DOT1L

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)
End	2,232,578 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	80,631,295 bp
RNA expression pattern
	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
	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
	84444
	208266
	ENSG00000104885
	ENSMUSG00000061589
	Q8TEK3
	n/a
	NM_032482
	NM_199322
	NP_115871
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

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 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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000104885 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000061589 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae)".
^ Slany RK (October 2016). "The molecular mechanics of mixed lineage leukemia". Oncogene. 35 (40): 5215–5223. doi:10.1038/onc.2016.30. PMID 26923329. S2CID 34116587.
^ Malla AB, Rainsford SR, Smith ZD, Lesch BJ (May 2023). "DOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement". Development. 150 (9). doi:10.1242/dev.201497. PMC 10259660. PMID 37082969.
^ Yao Y, Chen P, Diao J, Cheng G, Deng L, Anglin JL, et al. (2011). "Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies". Journal of the American Chemical Society. 133 (42): 16746–9. doi:10.1021/ja206312b. PMC 3492951. PMID 21936531.
^ Chen S, Li L, Chen Y, Hu J, Liu J, Liu YC, et al. (2016). "Identification of Novel Disruptor of Telomeric Silencing 1-like (DOT1L) Inhibitors through Structure-Based Virtual Screening and Biological Assays". Journal of Chemical Information and Modeling. 56 (3): 527–34. doi:10.1021/acs.jcim.5b00738. PMID 26914852.
^ Chen Y, Zhu WG (July 2016). "Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage". Acta Biochim. Biophys. Sin. (Shanghai). 48 (7): 603–16. doi:10.1093/abbs/gmw050. PMID 27217472.

External links

Overview of all the structural information available in the PDB for UniProt: Q8TEK3 (Histone-lysine N-methyltransferase, H3 lysine-79 specific) at the PDBe-KB.

This article on a gene on human chromosome 19 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000104885 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000061589 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae)".

[pmid26923329-6] Slany RK (October 2016). "The molecular mechanics of mixed lineage leukemia". Oncogene. 35 (40): 5215–5223. doi:10.1038/onc.2016.30. PMID 26923329. S2CID 34116587.

[7] Malla AB, Rainsford SR, Smith ZD, Lesch BJ (May 2023). "DOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement". Development. 150 (9). doi:10.1242/dev.201497. PMC 10259660. PMID 37082969.

[pmid21936531-8] Yao Y, Chen P, Diao J, Cheng G, Deng L, Anglin JL, et al. (2011). "Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies". Journal of the American Chemical Society. 133 (42): 16746–9. doi:10.1021/ja206312b. PMC 3492951. PMID 21936531.

[pmid26914852-9] Chen S, Li L, Chen Y, Hu J, Liu J, Liu YC, et al. (2016). "Identification of Novel Disruptor of Telomeric Silencing 1-like (DOT1L) Inhibitors through Structure-Based Virtual Screening and Biological Assays". Journal of Chemical Information and Modeling. 56 (3): 527–34. doi:10.1021/acs.jcim.5b00738. PMID 26914852.

[pmid27217472-10] Chen Y, Zhu WG (July 2016). "Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage". Acta Biochim. Biophys. Sin. (Shanghai). 48 (7): 603–16. doi:10.1093/abbs/gmw050. PMID 27217472.

[1]

References

Further reading

External links