Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD04KB1)

DOT Name Regucalcin (RGN)
Synonyms RC; Gluconolactonase; GNL; EC 3.1.1.17; Senescence marker protein 30; SMP-30
Gene Name RGN
Related Disease
Acute liver failure ( )
Adenocarcinoma ( )
Alzheimer disease ( )
Becker muscular dystrophy ( )
Breast cancer ( )
Breast carcinoma ( )
Cataract ( )
Colitis ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Coronary heart disease ( )
Depression ( )
Kidney failure ( )
Liver cancer ( )
Liver cirrhosis ( )
Male infertility ( )
Nephropathy ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Vascular dementia ( )
Vitelliform macular dystrophy ( )
Advanced cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Clear cell renal carcinoma ( )
Kidney cancer ( )
Lung adenocarcinoma ( )
Pulmonary emphysema ( )
Renal carcinoma ( )
Renal cell carcinoma ( )
Rhabdomyosarcoma ( )
Lung cancer ( )
Lung carcinoma ( )
Chronic hepatitis B virus infection ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Hyperlipidemia ( )
Hyperlipoproteinemia ( )
Invasive ductal breast carcinoma ( )
Keratoconjunctivitis sicca ( )
Neoplasm ( )
UniProt ID
RGN_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3G4E; 3G4H; 4GNB; 4GNC
EC Number
3.1.1.17
Pfam ID
PF08450
Sequence
MSSIKIECVLPENCRCGESPVWEEVSNSLLFVDIPAKKVCRWDSFTKQVQRVTMDAPVSS
VALRQSGGYVATIGTKFCALNWKEQSAVVLATVDNDKKNNRFNDGKVDPAGRYFAGTMAE
ETAPAVLERHQGALYSLFPDHHVKKYFDQVDISNGLDWSLDHKIFYYIDSLSYSVDAFDY
DLQTGQISNRRSVYKLEKEEQIPDGMCIDAEGKLWVACYNGGRVIRLDPVTGKRLQTVKL
PVDKTTSCCFGGKNYSEMYVTCARDGMDPEGLLRQPEAGGIFKITGLGVKGIAPYSYAG
Function
Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone. Can also hydrolyze diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium-binding protein. Modulates Ca(2+) signaling, and Ca(2+)-dependent cellular processes and enzyme activities.
KEGG Pathway
Pentose phosphate pathway (hsa00030 )
Ascorbate and aldarate metabolism (hsa00053 )
Metabolic pathways (hsa01100 )
Carbon metabolism (hsa01200 )
Biosynthesis of cofactors (hsa01240 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute liver failure DIS5EZKX Strong Altered Expression [1]
Adenocarcinoma DIS3IHTY Strong Altered Expression [2]
Alzheimer disease DISF8S70 Strong Altered Expression [3]
Becker muscular dystrophy DIS5IYHL Strong Biomarker [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Cataract DISUD7SL Strong Biomarker [6]
Colitis DISAF7DD Strong Biomarker [7]
Colon cancer DISVC52G Strong Biomarker [7]
Colon carcinoma DISJYKUO Strong Biomarker [7]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [8]
Coronary heart disease DIS5OIP1 Strong Biomarker [9]
Depression DIS3XJ69 Strong Altered Expression [10]
Kidney failure DISOVQ9P Strong Altered Expression [11]
Liver cancer DISDE4BI Strong Altered Expression [8]
Liver cirrhosis DIS4G1GX Strong Altered Expression [12]
Male infertility DISY3YZZ Strong Biomarker [13]
Nephropathy DISXWP4P Strong Biomarker [14]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [2]
Pancreatic cancer DISJC981 Strong Altered Expression [8]
Prostate cancer DISF190Y Strong Biomarker [15]
Prostate carcinoma DISMJPLE Strong Biomarker [15]
Vascular dementia DISVO82H Strong Biomarker [16]
Vitelliform macular dystrophy DISEFYYN Strong Biomarker [4]
Advanced cancer DISAT1Z9 moderate Biomarker [2]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W moderate Altered Expression [8]
Clear cell renal carcinoma DISBXRFJ moderate Biomarker [17]
Kidney cancer DISBIPKM moderate Altered Expression [17]
