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Protein

DNA (cytosine-5)-methyltransferase 3A

Gene

Dnmt3a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity.8 Publications

Catalytic activityi

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

Enzyme regulationi

Activated by binding to the regulatory factor DNMT3L.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei660S-adenosyl-L-methionineBy similarity1
Active sitei706PROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri489 – 519GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST31
Zinc fingeri530 – 586PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST57

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

BRENDAi2.1.1.37. 3474.
ReactomeiR-MMU-212300. PRC2 methylates histones and DNA.
R-MMU-3214858. RMTs methylate histone arginines.
R-MMU-5334118. DNA methylation.

Protein family/group databases

REBASEi3747. M.MmuDnmt3A.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 3A (EC:2.1.1.37)
Short name:
Dnmt3a
Alternative name(s):
DNA methyltransferase MmuIIIA
Short name:
DNA MTase MmuIIIA
Short name:
M.MmuIIIA
Gene namesi
Name:Dnmt3a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1261827. Dnmt3a.

Subcellular locationi

GO - Cellular componenti

  • chromosome, centromeric region Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • euchromatin Source: UniProtKB
  • heterochromatin Source: MGI
  • nuclear heterochromatin Source: MGI
  • nuclear matrix Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • XY body Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi302 – 303WP → ST: Prevents accumulation in pericentric heterochromatin. 1 Publication2
Mutagenesisi636F → A: Reduces activity about 20-fold. Loss of substrate binding. 1 Publication1
Mutagenesisi660E → A: Reduces activity about 15-fold. Loss of substrate binding. 1 Publication1
Mutagenesisi682D → A: Strongly reduces substrate binding. No effect on activity. 1 Publication1
Mutagenesisi705 – 706PC → VD: No effect on localization. 1 Publication2
Mutagenesisi706C → A: Reduces activity about 5-fold. Reduces DNA-binding capacity. 1 Publication1
Mutagenesisi707N → Q: Reduces activity about 3-fold. 1 Publication1
Mutagenesisi710S → A: No effect on activity. 1 Publication1
Mutagenesisi716R → A: Reduces activity about 30-fold. Reduces DNA-binding capacity. 1 Publication1
Mutagenesisi717K → A: Reduces activity about 3-fold. 1 Publication1
Mutagenesisi728F → A: Loss of activity du to the incapacity to bind the regulatory subunit DNMT3L. 1 Publication1
Mutagenesisi752E → A: Reduces activity about 10-fold. 1 Publication1
Mutagenesisi753N → A: Reduces activity about 10-fold. 1 Publication1
Mutagenesisi788R → A: Reduces activity about 15-fold. 1 Publication1
Mutagenesisi827R → A: Reduces activity about 2-fold. Reduces DNA-binding capacity. 1 Publication1
Mutagenesisi832R → A: Reduces DNA-binding capacity. No effect on activity. 1 Publication1
Mutagenesisi878R → A: Reduces activity about 6-fold. Reduces DNA-binding capacity. 1 Publication1
Mutagenesisi881R → A: Loss of activity. Strongly reduces substrate binding. 1 Publication1
Mutagenesisi883R → A: Reduces activity about 3-fold. Reduces DNA-binding capacity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3108652.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880441 – 908DNA (cytosine-5)-methyltransferase 3AAdd BLAST908

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei102PhosphoserineCombined sources1
Modified residuei120PhosphothreonineBy similarity1
Modified residuei167Omega-N-methylarginineCombined sources1
Modified residuei239PhosphoserineBy similarity1
Modified residuei251PhosphoserineBy similarity1
Modified residuei257PhosphothreonineCombined sources1
Modified residuei386PhosphoserineCombined sources1
Modified residuei389PhosphoserineCombined sources1

Post-translational modificationi

Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO88508.
MaxQBiO88508.
PaxDbiO88508.
PeptideAtlasiO88508.
PRIDEiO88508.

PTM databases

iPTMnetiO88508.
PhosphoSitePlusiO88508.

Expressioni

Tissue specificityi

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.1 Publication

Developmental stagei

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.1 Publication

Gene expression databases

BgeeiENSMUSG00000020661.
CleanExiMM_DNMT3A.
ExpressionAtlasiO88508. baseline and differential.
GenevisibleiO88508. MM.

