Details of Drug Off-Target (DOT)

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

• DOT Name: Secretogranin-2 (SCG2)
• Synonyms: PAP-alpha; EC 2.7.7.19; Polynucleotide adenylyltransferase alpha
• Gene Name: SCG2
• Related Disease:
  Adenocarcinoma
  Adenoma
  Advanced cancer
  Alzheimer disease
  Aortic valve stenosis
  Arteriosclerosis
  Atherosclerosis
  Benign neoplasm
  Cardiac failure
  Coeliac disease
  Congestive heart failure
  Coronary atherosclerosis
  Ewing sarcoma
  Fibromyalgia
  High blood pressure
  Malignant soft tissue neoplasm
  Matthew-Wood syndrome
  Multiple endocrine neoplasia type 1
  Myocardial ischemia
  Neoplasm
  Neuroendocrine neoplasm
  Osteoarthritis
  Pheochromocytoma
  Primitive neuroectodermal tumor
  Rheumatoid arthritis
  Sarcoma
  Tuberculosis
  Cerebral infarction
  Coronary heart disease
  Diabetic neuropathy
  Melanoma
  Myocardial infarction
  Prader-Willi syndrome
  Amyotrophic lateral sclerosis
  Arrhythmia
  Growth hormone-producing pituitary gland adenoma
  Neuroblastoma
  Pituitary gland disorder
  Type-1/2 diabetes
• UniProt ID: SCG2_BOVIN
• Pfam ID: PF01271
• Sequence:
  MAEAKTHWLGAVLSLIPLIFLLSEAEAASFQRNQLLQKEPDLRLENVQRFPSPEMIRALE
  YIEKLRQQAHKEESSPDYNPYQGVSVPLQQKENGDLPESSRDSLSEDEWMKIIAEALRQA
  ENEPQSAPKENKPYTLNSEKNFPMDMPDDYETQQWAERKLKHMRFPPMYEENSRDNPFKR
  TNEIVEEQYTPQNLATLESVFQELGKLTGPNSQKRERADEEQKLYTDDEDDIYKANNIAY
  EDVVGGEDWNPVEEKIESQTQEEVRDSKENADKTEQINDEMKRSGQLGLQDEDLRKESKD
  QLSDDVSKVITYLKRLVNAAGSGRSQNGQTGERAIRLFEKPLDPQSIYQLIEISRNLQIP
  PEDLIDMLKTGEKPVEPEQELEIPVEPEDISEVDLDHPDLFQNKMLSKNGYPKAPGHAVA
  EALSEGLSVEDILNLLGMESAANPKPPYFPNQYNREKVLSRLPYGPGRSKANQLPKAVWM
  PDVENRQMAYENLNDKDQELGEYLARMLVKYPEIMNANPAKRVPSQGSTEDDRQDENQIE
  QALKEHLSQHSSQETDKLASVSKRLPVGTPKSDDTPNRPYLDEDLLVKVLEYLNQEKAEK
  GREHIAKRAMENM
• Function: Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules.
• Tissue Specificity: .Highest levels detected in anterior pituitary followed by adrenal medulla and posterior pituitary (at protein level) . In the brain, high levels are found in the hypothalamus, comparable to those present in posterior pituitary with two- to six-fold lower levels present in the other brain regions investigated including caudate nucleus, hippocampus, thalamus and brainstem (at protein level) .
• Reactome Pathway:
  Post-translational protein phosphorylation (R-BTA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-BTA-381426)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Aortic valve stenosis	DISW7AQ9	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Benign neoplasm	DISDUXAD	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Coeliac disease	DISIY60C	Strong	Altered Expression	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[9]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[10]
Fibromyalgia	DISZJDS2	Strong	Altered Expression	[11]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[12]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[13]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[14]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Genetic Variation	[15]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Neuroendocrine neoplasm	DISNPLOO	Strong	Biomarker	[3]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[17]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[3]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[18]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[17]
Sarcoma	DISZDG3U	Strong	Biomarker	[13]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[19]
Cerebral infarction	DISR1WNP	moderate	Biomarker	[20]
Coronary heart disease	DIS5OIP1	moderate	Biomarker	[20]
Diabetic neuropathy	DISX6VF8	moderate	Biomarker	[21]
Melanoma	DIS1RRCY	moderate	Biomarker	[22]
Myocardial infarction	DIS655KI	moderate	Biomarker	[6]
Prader-Willi syndrome	DISYWMLU	moderate	Biomarker	[23]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[24]
Arrhythmia	DISFF2NI	Limited	Biomarker	[25]
Growth hormone-producing pituitary gland adenoma	DIS45N3K	Limited	Biomarker	[16]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[26]
Pituitary gland disorder	DIS7XB48	Limited	Biomarker	[16]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Reserpine	DM6VM38	Approved	Secretogranin-2 (SCG2) increases the Metabolic disorder ADR of Reserpine.	[28]