Lung adenocarcinoma DISD51WR moderate Altered Expression [8]
Pulmonary emphysema DIS5M7HZ moderate Biomarker [18]
Renal carcinoma DISER9XT moderate Altered Expression [17]
Renal cell carcinoma DISQZ2X8 moderate Biomarker [17]
Rhabdomyosarcoma DISNR7MS moderate Biomarker [19]
Lung cancer DISCM4YA Disputed Altered Expression [20]
Lung carcinoma DISTR26C Disputed Altered Expression [20]
Chronic hepatitis B virus infection DISHL4NT Limited Biomarker [21]
Hepatitis B virus infection DISLQ2XY Limited Biomarker [21]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [12]
High blood pressure DISY2OHH Limited Biomarker [22]
Hyperlipidemia DIS61J3S Limited Biomarker [23]
Hyperlipoproteinemia DISVBLBO Limited Biomarker [23]
Invasive ductal breast carcinoma DIS43J58 Limited Biomarker [24]
Keratoconjunctivitis sicca DISNOENH Limited Genetic Variation [25]
Neoplasm DISZKGEW Limited Altered Expression [17]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Regucalcin (RGN). [26]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Regucalcin (RGN). [36]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Regucalcin (RGN). [27]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Regucalcin (RGN). [28]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Regucalcin (RGN). [29]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Regucalcin (RGN). [30]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Regucalcin (RGN). [31]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Regucalcin (RGN). [32]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Regucalcin (RGN). [33]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Regucalcin (RGN). [34]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Regucalcin (RGN). [35]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Regucalcin (RGN). [37]
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⏷ Show the Full List of 10 Drug(s)

References

1 Senescence marker protein 30 in acute liver failure: validation of a mass spectrometry proteomics assay.BMC Gastroenterol. 2008 May 28;8:17. doi: 10.1186/1471-230X-8-17.
2 Live and let die: epigenetic modifications of Survivin and Regucalcin in non-small cell lung cancer tissues contribute to malignancy.Clin Epigenetics. 2019 Nov 12;11(1):157. doi: 10.1186/s13148-019-0770-6.
3 Regucalcin confers resistance to amyloid- toxicity in neuronally differentiated PC12 cells.FEBS Open Bio. 2018 Jan 20;8(3):349-360. doi: 10.1002/2211-5463.12374. eCollection 2018 Mar.
4 Bone Degeneration and Its Recovery in SMP30/GNL-Knockout Mice.J Nutr Health Aging. 2017;21(5):573-578. doi: 10.1007/s12603-016-0841-8.
5 [Erratum] Exogenous regucalcin suppresses the proliferation of human breast cancer MDA-MB-231 bone metastatic cells in vitro.Mol Med Rep. 2018 Feb;17(2):3432. doi: 10.3892/mmr.2017.8276. Epub 2017 Dec 12.
6 Downregulation of SMP30 in senescent human lens epithelial cells.Mol Med Rep. 2017 Oct;16(4):4022-4028. doi: 10.3892/mmr.2017.7106. Epub 2017 Jul 27.
7 Senescence marker protein 30 protects intestinal epithelial cells against inflammation-induced cell death by enhancing Nrf2 activity.Biochim Biophys Acta Mol Basis Dis. 2018 Dec;1864(12):3668-3678. doi: 10.1016/j.bbadis.2018.09.031. Epub 2018 Sep 26.
8 Prolonged survival of patients with colorectal cancer is associated with a higher regucalcin gene expression: Overexpression of regucalcin suppresses the growth of human colorectal carcinoma cells invitro.Int J Oncol. 2018 Sep;53(3):1313-1322. doi: 10.3892/ijo.2018.4458. Epub 2018 Jun 28.
9 Systems Pharmacology Identifies an Arterial Wall Regulatory Gene Network Mediating Coronary Artery Disease Side Effects of Antiretroviral Therapy.Circ Genom Precis Med. 2019 Jun;12(6):e002390. doi: 10.1161/CIRCGEN.118.002390. Epub 2019 May 6.
10 Suppressive role of regucalcin in liver cell proliferation: involvement in carcinogenesis.Cell Prolif. 2013 Jun;46(3):243-53. doi: 10.1111/cpr.12036.
11 The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review).Int J Mol Med. 2015 Nov;36(5):1191-9. doi: 10.3892/ijmm.2015.2343. Epub 2015 Sep 11.
12 Diagnostic Value of Serum SMP30 and Anti-SMP30 Antibody in Hepatocellular Carcinoma.Lab Med. 2018 Jul 5;49(3):203-210. doi: 10.1093/labmed/lmy004.
13 Regucalcin counteracts tert-butyl hydroperoxide and cadmium-induced oxidative stress in rat testis.J Appl Toxicol. 2017 Feb;37(2):159-166. doi: 10.1002/jat.3333. Epub 2016 Apr 25.
14 Regucalcin down-regulation in rat kidney tissue after treatment with nephrotoxicants.Toxicol Lett. 2008 Nov 10;182(1-3):84-90. doi: 10.1016/j.toxlet.2008.08.014. Epub 2008 Sep 2.
15 Suppressed glycolytic metabolism in the prostate of transgenic rats overexpressing calcium-binding protein regucalcin underpins reduced cell proliferation.Transgenic Res. 2016 Apr;25(2):139-48. doi: 10.1007/s11248-015-9918-0. Epub 2015 Nov 9.
16 Melatonin ameliorates brain oxidative stress and upregulates senescence marker protein-30 and osteopontin in a rat model of vascular dementia.Physiol Int. 2018 Mar 1;105(1):38-52. doi: 10.1556/2060.105.2018.1.1.
17 Prolonged survival of renal cancer patients is concomitant with a higher regucalcin gene expression in tumor tissues: Overexpression of regucalcin suppresses the growth of human renal cell carcinoma cells in vitro.Int J Oncol. 2019 Jan;54(1):188-198. doi: 10.3892/ijo.2018.4611. Epub 2018 Oct 30.
18 Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice.Biochem Biophys Res Commun. 2017 Oct 7;492(1):74-81. doi: 10.1016/j.bbrc.2017.08.035. Epub 2017 Aug 12.
19 The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles.Viruses. 2019 Oct 31;11(11):1005. doi: 10.3390/v11111005.
20 Survival of lung cancer patients is prolonged with higher regucalcin gene expression: suppressed proliferation of lung adenocarcinoma A549 cells in vitro.Mol Cell Biochem. 2017 Jun;430(1-2):37-46. doi: 10.1007/s11010-017-2952-x. Epub 2017 Feb 8.
21 Serum regucalcin is a useful indicator of liver injury severity in patients with hepatitis B virus-related liver diseases.Braz J Med Biol Res. 2019 Sep 30;52(10):e8845. doi: 10.1590/1414-431X20198845. eCollection 2019.
22 Senescence Marker Protein 30 Deficiency Exacerbates Pulmonary Hypertension in Hypoxia-Exposed Mice.Int Heart J. 2019 Nov 30;60(6):1430-1434. doi: 10.1536/ihj.19-190. Epub 2019 Nov 15.
23 Hyperlipidemia is induced in regucalcin transgenic rats with increasing age.Int J Mol Med. 2004 Oct;14(4):647-51.
24 Histopathological and in vivo evidence of regucalcin as a protective molecule in mammary gland carcinogenesis.Exp Cell Res. 2015 Jan 15;330(2):325-335. doi: 10.1016/j.yexcr.2014.08.007. Epub 2014 Aug 13.
25 RGN-259 (thymosin 4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model.Sci Rep. 2018 Jul 12;8(1):10500. doi: 10.1038/s41598-018-28861-5.
26 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
27 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
28 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
29 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
30 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
31 Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
32 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
33 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
34 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
35 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
36 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.
37 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.