DOT1L DOT1 like histone lysine methyltransferase [Homo sapiens (human)] - Gene

Summary

Official Symbol: DOT1Lprovided by HGNC
Official Full Name: DOT1 like histone lysine methyltransferaseprovided by HGNC
Primary source: HGNC:HGNC:24948
See related: Ensembl:ENSG00000104885 MIM:607375; AllianceGenome:HGNC:24948
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DOT1; KMT4
Summary: 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]
Expression: Broad expression in testis (RPKM 18.3), bone marrow (RPKM 5.1) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (2163933..2232578)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (2137178..2206142)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (2163932..2232577)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1.
Title: DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1.
Interplay between DOT1L and HDAC1 regulates Leishmania donovani infection in human THP-1 cells.
Title: Interplay between DOT1L and HDAC1 regulates Leishmania donovani infection in human THP-1 cells.
DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.
Title: DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.
DOT1L maintains NK cell phenotype and function for optimal tumor control.
Title: DOT1L maintains NK cell phenotype and function for optimal tumor control.
Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia.
Title: Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia.
The disruptor of telomeric silencing 1-like (DOT1L) promotes peritoneal fibrosis through the upregulation and activation of protein tyrosine kinases.
Title: The disruptor of telomeric silencing 1-like (DOT1L) promotes peritoneal fibrosis through the upregulation and activation of protein tyrosine kinases.
DOT1L decelerates the development of osteoporosis by inhibiting SRSF1 transcriptional activity via microRNA-181-mediated KAT2B inhibition.
Title: DOT1L decelerates the development of osteoporosis by inhibiting SRSF1 transcriptional activity via microRNA-181-mediated KAT2B inhibition.
Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.
Title: Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.
The effect of ITLN1, XCL2 and DOT1L variants on knee osteoarthritis risk in the Han population.
Title: The effect of ITLN1, XCL2 and DOT1L variants on knee osteoarthritis risk in the Han population.
DOT1L Epigenetically Regulates Autophagy and Mitochondria Fusion in Cell Lines of Renal Cancer.
Title: DOT1L Epigenetically Regulates Autophagy and Mitochondria Fusion in Cell Lines of Renal Cancer.

Submit: New GeneRIF Correction See all GeneRIFs (107)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of ten loci associated with height highlights new biological pathways in human growth. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Dot1L inhibits HIV-1 LTR-driven reporter gene expression in the presence of HIV-1 Tat	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC156606P3 (e-PCR)
- UniSTS:271410

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

A006Z36 (e-PCR)
- UniSTS:16296

D22S296 (e-PCR)
- UniSTS:147641

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables histone H3 methyltransferase activity	TAS Traceable Author Statement more info
enables histone H3K79 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K79 methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K79 methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K79 trimethyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables nucleic acid binding	EXP Inferred from Experiment more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coactivator activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of receptor signaling pathway via JAK-STAT	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription regulatory region DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in subtelomeric heterochromatin formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in telomere organization	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in chromosome, telomeric region	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: histone-lysine N-methyltransferase, H3 lysine-79 specific

Names: DOT1 like histone H3K79 methyltransferase; DOT1-like histone methyltransferase; DOT1-like protein; DOT1-like, histone H3 methyltransferase; H3-K79-HMTase; histone H3-K79 methyltransferase; histone methyltransferase DOT1L; lysine N-methyltransferase 4

NP_001398070.1

EC 2.1.1.360

NP_115871.1

EC 2.1.1.360

XP_011526661.1

EC 2.1.1.360

XP_011526663.1

EC 2.1.1.360

XP_047295469.1

EC 2.1.1.360

XP_047295470.1

EC 2.1.1.360

XP_047295471.1

EC 2.1.1.360

XP_054178319.1

EC 2.1.1.360

XP_054178320.1

EC 2.1.1.360

XP_054178321.1

EC 2.1.1.360

XP_054178322.1

EC 2.1.1.360

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029793.1 RefSeqGene

Range

4785..73430

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001411141.1 → NP_001398070.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform 2

Status: REVIEWED

Source sequence(s)

AC004490, AC005257, AC005263, AC093456

Consensus CDS

CCDS92483.1

UniProtKB/TrEMBL

A0A1C9J735, A0A8I5QL06

Related

ENSP00000510335.1, ENST00000686010.1
NM_032482.3 → NP_115871.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform 1

See identical proteins and their annotated locations for NP_115871.1

Status: REVIEWED

Source sequence(s)

AC005257, AC005263, AF509504, AL080221

Consensus CDS

CCDS42460.1

UniProtKB/Swiss-Prot

O60379, Q8TEK3, Q96JL1

UniProtKB/TrEMBL

A0A1C9J735

Related

ENSP00000381657.3, ENST00000398665.8

Conserved Domains (4) summary

pfam08123
Location:115 → 317

DOT1; Histone methylation protein DOT1

pfam09731
Location:330 → 683

Mitofilin; Mitochondrial inner membrane protein

cl25732
Location:483 → 658

SMC_N; RecF/RecN/SMC N terminal domain

cl28033
Location:775 → 1124

Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

2163933..2232578

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011528359.3 → XP_011526661.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X1

UniProtKB/TrEMBL

A0A1C9J735

Conserved Domains (3) summary

pfam08123
Location:115 → 317

DOT1; Histone methylation protein DOT1

pfam12718
Location:508 → 660

Tropomyosin_1; Tropomyosin like

pfam15035
Location:493 → 661

Rootletin; Ciliary rootlet component, centrosome cohesion
XM_047439515.1 → XP_047295471.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X4

UniProtKB/TrEMBL

A0A1C9J735
XM_047439514.1 → XP_047295470.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X3

UniProtKB/TrEMBL

A0A1C9J735
XM_047439513.1 → XP_047295469.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X2

UniProtKB/TrEMBL

A0A1C9J735
XM_011528361.3 → XP_011526663.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X5

UniProtKB/TrEMBL

A0A1C9J735

Conserved Domains (3) summary

pfam12718
Location:218 → 370

Tropomyosin_1; Tropomyosin like

pfam15035
Location:203 → 371

Rootletin; Ciliary rootlet component, centrosome cohesion

cl17173
Location:1 → 27

AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

2137178..2206142

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054322344.1 → XP_054178319.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X1

UniProtKB/TrEMBL

A0A1C9J732, A0A1C9J735
XM_054322346.1 → XP_054178321.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X4

UniProtKB/TrEMBL

A0A1C9J732, A0A1C9J735
XM_054322345.1 → XP_054178320.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X3

UniProtKB/TrEMBL

A0A1C9J732, A0A1C9J735
XM_054322347.1 → XP_054178322.1 histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X5

UniProtKB/TrEMBL

A0A1C9J732, A0A1C9J735