Interactioni

Subunit structurei

Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with DNMT1 and DNMT3B. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4) (By similarity). Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9, PIAS1 and PIAS2.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dnmt3lQ9CWR86EBI-995154,EBI-3043871
HellsQ608484EBI-995154,EBI-3043887

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199261. 18 interactors.
DIPiDIP-38005N.
IntActiO88508. 11 interactors.
MINTiMINT-2521021.
STRINGi10090.ENSMUSP00000020991.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3SW9X-ray3.05P/Q39-50[»]
3SWCX-ray2.33P/Q39-50[»]
ProteinModelPortaliO88508.
SMRiO88508.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini288 – 346PWWPPROSITE-ProRule annotationAdd BLAST59
Domaini478 – 610ADDPROSITE-ProRule annotationAdd BLAST133
Domaini630 – 908SAM-dependent MTase C5-typePROSITE-ProRule annotationAdd BLAST279

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni195 – 399Interaction with DNMT1 and DNMT3BBy similarityAdd BLAST205
Regioni490 – 582Interaction with the PRC2/EED-EZH2 complexAdd BLAST93
Regioni637 – 641S-adenosyl-L-methionine bindingBy similarity5
Regioni682 – 684S-adenosyl-L-methionine bindingBy similarity3
Regioni887 – 889S-adenosyl-L-methionine bindingBy similarity3

Domaini

The PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) (PubMed:20547484).1 Publication

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.PROSITE-ProRule annotation
Contains 1 ADD domain.PROSITE-ProRule annotation
Contains 1 GATA-type zinc finger.PROSITE-ProRule annotation
Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation
Contains 1 PWWP domain.PROSITE-ProRule annotation
Contains 1 SAM-dependent MTase C5-type domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri489 – 519GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST31
Zinc fingeri530 – 586PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST57

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IGHW. Eukaryota.
ENOG410XQ4Y. LUCA.
GeneTreeiENSGT00390000008341.
HOGENOMiHOG000230875.
HOVERGENiHBG051381.
InParanoidiO88508.
KOiK17398.
OMAiYTEMWVE.
OrthoDBiEOG091G01TP.
PhylomeDBiO88508.
TreeFamiTF329039.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR030487. DNMT3A.
IPR000313. PWWP_dom.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR23068:SF10. PTHR23068:SF10. 1 hit.
PfamiPF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTiSM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform 1 (identifier: O88508-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPSSGPGDTS SSSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR
60 70 80 90 100
KRKHPPVESS DTPKDPAVTT KSQPMAQDSG PSDLLPNGDL EKRSEPQPEE
110 120 130 140 150
GSPAAGQKGG APAEGEGTET PPEASRAVEN GCCVTKEGRG ASAGEGKEQK
160 170 180 190 200
QTNIESMKME GSRGRLRGGL GWESSLRQRP MPRLTFQAGD PYYISKRKRD
210 220 230 240 250
EWLARWKREA EKKAKVIAVM NAVEENQASG ESQKVEEASP PAVQQPTDPA
260 270 280 290 300
SPTVATTPEP VGGDAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS
310 320 330 340 350
WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF
360 370 380 390 400
HQATYNKQPM YRKAIYEVLQ VASSRAGKLF PACHDSDESD SGKAVEVQNK
410 420 430 440 450
QMIEWALGGF QPSGPKGLEP PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA
460 470 480 490 500
KKPRKSTTEK PKVKEIIDER TRERLVYEVR QKCRNIEDIC ISCGSLNVTL
510 520 530 540 550
EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR EVLMCGNNNC
560 570 580 590 600
CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR
610 620 630 640 650
LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG
660 670 680 690 700
IQVDRYIASE VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV
710 720 730 740 750
IGGSPCNDLS IVNPARKGLY EGTGRLFFEF YRLLHDARPK EGDDRPFFWL
760 770 780 790 800
FENVVAMGVS DKRDISRFLE SNPVMIDAKE VSAAHRARYF WGNLPGMNRP
810 820 830 840 850
LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK DQHFPVFMNE
860 870 880 890 900
KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP

LKEYFACV
Length:908
Mass (Da):101,672
Last modified:May 1, 2000 - v2
Checksum:i5F98D5A8092C84A5
GO
Isoform 2 (identifier: O88508-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-219: Missing.

