DOT1L

DOT1-like (Disruptor of telomeric silencing 1-like), histone H3K79 methyltransferase (S. cerevisiae), also known as DOT1L, is a protein found in humans, as well as other eukaryotes.^[5]

DOT1L
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1NW3, 2MV7, 3QOW, 3QOX, 3SR4, 3SX0, 3UWP, 4EK9, 4EKG, 4EKI, 4EQZ, 4ER0, 4ER3, 4ER5, 4ER6, 4ER7, 4HRA, 4WVL, 5DSX, 5JUW, 5DRT, 5DTM, 5DTQ, 5DT2, 5DRY, 5DTR
Identifiers
Aliases	DOT1L, DOT1, KMT4, DOT1 like histone lysine methyltransferase
External IDs	OMIM: 607375; MGI: 2143886; HomoloGene: 32779; GeneCards: DOT1L; OMA:DOT1L - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 2,163,933 bp[1] End 2,232,578 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 C1 Start 80,591,040 bp[2] End 80,631,295 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right testis left testis mucosa of ileum ventricular zone sural nerve ganglionic eminence sperm right hemisphere of cerebellum right lobe of thyroid gland mucosa of transverse colon Top expressed in cerebellar cortex zygote hand superior frontal gyrus lobe of cerebellum primary visual cortex cerebellar vermis muscle of thigh genital tubercle spermatid More reference expression data BioGPS More reference expression data
Gene ontology Molecular function methyltransferase activity transferase activity DNA binding transcription factor binding protein binding histone methyltransferase activity histone-lysine N-methyltransferase activity histone methyltransferase activity (H3-K79 specific) Cellular component nucleoplasm nucleus telomere intracellular membrane-bounded organelle protein-containing complex Biological process telomere organization methylation regulation of transcription regulatory region DNA binding regulation of receptor signaling pathway via JAK-STAT positive regulation of transcription by RNA polymerase II positive regulation of cell population proliferation histone H3-K79 methylation DNA damage checkpoint signaling DNA repair chromatin organization regulation of cell cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 84444 208266 Ensembl ENSG00000104885 ENSMUSG00000061589 UniProt Q8TEK3 n/a RefSeq (mRNA) NM_032482 NM_199322 RefSeq (protein) NP_115871 n/a Location (UCSC) Chr 19: 2.16 – 2.23 Mb Chr 10: 80.59 – 80.63 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias.^[6] DOT1L also plays a role in spermatogenesis, where it acts as a transcriptional activator for genes responsible for the histone-to-protamine transition.^[7]

Small molecule inhibitors of Dot1L catalytic activity have been developed.^[8][9]

All three forms of H3K79 methylation (H3K79me1; H3K79me2; H3K79me3) are catalyzed by DOT1 in yeast or DOT1L in mammals. H3K79 methylation participates in the DNA damage response and has multiple roles in nucleotide excision repair and sister chromatid recombinational repair.^[10]