References

• [1] Chromogranin A and B and secretogranin II in prostatic adenocarcinomas: neuroendocrine expression in patients untreated and treated with androgen deprivation therapy.Prostate. 1998 Feb 1;34(2):113-20. doi: 10.1002/(sici)1097-0045(19980201)34:2<113::aid-pros5>3.0.co;2-l.
• [2] Secretogranin II (SgII) distribution and processing studies in human normal and adenomatous anterior pituitaries using new polyclonal antibodies.Regul Pept. 1997 Feb 26;68(3):155-63. doi: 10.1016/s0167-0115(96)02110-6.
• [3] Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66.J Mol Endocrinol. 2012 Feb 6;48(2):115-27. doi: 10.1530/JME-11-0077. Print 2012 Apr.
• [4] A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease.Proteomics Clin Appl. 2018 Jan;12(1). doi: 10.1002/prca.201700131. Epub 2017 Nov 23.
• [5] Circulating secretoneurin concentrations in patients with moderate to severe aortic stenosis.Clin Biochem. 2019 Sep;71:17-23. doi: 10.1016/j.clinbiochem.2019.06.008. Epub 2019 Jun 19.
• [6] Secretoneurin gene therapy improves hind limb and cardiac ischaemia in Apo E??mice without influencing systemic atherosclerosis.Cardiovasc Res. 2015 Jan 1;105(1):96-106. doi: 10.1093/cvr/cvu237. Epub 2014 Nov 5.
• [7] Secretogranin II; a protein increased in the myocardium and circulation in heart failure with cardioprotective properties.PLoS One. 2012;7(5):e37401. doi: 10.1371/journal.pone.0037401. Epub 2012 May 24.
• [8] Angiogenesis-related gene expression analysis in celiac disease.Autoimmunity. 2012 May;45(3):264-70. doi: 10.3109/08916934.2011.637531. Epub 2012 Jan 9.
• [9] Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress.Eur J Pharmacol. 2018 Mar 5;822:13-24. doi: 10.1016/j.ejphar.2018.01.008. Epub 2018 Jan 11.
• [10] Neural and mesenchymal differentiations in Ewing's sarcoma cell lines. Morphological, immunophenotypic, molecular biological and cytogenetic evidence.Int J Cancer. 1995 Nov 27;63(5):738-43. doi: 10.1002/ijc.2910630522.
• [11] Immunohistochemical and molecular studies of serotonin, substance P, galanin, pituitary adenylyl cyclase-activating polypeptide, and secretoneurin in fibromyalgic muscle tissue.Arthritis Rheum. 1998 Sep;41(9):1689-94. doi: 10.1002/1529-0131(199809)41:9<1689::AID-ART21>3.0.CO;2-X.
• [12] An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension.Hum Mol Genet. 2007 Jul 15;16(14):1752-64. doi: 10.1093/hmg/ddm123. Epub 2007 Jun 21.
• [13] Secretogranin II expression in Ewing's sarcomas and primitive neuroectodermal tumors.Diagn Mol Pathol. 1992 Sep;1(3):165-72.
• [14] Perineural invasion in pancreatic cancer: proteomic analysis and invitro modelling.Mol Oncol. 2019 May;13(5):1075-1091. doi: 10.1002/1878-0261.12463. Epub 2019 Mar 5.
• [15] The search for the MEN1 gene. The European Consortium on MEN-1.J Intern Med. 1998 Jun;243(6):441-6. doi: 10.1046/j.1365-2796.1998.00347.x.
• [16] Characterization of the EM66 Biomarker in the Pituitary and Plasma of Healthy Subjects With Different Gonadotroph Status and Patients With Gonadotroph Tumor.Front Endocrinol (Lausanne). 2019 Feb 22;10:102. doi: 10.3389/fendo.2019.00102. eCollection 2019.
• [17] Expression of the precursor of secretoneurin, secretogranin II, in the synovium of patients with rheumatoid arthritis and osteoarthritis.J Rheumatol. 2000 Oct;27(10):2347-50.
• [18] Neuroendocrine differentiation in Ewing's sarcomas and primitive neuroectodermal tumors revealed by reverse transcriptase-polymerase chain reaction of chromogranin mRNA.Diagn Mol Pathol. 1998 Feb;7(1):36-43. doi: 10.1097/00019606-199802000-00007.
• [19] Rifampin resistance, Beijing-W clade-single nucleotide polymorphism cluster group 2 phylogeny, and the Rv2629 191-C allele in Mycobacterium tuberculosis strains.J Clin Microbiol. 2008 Aug;46(8):2555-60. doi: 10.1128/JCM.00666-08. Epub 2008 Jun 11.
• [20] Secretoneurin: a new player in angiogenesis and chemotaxis linking nerves, blood vessels and the immune system.Curr Protein Pept Sci. 2005 Aug;6(4):373-85. doi: 10.2174/1389203054546334.
• [21] Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy.FASEB J. 2018 Sep;32(9):4815-4823. doi: 10.1096/fj.201701391R. Epub 2018 Apr 13.
• [22] Desmoglein 2 depletion leads to increased migration and upregulation of the chemoattractant secretoneurin in melanoma cells.PLoS One. 2014 Feb 18;9(2):e89491. doi: 10.1371/journal.pone.0089491. eCollection 2014.
• [23] Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader-Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes.Hum Mol Genet. 2003 Oct 15;12(20):2723-32. doi: 10.1093/hmg/ddg291. Epub 2003 Aug 27.
• [24] Chromogranin peptides in amyotrophic lateral sclerosis.Regul Pept. 2009 Jan 8;152(1-3):13-21. doi: 10.1016/j.regpep.2008.07.009. Epub 2008 Aug 5.
• [25] Secretoneurin Is an Endogenous Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor That Attenuates Ca(2+)-Dependent Arrhythmia.Circ Arrhythm Electrophysiol. 2019 Apr;12(4):e007045. doi: 10.1161/CIRCEP.118.007045.
• [26] Secretogranin II: a key AP-1-regulated protein that mediates neuronal differentiation and protection from nitric oxide-induced apoptosis of neuroblastoma cells.Cell Death Differ. 2008 May;15(5):879-88. doi: 10.1038/cdd.2008.8. Epub 2008 Feb 1.
• [27] Topical secretoneurin gene therapy accelerates diabetic wound healing by interaction between heparan-sulfate proteoglycans and basic FGF.Angiogenesis. 2014 Jan;17(1):27-36. doi: 10.1007/s10456-013-9375-4. Epub 2013 Aug 6.
• [28] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.