Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOIWE5G)

• DOT Name: cAMP-dependent protein kinase inhibitor gamma (PKIG)
• Synonyms: PKI-gamma
• Gene Name: PKIG
• Related Disease:
  Adenosine deaminase defciency
  Severe combined immunodeficiency
  Ankylosing spondylitis
  Crohn disease
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: IPKG_HUMAN
• Pfam ID: PF02827
• Sequence:
  MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEGAEGQVEGSAPD
  KEAGNQPQSSDGTTSS
• Function: Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenosine deaminase defciency	DISC2C93	Strong	Genetic Variation	[1]
Severe combined immunodeficiency	DIS6MF4Q	Strong	CausalMutation	[2]
Ankylosing spondylitis	DISRC6IR	moderate	Genetic Variation	[3]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[3]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[3]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[3]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	cAMP-dependent protein kinase inhibitor gamma (PKIG) affects the response to substance of Acetaminophen.	[16]

13 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 cAMP-dependent protein kinase inhibitor gamma (PKIG).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[9]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of cAMP-dependent protein kinase inhibitor gamma (PKIG).	[15]

References

• [1] Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decades Experience.J Investig Allergol Clin Immunol. 2017;27(5):299-304. doi: 10.18176/jiaci.0147. Epub 2017 Mar 7.
• [2] Gene therapy for immunodeficiency due to adenosine deaminase deficiency.N Engl J Med. 2009 Jan 29;360(5):447-58. doi: 10.1056/NEJMoa0805817.
• [3] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [4] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [11] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [16] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.