Accumulates in the major satellite repeats at pericentric heterochromatin. |
| Tissue specificity | Isoform 1 is expressed ubiquitously at low levels. Expression of isoform 2 is restricted to tissues containing cells which are undergoing active de novo methylation, including spleen, testis and thymus. Ref.4 |
| Developmental stage | At E7.5, the protein is moderately expressed in embryonic ectoderm and weakly in mesodermal cells. At E8.5 and E9.5, the expression become ubiquitous with an increase in the somites and in the ventral part of the embryo. Ref.5 |
| Domain | The PWWP domain is essential for targeting to pericentric heterochromatin. |
| Post-translational modification | Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription. Ref.13 |
| Sequence similarities | Belongs to the C5-methyltransferase family. Contains 1 ADD-type zinc finger. Contains 1 PWWP domain. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select] | ||||||
| Isoform 1 (identifier: O88508-1) 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: O88508-2) The sequence of this isoform differs from the canonical sequence as follows: 1-219: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 908 | 908 | DNA (cytosine-5)-methyltransferase 3A | PRO_0000088044 | |||||
Regions | |||||||||
| Domain | 288 – 346 | 59 | PWWP | ||||||
| Zinc finger | 490 – 582 | 93 | ADD-type | ||||||
| Region | 195 – 399 | 205 | Interaction with DNMT1 and DNMT3B By similarity | ||||||
| Region | 490 – 582 | 93 | Interaction with the PRC2/EED-EZH2 complex | ||||||
Sites | |||||||||
| Active site | 706 | 1 | By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 102 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 219 | 219 | Missing in isoform 2. | VSP_009423 | |||||
Experimental info | |||||||||
| Mutagenesis | 302 – 303 | 2 | WP → ST: Prevents accumulation in pericentric heterochromatin. Ref.11 | ||||||
| Mutagenesis | 636 | 1 | F → A: Reduces activity about 20-fold. Loss of substrate binding. Ref.11 Ref.16 | ||||||
| Mutagenesis | 660 | 1 | E → A: Reduces activity about 15-fold. Loss of substrate binding. Ref.11 Ref.16 | ||||||
| Mutagenesis | 682 | 1 | D → A: Strongly reduces substrate binding. No effect on activity. Ref.11 Ref.16 | ||||||
| Mutagenesis | 705 – 706 | 2 | PC → VD: No effect on localization. Ref.11 Ref.16 | ||||||
| Mutagenesis | 706 | 1 | C → A: Reduces activity about 5-fold. Reduces DNA-binding capacity. Ref.11 Ref.16 | ||||||
| Mutagenesis | 707 | 1 | N → Q: Reduces activity about 3-fold. Ref.11 Ref.16 | ||||||
| Mutagenesis | 710 | 1 | S → A: No effect on activity. Ref.11 Ref.16 | ||||||
| Mutagenesis | 716 | 1 | R → A: Reduces activity about 30-fold. Reduces DNA-binding capacity. Ref.11 Ref.16 | ||||||
| Mutagenesis | 717 | 1 | K → A: Reduces activity about 3-fold. Ref.11 Ref.16 | ||||||
| Mutagenesis | 728 | 1 | F → A: Loss of activity du to the incapacity to bind the regulatory subunit DNMT3L. Ref.19 Ref.11 | ||||||
| Mutagenesis | 752 | 1 | E → A: Reduces activity about 10-fold. Ref.11 Ref.16 | ||||||
| Mutagenesis | 753 | 1 | N → A: Reduces activity about 10-fold. Ref.11 Ref.16 | ||||||
| Mutagenesis | 788 | 1 | R → A: Reduces activity about 15-fold. Ref.11 Ref.16 | ||||||
| Mutagenesis | 827 | 1 | R → A: Reduces activity about 2-fold. Reduces DNA-binding capacity. Ref.11 Ref.16 | ||||||
| Mutagenesis | 832 | 1 | R → A: Reduces DNA-binding capacity. No effect on activity. Ref.11 Ref.16 | ||||||
