UniProtKB - Q9CWR8 (DNM3L_MOUSE)
DNA (cytosine-5)-methyltransferase 3-like
Dnmt3l
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 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 86 – 116 | GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST | 31 | |
Zinc fingeri | 127 – 183 | PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST | 57 |
GO - Molecular functioni
- enzyme activator activity Source: MGI
- enzyme binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- C-5 methylation of cytosine Source: MGI
- chorionic trophoblast cell differentiation Source: MGI
- DNA methylation Source: MGI
- DNA methylation involved in gamete generation Source: UniProtKB
- DNA methylation on cytosine Source: UniProtKB
- genomic 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 process | Differentiation, Spermatogenesis |
Ligand | Metal-binding, Zinc |
Protein family/group databases
REBASEi | 6168, M.MmuDnmt3L |
Names & Taxonomyi
Protein namesi | Recommended name: DNA (cytosine-5)-methyltransferase 3-like |
Gene namesi | Name:Dnmt3l |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1859287, Dnmt3l |
VEuPathDBi | HostDB:ENSMUSG00000000730 |
Subcellular locationi
Nucleus
- Nucleus Curated
Nucleus
- condensed nuclear chromosome Source: MGI
- nucleoplasm Source: Reactome
- nucleus Source: MGI
Other locations
- catalytic complex Source: MGI
- cytoplasm Source: MGI
- heterochromatin Source: MGI
Keywords - Cellular componenti
NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 297 | F → A or E: Loss of binding to DNMT3A. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000088048 | 1 – 421 | DNA (cytosine-5)-methyltransferase 3-likeAdd BLAST | 421 |
Proteomic databases
PaxDbi | Q9CWR8 |
PRIDEi | Q9CWR8 |
PTM databases
iPTMneti | Q9CWR8 |
PhosphoSitePlusi | Q9CWR8 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000000730, Expressed in liver and 122 other tissues |
Genevisiblei | Q9CWR8, 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).
Interacts with SPOCD1 (PubMed:32674113).
By similarity2 PublicationsBinary interactionsi
Q9CWR8
GO - Molecular functioni
- enzyme binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 207659, 6 interactors |
DIPi | DIP-49029N |
IntActi | Q9CWR8, 8 interactors |
MINTi | Q9CWR8 |
STRINGi | 10090.ENSMUSP00000121562 |
Miscellaneous databases
RNActi | Q9CWR8, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 75 – 207 | ADDPROSITE-ProRule annotationAdd BLAST | 133 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 39 | DisorderedSequence analysisAdd BLAST | 39 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1 – 31 | Polar residuesSequence analysisAdd BLAST | 31 |
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 86 – 116 | GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST | 31 | |
Zinc fingeri | 127 – 183 | PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST | 57 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502SIGQ, Eukaryota |
GeneTreei | ENSGT00940000162228 |
HOGENOMi | CLU_006958_9_0_1 |
InParanoidi | Q9CWR8 |
OMAi | EDVCICC |
OrthoDBi | 1015783at2759 |
PhylomeDBi | Q9CWR8 |
TreeFami | TF329039 |
Family and domain databases
Gene3Di | 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR025766, ADD IPR040552, DNMT3_ADD IPR030486, DNMT3L IPR029063, SAM-dependent_MTases IPR011011, Znf_FYVE_PHD |
PANTHERi | PTHR23068:SF13, PTHR23068:SF13, 1 hit |
Pfami | View protein in Pfam PF17980, ADD_DNMT3, 1 hit |
SUPFAMi | SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS51533, ADD, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketD3YUQ4 | D3YUQ4_MOUSE | DNA (cytosine-5)-methyltransferase ... | Dnmt3l | 126 | Annotation score: |
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 |
CCDSi | CCDS23962.1 |
RefSeqi | NP_001075164.1, NM_001081695.2 NP_001271126.1, NM_001284197.1 NP_062321.1, NM_019448.4 |
Genome annotation databases
Ensembli | ENSMUST00000000746; ENSMUSP00000000746; ENSMUSG00000000730 ENSMUST00000138785; ENSMUSP00000121562; ENSMUSG00000000730 ENSMUST00000151242; ENSMUSP00000116970; ENSMUSG00000000730 |
GeneIDi | 54427 |
KEGGi | mmu:54427 |
UCSCi | uc007fxe.2, mouse |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS23962.1 |
RefSeqi | NP_001075164.1, NM_001081695.2 NP_001271126.1, NM_001284197.1 NP_062321.1, NM_019448.4 |
3D structure databases
AlphaFoldDBi | Q9CWR8 |
SMRi | Q9CWR8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 207659, 6 interactors |
DIPi | DIP-49029N |
IntActi | Q9CWR8, 8 interactors |
MINTi | Q9CWR8 |
STRINGi | 10090.ENSMUSP00000121562 |
Protein family/group databases
REBASEi | 6168, M.MmuDnmt3L |
PTM databases
iPTMneti | Q9CWR8 |
PhosphoSitePlusi | Q9CWR8 |
Proteomic databases
PaxDbi | Q9CWR8 |
PRIDEi | Q9CWR8 |
Protocols and materials databases
DNASUi | 54427 |
Genome annotation databases
Ensembli | ENSMUST00000000746; ENSMUSP00000000746; ENSMUSG00000000730 ENSMUST00000138785; ENSMUSP00000121562; ENSMUSG00000000730 ENSMUST00000151242; ENSMUSP00000116970; ENSMUSG00000000730 |
GeneIDi | 54427 |
KEGGi | mmu:54427 |
UCSCi | uc007fxe.2, mouse |
Organism-specific databases
CTDi | 29947 |
MGIi | MGI:1859287, Dnmt3l |
VEuPathDBi | HostDB:ENSMUSG00000000730 |
Phylogenomic databases
eggNOGi | ENOG502SIGQ, Eukaryota |
GeneTreei | ENSGT00940000162228 |
HOGENOMi | CLU_006958_9_0_1 |
InParanoidi | Q9CWR8 |
OMAi | EDVCICC |
OrthoDBi | 1015783at2759 |
PhylomeDBi | Q9CWR8 |
TreeFami | TF329039 |
Miscellaneous databases
BioGRID-ORCSi | 54427, 3 hits in 75 CRISPR screens |
ChiTaRSi | Dnmt3l, mouse |
PROi | PR:Q9CWR8 |
RNActi | Q9CWR8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000000730, Expressed in liver and 122 other tissues |
Genevisiblei | Q9CWR8, MM |
Family and domain databases
Gene3Di | 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR025766, ADD IPR040552, DNMT3_ADD IPR030486, DNMT3L IPR029063, SAM-dependent_MTases IPR011011, Znf_FYVE_PHD |
PANTHERi | PTHR23068:SF13, PTHR23068:SF13, 1 hit |
Pfami | View protein in Pfam PF17980, ADD_DNMT3, 1 hit |
SUPFAMi | SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS51533, ADD, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DNM3L_MOUSE | |
Accessioni | Q9CWR8Primary (citable) accession number: Q9CWR8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 26, 2001 |
Last sequence update: | June 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 157 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot