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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. 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

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

Genomics for DNMT3L Gene

Regulatory Elements for DNMT3L Gene

Enhancers for DNMT3L Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH21G044192 2 FANTOM5 Ensembl ENCODE dbSUPER 11.8 +72.1 72088 5.8 HDGF PKNOX1 CREB3L1 SIN3A YBX1 ZBTB7B ZNF766 ZNF143 ZNF207 FOS ICOSLG DNMT3L PWP2 AIRE ENSG00000184441 TRAPPC10 TRPM2 PDXK LOC105377139 ENSG00000232124
GH21G044237 0.8 ENCODE 12.6 +29.7 29736 0.2 PKNOX1 JUN ZBTB40 CTBP1 POLR2A ZSCAN5C PATZ1 FOS RCOR1 RFX1 DNMT3L PIR49071 ICOSLG
GH21G044702 1.4 FANTOM5 Ensembl ENCODE 4.8 -436.8 -436786 2.5 FOXA2 ZNF473 KLF17 ZNF48 RARA SLC30A9 ZNF366 EGR1 FOS EGR2 TSPEAR DNMT3L AIRE GC21M045245 KRTAP10-13P
GH21G044263 0.9 FANTOM5 ENCODE 3.6 +3.5 3485 0.9 ZFHX2 NR2F1 GLIS1 PATZ1 PRDM10 ZIC2 PRDM1 EGR2 ICOSLG AIRE ENSG00000184441 DNMT3L KRTAP12-2 KRTAP10-6 KRTAP12-4 KRTAP12-1 KRTAP10-11 KRTAP10-12
GH21G044278 0.8 dbSUPER 0.4 -13.1 -13060 4.0 ZBTB21 INSM2 KLF17 ZIC2 ZFHX2 GATA3 ZNF366 ZBTB48 POLR2A SCRT2 PFKL ENSG00000184441 ICOSLG C21orf2 AIRE DNMT3L
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around DNMT3L on UCSC Golden Path with GeneCards custom track

Genomic Location for DNMT3L Gene

Chromosome:
21
Start:
44,246,339 bp from pter
End:
44,267,138 bp from pter
Size:
20,800 bases
Orientation:
Minus strand

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

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DNMT3L Gene

No data available for DME Specific Peptides for DNMT3L Gene

Domains & Families for DNMT3L Gene

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 Gene Families and 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).

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

Clone Products

Flow Cytometry 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

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 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 NAS,IEA 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

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

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

(1) Additional Compounds for DNMT3L Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(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

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

Clone Products

Flow Cytometry 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 34 35
  • 99.4 (n)
cow
(Bos Taurus)
Mammalia DNMT3L 34 35
  • 81.84 (n)
dog
(Canis familiaris)
Mammalia DNMT3L 34 35
  • 80.26 (n)
rat
(Rattus norvegicus)
Mammalia Dnmt3l 34
  • 72.37 (n)
mouse
(Mus musculus)
Mammalia Dnmt3l 34 16 35
  • 71.63 (n)
oppossum
(Monodelphis domestica)
Mammalia DNMT3L 35
  • 58 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DNMT3L 35
  • 39 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.20876 34
zebrafish
(Danio rerio)
Actinopterygii dnmt5 35
  • 10 (a)
ManyToMany
dnmt3 35
  • 9 (a)
ManyToMany
dnmt3b 35
  • 9 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 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 Sequence Context AA Info Type
rs1000011395 -- 44,263,295(+) GGTAA(C/T)CCCCC upstream-variant-2KB
rs1000256610 -- 44,248,517(+) TGGAT(A/G)AGCGT intron-variant
rs1000326260 -- 44,252,615(+) GAGTG(A/G)TGGCT intron-variant
rs1000380154 -- 44,252,730(+) AATAT(A/G)AAAAA intron-variant
rs1000443273 -- 44,262,977(+) GCTGT(A/G)GGGGA upstream-variant-2KB

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)

Relevant External Links 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

(6) MalaCards diseases for DNMT3L Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
testicular spermatocytic seminoma
  • spermatocytic seminoma
testis seminoma
  • seminoma
testicular malignant germ cell cancer
  • malignant germ cell tumor of testis
alpha thalassemia-x-linked intellectual disability syndrome
  • alpha-thalassemia/mental retardation syndrome nondeletion type
diabetes mellitus, transient neonatal, 1
  • diabetes mellitus, transient neonatal
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for DNMT3L

Genetic Association Database (GAD)
DNMT3L
Human Genome Epidemiology (HuGE) Navigator
DNMT3L
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
DNMT3L
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 64
  2. A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. (PMID: 19246518) El-Maarri O. … ChAcdin F. (Hum. Mol. Genet. 2009) 3 22 46 64
  3. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. (PMID: 17687327) Ooi S.K. … Bestor T.H. (Nature 2007) 3 4 22 64
  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 64
  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 T.Y. (Int. J. Oncol. 2010) 3 22 64

Products for DNMT3L Gene

Sources for DNMT3L Gene

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