Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1MVXC7)

DOT Name Calcipressin-1 (RCAN1)
Synonyms Adapt78; Down syndrome critical region protein 1; Myocyte-enriched calcineurin-interacting protein 1; MCIP1; Regulator of calcineurin 1
Gene Name RCAN1
Related Disease
Hyperglycemia ( )
Myocardial infarction ( )
Nervous system disease ( )
Non-insulin dependent diabetes ( )
Adult glioblastoma ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Congenital heart disease ( )
Craniosynostosis ( )
Diabetic kidney disease ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
HIV infectious disease ( )
Huntington disease ( )
Lung neoplasm ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Nephropathy ( )
Neuroblastoma ( )
Obesity ( )
Rheumatoid arthritis ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
Advanced cancer ( )
Clear cell renal carcinoma ( )
Coronary atherosclerosis ( )
Fetal growth restriction ( )
High blood pressure ( )
Immune system disorder ( )
Juvenile Huntington disease ( )
Myocardial ischemia ( )
Periodontitis ( )
Retinopathy ( )
Small-cell lung cancer ( )
Type-1/2 diabetes ( )
Adult lymphoma ( )
Anxiety ( )
Anxiety disorder ( )
Intellectual disability ( )
Kaposi sarcoma ( )
Lymphoma ( )
Malaria ( )
Pediatric lymphoma ( )
UniProt ID
RCAN1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6UUQ
Pfam ID
PF04847
Sequence
MEDGVAGPQLGAAAEAAEAAEARARPGVTLRPFAPLSGAAEADEGGGDWSFIDCEMEEVD
LQDLPSATIACHLDPRVFVDGLCRAKFESLFRTYDKDITFQYFKSFKRVRINFSNPFSAA
DARLQLHKTEFLGKEMKLYFAQTLHIGSSHLAPPNPDKQFLISPPASPPVGWKQVEDATP
VINYDLLYAISKLGPGEKYELHAATDTTPSVVVHVCESDQEKEEEEEMERMRRPKPKIIQ
TRRPEYTPIHLS
Function Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development.
Tissue Specificity Highly expressed heart, brain and skeletal muscle. Also expressed in all other tissues.
KEGG Pathway
Thyroid hormone sig.ling pathway (hsa04919 )
Oxytocin sig.ling pathway (hsa04921 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hyperglycemia DIS0BZB5 Definitive Altered Expression [1]
Myocardial infarction DIS655KI Definitive Altered Expression [2]
Nervous system disease DISJ7GGT Definitive Altered Expression [1]
Non-insulin dependent diabetes DISK1O5Z Definitive Altered Expression [1]
Adult glioblastoma DISVP4LU Strong Biomarker [3]
Alzheimer disease DISF8S70 Strong Biomarker [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Congenital heart disease DISQBA23 Strong Genetic Variation [6]
Craniosynostosis DIS6J405 Strong Biomarker [7]
Diabetic kidney disease DISJMWEY Strong Altered Expression [8]
Glioblastoma multiforme DISK8246 Strong Biomarker [3]
Glioma DIS5RPEH Strong Biomarker [9]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [10]
HIV infectious disease DISO97HC Strong Altered Expression [8]
Huntington disease DISQPLA4 Strong Biomarker [11]
Lung neoplasm DISVARNB Strong Biomarker [12]
Melanoma DIS1RRCY Strong Altered Expression [13]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [14]
Neoplasm DISZKGEW Strong Altered Expression [10]
Nephropathy DISXWP4P Strong Altered Expression [8]
Neuroblastoma DISVZBI4 Strong Altered Expression [15]
Obesity DIS47Y1K Strong Altered Expression [16]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [17]
Thyroid cancer DIS3VLDH Strong Altered Expression [14]
Thyroid gland carcinoma DISMNGZ0 Strong Altered Expression [14]
Thyroid tumor DISLVKMD Strong Altered Expression [14]
Advanced cancer DISAT1Z9 moderate Biomarker [18]
Clear cell renal carcinoma DISBXRFJ moderate Biomarker [19]
Coronary atherosclerosis DISKNDYU moderate Altered Expression [20]
Fetal growth restriction DIS5WEJ5 moderate Altered Expression [21]
High blood pressure DISY2OHH moderate Genetic Variation [22]
Immune system disorder DISAEGPH moderate Altered Expression [23]
Juvenile Huntington disease DIS1IQJG moderate Biomarker [11]
Myocardial ischemia DISFTVXF moderate Altered Expression [20]
Periodontitis DISI9JOI moderate Biomarker [24]
Retinopathy DISB4B0F moderate Biomarker [25]
Small-cell lung cancer DISK3LZD moderate Biomarker [26]
Type-1/2 diabetes DISIUHAP moderate Biomarker [16]
Adult lymphoma DISK8IZR Limited Biomarker [9]
Anxiety DISIJDBA Limited Biomarker [27]
Anxiety disorder DISBI2BT Limited Biomarker [27]
Intellectual disability DISMBNXP Limited Altered Expression [28]
Kaposi sarcoma DISC1H1Z Limited Altered Expression [29]
Lymphoma DISN6V4S Limited Biomarker [9]
Malaria DISQ9Y50 Limited Biomarker [30]
Pediatric lymphoma DIS51BK2 Limited Biomarker [9]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Etoposide DMNH3PG Approved Calcipressin-1 (RCAN1) affects the response to substance of Etoposide. [53]
