Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHO59JC)

• DOT Name: Protein LLP homolog (LLPH)
• Synonyms: Protein LAPS18-like
• Gene Name: LLPH
• UniProt ID: LLPH_HUMAN
• PDB ID: 6LSS; 6LU8; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY; 8FKZ; 8FL0; 8FL2; 8FL3; 8FL4; 8FL6; 8FL7; 8FL9; 8FLA; 8FLB; 8FLC; 8FLD; 8FLE; 8FLF; 8IDT; 8IDY; 8IE3; 8INE; 8INF; 8INK; 8IPD; 8IPX; 8IPY; 8IR1; 8IR3
• Pfam ID: PF10169
• Sequence:
  MAKSLRSKWKRKMRAEKRKKNAPKEASRLKSILKLDGDVLMKDVQEIATVVVPKPKHCQE
  KMQCEVKDEKDDMKMETDIKRNKKTLLDQHGQYPIWMNQRQRKRLKAKREKRKGKSKAKA
  VKVAKGLAW
• Function: In hippocampal neurons, regulates dendritic and spine growth and synaptic transmission.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Protein LLP homolog (LLPH).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein LLP homolog (LLPH).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Protein LLP homolog (LLPH).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein LLP homolog (LLPH).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein LLP homolog (LLPH).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein LLP homolog (LLPH).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein LLP homolog (LLPH).	[6]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Protein LLP homolog (LLPH).	[8]

References

• [1] 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.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [8] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.