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UniProtKB - O88508 (DNM3A_MOUSE)

Protein

DNA (cytosine-5)-methyltransferase 3A

Gene

Dnmt3a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionChromatin regulator, DNA-binding, Methyltransferase, Repressor, Transferase
Biological processTranscription, Transcription regulation
LigandMetal-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

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1261827 Dnmt3a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
Cross-linki158Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
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

Isopeptide bond, 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

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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi199261, 18 interactors
DIPiDIP-38005N
IntActiO88508, 13 interactors
MINTiO88508
STRINGi10090.ENSMUSP00000020991

Structurei

3D structure databases

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

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
OrthoDBiEOG091G01TP
PhylomeDBiO88508
TreeFamiTF329039

Family and domain databases

InterProiView protein in InterPro
IPR025766 ADD
IPR018117 C5_DNA_meth_AS
IPR001525 C5_MeTfrase
IPR030487 DNMT3A
IPR000313 PWWP_dom
IPR029063 SAM-dependent_MTases
PANTHERiPTHR23068:SF10 PTHR23068:SF10, 1 hit
PfamiView protein in Pfam
PF00145 DNA_methylase, 1 hit
PF00855 PWWP, 1 hit
SMARTiView protein in SMART
SM00293 PWWP, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51533 ADD, 1 hit
PS00094 C5_MTASE_1, 1 hit
PS50812 PWWP, 1 hit
PS51679 SAM_MT_C5, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3UX07G3UX07_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
193Annotation score:
G3UZK0G3UZK0_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
181Annotation score:
G3UZF8G3UZF8_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
140Annotation score:
G3UZG8G3UZG8_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
107Annotation score:
G3UXY2G3UXY2_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
332Annotation score:
G3UZH2G3UZH2_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
72Annotation score:
G3UZN5G3UZN5_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
184Annotation score:
G3UX63G3UX63_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
94Annotation score:
G3UY43G3UY43_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
72Annotation score:
G3UZU0G3UZU0_MOUSE
DNA (cytosine-5)-methyltransferase ...
Dnmt3a
41Annotation score:
There is more potential isoformShow all

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

Similar proteinsi

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, 13 interactors
MINTiO88508
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
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

Miscellaneous databases

ChiTaRSiDnmt3a mouse
PROiPR:O88508
SOURCEiSearch...

Gene expression databases

CleanExiMM_DNMT3A
ExpressionAtlasiO88508 baseline and differential
GenevisibleiO88508 MM

Family and domain databases

InterProiView protein in InterPro
IPR025766 ADD
IPR018117 C5_DNA_meth_AS
IPR001525 C5_MeTfrase
IPR030487 DNMT3A
IPR000313 PWWP_dom
IPR029063 SAM-dependent_MTases
PANTHERiPTHR23068:SF10 PTHR23068:SF10, 1 hit
PfamiView protein in Pfam
PF00145 DNA_methylase, 1 hit
PF00855 PWWP, 1 hit
SMARTiView protein in SMART
SM00293 PWWP, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51533 ADD, 1 hit
PS00094 C5_MTASE_1, 1 hit
PS50812 PWWP, 1 hit
PS51679 SAM_MT_C5, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDNM3A_MOUSE
AccessioniPrimary (citable) accession number: O88508
Secondary accession number(s): Q3TZK8
, Q3UH24, Q8CJ60, Q922J0, Q9CSE1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 184 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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