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22 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Calcipressin-1 (RCAN1). [31]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Calcipressin-1 (RCAN1). [32]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Calcipressin-1 (RCAN1). [33]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Calcipressin-1 (RCAN1). [34]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Calcipressin-1 (RCAN1). [35]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Calcipressin-1 (RCAN1). [36]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Calcipressin-1 (RCAN1). [38]
Testosterone DM7HUNW Approved Testosterone increases the expression of Calcipressin-1 (RCAN1). [38]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Calcipressin-1 (RCAN1). [35]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Calcipressin-1 (RCAN1). [39]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Calcipressin-1 (RCAN1). [40]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Calcipressin-1 (RCAN1). [42]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Calcipressin-1 (RCAN1). [43]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Calcipressin-1 (RCAN1). [44]
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 increases the expression of Calcipressin-1 (RCAN1). [45]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Calcipressin-1 (RCAN1). [46]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Calcipressin-1 (RCAN1). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Calcipressin-1 (RCAN1). [48]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Calcipressin-1 (RCAN1). [49]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Calcipressin-1 (RCAN1). [50]
geraniol DMS3CBD Investigative geraniol increases the expression of Calcipressin-1 (RCAN1). [51]
Lithium chloride DMHYLQ2 Investigative Lithium chloride increases the expression of Calcipressin-1 (RCAN1). [52]
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⏷ Show the Full List of 22 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the phosphorylation of Calcipressin-1 (RCAN1). [37]
Menadione DMSJDTY Approved Menadione increases the phosphorylation of Calcipressin-1 (RCAN1). [37]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Dipyridamole DMXY30O Approved Dipyridamole affects the binding of Calcipressin-1 (RCAN1). [41]
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References

1 The neuronal and endocrine roles of RCAN1 in health and disease.Clin Exp Pharmacol Physiol. 2018 Apr;45(4):377-383. doi: 10.1111/1440-1681.12884. Epub 2017 Nov 29.
2 MCIP1 overexpression suppresses left ventricular remodeling and sustains cardiac function after myocardial infarction.Circ Res. 2004 Feb 20;94(3):e18-26. doi: 10.1161/01.RES.0000118597.54416.00. Epub 2004 Jan 22.
3 Down syndrome candidate region 1 increases the stability of the IkappaBalpha protein: implications for its anti-inflammatory effects.J Biol Chem. 2006 Dec 22;281(51):39051-61. doi: 10.1074/jbc.M604659200. Epub 2006 Oct 24.
4 Regulator of calcineurin 1 is a novel RNA-binding protein to regulate neuronal apoptosis.Mol Psychiatry. 2021 Apr;26(4):1361-1375. doi: 10.1038/s41380-019-0487-0. Epub 2019 Aug 27.
5 A major role for RCAN1 in atherosclerosis progression.EMBO Mol Med. 2013 Dec;5(12):1901-17. doi: 10.1002/emmm.201302842. Epub 2013 Oct 15.
6 RCAN1 Mutation and Functional Characterization in Children with Sporadic Congenital Heart Disease.Pediatr Cardiol. 2018 Feb;39(2):226-235. doi: 10.1007/s00246-017-1746-y. Epub 2017 Oct 9.
7 The human bitter taste receptor T2R38 is broadly tuned for bacterial compounds.PLoS One. 2017 Sep 13;12(9):e0181302. doi: 10.1371/journal.pone.0181302. eCollection 2017.
8 Epigenetic regulation of RCAN1 expression in kidney disease and its role in podocyte injury.Kidney Int. 2018 Dec;94(6):1160-1176. doi: 10.1016/j.kint.2018.07.023. Epub 2018 Oct 23.
9 The regulator of calcineurin 1 (RCAN1) inhibits nuclear factor kappaB signaling pathway and suppresses human malignant glioma cells growth.Oncotarget. 2017 Feb 14;8(7):12003-12012. doi: 10.18632/oncotarget.14479.
10 The competing endogenous circular RNA ADAMTS14 suppressed hepatocellular carcinoma progression through regulating microRNA-572/regulator of calcineurin 1.J Cell Physiol. 2019 Mar;234(3):2460-2470. doi: 10.1002/jcp.26764. Epub 2018 Oct 14.
11 Regulator of calcineurin (RCAN1-1L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro.J Biol Chem. 2009 May 1;284(18):11845-53. doi: 10.1074/jbc.M900639200. Epub 2009 Mar 6.
