Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

DOT1L (Q8TEK3) - Overview - Molecular Target Synopsis

Protein


DOT1L, Histone-lysine N-methyltransferase, H3 lysine-79 specific
Enzyme Classification 2.1.1.43
UniProt Q8TEK3

Also Known as DOT1L_HUMAN, DOT1L, KIAA1814, KMT4

Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones (PubMed:12123582). Binds to DNA (PubMed:12628190). Interacts with MLLT10.

6JMA
CRYO-EM STRUCTURE OF DOT1L BOUND TO H2B UBIQUITINATED NUCLEOSOME
RCSB/PDB
Inspect Structure
See all 3D Structures for DOT1L

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: DOT1L is active in the following subcellular-locations: nucleus.
GO terms: DOT1L is active in the following subcellular-locations: chromosome, intracellular membrane-bounded organelle, nucleoplasm, nucleus, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DOT1L has gain in 0 cell-lines, loss in 5 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: K_562, SR, HL_60

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H187, MHH-NB-11, CPC-N

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, NHLF

(see details)

3D Structures


For DOT1L there are:
37 structures (47 chains) solved
34 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

DOT1L is solved in complex with the approved drug(s):

ADN/ADENOSINE (5MVS_A, 5MVS_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DOT1L has been screened with 190 compounds (299 bioactivities), 41 compounds have bioactivities that show binding affinity of <= 500nM (97 bioactivities). (see details)