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Protein

DNA (cytosine-5)-methyltransferase 3-like

Gene

Dnmt3l

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme and pathway databases

ReactomeiR-MMU-5334118. DNA methylation.

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

GO - Cellular componenti

  • condensed nuclear chromosome Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • nuclear heterochromatin Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI

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. 6 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:SF15. PTHR23068:SF15. 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

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.

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: June 7, 2017
This is version 132 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot