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) [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

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

1. GRCh38: Ensembl release 89: ENSG00000104885 – Ensembl, May 2017
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.
5. "Entrez Gene: DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae)".
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.
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.
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.
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.

Further reading

• Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "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". DNA Research. 8 (2): 85–95. doi: 10.1093/dnares/8.2.85 . PMID   11347906.
• Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, et al. (June 2002). "Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain". Current Biology. 12 (12): 1052–8. Bibcode:2002CBio...12.1052F. doi: 10.1016/S0960-9822(02)00901-6 . PMID   12123582. S2CID   17263035.
• Min J, Feng Q, Li Z, Zhang Y, Xu RM (March 2003). "Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase". Cell. 112 (5): 711–23. doi: 10.1016/S0092-8674(03)00114-4 . PMID   12628190. S2CID   17822742.
• Jikuya H, Takano J, Kikuno R, Hirosawa M, Nagase T, Nomura N, et al. (February 2003). "Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones". DNA Research. 10 (1): 49–57. doi: 10.1093/dnares/10.1.49 . PMID   12693554.
• Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, et al. (April 2005). "hDOT1L links histone methylation to leukemogenesis". Cell. 121 (2): 167–78. doi: 10.1016/j.cell.2005.02.020 . PMID   15851025. S2CID   15638573.
• Sistayanarain A, Tsuneyama K, Zheng H, Takahashi H, Nomoto K, Cheng C, et al. (2006). "Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma". Anticancer Research. 26 (5A): 3585–93. PMID   17094487.

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 .