Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIX5RFV)

• DOT Name: DnaJ homolog subfamily C member 24 (DNAJC24)
• Synonyms: CSL-type zinc finger-containing protein 3; Diphthamide biosynthesis protein 4
• Gene Name: DNAJC24
• Related Disease: Glaucoma/ocular hypertension
• UniProt ID: DJC24_HUMAN
• PDB ID: 2L6L
• Pfam ID: PF00226 ; PF05207
• Sequence:
  MMAVEQMPKKDWYSILGADPSANISDLKQKYQKLILMYHPDKQSTDVPAGTVEECVQKFI
  EIDQAWKILGNEETKREYDLQRCEDDLRNVGPVDAQVYLEEMSWNEGDHSFYLSCRCGGK
  YSVSKDEAEEVSLISCDTCSLIIELLHYN
• Function: Stimulates the ATPase activity of several Hsp70-type chaperones. This ability is enhanced by iron-binding. The iron-bound form is redox-active and can function as electron carrier. Plays a role in the diphthamide biosynthesis, a post-translational modification of histidine which occurs in translation elongation factor 2 (EEF2) which can be ADP-ribosylated by diphtheria toxin and by Pseudomonas exotoxin A (Eta).
• Reactome Pathway: Synthesis of diphthamide-EEF2 (R-HSA-5358493)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glaucoma/ocular hypertension	DISLBXBY	Strong	Genetic Variation	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of DnaJ homolog subfamily C member 24 (DNAJC24).	[2]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DnaJ homolog subfamily C member 24 (DNAJC24).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DnaJ homolog subfamily C member 24 (DNAJC24).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of DnaJ homolog subfamily C member 24 (DNAJC24).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DnaJ homolog subfamily C member 24 (DNAJC24).	[6]

References

• [1] Genome-wide association and admixture analysis of glaucoma in the Women's Health Initiative.Hum Mol Genet. 2014 Dec 15;23(24):6634-43. doi: 10.1093/hmg/ddu364. Epub 2014 Jul 15.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.