Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKOQYF8)

DOT Name	cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)
Synonyms	PKA C-gamma; EC 2.7.11.11
Gene Name	PRKACG
Related Disease	B-cell neoplasm ( ) Melanoma ( ) Thyroid gland papillary carcinoma ( ) Advanced cancer ( ) Bladder cancer ( ) Gastric cancer ( ) Glioma ( ) Hepatocellular carcinoma ( ) Inherited bleeding disorder, platelet-type ( ) Meier-Gorlin syndrome ( ) Non-small-cell lung cancer ( ) Qualitative platelet defect ( ) Thrombocytopenia ( ) Tuberculosis ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Ductal breast carcinoma in situ ( ) Osteoarthritis ( ) Pancreatic cancer ( ) Platelet-type bleeding disorder 19 ( ) Breast cancer ( ) Breast carcinoma ( ) Cutaneous melanoma ( ) Pneumonia ( )
UniProt ID	KAPCG_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.7.11.11
Pfam ID	PF00069
Sequence	MGNAPAKKDTEQEESVNEFLAKARGDFLYRWGNPAQNTASSDQFERLRTLGMGSFGRVML VRHQETGGHYAMKILNKQKVVKMKQVEHILNEKRILQAIDFPFLVKLQFSFKDNSYLYLV MEYVPGGEMFSRLQRVGRFSEPHACFYAAQVVLAVQYLHSLDLIHRDLKPENLLIDQQGY LQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAVGFPPFY ADQPIQIYEKIVSGRVRFPSKLSSDLKHLLRSLLQVDLTKRFGNLRNGVGDIKNHKWFAT TSWIAIYEKKVEAPFIPKYTGPGDASNFDDYEEEELRISINEKCAKEFSEF
Function	Phosphorylates a large number of substrates in the cytoplasm and the nucleus.
Tissue Specificity	Testis specific. But important tissues such as brain and ovary have not been analyzed for the content of transcript.
KEGG Pathway	Endocrine resistance (hsa01522 ) MAPK sig.ling pathway (hsa04010 ) Ras sig.ling pathway (hsa04014 ) Calcium sig.ling pathway (hsa04020 ) cAMP sig.ling pathway (hsa04024 ) Chemokine sig.ling pathway (hsa04062 ) Oocyte meiosis (hsa04114 ) Autophagy - animal (hsa04140 ) Longevity regulating pathway (hsa04211 ) Longevity regulating pathway - multiple species (hsa04213 ) Adrenergic sig.ling in cardiomyocytes (hsa04261 ) Vascular smooth muscle contraction (hsa04270 ) Wnt sig.ling pathway (hsa04310 ) Hedgehog sig.ling pathway (hsa04340 ) Apelin sig.ling pathway (hsa04371 ) Tight junction (hsa04530 ) Gap junction (hsa04540 ) Platelet activation (hsa04611 ) Circadian entrainment (hsa04713 ) Thermogenesis (hsa04714 ) Long-term potentiation (hsa04720 ) Retrograde endocan.binoid sig.ling (hsa04723 ) Glutamatergic sy.pse (hsa04724 ) Cholinergic sy.pse (hsa04725 ) Serotonergic sy.pse (hsa04726 ) GABAergic sy.pse (hsa04727 ) Dopaminergic sy.pse (hsa04728 ) Olfactory transduction (hsa04740 ) Taste transduction (hsa04742 ) Inflammatory mediator regulation of TRP channels (hsa04750 ) Insulin sig.ling pathway (hsa04910 ) Insulin secretion (hsa04911 ) GnRH sig.ling pathway (hsa04912 ) Ovarian steroidogenesis (hsa04913 ) Progesterone-mediated oocyte maturation (hsa04914 ) Estrogen sig.ling pathway (hsa04915 ) Melanogenesis (hsa04916 ) Thyroid hormone synthesis (hsa04918 ) Thyroid hormone sig.ling pathway (hsa04919 ) Oxytocin sig.ling pathway (hsa04921 ) Glucagon sig.ling pathway (hsa04922 ) Regulation of lipolysis in adipocytes (hsa04923 ) Renin secretion (hsa04924 ) Aldosterone synthesis and secretion (hsa04925 ) Relaxin sig.ling pathway (hsa04926 ) Cortisol synthesis and secretion (hsa04927 ) Parathyroid hormone synthesis, secretion and action (hsa04928 ) Cushing syndrome (hsa04934 ) Growth hormone synthesis, secretion and action (hsa04935 ) Endocrine and other factor-regulated calcium reabsorption (hsa04961 ) Vasopressin-regulated water reabsorption (hsa04962 ) Salivary secretion (hsa04970 ) Gastric acid secretion (hsa04971 ) Bile secretion (hsa04976 ) Parkinson disease (hsa05012 ) Prion disease (hsa05020 ) Cocaine addiction (hsa05030 ) Amphetamine addiction (hsa05031 ) Morphine addiction (hsa05032 ) Alcoholism (hsa05034 ) Vibrio cholerae infection (hsa05110 ) Amoebiasis (hsa05146 ) Human cytomegalovirus infection (hsa05163 ) Human papillomavirus infection (hsa05165 ) Human T-cell leukemia virus 1 infection (hsa05166 ) Pathways in cancer (hsa05200 ) Viral carcinogenesis (hsa05203 ) Proteoglycans in cancer (hsa05205 ) Chemical carcinogenesis - receptor activation (hsa05207 ) Dilated cardiomyopathy (hsa05414 )
Reactome Pathway	PKA-mediated phosphorylation of key metabolic factors (R-HSA-163358 ) Triglyceride catabolism (R-HSA-163560 ) PKA activation (R-HSA-163615 ) PKA activation in glucagon signalling (R-HSA-164378 ) DARPP-32 events (R-HSA-180024 ) Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676 ) Rap1 signalling (R-HSA-392517 ) Regulation of insulin secretion (R-HSA-422356 ) Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040 ) VEGFA-VEGFR2 Pathway (R-HSA-4420097 ) CREB1 phosphorylation through the activation of Adenylate Cyclase (R-HSA-442720 ) Degradation of GLI1 by the proteasome (R-HSA-5610780 ) Degradation of GLI2 by the proteasome (R-HSA-5610783 ) GLI3 is processed to GLI3R by the proteasome (R-HSA-5610785 ) Hedgehog 'off' state (R-HSA-5610787 ) CD209 (DC-SIGN) signaling (R-HSA-5621575 ) MAPK6/MAPK4 signaling (R-HSA-5687128 ) RET signaling (R-HSA-8853659 ) HDL assembly (R-HSA-8963896 ) ROBO receptors bind AKAP5 (R-HSA-9010642 ) GPER1 signaling (R-HSA-9634597 ) Regulation of glycolysis by fructose 2,6-bisphosphate metabolism (R-HSA-9634600 ) ADORA2B mediated anti-inflammatory cytokines production (R-HSA-9660821 ) FCGR3A-mediated IL10 synthesis (R-HSA-9664323 ) Factors involved in megakaryocyte development and platelet production (R-HSA-983231 ) PKA-mediated phosphorylation of CREB (R-HSA-111931 )

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[6]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Inherited bleeding disorder, platelet-type	DISIUNXT	Strong	Genetic Variation	[7]
Meier-Gorlin syndrome	DISCFIU3	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[9]
Qualitative platelet defect	DISNG54P	Strong	Biomarker	[10]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[10]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[11]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[5]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Biomarker	[12]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[13]
Pancreatic cancer	DISJC981	moderate	Biomarker	[14]
Platelet-type bleeding disorder 19	DISPVLDT	Supportive	Autosomal recessive	[10]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[15]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[15]
Cutaneous melanoma	DIS3MMH9	Disputed	Biomarker	[2]
Pneumonia	DIS8EF3M	Limited	Genetic Variation	[16]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas 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 increases the methylation of cAMP-dependent protein kinase catalytic subunit gamma (PRKACG).	[17]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of cAMP-dependent protein kinase catalytic subunit gamma (PRKACG).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of cAMP-dependent protein kinase catalytic subunit gamma (PRKACG).	[19]
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References

1	Effects of propofol on proliferation and anti-apoptosis of neuroblastoma SH-SY5Y cell line: new insights into neuroprotection.Brain Res. 2011 Apr 12;1384:42-50. doi: 10.1016/j.brainres.2011.02.004. Epub 2011 Feb 25.
