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Aliases for DNMT3L Gene

Aliases for DNMT3L Gene

  • DNA Methyltransferase 3 Like 2 3 5
  • Cytosine-5-Methyltransferase 3-Like Protein 2
  • DNA (Cytosine-5-)-Methyltransferase 3-Like 2

External Ids for DNMT3L Gene

Previous GeneCards Identifiers for DNMT3L Gene

  • GC21M042176
  • GC21M042259
  • GC21M044522
  • GC21M044490
  • GC21M045666
  • GC21M031037

Summaries for DNMT3L Gene

Entrez Gene Summary for DNMT3L Gene

  • CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a nuclear protein with similarity to DNA methyltransferases, but is not thought to function as a DNA methyltransferase as it does not contain the amino acid residues necessary for methyltransferase activity. However, it does stimulate de novo methylation by DNA cytosine methyltransferase 3 alpha and is thought to be required for the establishment of maternal genomic imprints. This protein also mediates transcriptional repression through interaction with histone deacetylase 1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

GeneCards Summary for DNMT3L Gene

DNMT3L (DNA Methyltransferase 3 Like) is a Protein Coding gene. Diseases associated with DNMT3L include Testicular Spermatocytic Seminoma and Testis Seminoma. Among its related pathways are Gene Expression and Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. Gene Ontology (GO) annotations related to this gene include enzyme binding and enzyme activator activity. An important paralog of this gene is LOC102724184.

UniProtKB/Swiss-Prot for DNMT3L Gene

  • Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context (By similarity). Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain (PubMed:17687327). 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:17687327). Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role in embryonic stem cells and germ cells (By similarity). In germ cells, required for the methylation of imprinted loci together with DNMT3A (By similarity). In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization (By similarity). Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation (By similarity). 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 (By similarity). 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 (By similarity). Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression (By similarity).

Gene Wiki entry for DNMT3L Gene

Additional gene information for DNMT3L Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DNMT3L Gene

Genomics for DNMT3L Gene

GeneHancer (GH) Regulatory Elements for DNMT3L Gene

Promoters and enhancers for DNMT3L Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH21I044261 Promoter 0.8 EPDnew 550.4 +5.3 5251 0.1 KLF1 EGR1 VEZF1 KLF8 EGR2 GC21P044264 DNMT3L GC21P044253
GH21I044192 Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 11.9 +72.1 72087 5.8 HDGF PKNOX1 ARNT SIN3A ZBTB7B IRF4 ZNF766 E2F8 ZNF207 ZNF143 LOC105377139 UBE2G2 ICOSLG DNMT3L PWP2 RRP1B AIRE ENSG00000184441 TRAPPC10 TRPM2
GH21I044237 Enhancer 0.7 ENCODE 12.6 +29.7 29735 0.2 PKNOX1 ZBTB40 CTBP1 PATZ1 ZSCAN5C FOS RCOR1 SMARCE1 ZNF687 RFX1 DNMT3L ICOSLG PIR49071
GH21I044702 Enhancer 1.2 FANTOM5 Ensembl ENCODE 4.8 -436.8 -436786 2.5 DRAP1 USF1 FOXA2 SAP130 CEBPG ZIC2 ZNF48 RARA SLC30A9 E2F1 GC21M045510 KRTAP10-13P TSPEAR DNMT3L AIRE
GH21I044263 Enhancer 0.8 FANTOM5 ENCODE 3.6 +3.5 3485 0.9 USF1 ZIC2 ZFHX2 PATZ1 GLIS1 PRDM10 PRDM1 EGR2 GC21P044264 ICOSLG AIRE ENSG00000184441 DNMT3L KRTAP12-2 KRTAP10-6 KRTAP12-4 KRTAP12-1 KRTAP10-11
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around DNMT3L on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the DNMT3L gene promoter:

Genomic Locations for DNMT3L Gene

Genomic Locations for DNMT3L Gene
chr21:44,246,339-44,267,138
(GRCh38/hg38)
Size:
20,800 bases
Orientation:
Minus strand
chr21:45,666,222-45,682,099
(GRCh37/hg19)

Genomic View for DNMT3L Gene

Genes around DNMT3L on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DNMT3L Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DNMT3L Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DNMT3L Gene

Proteins for DNMT3L Gene

  • Protein details for DNMT3L Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UJW3-DNM3L_HUMAN
    Recommended name:
    DNA (cytosine-5)-methyltransferase 3-like
    Protein Accession:
    Q9UJW3
    Secondary Accessions:
    • E9PB42
    • Q9BUJ4

    Protein attributes for DNMT3L Gene

    Size:
    386 amino acids
    Molecular mass:
    43583 Da
    Quaternary structure:
    • Homodimer (PubMed:17687327, PubMed:17713477). Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (PubMed:17713477). Interacts with histone H3 (via N-terminus); interaction is strongly inhibited by methylation at lysine 4 (H3K4me) (PubMed:17687327). Interacts with EZH2; the interaction is direct (By similarity).
    Miscellaneous:
    • Interaction with histone H3 is strongly inhibited by methylation at lysine 4 (H3K4me).

