Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGOQM6B)

DOT Name Adenylate cyclase type 3 (ADCY3)
Synonyms EC 4.6.1.1; ATP pyrophosphate-lyase 3; Adenylate cyclase type III; AC-III; Adenylate cyclase, olfactive type; Adenylyl cyclase 3; AC3
Gene Name ADCY3
Related Disease
Classic lissencephaly ( )
Congenital diarrhea 5 with tufting enteropathy ( )
Matthew-Wood syndrome ( )
Metabolic disorder ( )
Neoplasm ( )
Type-1 diabetes ( )
Adenoma ( )
Advanced cancer ( )
Bipolar disorder ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Dental caries ( )
Inflammatory bowel disease ( )
Major depressive disorder ( )
Mood disorder ( )
Non-insulin dependent diabetes ( )
Obsolete body mass index quantitative trait locus 19 ( )
Ulcerative colitis ( )
Ankylosing spondylitis ( )
Crohn disease ( )
Gastric cancer ( )
Obesity ( )
Psoriasis ( )
Sclerosing cholangitis ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
UniProt ID
ADCY3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
4.6.1.1
Pfam ID
PF16214 ; PF00211
Sequence
MPRNQGFSEPEYSAEYSAEYSVSLPSDPDRGVGRTHEISVRNSGSCLCLPRFMRLTFVPE
SLENLYQTYFKRQRHETLLVLVVFAALFDCYVVVMCAVVFSSDKLASLAVAGIGLVLDII
LFVLCKKGLLPDRVTRRVLPYVLWLLITAQIFSYLGLNFARAHAASDTVGWQVFFVFSFF
ITLPLSLSPIVIISVVSCVVHTLVLGVTVAQQQQEELKGMQLLREILANVFLYLCAIAVG
IMSYYMADRKHRKAFLEARQSLEVKMNLEEQSQQQENLMLSILPKHVADEMLKDMKKDES
QKDQQQFNTMYMYRHENVSILFADIVGFTQLSSACSAQELVKLLNELFARFDKLAAKYHQ
LRIKILGDCYYCICGLPDYREDHAVCSILMGLAMVEAISYVREKTKTGVDMRVGVHTGTV
LGGVLGQKRWQYDVWSTDVTVANKMEAGGIPGRVHISQSTMDCLKGEFDVEPGDGGSRCD
YLEEKGIETYLIIASKPEVKKTATQNGLNGSALPNGAPASSKSSSPALIETKEPNGSAHS
SGSTSEKPEEQDAQADNPSFPNPRRRLRLQDLADRVVDASEDEHELNQLLNEALLERESA
QVVKKRNTFLLSMRFMDPEMETRYSVEKEKQSGAAFSCSCVVLLCTALVEILIDPWLMTN
YVTFMVGEILLLILTICSLAAIFPRAFPKKLVAFSTWIDRTRWARNTWAMLAIFILVMAN
VVDMLSCLQYYTGPSNATAGMETEGSCLENPKYYNYVAVLSLIATIMLVQVSHMVKLTLM
LLVAGAVATINLYAWRPVFDEYDHKRFREHDLPMVALEQMQGFNPGLNGTDRLPLVPSKY
SMTVMVFLMMLSFYYFSRHVEKLARTLFLWKIEVHDQKERVYEMRRWNEALVTNMLPEHV
ARHFLGSKKRDEELYSQTYDEIGVMFASLPNFADFYTEESINNGGIECLRFLNEIISDFD
SLLDNPKFRVITKIKTIGSTYMAASGVTPDVNTNGFASSNKEDKSERERWQHLADLADFA
LAMKDTLTNINNQSFNNFMLRIGMNKGGVLAGVIGARKPHYDIWGNTVNVASRMESTGVM
GNIQVVEETQVILREYGFRFVRRGPIFVKGKGELLTFFLKGRDKLATFPNGPSVTLPHQV
VDNS
Function
Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet.
Tissue Specificity
Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) . Expressed in brain, heart, kidney, liver, lung, pancreas islets, placenta, and skeletal muscle . Detected in testis .
