DOT1L Gene (Protein Coding)

DOT1 Like Histone Lysine Methyltransferase

GC19P002164
GIFtS:
46
The protein encoded by this gene is a histone methyltransferase that methylates lysine-79 of histone H3. It is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. [provided by RefSeq, Aug 2011] See more...

Aliases for DOT1L Gene

Aliases for DOT1L Gene

  • DOT1 Like Histone Lysine Methyltransferase 2 3 5
  • Histone-Lysine N-Methyltransferase, H3 Lysine-79 Specific 3 4
  • Histone H3-K79 Methyltransferase 3 4
  • Histone Methyltransferase DOT1L 2 3
  • Lysine N-Methyltransferase 4 3 4
  • DOT1-Like Protein 3 4
  • H3-K79-HMTase 3 4
  • KMT4 3 4
  • DOT1-Like, Histone H3 Methyltransferase (S. Cerevisiae) 2
  • DOT1 Like Histone H3K79 Methyltransferase 3
  • DOT1-Like, Histone H3 Methyltransferase 3
  • DOT1-Like Histone Methyltransferase 3
  • EC 2.1.1.43 4
  • KIAA1814 4
  • DOT1 3

External Ids for DOT1L Gene

Previous GeneCards Identifiers for DOT1L Gene

  • GC19P002248
  • GC19P002104
  • GC19P002115
  • GC19P001935

Summaries for DOT1L Gene

Entrez Gene Summary for DOT1L Gene

  • The protein encoded by this gene is a histone methyltransferase that methylates lysine-79 of histone H3. It is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. [provided by RefSeq, Aug 2011]

GeneCards Summary for DOT1L Gene

DOT1L (DOT1 Like Histone Lysine Methyltransferase) is a Protein Coding gene. Diseases associated with DOT1L include Leukemia, Acute Myeloid. Among its related pathways are PKMTs methylate histone lysines and Transcriptional misregulation in cancer. Gene Ontology (GO) annotations related to this gene include transcription factor binding and histone methyltransferase activity.

UniProtKB/Swiss-Prot Summary for DOT1L Gene

  • Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones (PubMed:12123582). Binds to DNA (PubMed:12628190).

Tocris Summary for DOT1L Gene

  • Lysine methyltransferases are enyzmes that catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to the lysine residues on histones, particularly histones H3 and H4. The dysregulation of this methylation is critical in the development of cancer.

Gene Wiki entry for DOT1L Gene

Additional gene information for DOT1L Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DOT1L Gene

Genomics for DOT1L Gene

GeneHancer (GH) Regulatory Elements for DOT1L Gene

Promoters and enhancers for DOT1L Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DOT1L on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the DOT1L gene promoter:
  • FOXI1
  • GATA-2
  • GCNF
  • GCNF-1
  • GCNF-2
  • MIF-1
  • NRSF form 1
  • NRSF form 2
  • Pax-4a
  • Sp1

Genomic Locations for DOT1L Gene

Genomic Locations for DOT1L Gene
chr19:2,163,933-2,232,578
(GRCh38/hg38)
Size:
68,646 bases
Orientation:
Plus strand
chr19:2,164,148-2,232,577
(GRCh37/hg19)
Size:
68,430 bases
Orientation:
Plus strand

Genomic View for DOT1L Gene

Genes around DOT1L on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DOT1L Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DOT1L Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for DOT1L Gene

Proteins for DOT1L Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for DOT1L Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TEK3-DOT1L_HUMAN
    Recommended name:
    Histone-lysine N-methyltransferase, H3 lysine-79 specific
    Protein Accession:
    Q8TEK3
    Secondary Accessions:
    • O60379
    • Q96JL1

    Protein attributes for DOT1L Gene

    Size:
    1537 amino acids
    Molecular mass:
    164856 Da
    Quaternary structure:
    • Interacts with MLLT10.
    Miscellaneous:
    • In contrast to other lysine histone methyltransferases, it does not contain a SET domain, suggesting the existence of another mechanism for methylation of lysine residues of histones.
    SequenceCaution:
    • Sequence=AAC08316.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for DOT1L Gene

    Alternative splice isoforms for DOT1L Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DOT1L Gene

Protein Expression for DOT1L Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for DOT1L Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DOT1L Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Boster Bio Antibodies for DOT1L

No data available for DME Specific Peptides for DOT1L Gene

Domains & Families for DOT1L Gene

Gene Families for DOT1L Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for DOT1L Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for DOT1L Gene

GenScript: Design optimal peptide antigens:
  • Lysine N-methyltransferase 4 (DOT1L_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8TEK3

UniProtKB/Swiss-Prot:

DOT1L_HUMAN :
  • Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.
Family:
  • Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.
genes like me logo Genes that share domains with DOT1L: view

Function for DOT1L Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for DOT1L Gene

UniProtKB/Swiss-Prot Function:
Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones (PubMed:12123582). Binds to DNA (PubMed:12628190).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43; Evidence={ECO:0000255 PROSITE-ProRule:PRU00902, ECO:0000269 PubMed:12123582};.

