Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQZ6HX0)

• DOT Name: Salivary acidic proline-rich phosphoprotein 1/2 (PRH1)
• Synonyms: Db-s; PRP-1/PRP-2; Parotid acidic protein; Pa; Parotid double-band protein; Parotid isoelectric focusing variant protein; PIF-S; Parotid proline-rich protein 1/2; Pr1/Pr2; Protein C
• Gene Name: PRH1
• Related Disease:
  Pseudotumor cerebri
  Beta-thalassemia major
  Cerebral palsy
  Coagulation defect
  Congenital vertical talus
  Dental caries
  Familial hypertrophic cardiomyopathy
  Hepatitis C virus infection
  Hypercholesterolemia, familial, 1
  Hypertrophic cardiomyopathy
  Isolated cleft palate
  Myocardial infarction
  Myositis disease
  Pulmonary fibrosis
  Stroke
  Thrombophilia
  Arthrogryposis
  High blood pressure
  Myopathy
  Cardiomyopathy
  Disseminated intravascular coagulation
• UniProt ID: PRPC_HUMAN
• Pfam ID: PF15240
• Sequence:
  MLLILLSVALLAFSSAQDLDEDVSQEDVPLVISDGGDSEQFIDEERQGPPLGGQQSQPSA
  GDGNQNDGPQQGPPQQGGQQQQGPPPPQGKPQGPPQQGGHPPPPQGRPQGPPQQGGHPRP
  PRGRPQGPPQQGGHQQGPPPPPPGKPQGPPPQGGRPQGPPQGQSPQ
• Function: PRP's act as highly potent inhibitors of crystal growth of calcium phosphates. They provide a protective and reparative environment for dental enamel which is important for the integrity of the teeth.
• KEGG Pathway: Salivary secretion (hsa04970)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pseudotumor cerebri	DISLLY7S	Definitive	Genetic Variation	[1]
Beta-thalassemia major	DISW06BV	Strong	Biomarker	[2]
Cerebral palsy	DIS82ODL	Strong	Biomarker	[3]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[4]
Congenital vertical talus	DISZF3HD	Strong	Genetic Variation	[5]
Dental caries	DISRBCMD	Strong	Genetic Variation	[6]
Familial hypertrophic cardiomyopathy	DISQ89HN	Strong	Genetic Variation	[7]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[8]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Genetic Variation	[7]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Altered Expression	[9]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Biomarker	[10]
Myositis disease	DISCIXF0	Strong	Biomarker	[11]
Pulmonary fibrosis	DISQKVLA	Strong	Altered Expression	[12]
Stroke	DISX6UHX	Strong	Biomarker	[13]
Thrombophilia	DISQR7U7	Strong	Genetic Variation	[14]
Arthrogryposis	DISC81CM	moderate	Biomarker	[15]
High blood pressure	DISY2OHH	moderate	Biomarker	[16]
Myopathy	DISOWG27	moderate	Biomarker	[15]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[17]
Disseminated intravascular coagulation	DISCAVOZ	Limited	Altered Expression	[18]

2 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 Salivary acidic proline-rich phosphoprotein 1/2 (PRH1).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Salivary acidic proline-rich phosphoprotein 1/2 (PRH1).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Salivary acidic proline-rich phosphoprotein 1/2 (PRH1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Salivary acidic proline-rich phosphoprotein 1/2 (PRH1).	[22]

References

• [1] Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension.J Neuroophthalmol. 2019 Mar;39(1):50-55. doi: 10.1097/WNO.0000000000000648.
• [2] Low levels of coagulation inhibitors: A high-risk thrombotic factor in thalassemic patients.Rev Clin Esp (Barc). 2020 Apr;220(3):162-166. doi: 10.1016/j.rce.2019.05.012. Epub 2019 Oct 2.
• [3] Sodium butyrate ameliorates Corynebacterium pseudotuberculosis infection in RAW264.7 macrophages and C57BL/6 mice.Microb Pathog. 2019 Jun;131:144-149. doi: 10.1016/j.micpath.2019.04.008. Epub 2019 Apr 6.
• [4] Variation of endothelium-related hemostatic factors during sepsis.Microcirculation. 2018 Nov;25(8):e12500. doi: 10.1111/micc.12500. Epub 2018 Oct 10.
• [5] Inherited protein-C deficiency, factor V G 1691 A and FV A 4070 G mutations in a child with internal cerebral venous thrombosis.Pediatr Radiol. 2000 Jun;30(6):420-3. doi: 10.1007/s002470050776.
• [6] Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2.EBioMedicine. 2017 Dec;26:38-46. doi: 10.1016/j.ebiom.2017.11.019. Epub 2017 Nov 22.
• [7] Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.J Mol Biol. 1999 Feb 26;286(3):933-49. doi: 10.1006/jmbi.1998.2522.
• [8] Peripheral B cells may serve as a reservoir for persistent hepatitis C virus infection.J Innate Immun. 2010;2(6):607-17. doi: 10.1159/000317690. Epub 2010 Aug 17.
• [9] Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy.J Mol Cell Cardiol. 2018 Oct;123:59-63. doi: 10.1016/j.yjmcc.2018.08.023. Epub 2018 Aug 28.
• [10] Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction.J Mol Cell Cardiol. 2012 Jan;52(1):154-64. doi: 10.1016/j.yjmcc.2011.09.011. Epub 2011 Sep 19.
• [11] Autoantibodies in canine masticatory muscle myositis recognize a novel myosin binding protein-C family member.J Immunol. 2007 Oct 1;179(7):4939-44. doi: 10.4049/jimmunol.179.7.4939.
• [12] Citrus Alkaline Extract Delayed the Progression of Pulmonary Fibrosis by Inhibiting p38/NF-B Signaling Pathway-Induced Cell Apoptosis.Evid Based Complement Alternat Med. 2019 Feb 4;2019:1528586. doi: 10.1155/2019/1528586. eCollection 2019.
• [13] Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study.BMC Neurol. 2004 Dec 1;4(1):21. doi: 10.1186/1471-2377-4-21.
• [14] Risk Factors for Thrombosis Development in Mexican Patients.Ann Vasc Surg. 2015 Nov;29(8):1625-32. doi: 10.1016/j.avsg.2015.05.035. Epub 2015 Aug 24.
• [15] Myosin Binding Protein-C Slow Phosphorylation is Altered in Duchenne Dystrophy and Arthrogryposis Myopathy in Fast-Twitch Skeletal Muscles.Sci Rep. 2015 Aug 19;5:13235. doi: 10.1038/srep13235.
• [16] Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology.J Physiol. 2014 Aug 1;592(15):3189-200. doi: 10.1113/jphysiol.2013.270306. Epub 2014 Apr 22.
• [17] Altered interactions between cardiac myosin binding protein-C and -cardiac actin variants associated with cardiomyopathies.Arch Biochem Biophys. 2014 May 15;550-551:28-32. doi: 10.1016/j.abb.2014.04.003. Epub 2014 Apr 13.
• [18] A novel fibrinogenase from Agkistrodon acutus venom protects against DIC via direct degradation of thrombosis and activation of protein C.Biochem Pharmacol. 2012 Oct 1;84(7):905-13. doi: 10.1016/j.bcp.2012.06.011. Epub 2012 Jun 20.
• [19] 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.
• [20] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [21] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [22] 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.