    Three dimensional structures from OCA and Proteopedia for DNMT3L Gene

    Alternative splice isoforms for DNMT3L Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DNMT3L Gene

Post-translational modifications for DNMT3L Gene

No Post-translational modifications

Other Protein References for DNMT3L Gene

No data available for DME Specific Peptides for DNMT3L Gene

Domains & Families for DNMT3L Gene

Gene Families for DNMT3L Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for DNMT3L Gene

Suggested Antigen Peptide Sequences for DNMT3L Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with DNMT3L: view

No data available for UniProtKB/Swiss-Prot for DNMT3L Gene

Function for DNMT3L Gene

Molecular function for DNMT3L Gene

UniProtKB/Swiss-Prot Function:
Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context (By similarity). Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain (PubMed:17687327). 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:17687327). Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role in embryonic stem cells and germ cells (By similarity). In germ cells, required for the methylation of imprinted loci together with DNMT3A (By similarity). In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization (By similarity). Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation (By similarity). 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 (By similarity). 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 (By similarity). Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression (By similarity).

Phenotypes From GWAS Catalog for DNMT3L Gene

Gene Ontology (GO) - Molecular Function for DNMT3L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12202768
GO:0008047 enzyme activator activity IDA 16543361
GO:0019899 enzyme binding IPI,IEA 12202768
GO:0030234 enzyme regulator activity IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with DNMT3L: view
genes like me logo Genes that share phenotypes with DNMT3L: view

Animal Models for DNMT3L Gene

MGI Knock Outs for DNMT3L:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for DNMT3L Gene

Localization for DNMT3L Gene

Subcellular locations from UniProtKB/Swiss-Prot for DNMT3L Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DNMT3L gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear speckles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DNMT3L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus NAS 12202768
GO:0005829 cytosol IDA,HDA 16780588
GO:0035098 colocalizes_with ESC/E(Z) complex ISS --
genes like me logo Genes that share ontologies with DNMT3L: view

Pathways & Interactions for DNMT3L Gene

genes like me logo Genes that share pathways with DNMT3L: view

Pathways by source for DNMT3L Gene

Gene Ontology (GO) - Biological Process for DNMT3L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006306 DNA methylation IEA,NAS 12202768
GO:0006349 regulation of gene expression by genetic imprinting NAS 12202768
GO:0007141 male meiosis I ISS --
GO:0007283 spermatogenesis NAS 11934864
GO:0030154 cell differentiation IEA --
genes like me logo Genes that share ontologies with DNMT3L: view

No data available for SIGNOR curated interactions for DNMT3L Gene

Drugs & Compounds for DNMT3L Gene

(4) Drugs for DNMT3L Gene - From: ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Thioguanine Approved Pharma Purine antimetabolite 83
s-adenosylhomocysteine Experimental Pharma 0
Lomeguatrib Pharma MGMT inhibitor 0

(2) Additional Compounds for DNMT3L Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
s-adenosylmethionine
  • (3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine
  • 2-S-Adenosyl-L-methionine
  • 5'-Deoxyadenosine-5'-L-methionine disulfate ditosylate
  • 5'-Deoxyadenosine-5'-L-methionine disulphate ditosylate
  • Active methionine
29908-03-0

(2) ApexBio Compounds for DNMT3L Gene

Compound Action Cas Number
Lomeguatrib MGMT inhibitor 192441-08-0
Thioguanine Purine antimetabolite 154-42-7
genes like me logo Genes that share compounds with DNMT3L: view

Drug Products

Transcripts for DNMT3L Gene

mRNA/cDNA for DNMT3L Gene

Unigene Clusters for DNMT3L Gene

DNA (cytosine-5-)-methyltransferase 3-like:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for DNMT3L Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b
SP1:
SP2:

Relevant External Links for DNMT3L Gene

GeneLoc Exon Structure for
DNMT3L
ECgene alternative splicing isoforms for
DNMT3L

Expression for DNMT3L Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for DNMT3L Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DNMT3L Gene

This gene is overexpressed in Liver (x21.0) and Kidney - Cortex (x20.0).

Protein differential expression in normal tissues from HIPED for DNMT3L Gene

This gene is overexpressed in Plasma (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for DNMT3L Gene



Protein tissue co-expression partners for DNMT3L Gene

NURSA nuclear receptor signaling pathways regulating expression of DNMT3L Gene:

DNMT3L

SOURCE GeneReport for Unigene cluster for DNMT3L Gene:

Hs.592165

mRNA Expression by UniProt/SwissProt for DNMT3L Gene:

Q9UJW3-DNM3L_HUMAN
Tissue specificity: Expressed at low levels in several tissues including testis, ovary, and thymus.
genes like me logo Genes that share expression patterns with DNMT3L: view

No data available for Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for DNMT3L Gene

Orthologs for DNMT3L Gene

This gene was present in the common ancestor of chordates.