Enzyme Numbers (IUBMB) for DOT1L Gene

Phenotypes From GWAS Catalog for DOT1L Gene

Gene Ontology (GO) - Molecular Function for DOT1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
GO:0005515 protein binding IPI 20153263
GO:0008168 methyltransferase activity IEA --
GO:0016740 transferase activity IEA --
GO:0018024 histone-lysine N-methyltransferase activity IEA,TAS --
genes like me logo Genes that share ontologies with DOT1L: view
genes like me logo Genes that share phenotypes with DOT1L: view

Animal Models for DOT1L Gene

MGI Knock Outs for DOT1L:
  • Dot1l Dot1l<tm1a(KOMP)Wtsi>
  • Dot1l Dot1l<tm1.1Tche>
  • Dot1l Dot1l<tm1.2Wezh>

Animal Model Products

  • Taconic Biosciences Mouse Models for DOT1L

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DOT1L

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DOT1L Gene

Localization for DOT1L Gene

Subcellular locations from UniProtKB/Swiss-Prot for DOT1L Gene

Nucleus.

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 DOT1L gene
Compartment Confidence
nucleus 5
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DOT1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000781 chromosome, telomeric region IEA --
GO:0005634 nucleus IDA,IEA 15851025
GO:0005654 nucleoplasm TAS --
GO:0032991 protein-containing complex IDA 15851025
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with DOT1L: view

Pathways & Interactions for DOT1L Gene

genes like me logo Genes that share pathways with DOT1L: view

Pathways by source for DOT1L Gene

1 BioSystems pathway for DOT1L Gene
1 Cell Signaling Technology pathway for DOT1L Gene
1 GeneTex pathway for DOT1L Gene

SIGNOR curated interactions for DOT1L Gene

Activates:

Gene Ontology (GO) - Biological Process for DOT1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000077 DNA damage checkpoint IBA 21873635
GO:0006325 chromatin organization IEA --
GO:0006342 chromatin silencing IEA --
GO:0006348 chromatin silencing at telomere IBA 21873635
GO:0008284 positive regulation of cell proliferation IDA 15851025
genes like me logo Genes that share ontologies with DOT1L: view

Drugs & Compounds for DOT1L Gene

Products:

  1. Drug

(14) Drugs for DOT1L Gene - From: PharmGKB, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Hydrochlorothiazide Approved, Vet_approved Pharma Inhibition, Inhibitor 443
Entacapone Approved, Investigational Pharma COMT inhibitor, Potent COMT inhibitor; blocks alpha-synuclein aggregation 55
D-Lysine Approved, Experimental Nutra Full agonist, Agonist 0
s-adenosylhomocysteine Experimental Pharma 0
EPZ004777 Pharma DOT1L inhibitor 0

(1) Additional Compounds for DOT1L Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
s-adenosylmethionine
  • (3S)-5'-[(3-amino-3-Carboxypropyl)methylsulfonio]-5'-deoxyadenosine, inner salt
  • [1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium
  • Acylcarnitine
  • AdoMet
  • S-(5'-Deoxyadenosin-5'-yl)-L-methionine
 485-80-3

(7) ApexBio Compounds for DOT1L Gene

Compound Action Cas Number
Entacapone COMT inhibitor 130929-57-6
EPZ004777 DOT1L inhibitor 1338466-77-5
EPZ004777 HCl DOT1L inhibitor,potent and selective 1380316-03-9
EPZ5676 DOT1L inhibitor,potent and SAM competitive 1380288-87-8
PFI-2 1627676-59-8
SGC 0946 DOT1L inhibitor,highly potent and selective 1561178-17-3
SGI-1027 DNMT inhibitor 1020149-73-8
genes like me logo Genes that share compounds with DOT1L: view

Transcripts for DOT1L Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for DOT1L Gene

(1) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(175) Selected AceView cDNA sequences:
(9) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DOT1L

Alternative Splicing Database (ASD) splice patterns (SP) for DOT1L Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18 ^ 19 ^ 20 ^ 21a ·
SP1: - - - -
SP2: -
SP3: - -
SP4:
SP5:
SP6:

ExUns: 21b ^ 22 ^ 23 ^ 24 ^ 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32a · 32b
SP1: - -
SP2:
SP3:
SP4:
SP5:
SP6:

Relevant External Links for DOT1L Gene

GeneLoc Exon Structure for
DOT1L
ECgene alternative splicing isoforms for
DOT1L

Expression for DOT1L Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for DOT1L Gene

mRNA expression in normal human tissues for DOT1L Gene
mRNA expression by GTEx for DOT1L GenemRNA expression by BioGPS for DOT1L Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DOT1L Gene

This gene is overexpressed in Testis (x6.5).

