DOT1L

Protein-coding gene in the species Homo sapiens

DOT1L
Available structures
PDBHuman 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
AliasesDOT1L, DOT1, KMT4, DOT1 like histone lysine methyltransferase
External IDsOMIM: 607375; MGI: 2143886; HomoloGene: 32779; GeneCards: DOT1L; OMA:DOT1L - orthologs
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for DOT1L
Genomic location for DOT1L
Band19p13.3Start2,163,933 bp[1]
End2,232,578 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for DOT1L
Genomic location for DOT1L
Band10|10 C1Start80,591,040 bp[2]
End80,631,295 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
SpeciesHumanMouse
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 MbChr 10: 80.59 – 80.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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. ^ a b c GRCh38: Ensembl release 89: ENSG00000104885 – Ensembl, May 2017
  2. ^ a b c 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.
  • 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.
  • v
  • t
  • e
  • 1nw3: Structure of the Catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase
    1nw3: Structure of the Catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase


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