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Protein

DNA (cytosine-5)-methyltransferase 3-like

Gene

Dnmt3l

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

Functioni

Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context (PubMed:11719692, PubMed:15318244, PubMed:15671018, PubMed:24074865). Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain (PubMed:15671018). Acts by accelerating the binding of DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases (PubMed:15671018). Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3 (By similarity). Plays a key role in embryonic stem cells and germ cells (PubMed:11719692, PubMed:15318244, PubMed:24074865). In germ cells, required for the methylation of imprinted loci together with DNMT3A (PubMed:11719692). In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization (PubMed:15318244). Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation (PubMed:24074865). While it promotes DNA methylation of housekeeping genes together with DNMT3A and DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter of bivalent genes (PubMed:24074865). Interacts with the EZH2 component of the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B with the PRC2/EED-EZH2 complex, leading to maintain low methylation levels at the promoters of bivalent genes (PubMed:24074865). Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression (PubMed:24074865).By similarity4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri86 – 116GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST31
Zinc fingeri127 – 183PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST57

GO - Molecular functioni

  • enzyme activator activity Source: MGI
  • enzyme binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • chorionic trophoblast cell differentiation Source: MGI
  • DNA methylation Source: MGI
  • DNA methylation involved in gamete generation Source: UniProtKB
  • DNA methylation on cytosine Source: UniProtKB
  • genetic imprinting Source: MGI
  • in utero embryonic development Source: MGI
  • male meiosis I Source: UniProtKB
  • methylation Source: MGI
  • negative regulation of DNA methylation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transposition Source: MGI
  • placenta development Source: MGI
  • positive regulation of DNA methylation Source: UniProtKB
  • spermatogenesis Source: UniProtKB
  • stem cell differentiation Source: UniProtKB

Keywordsi

Biological processDifferentiation, Spermatogenesis
LigandMetal-binding, Zinc

Protein family/group databases

REBASEi6168 M.MmuDnmt3L

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 3-like
Gene namesi
Name:Dnmt3l
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1859287 Dnmt3l

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

Nucleus

Pathology & Biotechi

Disruption phenotypei

Oogenesis in female mice takes place normally, but the heterozygous offspring of homozygous mutant females die before mid-gestation due to biallelic expression of imprinted genes normally methylated and silenced on the allele of maternal origin (PubMed:11719692). Male mice are viable but sterile, with a complete absence of germ cells in adult males (PubMed:11719692). Spermatocytes show asynapsis or abnormal synapsis, and do not progress to the full pachytene stage due to demethylation of methylation of both long-terminal-repeat (LTR) and non-LTR retrotransposons (PubMed:15318244).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi297F → A or E: Loss of binding to DNMT3A. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880481 – 421DNA (cytosine-5)-methyltransferase 3-likeAdd BLAST421

Proteomic databases

PaxDbiQ9CWR8
PRIDEiQ9CWR8

PTM databases

iPTMnetiQ9CWR8
PhosphoSitePlusiQ9CWR8

Expressioni

Tissue specificityi

Expressed in testis, thymus, ovary, and heart (PubMed:11306809).1 Publication

Developmental stagei

In testis, first observed in non-dividing prospermatogonia after 12.5 dpc and is highest at about the time of birth; expression declines rapidly after birth and is extinguished by 6 days post partum, when most prospermatogonia have differentiated into dividing spermatogonial stem cells (PubMed:15318244).1 Publication

Gene expression databases

BgeeiENSMUSG00000000730
CleanExiMM_DNMT3L
ExpressionAtlasiQ9CWR8 baseline and differential
GenevisibleiQ9CWR8 MM

Interactioni

Subunit structurei

Homodimer (By similarity). Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (By similarity). Interacts with histone H3 (via N-terminus); interaction is strongly inhibited by methylation at lysine 4 (H3K4me) (By similarity). Interacts with EZH2; the interaction is direct (PubMed:24074865).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi207659, 6 interactors
DIPiDIP-49029N
IntActiQ9CWR8, 7 interactors
STRINGi10090.ENSMUSP00000000746

Structurei

3D structure databases

ProteinModelPortaliQ9CWR8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini75 – 207ADDPROSITE-ProRule annotationAdd BLAST133

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri86 – 116GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST31
Zinc fingeri127 – 183PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST57

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IIXK Eukaryota
ENOG4111C55 LUCA
GeneTreeiENSGT00390000008341
HOGENOMiHOG000246422
HOVERGENiHBG051382
InParanoidiQ9CWR8
KOiK17400
OMAiHTQHPLF
OrthoDBiEOG091G08YY
PhylomeDBiQ9CWR8
TreeFamiTF329039

Family and domain databases

InterProiView protein in InterPro
IPR025766 ADD
IPR030486 DNMT3L
IPR011011 Znf_FYVE_PHD
PANTHERiPTHR23068:SF13 PTHR23068:SF13, 1 hit
SUPFAMiSSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS51533 ADD, 1 hit

Sequencei

Sequence statusi: Complete.

Q9CWR8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSRETPSSC SKTLETLDLE TSDSSSPDAD SPLEEQWLKS SPALKEDSVD
60 70 80 90 100
VVLEDCKEPL SPSSPPTGRE MIRYEVKVNR RSIEDICLCC GTLQVYTRHP
110 120 130 140 150
LFEGGLCAPC KDKFLESLFL YDDDGHQSYC TICCSGGTLF ICESPDCTRC
160 170 180 190 200
YCFECVDILV GPGTSERINA MACWVCFLCL PFSRSGLLQR RKRWRHQLKA
210 220 230 240 250
FHDQEGAGPM EIYKTVSAWK RQPVRVLSLF RNIDKVLKSL GFLESGSGSG
260 270 280 290 300
GGTLKYVEDV TNVVRRDVEK WGPFDLVYGS TQPLGSSCDR CPGWYMFQFH
310 320 330 340 350
RILQYALPRQ ESQRPFFWIF MDNLLLTEDD QETTTRFLQT EAVTLQDVRG
360 370 380 390 400
RDYQNAMRVW SNIPGLKSKH APLTPKEEEY LQAQVRSRSK LDAPKVDLLV
410 420
KNCLLPLREY FKYFSQNSLP L
Length:421
Mass (Da):47,993
Last modified:June 1, 2001 - v1
Checksum:i6C996D220C6F6D83
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ404467 mRNA Translation: CAB94726.1
AF220524 mRNA Translation: AAF73868.1
AK010434 mRNA Translation: BAB26936.1
BC083147 mRNA Translation: AAH83147.1
CCDSiCCDS23962.1
RefSeqiNP_001075164.1, NM_001081695.2
NP_001271126.1, NM_001284197.1
NP_062321.1, NM_019448.4
UniGeneiMm.13433

Genome annotation databases

EnsembliENSMUST00000000746; ENSMUSP00000000746; ENSMUSG00000000730
ENSMUST00000138785; ENSMUSP00000121562; ENSMUSG00000000730
ENSMUST00000151242; ENSMUSP00000116970; ENSMUSG00000000730
GeneIDi54427
KEGGimmu:54427
UCSCiuc007fxe.2 mouse

Similar proteinsi

Entry informationi

Entry nameiDNM3L_MOUSE
AccessioniPrimary (citable) accession number: Q9CWR8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: June 1, 2001
Last modified: April 25, 2018
This is version 137 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

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