KEGG Pathway
Purine metabolism (hsa00230 )
Metabolic pathways (hsa01100 )
Endocrine resistance (hsa01522 )
Rap1 sig.ling pathway (hsa04015 )
Calcium sig.ling pathway (hsa04020 )
cGMP-PKG sig.ling pathway (hsa04022 )
cAMP sig.ling pathway (hsa04024 )
Chemokine sig.ling pathway (hsa04062 )
Phospholipase D sig.ling pathway (hsa04072 )
Oocyte meiosis (hsa04114 )
Longevity regulating pathway (hsa04211 )
Longevity regulating pathway - multiple species (hsa04213 )
Adrenergic sig.ling in cardiomyocytes (hsa04261 )
Vascular smooth muscle contraction (hsa04270 )
Apelin sig.ling pathway (hsa04371 )
Gap junction (hsa04540 )
Platelet activation (hsa04611 )
Circadian entrainment (hsa04713 )
Thermogenesis (hsa04714 )
Retrograde endocan.binoid sig.ling (hsa04723 )
Glutamatergic sy.pse (hsa04724 )
Cholinergic sy.pse (hsa04725 )
GABAergic sy.pse (hsa04727 )
Olfactory transduction (hsa04740 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
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 )
Oxytocin sig.ling pathway (hsa04921 )
Regulation of lipolysis in adipocytes (hsa04923 )
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 )
Vasopressin-regulated water reabsorption (hsa04962 )
Salivary secretion (hsa04970 )
Gastric acid secretion (hsa04971 )
Pancreatic secretion (hsa04972 )
Bile secretion (hsa04976 )
Morphine addiction (hsa05032 )
Vibrio cholerae infection (hsa05110 )
Human cytomegalovirus infection (hsa05163 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Pathways in cancer (hsa05200 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Dilated cardiomyopathy (hsa05414 )
Reactome Pathway
PKA activation (R-HSA-163615 )
PKA activation in glucagon signalling (R-HSA-164378 )
Adenylate cyclase activating pathway (R-HSA-170660 )
Adenylate cyclase inhibitory pathway (R-HSA-170670 )
Olfactory Signaling Pathway (R-HSA-381753 )
G alpha (s) signalling events (R-HSA-418555 )
G alpha (i) signalling events (R-HSA-418594 )
G alpha (z) signalling events (R-HSA-418597 )
Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040 )
Hedgehog 'off' state (R-HSA-5610787 )
GPER1 signaling (R-HSA-9634597 )
ADORA2B mediated anti-inflammatory cytokines production (R-HSA-9660821 )
FCGR3A-mediated IL10 synthesis (R-HSA-9664323 )
Glucagon signaling in metabolic regulation (R-HSA-163359 )

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Classic lissencephaly DISR8S3S Definitive Biomarker [1]
Congenital diarrhea 5 with tufting enteropathy DISPAMX4 Definitive Biomarker [1]
Matthew-Wood syndrome DISA7HR7 Definitive Biomarker [2]
Metabolic disorder DIS71G5H Definitive Biomarker [3]
Neoplasm DISZKGEW Definitive Altered Expression [4]
Type-1 diabetes DIS7HLUB Definitive Altered Expression [5]
Adenoma DIS78ZEV Strong Biomarker [6]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Bipolar disorder DISAM7J2 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Genetic Variation [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [6]
Dental caries DISRBCMD Strong Genetic Variation [9]
Inflammatory bowel disease DISGN23E Strong Biomarker [10]
Major depressive disorder DIS4CL3X Strong Genetic Variation [7]
Mood disorder DISLVMWO Strong Biomarker [7]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [11]
Obsolete body mass index quantitative trait locus 19 DISM0UHU Strong Autosomal recessive [12]
Ulcerative colitis DIS8K27O Strong Genetic Variation [10]
Ankylosing spondylitis DISRC6IR moderate Genetic Variation [13]
Crohn disease DIS2C5Q8 Limited Genetic Variation [14]
Gastric cancer DISXGOUK Limited Biomarker [15]
Obesity DIS47Y1K Limited Biomarker [16]
Psoriasis DIS59VMN Limited Genetic Variation [13]
Sclerosing cholangitis DIS7GZNB Limited Genetic Variation [13]
Stomach cancer DISKIJSX Limited Biomarker [15]
Type-1/2 diabetes DISIUHAP Limited Genetic Variation [16]
