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 Publications

Regions

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
Inferred from direct assayⁱ
- 16543361
enzyme binding
Source: UniProtKB
Inferred from sequence or structural similarityⁱ
- 12202768
metal ion binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

chorionic trophoblast cell differentiation
Source: MGI
Inferred from mutant phenotypeⁱ
- 16920095
DNA methylation
Source: MGI
Inferred from mutant phenotypeⁱ
- 25503965
DNA methylation involved in gamete generation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15318244
DNA methylation on cytosine
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15318244
genetic imprinting
Source: MGI
Inferred from mutant phenotypeⁱ
- 16920095
in utero embryonic development
Source: MGI
Inferred from mutant phenotypeⁱ
- 11934864
male meiosis I
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15318244
methylation
Source: MGI
Inferred from mutant phenotypeⁱ
- 16920095
negative regulation of DNA methylation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24074865
negative regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from sequence or structural similarityⁱ
- 12202768
negative regulation of transposition
Source: MGI
Inferred from mutant phenotypeⁱ
- 25503965
placenta development
Source: MGI
Inferred from mutant phenotypeⁱ
- 16920095
positive regulation of DNA methylation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24074865
spermatogenesis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15318244
stem cell differentiation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24074865

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Differentiation, Spermatogenesis
Ligand	Metal-binding, Zinc

Protein family/group databases

REBASEⁱ	6168 M.MmuDnmt3L

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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 10

Organism-specific databases

MGIⁱ	MGI:1859287 Dnmt3l

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 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

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

Bgeeⁱ	ENSMUSG00000000730 Expressed in 86 organ(s), highest expression level in liver
CleanExⁱ	MM_DNMT3L
ExpressionAtlasⁱ	Q9CWR8 baseline and differential
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).By similarity1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
Dnmt3a	O88508	6	EBI-3043871,EBI-995154
Dnmt3a	O88508-1	6	EBI-3043871,EBI-15650457
Dnmt3b	O88509	6	EBI-3043871,EBI-7987547
EZH2	Q15910	2	EBI-3043871,EBI-530054	From Homo sapiens.
Ezh2	Q61188	10	EBI-3043871,EBI-904311

GO - Molecular functionⁱ

enzyme binding
Source: UniProtKB
Inferred from sequence or structural similarityⁱ
- 12202768

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	207659, 6 interactors
Database of interacting proteins More...DIPⁱ	DIP-49029N
IntActⁱ	Q9CWR8, 7 interactors
STRINGⁱ	10090.ENSMUSP00000000746

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q9CWR8
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	75 – 207	ADDPROSITE-ProRule annotationAdd BLAST		133

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-finger

Phylogenomic databases

eggNOGⁱ	ENOG410IIXK Eukaryota ENOG4111C55 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000008341
HOGENOMⁱ	HOG000246422
HOVERGENⁱ	HBG051382
InParanoidⁱ	Q9CWR8
KEGG Orthology (KO) More...KOⁱ	K17400
OMAⁱ	HTQHPLF
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G08YY
PhylomeDBⁱ	Q9CWR8
TreeFamⁱ	TF329039

Family and domain databases

InterProⁱ	View protein in InterPro IPR025766 ADD IPR030486 DNMT3L IPR011011 Znf_FYVE_PHD
PANTHERⁱ	PTHR23068:SF13 PTHR23068:SF13, 1 hit
SUPFAMⁱ	SSF57903 SSF57903, 1 hit
PROSITEⁱ	View protein in PROSITE PS51533 ADD, 1 hit

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show all Align All

Q9CWR8-1 [UniParc]FASTA Add 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

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	D3YUQ4	D3YUQ4_MOUSE		DNA (cytosine-5)-methyltransferase ... DNA (cytosine-5)-methyltransferase 3-like	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS23962.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001075164.1, NM_001081695.2 NP_001271126.1, NM_001284197.1 NP_062321.1, NM_019448.4
UniGeneⁱ	Mm.13433

