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Protein

DNA (cytosine-5)-methyltransferase 3A

Gene

Dnmt3a

Organism
Rattus norvegicus (Rat)
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. Can actively repress transcription through the recruitment of HDAC activity (By similarity).By similarity

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.By similarity

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

Keywordsi

Molecular functionChromatin regulator, DNA-binding, Methyltransferase, Repressor, Transferase
Biological processTranscription, Transcription regulation
LigandMetal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-212300 PRC2 methylates histones and DNA
R-RNO-3214858 RMTs methylate histone arginines

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 3A (EC:2.1.1.37)
Short name:
Dnmt3a
Gene namesi
Name:Dnmt3a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi1303336 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003130301 – 908DNA (cytosine-5)-methyltransferase 3AAdd BLAST908

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei102PhosphoserineCombined sources1
Modified residuei120PhosphothreonineCombined sources1
Cross-linki158Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei167Omega-N-methylarginineBy similarity1
Modified residuei239PhosphoserineCombined sources1
Modified residuei251PhosphoserineCombined sources1
Modified residuei257PhosphothreonineBy similarity1
Modified residuei386PhosphoserineBy similarity1
Modified residuei389PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ1LZ53
PRIDEiQ1LZ53

PTM databases

iPTMnetiQ1LZ53
PhosphoSitePlusiQ1LZ53

Expressioni

Gene expression databases

BgeeiENSRNOG00000026649 Expressed in 9 organ(s), highest expression level in skeletal muscle tissue
GenevisibleiQ1LZ53 RN

Interactioni

Subunit structurei

Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (By similarity). Interacts with DNMT1 and DNMT3B. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain (By similarity). Interacts with the PRC2/EED-EZH2 complex (By similarity). Interacts with UBC9, PIAS1 and PIAS2 (By similarity). Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). Interacts with UHRF1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000046524

Structurei

3D structure databases

ProteinModelPortaliQ1LZ53
SMRiQ1LZ53
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini257 – 315PWWPPROSITE-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 complexBy similarityAdd BLAST93
Regioni637 – 641S-adenosyl-L-methionine bindingBy similarity5
Regioni682 – 684S-adenosyl-L-methionine bindingBy similarity3
Regioni887 – 889S-adenosyl-L-methionine bindingBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi479 – 527Cys-richAdd BLAST49

Domaini

The PWWP domain is essential for targeting to pericentric heterochromatin.

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
InParanoidiQ1LZ53
KOiK17398
OMAiYTEMWVE
OrthoDBiEOG091G01TP
PhylomeDBiQ1LZ53
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
Isoform 1 (identifier: Q1LZ53-1) [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 ISSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR
60 70 80 90 100
KRKHPPVESS DTPKDPAVTT KSQPTAQDSG 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 NAVEESQASG ESQKVEEASP PAVQQPTDPA
260 270 280 290 300
SPTVATTPEP VGADAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS
310 320 330 340 350
WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF
360 370 380 390 400
HQATYNKQPM YRKAIYEVLQ VASSRAGKLF PACHDSDESD TGKAVEVQNK
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):101,669
Last modified:May 30, 2006 - v1
Checksum:i6CCE9EB4E9CEB409
GO
Isoform 2 (identifier: Q1LZ53-2) [UniParc]FASTAAdd to basket

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

Show »
Length:689
Mass (Da):77,825
Checksum:i1C75674CFC1C97BE
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0299861 – 219Missing in isoform 2. 1 PublicationAdd BLAST219

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BN000395 mRNA Translation: CAE52317.1
BN000396 mRNA Translation: CAE52318.1
RefSeqiNP_001003957.1, NM_001003957.1 [Q1LZ53-2]
NP_001003958.1, NM_001003958.1 [Q1LZ53-1]
XP_017449755.1, XM_017594266.1 [Q1LZ53-1]
XP_017449756.1, XM_017594267.1 [Q1LZ53-1]
XP_017449757.1, XM_017594268.1 [Q1LZ53-1]
UniGeneiRn.92659

Genome annotation databases

EnsembliENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649 [Q1LZ53-1]
ENSRNOT00000089093; ENSRNOP00000069441; ENSRNOG00000026649 [Q1LZ53-2]
GeneIDi444984
KEGGirno:444984

Keywords - Coding sequence diversityi

Alternative promoter usage

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BN000395 mRNA Translation: CAE52317.1
BN000396 mRNA Translation: CAE52318.1
RefSeqiNP_001003957.1, NM_001003957.1 [Q1LZ53-2]
NP_001003958.1, NM_001003958.1 [Q1LZ53-1]
XP_017449755.1, XM_017594266.1 [Q1LZ53-1]
XP_017449756.1, XM_017594267.1 [Q1LZ53-1]
XP_017449757.1, XM_017594268.1 [Q1LZ53-1]
UniGeneiRn.92659

3D structure databases

ProteinModelPortaliQ1LZ53
SMRiQ1LZ53
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000046524

PTM databases

iPTMnetiQ1LZ53
PhosphoSitePlusiQ1LZ53

Proteomic databases

PaxDbiQ1LZ53
PRIDEiQ1LZ53

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649 [Q1LZ53-1]
ENSRNOT00000089093; ENSRNOP00000069441; ENSRNOG00000026649 [Q1LZ53-2]
GeneIDi444984
KEGGirno:444984

Organism-specific databases

CTDi1788
RGDi1303336 Dnmt3a

Phylogenomic databases

eggNOGiENOG410IGHW Eukaryota
ENOG410XQ4Y LUCA
GeneTreeiENSGT00390000008341
HOGENOMiHOG000230875
HOVERGENiHBG051381
InParanoidiQ1LZ53
KOiK17398
OMAiYTEMWVE
OrthoDBiEOG091G01TP
PhylomeDBiQ1LZ53
TreeFamiTF329039

Enzyme and pathway databases

ReactomeiR-RNO-212300 PRC2 methylates histones and DNA
R-RNO-3214858 RMTs methylate histone arginines

Miscellaneous databases

PROiPR:Q1LZ53

Gene expression databases

BgeeiENSRNOG00000026649 Expressed in 9 organ(s), highest expression level in skeletal muscle tissue
GenevisibleiQ1LZ53 RN

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_RAT
AccessioniPrimary (citable) accession number: Q1LZ53
Secondary accession number(s): Q1LZ52
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: May 30, 2006
Last modified: November 7, 2018
This is version 103 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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