Protein differential expression in normal tissues from HIPED for DOT1L Gene

This gene is overexpressed in Breast (44.3) and Bone (22.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for DOT1L Gene



Protein tissue co-expression partners for DOT1L Gene

NURSA nuclear receptor signaling pathways regulating expression of DOT1L Gene:

DOT1L

SOURCE GeneReport for Unigene cluster for DOT1L Gene:

Hs.713641

Evidence on tissue expression from TISSUES for DOT1L Gene

  • Nervous system(4.4)
  • Spleen(4.1)
genes like me logo Genes that share expression patterns with DOT1L: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for DOT1L Gene

Orthologs for DOT1L Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for DOT1L Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia DOT1L 33 32
  • 99.24 (n)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 33
  • 89 (a)
 OneToMany
-- 33
  • 85 (a)
 OneToMany
-- 33
  • 55 (a)
 OneToMany
dog
(Canis familiaris)
 Mammalia DOT1L 33 32
  • 85.25 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia DOT1L 33 32
  • 84.5 (n)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Dot1l 32
  • 83.03 (n)
mouse
(Mus musculus)
 Mammalia Dot1l 17 33 32
  • 82.31 (n)
oppossum
(Monodelphis domestica)
 Mammalia DOT1L 33
  • 67 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves DOT1L 33 32
  • 75.02 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia DOT1L 33
  • 97 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia dot1l 32
  • 65.39 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.14561 32
zebrafish
(Danio rerio)
 Actinopterygii dot1l 33 32
  • 65.26 (n)
 OneToOne
fruit fly
(Drosophila melanogaster)
 Insecta gpp 33
  • 17 (a)
 OneToOne
worm
(Caenorhabditis elegans)
 Secernentea dot-1.4 33
  • 26 (a)
 OneToMany
dot-1.2 33
  • 26 (a)
 OneToMany
dot-1.3 33
  • 25 (a)
 OneToMany
dot-1.5 33
  • 25 (a)
 OneToMany
dot-1.1 33
  • 20 (a)
 OneToMany
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes DOT1 33
  • 17 (a)
 OneToOne
Species where no ortholog for DOT1L 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)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • 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)
  • 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)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • wheat (Triticum aestivum)

Evolution for DOT1L Gene

ENSEMBL:
Gene Tree for DOT1L (if available)
TreeFam:
Gene Tree for DOT1L (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DOT1L: view image

Paralogs for DOT1L Gene

No data available for Paralogs for DOT1L Gene

Variants for DOT1L Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for DOT1L Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs1000003642 -- 2,190,326(+) C/T genic_upstream_transcript_variant, intron_variant
rs1000004085 -- 2,171,769(+) T/C genic_upstream_transcript_variant, intron_variant
rs1000052391 -- 2,218,662(+) G/A intron_variant
rs1000091927 -- 2,222,666(+) C/T intron_variant
rs1000113411 -- 2,177,790(+) C/G genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for DOT1L Gene

Variant ID Type Subtype PubMed ID
dgv6218n54 CNV loss 21841781
nsv2389 CNV insertion 18451855
nsv470108 CNV loss 18288195
nsv578382 CNV loss 21841781
nsv578383 CNV loss 21841781
nsv828393 CNV loss 20364138
nsv828394 CNV gain 20364138
nsv828395 CNV loss 20364138
nsv833706 CNV loss 17160897
nsv833707 CNV loss 17160897
nsv953943 CNV deletion 24416366

Variation tolerance for DOT1L Gene

Residual Variation Intolerance Score: 0.596% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.43; 81.91% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DOT1L Gene

Human Gene Mutation Database (HGMD)
DOT1L
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DOT1L

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DOT1L Gene

Disorders for DOT1L Gene

MalaCards: The human disease database

(1) MalaCards diseases for DOT1L Gene - From: DISEASES

Disorder Aliases PubMed IDs
leukemia, acute myeloid
  • aml
- elite association - COSMIC cancer census association via MalaCards
Search DOT1L in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DOT1L

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 DOT1L: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DOT1L Gene

Publications for DOT1L Gene

  1. Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. (PMID: 12628190) Min J … Xu RM (Cell 2003) 3 4 23 56
  2. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. (PMID: 12123582) Feng Q … Zhang Y (Current biology : CB 2002) 2 3 4 56
  3. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 11347906) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 2001) 2 3 4 56
  4. A large-scale candidate gene association study of age at menarche and age at natural menopause. (PMID: 20734064) He C … Hunter DJ (Human genetics 2010) 3 43 56
  5. The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature. (PMID: 20546612) Zhao J … Grant SF (BMC medical genetics 2010) 3 43 56

ExternalLinks

View latest publications for DOT1L gene in Mastermind

Products for DOT1L Gene

  • ApexBio