Show »
Length:689
Mass (Da):77,824
Checksum:i0C1093AF43717684
GO

Sequence cautioni

The sequence BAB28644 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti151Q → P in AAH07466 (PubMed:12138111).Curated1
Sequence conflicti775M → T in BAB28644 (PubMed:16141072).Curated1
Sequence conflicti781V → G in BAB28644 (PubMed:16141072).Curated1
Sequence conflicti791W → R in BAB28644 (PubMed:16141072).Curated1
Sequence conflicti809L → P in BAB28644 (PubMed:16141072).Curated1
Sequence conflicti904Y → I in BAB28644 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0094231 – 219Missing in isoform 2. 2 PublicationsAdd BLAST219

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS25784.1. [O88508-2]
CCDS36397.1. [O88508-1]
RefSeqiNP_001258682.1. NM_001271753.1. [O88508-1]
NP_031898.1. NM_007872.4. [O88508-1]
NP_714965.1. NM_153743.4. [O88508-2]
XP_006515016.1. XM_006514953.3. [O88508-1]
XP_006515019.1. XM_006514956.3. [O88508-1]
UniGeneiMm.470389.
Mm.5001.

Genome annotation databases

EnsembliENSMUST00000020991; ENSMUSP00000020991; ENSMUSG00000020661. [O88508-1]
ENSMUST00000111186; ENSMUSP00000106817; ENSMUSG00000020661. [O88508-2]
ENSMUST00000172689; ENSMUSP00000133543; ENSMUSG00000020661. [O88508-2]
ENSMUST00000174817; ENSMUSP00000134009; ENSMUSG00000020661. [O88508-1]
GeneIDi13435.
KEGGimmu:13435.
UCSCiuc007mxb.1. mouse. [O88508-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS25784.1. [O88508-2]
CCDS36397.1. [O88508-1]
RefSeqiNP_001258682.1. NM_001271753.1. [O88508-1]
NP_031898.1. NM_007872.4. [O88508-1]
NP_714965.1. NM_153743.4. [O88508-2]
XP_006515016.1. XM_006514953.3. [O88508-1]
XP_006515019.1. XM_006514956.3. [O88508-1]
UniGeneiMm.470389.
Mm.5001.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3SW9X-ray3.05P/Q39-50[»]
3SWCX-ray2.33P/Q39-50[»]
ProteinModelPortaliO88508.
SMRiO88508.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199261. 18 interactors.
DIPiDIP-38005N.
IntActiO88508. 11 interactors.
MINTiMINT-2521021.
STRINGi10090.ENSMUSP00000020991.

Chemistry databases

ChEMBLiCHEMBL3108652.

Protein family/group databases

REBASEi3747. M.MmuDnmt3A.

PTM databases

iPTMnetiO88508.
PhosphoSitePlusiO88508.

Proteomic databases

EPDiO88508.
MaxQBiO88508.
PaxDbiO88508.
PeptideAtlasiO88508.
PRIDEiO88508.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020991; ENSMUSP00000020991; ENSMUSG00000020661. [O88508-1]
ENSMUST00000111186; ENSMUSP00000106817; ENSMUSG00000020661. [O88508-2]
ENSMUST00000172689; ENSMUSP00000133543; ENSMUSG00000020661. [O88508-2]
ENSMUST00000174817; ENSMUSP00000134009; ENSMUSG00000020661. [O88508-1]
GeneIDi13435.
KEGGimmu:13435.
UCSCiuc007mxb.1. mouse. [O88508-1]

Organism-specific databases

CTDi1788.
MGIiMGI:1261827. Dnmt3a.

Phylogenomic databases

eggNOGiENOG410IGHW. Eukaryota.
ENOG410XQ4Y. LUCA.
GeneTreeiENSGT00390000008341.
HOGENOMiHOG000230875.
HOVERGENiHBG051381.
InParanoidiO88508.
KOiK17398.
OMAiYTEMWVE.
OrthoDBiEOG091G01TP.
PhylomeDBiO88508.
TreeFamiTF329039.

Enzyme and pathway databases

BRENDAi2.1.1.37. 3474.
ReactomeiR-MMU-212300. PRC2 methylates histones and DNA.
R-MMU-3214858. RMTs methylate histone arginines.
R-MMU-5334118. DNA methylation.

Miscellaneous databases

ChiTaRSiDnmt3a. mouse.
PROiO88508.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020661.
CleanExiMM_DNMT3A.
ExpressionAtlasiO88508. baseline and differential.
GenevisibleiO88508. MM.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR030487. DNMT3A.
IPR000313. PWWP_dom.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR23068:SF10. PTHR23068:SF10. 1 hit.
PfamiPF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTiSM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDNM3A_MOUSE
AccessioniPrimary (citable) accession number: O88508
Secondary accession number(s): Q3TZK8
, Q3UH24, Q8CJ60, Q922J0, Q9CSE1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 168 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.