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⏷ Show the Full List of 26 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Adenylate cyclase type 3 (ADCY3). [17]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Adenylate cyclase type 3 (ADCY3). [20]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Adenylate cyclase type 3 (ADCY3). [24]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Adenylate cyclase type 3 (ADCY3). [27]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Adenylate cyclase type 3 (ADCY3). [18]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Adenylate cyclase type 3 (ADCY3). [19]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Adenylate cyclase type 3 (ADCY3). [21]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Adenylate cyclase type 3 (ADCY3). [22]
Menadione DMSJDTY Approved Menadione decreases the expression of Adenylate cyclase type 3 (ADCY3). [21]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Adenylate cyclase type 3 (ADCY3). [23]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Adenylate cyclase type 3 (ADCY3). [25]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Adenylate cyclase type 3 (ADCY3). [26]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Adenylate cyclase type 3 (ADCY3). [23]
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⏷ Show the Full List of 9 Drug(s)

References

1 Gene Profiling of Nucleus Basalis Tau Containing Neurons in Chronic Traumatic Encephalopathy: A Chronic Effects of Neurotrauma Consortium Study.J Neurotrauma. 2018 Jun 1;35(11):1260-1271. doi: 10.1089/neu.2017.5368. Epub 2018 Apr 5.
2 Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8.J Hum Genet. 2019 Jun;64(6):521-534. doi: 10.1038/s10038-019-0584-6. Epub 2019 Mar 11.
3 Genetic variation of the adenylyl cyclase 3 (AC3) locus and its influence on type 2 diabetes and obesity susceptibility in Swedish men.Int J Obes (Lond). 2008 Mar;32(3):407-12. doi: 10.1038/sj.ijo.0803742. Epub 2007 Sep 25.
4 Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway.Oncotarget. 2013 Oct;4(10):1791-803. doi: 10.18632/oncotarget.1324.
5 Impairment of amyloid precursor protein alpha-processing in cerebral microvessels of type 1 diabetic mice.J Cereb Blood Flow Metab. 2019 Jun;39(6):1085-1098. doi: 10.1177/0271678X17746981. Epub 2017 Dec 18.
6 Evolution and heterogeneity of non-hereditary colorectal cancer revealed by single-cell exome sequencing.Oncogene. 2017 May 18;36(20):2857-2867. doi: 10.1038/onc.2016.438. Epub 2016 Dec 12.
7 Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.Mol Psychiatry. 2012 Jan;17(1):36-48. doi: 10.1038/mp.2010.109. Epub 2010 Nov 2.
8 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
9 Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.Nat Commun. 2019 Jun 24;10(1):2773. doi: 10.1038/s41467-019-10630-1.
10 Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.Gastroenterology. 2017 Jan;152(1):206-217.e2. doi: 10.1053/j.gastro.2016.09.032. Epub 2016 Sep 28.
11 Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes.Nat Genet. 2018 Feb;50(2):172-174. doi: 10.1038/s41588-017-0022-7. Epub 2018 Jan 8.
12 Loss-of-function mutations in ADCY3 cause monogenic severe obesity. Nat Genet. 2018 Feb;50(2):175-179. doi: 10.1038/s41588-017-0023-6. Epub 2018 Jan 8.
13 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.
14 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
15 LINC00319 acts as a microRNA-335-5p sponge to accelerate tumor growth and metastasis in gastric cancer by upregulating ADCY3.Am J Physiol Gastrointest Liver Physiol. 2020 Jan 1;318(1):G10-G22. doi: 10.1152/ajpgi.00405.2018. Epub 2019 Aug 21.
16 New ADCY3 Variants Dance in Obesity Etiology.Trends Endocrinol Metab. 2018 Jun;29(6):361-363. doi: 10.1016/j.tem.2018.02.004. Epub 2018 Feb 14.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
19 Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
20 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.
21 Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
22 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
23 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
24 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.
25 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
26 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
27 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.