| Mutagenesis | 878 | 1 | R → A: Reduces activity about 6-fold. Reduces DNA-binding capacity. Ref.11 Ref.16 | ||||||
| Mutagenesis | 881 | 1 | R → A: Loss of activity. Strongly reduces substrate binding. Ref.11 Ref.16 | ||||||
| Mutagenesis | 883 | 1 | R → A: Reduces activity about 3-fold. Reduces DNA-binding capacity. Ref.11 Ref.16 | ||||||
| Sequence conflict | 151 | 1 | Q → P in AAH07466. Ref.4 | ||||||
| Sequence conflict | 775 | 1 | M → T in BAB28644. Ref.3 | ||||||
| Sequence conflict | 781 | 1 | V → G in BAB28644. Ref.3 | ||||||
| Sequence conflict | 791 | 1 | W → R in BAB28644. Ref.3 | ||||||
| Sequence conflict | 809 | 1 | L → P in BAB28644. Ref.3 | ||||||
| Sequence conflict | 904 | 1 | Y → I in BAB28644. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' 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: 9662389] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Mammary gland. |
| [3] | "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. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6 and C57BL/6J. Tissue: Brain, Embryo and Skin. |
| [4] | "A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation." Chen T., Ueda Y., Xie S., Li E. J. Biol. Chem. 277:38746-38754(2002) [PubMed: 12138111] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, ALTERNATIVE PROMOTER USAGE, TISSUE SPECIFICITY. Strain: 129/SvJ. |
| [5] | "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: 10555141] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE. |
| [6] | "Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: the enzyme modifies DNA in a non-processive manner and also methylates non-CpG correction sites." Gowher H., Jeltsch A. J. Mol. Biol. 309:1201-1208(2001) [PubMed: 11399089] [Abstract] Cited for: FUNCTION. |
| [7] | Erratum Gowher H., Jeltsch A. J. Mol. Biol. 310:951-951(2001) |
| [8] | "Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription." Fuks F., Burgers W.A., Godin N., Kasai M., Kouzarides T. EMBO J. 20:2536-2544(2001) [PubMed: 11350943] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZNF238 AND HDAC1. |
| [9] | "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: 11919202] [Abstract] Cited for: FUNCTION. |
| [10] | "Biochemical fractionation reveals association of DNA methyltransferase (Dnmt) 3b with Dnmt1 and that of Dnmt 3a with a histone H3 methyltransferase and Hdac1." Datta J., Ghoshal K., Sharma S.M., Tajima S., Jacob S.T. J. Cell. Biochem. 88:855-864(2003) [PubMed: 12616525] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH HDAC1. |
| [11] | "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: 15456878] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 302-VAL-PRO-303 AND 705-PRO-CYS-706. |
| [12] | "Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting." Kaneda M., Okano M., Hata K., Sado T., Tsujimoto N., Li E., Sasaki H. Nature 429:900-903(2004) [PubMed: 15215868] [Abstract] Cited for: FUNCTION. |
| [13] | "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription." Ling Y., Sankpal U.T., Robertson A.K., McNally J.G., Karpova T., Robertson K.D. Nucleic Acids Res. 32:598-610(2004) [PubMed: 14752048] [Abstract] Cited for: SUMOYLATION, INTERACTION WITH UBC9; PIAS1 AND PIAS2. |
| [14] | "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: 15671018] [Abstract] Cited for: ENZYME REGULATION. |
| [15] | "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: 16567415] [Abstract] Cited for: FUNCTION. |
