Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT59TQ6P)

• DOT Name: Small membrane A-kinase anchor protein (C2ORF88)
• Synonyms: Small membrane AKAP; smAKAP
• Gene Name: C2ORF88
• Related Disease: Juvenile idiopathic arthritis
• UniProt ID: SMAKA_HUMAN
• PDB ID: 5HVZ
• Pfam ID: PF15127
• Sequence:
  MGCMKSKQTFPFPTIYEGEKQHESEEPFMPEERCLPRMASPVNVKEEVKEPPGTNTVILE
  YAHRLSQDILCDALQQWACNNIKYHDIPYIESEGP
• Function: Binds to type I regulatory subunits of protein kinase A (PKA-RI) and may anchor/target them to the plasma membrane.
• Tissue Specificity: Expressed in heart (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[12]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Small membrane A-kinase anchor protein (C2ORF88).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Small membrane A-kinase anchor protein (C2ORF88).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Small membrane A-kinase anchor protein (C2ORF88).	[11]

References

• [1] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.