Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXXM7I5)

• DOT Name: Golgi pH regulator A (GPR89A)
• Synonyms: Protein GPR89A; Putative MAPK-activating protein PM01; Putative NF-kappa-B-activating protein 90
• Gene Name: GPR89A
• UniProt ID: GPHRA_HUMAN
• Pfam ID: PF12430 ; PF12537
• Sequence:
  MSFLIDSSIMITSQILFFGFGWLFFMRQLFKDYEIRQYVVQVIFSVTFAFSCTMFELIIF
  EILGVLNSSSRYFHWKMNLCVILLILVFMVPFYIGYFIVSNIRLLHKQRLLFSCLLWLTF
  MYFFWKLGDPFPILSPKHGILSIEQLISRVGVIGVTLMALLSGFGAVNCPYTYMSYFLRN
  VTDTDILALERRLLQTMDMIISKKKRMAMARRTMFQKGEVHNKPSGFWGMIKSVTTSASG
  SENLTLIQQEVDALEELSRQLFLETADLYATKERIEYSKTFKGKYFNFLGYFFSIYCVWK
  IFMATINIVFDRVGKTDPVTRGIEITVNYLGIQFDVKFWSQHISFILVGIIIVTSIRGLL
  ITLTKFFYAISSSKSSNVIVLLLAQIMGMYFVSSVLLIRMSMPLEYRTIITEVLGELQFN
  FYHRWFDVIFLVSALSSILFLYLAHKQAPEKQMAP
• Function: Voltage dependent anion channel required for acidification and functions of the Golgi apparatus that may function in counter-ion conductance. Plays a role in lymphocyte development, probably by acting as a RABL3 effector in hematopoietic cells.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Golgi pH regulator A (GPR89A).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Golgi pH regulator A (GPR89A).	[4]

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 Golgi pH regulator A (GPR89A).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Golgi pH regulator A (GPR89A).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Golgi pH regulator A (GPR89A).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Golgi pH regulator A (GPR89A).	[6]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Golgi pH regulator A (GPR89A).	[7]

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] 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.
• [5] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [7] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.