12 A single extra copy of Dscr1 improves survival of mice developing spontaneous lung tumors through suppression of tumor angiogenesis.Cancer Lett. 2014 Jan 1;342(1):70-81. doi: 10.1016/j.canlet.2013.08.047. Epub 2013 Sep 16.
13 Vascular endothelial growth factor- and thrombin-induced termination factor, Down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis.J Biol Chem. 2004 Nov 26;279(48):50537-54. doi: 10.1074/jbc.M406454200. Epub 2004 Sep 23.
14 RCAN1-4 is a thyroid cancer growth and metastasis suppressor.JCI Insight. 2017 Mar 9;2(5):e90651. doi: 10.1172/jci.insight.90651.
15 The regulator of calcineurin 1 increases adenine nucleotide translocator 1 and leads to mitochondrial dysfunctions.J Neurochem. 2017 Jan;140(2):307-319. doi: 10.1111/jnc.13900. Epub 2016 Dec 20.
16 A single extra copy of Down syndrome critical region 1-4 results in impaired hepatic glucose homeostasis.Mol Metab. 2019 Mar;21:82-89. doi: 10.1016/j.molmet.2018.12.002. Epub 2018 Dec 5.
17 Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
18 RCAN1 in the inverse association between Alzheimer's disease and cancer.Oncotarget. 2017 Dec 11;9(1):54-66. doi: 10.18632/oncotarget.23094. eCollection 2018 Jan 2.
19 RCAN1.4 acts as a suppressor of cancer progression and sunitinib resistance in clear cell renal cell carcinoma.Exp Cell Res. 2018 Nov 15;372(2):118-128. doi: 10.1016/j.yexcr.2018.09.017. Epub 2018 Sep 27.
20 Calcineurin and its regulator, RCAN1, confer time-of-day changes in susceptibility of the heart to ischemia/reperfusion.J Mol Cell Cardiol. 2014 Sep;74:103-11. doi: 10.1016/j.yjmcc.2014.05.004. Epub 2014 May 15.
21 Unbalanced placental expression of imprinted genes in human intrauterine growth restriction.Placenta. 2006 Jun-Jul;27(6-7):540-9. doi: 10.1016/j.placenta.2005.07.004. Epub 2005 Aug 24.
22 Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture.Nat Commun. 2018 Nov 15;9(1):4795. doi: 10.1038/s41467-018-07071-7.
23 Upregulation of RCAN1 causes Down syndrome-like immune dysfunction.J Med Genet. 2013 Jul;50(7):444-54. doi: 10.1136/jmedgenet-2013-101522. Epub 2013 May 3.
24 Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues.J Periodontal Res. 2011 Jun;46(3):345-53. doi: 10.1111/j.1600-0765.2011.01349.x. Epub 2011 Mar 7.
25 Secretion of Down Syndrome Critical Region 1 Isoform 4 in Ischemic Retinal Ganglion Cells Displays Anti-Angiogenic Properties Via NFATc1-Dependent Pathway.Mol Neurobiol. 2017 Oct;54(8):6556-6571. doi: 10.1007/s12035-016-0092-z. Epub 2016 Oct 12.
26 The effect of RCAN1 on the biological behaviors of small cell lung cancer.Tumour Biol. 2017 Jun;39(6):1010428317700405. doi: 10.1177/1010428317700405.
27 Regulator of calcineurin 1 modulates expression of innate anxiety and anxiogenic responses to selective serotonin reuptake inhibitor treatment.J Neurosci. 2013 Oct 23;33(43):16930-44. doi: 10.1523/JNEUROSCI.3513-12.2013.
28 The Drosophila homolog of Down's syndrome critical region 1 gene regulates learning: implications for mental retardation.Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15794-9. doi: 10.1073/pnas.2536696100. Epub 2003 Dec 10.
29 Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLC1 and activating NFAT1-dependent RCAN1 expression.PLoS Pathog. 2012 Sep;8(9):e1002927. doi: 10.1371/journal.ppat.1002927. Epub 2012 Sep 27.
30 ELISA detection of vivax malaria with recombinant multiple stage-specific antigens and its application to survey of residents in endemic areas.Korean J Parasitol. 2003 Dec;41(4):203-7. doi: 10.3347/kjp.2003.41.4.203.
31 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
32 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
33 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
34 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
35 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
36 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
37 Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein. Free Radic Biol Med. 2003 Sep 1;35(5):528-39. doi: 10.1016/s0891-5849(03)00358-7.
38 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
39 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.
40 Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
41 Inhibiting the calcineurin-NFAT (nuclear factor of activated T cells) signaling pathway with a regulator of calcineurin-derived peptide without affecting general calcineurin phosphatase activity. J Biol Chem. 2009 Apr 3;284(14):9394-401. doi: 10.1074/jbc.M805889200. Epub 2009 Feb 3.
42 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
43 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.
44 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.
45 Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
46 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
47 Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
48 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
49 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
50 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
51 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
52 Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.
53 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.