Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHZRJ56)

• DOT Name: G kinase-anchoring protein 1 (GKAP1)
• Synonyms: cGMP-dependent protein kinase-anchoring protein of 42 kDa
• Gene Name: GKAP1
• UniProt ID: GKAP1_HUMAN
• Sequence:
  MASAVLSSVPTTASRFALLQVDSGSGSDSEPGKGKGRNTGKSQTLGSKSTTNEKKREKRR
  KKKEQQQSEANELRNLAFKKIPQKSSHAVCNAQHDLPLSNPVQKDSREENWQEWRQRDEQ
  LTSEMFEADLEKALLLSKLEYEEHKKEYEDAENTSTQSKVMNKKDKRKNHQGKDRPLTVS
  LKDFHSEDHISKKTEELSSSQTLSHDGGFFNRLEDDVHKILIREKRREQLTEYNGTDNCT
  AHEHNQEVVLKDGRIERLKLELERKDAEIQKLKNVITQWEAKYKEVKARNAQLLKMLQEG
  EMKDKAEILLQVDESQSIKNELTIQVTSLHAALEQERSKVKVLQAELAKYQGGRKGKRNS
  ESDQCR
• Function: Regulates insulin-dependent IRS1 tyrosine phosphorylation in adipocytes by modulating the availability of IRS1 to IR tyrosine kinase. Its association with IRS1 is required for insulin-induced translocation of SLC2A4 to the cell membrane. Involved in TNF-induced impairment of insulin-dependent IRS1 tyrosine phosphorylation.

Molecular Interaction Atlas (MIA) of This DOT

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 G kinase-anchoring protein 1 (GKAP1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of G kinase-anchoring protein 1 (GKAP1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of G kinase-anchoring protein 1 (GKAP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of G kinase-anchoring protein 1 (GKAP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of G kinase-anchoring protein 1 (GKAP1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of G kinase-anchoring protein 1 (GKAP1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of G kinase-anchoring protein 1 (GKAP1).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of G kinase-anchoring protein 1 (GKAP1).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of G kinase-anchoring protein 1 (GKAP1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of G kinase-anchoring protein 1 (GKAP1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of G kinase-anchoring protein 1 (GKAP1).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of G kinase-anchoring protein 1 (GKAP1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of G kinase-anchoring protein 1 (GKAP1).	[12]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of G kinase-anchoring protein 1 (GKAP1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of G kinase-anchoring protein 1 (GKAP1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of G kinase-anchoring protein 1 (GKAP1).	[15]

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] 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.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [12] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [13] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [14] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [15] 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.