Genome annotation databases

Ensemblⁱ	ENSMUST00000000746; ENSMUSP00000000746; ENSMUSG00000000730 ENSMUST00000138785; ENSMUSP00000121562; ENSMUSG00000000730 ENSMUST00000151242; ENSMUSP00000116970; ENSMUSG00000000730
GeneIDⁱ	54427
KEGGⁱ	mmu:54427
UCSC genome browser More...UCSCⁱ	uc007fxe.2 mouse

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9CWR8	DNA (Cytosine-5-)-methyltransferase 3-like, isoform CRA_b		MOUSE		421	UniRef100_Q9CWR8
DNA (cytosine-5)-methyltransferase 3-like		MOUSE		126

Protein	Similar proteins		Species	Score	Length	Source
Q9CWR8	DNA (Cytosine-5-)-methyltransferase 3-like, isoform CRA_b		MOUSE		421	UniRef90_Q9CWR8
UPI000A30FD0F		MUSPA		422
UPI000A3160CD		MUSCR		415
DNA (cytosine-5)-methyltransferase 3-like		MOUSE		126
UPI000A3192A6		MUSCR		120

Protein	Similar proteins		Species	Score	Length	Source
Q9CWR8	DNA (cytosine-5)-methyltransferase 3-like		RAT		422	UniRef50_Q9CWR8
DNA (Cytosine-5-)-methyltransferase 3-like, isoform CRA_b		MOUSE		421
DNA (Cytosine-5)-methyltransferase 3-like protein (Fragment)		HETGA		375
DNA (Cytosine-5)-methyltransferase 3-like		DIPOR		495
Uncharacterized protein		PIG		401
+21

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
UniGeneⁱ	Mm.13433

3D structure databases

ProteinModelPortalⁱ	Q9CWR8
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	207659, 6 interactors
DIPⁱ	DIP-49029N
IntActⁱ	Q9CWR8, 7 interactors
STRINGⁱ	10090.ENSMUSP00000000746

Protein family/group databases

REBASEⁱ	6168 M.MmuDnmt3L

REBASEⁱ

6168 M.MmuDnmt3L

PTM databases

iPTMnetⁱ	Q9CWR8
PhosphoSitePlusⁱ	Q9CWR8

Proteomic databases

PaxDbⁱ	Q9CWR8
PRIDEⁱ	Q9CWR8

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

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

Phylogenomic databases

eggNOGⁱ	ENOG410IIXK Eukaryota ENOG4111C55 LUCA
GeneTreeⁱ	ENSGT00390000008341
HOGENOMⁱ	HOG000246422
HOVERGENⁱ	HBG051382
InParanoidⁱ	Q9CWR8
KOⁱ	K17400
OMAⁱ	HTQHPLF
OrthoDBⁱ	EOG091G08YY
PhylomeDBⁱ	Q9CWR8
TreeFamⁱ	TF329039

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:Q9CWR8
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000000730 Expressed in 86 organ(s), highest expression level in liver
CleanExⁱ	MM_DNMT3L
ExpressionAtlasⁱ	Q9CWR8 baseline and differential
Genevisibleⁱ	Q9CWR8 MM

Family and domain databases

InterProⁱ	View protein in InterPro IPR025766 ADD IPR030486 DNMT3L IPR011011 Znf_FYVE_PHD
PANTHERⁱ	PTHR23068:SF13 PTHR23068:SF13, 1 hit
SUPFAMⁱ	SSF57903 SSF57903, 1 hit
PROSITEⁱ	View protein in PROSITE PS51533 ADD, 1 hit
ProtoNetⁱ	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:	September 12, 2018
	This is version 138 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

Complete proteome, Reference proteome

Documents

MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q9CWR8 (DNM3L_MOUSE)

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DNA (cytosine-5)-methyltransferase 3-like

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Zinc finger

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