| [16] | "Mutational analysis of the catalytic domain of the murine Dnmt3a DNA-(cytosine C5)-methyltransferase." Gowher H., Loutchanwoot P., Vorobjeva O., Handa V., Jurkowska R.Z., Jurkowski T.P., Jeltsch A. J. Mol. Biol. 357:928-941(2006) [PubMed: 16472822] [Abstract] Cited for: MUTAGENESIS OF PHE-636; GLU-660; ASP-682; CYS-706; ASN-707; SER-710; ARG-716; LYS-717; GLU-752; ASN-753; ARG-788; ARG-827; ARG-832; ARG-878; ARG-881 AND ARG-883. |
| [17] | "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: 16357870] [Abstract] Cited for: INTERACTION WITH THE PRC2/EED-EZH2 COMPLEX. |
| [18] | 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) |
| [19] | "Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation." Jia D., Jurkowska R.Z., Zhang X., Jeltsch A., Cheng X. Nature 449:248-251(2007) [PubMed: 17713477] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF PHE-728. |
| [20] | "Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by histone H1." Takeshima H., Suetake I., Tajima S. J. Mol. Biol. 383:810-821(2008) [PubMed: 18823905] [Abstract] Cited for: FUNCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AF068625 mRNA. Translation: AAC40177.2. AF480164 mRNA. Translation: AAN40038.1. AK013096 mRNA. Translation: BAB28644.2. Different initiation. AK090132 mRNA. Translation: BAC41110.1. AK147263 mRNA. Translation: BAE27806.1. AK147627 mRNA. Translation: BAE28033.1. AK147642 mRNA. Translation: BAE28043.1. AK147676 mRNA. Translation: BAE28067.1. AK157792 mRNA. Translation: BAE34200.1. BC007466 mRNA. Translation: AAH07466.1. | |
| IPI | IPI00131694. IPI00172129. |
| RefSeq | NP_031898.1. NP_714965.1. |
| UniGene | Mm.470389 Mm.5001 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1KHC based on UniProtKB O88509. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | O88508. 1 interaction. |
| STRING | O88508. |
Protein family/group databases | |
| REBASE | 3747. M.MmuDnmt3A. |
PTM databases | |
| PhosphoSite | O88508. |
Proteomic databases | |
| PRIDE | O88508. |
Genome annotation databases | |
| Ensembl | ENSMUST00000020991; ENSMUSP00000020991; ENSMUSG00000020661; Mus musculus. [Genome view] ENSMUST00000085826; ENSMUSP00000082985; ENSMUSG00000020661; Mus musculus. [Genome view] ENSMUST00000111186; ENSMUSP00000106817; ENSMUSG00000020661; Mus musculus. [Genome view] |
| GeneID | 13435. |
| KEGG | mmu:13435. |
| UCSC | uc007mxb.1. mouse. uc007mxd.1. mouse. |
Organism-specific databases | |
| CTD | 13435. |
| MGI | MGI:1261827. Dnmt3a. |
Phylogenomic databases | |
| HOGENOM | O88508. |
| HOVERGEN | O88508. |
| OMA | TNIESMK. |
Enzyme and pathway databases | |
| BRENDA | 2.1.1.37. 244. |
Gene expression databases | |
| ArrayExpress | O88508. |
| Bgee | O88508. |
| CleanEx | MM_DNMT3A. |
| Genevestigator | O88508. |
| GermOnline | ENSMUSG00000020661. Mus musculus. |
Family and domain databases | |
| InterPro | IPR001525. C5_DNA_meth. IPR018117. C5_DNA_meth_AS. IPR000313. PWWP. [Graphical view] |
| Pfam | PF00145. DNA_methylase. 1 hit. PF00855. PWWP. 1 hit. [Graphical view] |
| SMART | SM00293. PWWP. 1 hit. [Graphical view] |
| PROSITE | PS00094. C5_MTASE_1. 1 hit. PS00095. C5_MTASE_2. False negative. PS50812. PWWP. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 283867. |
| SOURCE | Search... |
Entry information
| Entry name | DNM3A_MOUSE | ||||||||
| Accession | Primary (citable) accession number: O88508 Secondary accession number(s): Q3TZK8 Q9CSE1 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