2	Long-term Survival of Stage IV Melanoma Patients Treated with BOLD Combination Chemotherapy and Intermediate-dose Subcutaneous Interferon-alpha.Anticancer Res. 2018 Nov;38(11):6393-6397. doi: 10.21873/anticanres.12999.
3	Ang1/Tie2 induces cell proliferation and migration in human papillary thyroid carcinoma via the PI3K/AKT pathway.Oncol Lett. 2018 Jan;15(1):1313-1318. doi: 10.3892/ol.2017.7367. Epub 2017 Nov 8.
4	Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit.J Pain Symptom Manage. 2018 Oct;56(4):560-566. doi: 10.1016/j.jpainsymman.2018.07.011. Epub 2018 Jul 20.
5	Mutations in FGFR3 and PIK3CA, singly or combined with RAS and AKT1, are associated with AKT but not with MAPK pathway activation in urothelial bladder cancer.Hum Pathol. 2012 Oct;43(10):1573-82. doi: 10.1016/j.humpath.2011.10.026. Epub 2012 Mar 12.
6	High expression of PFTK1 in cancer cells predicts poor prognosis in colorectal cancer.Mol Med Rep. 2017 Jul;16(1):224-230. doi: 10.3892/mmr.2017.6560. Epub 2017 May 10.
7	Update on the inherited platelet disorders.Curr Opin Hematol. 2015 Sep;22(5):460-6. doi: 10.1097/MOH.0000000000000171.
8	A genetic dissection of antipsychotic induced movement disorders.Curr Med Chem. 2013;20(3):312-30.
9	Drug resistance to targeted therapeutic strategies in non-small cell lung cancer.Pharmacol Ther. 2020 Feb;206:107438. doi: 10.1016/j.pharmthera.2019.107438. Epub 2019 Nov 9.
10	A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene. Blood. 2014 Oct 16;124(16):2554-63. doi: 10.1182/blood-2014-01-551820. Epub 2014 Jul 24.
11	Synthesis and antimycobacterial activity of imidazo[1,2-b][1,2,4,5]tetrazines.Eur J Med Chem. 2019 Sep 15;178:39-47. doi: 10.1016/j.ejmech.2019.05.081. Epub 2019 May 31.
12	Analysis of gene expression in ductal carcinoma in situ of the breast.Clin Cancer Res. 2002 Dec;8(12):3788-95.
13	Effect of silibinin on CFLAR-JNK pathway in oleic acid-treated HepG2 cells.Biomed Pharmacother. 2018 Dec;108:716-723. doi: 10.1016/j.biopha.2018.09.089. Epub 2018 Sep 21.
14	Primate-specific miRNA-637 inhibited tumorigenesis in human pancreatic ductal adenocarcinoma cells by suppressing Akt1 expression.Exp Cell Res. 2018 Feb 15;363(2):310-314. doi: 10.1016/j.yexcr.2018.01.026.
15	RNAi-mediated downregulation of CDKL1 inhibits growth and colony-formation ability, promotes apoptosis of human melanoma cells.J Dermatol Sci. 2015 Jul;79(1):57-63. doi: 10.1016/j.jdermsci.2015.03.020. Epub 2015 Apr 9.
16	Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies.J Exp Med. 2008 Jan 21;205(1):117-31. doi: 10.1084/jem.20071168. Epub 2007 Dec 31.
17	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.
18	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.
19	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.