Orthologs for DNMT3L Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DNMT3L 33 34
  • 99.4 (n)
cow
(Bos Taurus)
Mammalia DNMT3L 33 34
  • 81.84 (n)
dog
(Canis familiaris)
Mammalia DNMT3L 33 34
  • 80.26 (n)
rat
(Rattus norvegicus)
Mammalia Dnmt3l 33
  • 72.37 (n)
mouse
(Mus musculus)
Mammalia Dnmt3l 33 16 34
  • 71.63 (n)
oppossum
(Monodelphis domestica)
Mammalia DNMT3L 34
  • 58 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DNMT3L 34
  • 39 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.20876 33
zebrafish
(Danio rerio)
Actinopterygii dnmt5 34
  • 10 (a)
ManyToMany
dnmt3 34
  • 9 (a)
ManyToMany
dnmt3b 34
  • 9 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 17 (a)
OneToMany
Species where no ortholog for DNMT3L was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for DNMT3L Gene

ENSEMBL:
Gene Tree for DNMT3L (if available)
TreeFam:
Gene Tree for DNMT3L (if available)

Paralogs for DNMT3L Gene

Paralogs for DNMT3L Gene

(1) SIMAP similar genes for DNMT3L Gene using alignment to 3 proteins:

Pseudogenes.org Pseudogenes for DNMT3L Gene

genes like me logo Genes that share paralogs with DNMT3L: view

Variants for DNMT3L Gene

Sequence variations from dbSNP and Humsavar for DNMT3L Gene

SNP ID Clin Chr 21 pos Variation AA Info Type
rs1000011395 -- 44,263,295(-) C/A/T upstream_transcript_variant
rs1000256610 -- 44,248,517(-) G/A intron_variant
rs1000326260 -- 44,252,615(-) G/A intron_variant
rs1000380154 -- 44,252,730(-) A/G intron_variant
rs1000443273 -- 44,262,977(-) G/A upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for DNMT3L Gene

Variant ID Type Subtype PubMed ID
dgv2400n106 CNV deletion 24896259
dgv7881n54 CNV loss 21841781
dgv7882n54 CNV gain+loss 21841781
dgv7883n54 CNV loss 21841781
dgv7884n54 CNV loss 21841781
esv23445 CNV gain+loss 19812545
esv2659125 CNV deletion 23128226
esv2723638 CNV deletion 23290073
esv33817 CNV loss 17666407
nsv1073137 CNV deletion 25765185
nsv1130191 CNV deletion 24896259
nsv1152111 CNV deletion 26484159
nsv526276 CNV loss 19592680
nsv587740 CNV loss 21841781
nsv587741 CNV loss 21841781
nsv587742 CNV loss 21841781
nsv587743 CNV gain 21841781
nsv587744 CNV gain 21841781
nsv587758 CNV gain 21841781
nsv587759 CNV gain+loss 21841781
nsv587764 CNV loss 21841781
nsv953645 CNV deletion 24416366

Variation tolerance for DNMT3L Gene

Residual Variation Intolerance Score: 80.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.06; 68.82% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DNMT3L Gene

Human Gene Mutation Database (HGMD)
DNMT3L
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DNMT3L

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DNMT3L Gene

Disorders for DNMT3L Gene

MalaCards: The human disease database

(8) MalaCards diseases for DNMT3L Gene - From: HGMD and DISEASES

Disorder Aliases PubMed IDs
testicular spermatocytic seminoma
  • spermatocytic seminoma
testis seminoma
  • seminoma
testicular malignant germ cell cancer
  • malignant germ cell tumor of testis
taylor's syndrome
  • congestion-fibrosis syndrome
alpha thalassemia-x-linked intellectual disability syndrome
  • alpha-thalassemia/mental retardation syndrome nondeletion type
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for DNMT3L

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with DNMT3L: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DNMT3L Gene

Publications for DNMT3L Gene

  1. Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family. (PMID: 10857753) Aapola U … Peterson P (Genomics 2000) 2 3 4 22 58
  2. A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. (PMID: 19246518) El-Maarri O … Chédin F (Human molecular genetics 2009) 3 22 44 58
  3. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. (PMID: 17687327) Ooi SK … Bestor TH (Nature 2007) 3 4 22 58
  4. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. (PMID: 17713477) Jia D … Cheng X (Nature 2007) 3 4 22 58
  5. DNA methyltransferase 3-like affects promoter methylation of thymine DNA glycosylase independently of DNMT1 and DNMT3B in cancer cells. (PMID: 20428781) Kim H … Kim TY (International journal of oncology 2010) 3 22 58

Products for DNMT3L Gene

Sources for DNMT3L Gene

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