Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6JHAWM)

DOT Name Neuronal calcium sensor 1 (NCS1)
Synonyms NCS-1; Frequenin homolog; Frequenin-like protein; Frequenin-like ubiquitous protein
Gene Name NCS1
Related Disease
Autism ( )
Bipolar disorder ( )
Wolfram syndrome ( )
X-linked intellectual disability ( )
Alzheimer disease ( )
Cerebral infarction ( )
Cognitive impairment ( )
Depression ( )
Fragile X syndrome ( )
Lung squamous cell carcinoma ( )
Mental disorder ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Substance abuse ( )
Anxiety disorder ( )
Arrhythmia ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Cocaine addiction ( )
Hepatocellular carcinoma ( )
Liver cancer ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Nervous system disease ( )
Neuroblastoma ( )
Schizophrenia ( )
UniProt ID
NCS1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1G8I; 2LCP; 4GUK; 5O9S; 6QI4
Pfam ID
PF00036 ; PF13499
Sequence
MGKSNSKLKPEVVEELTRKTYFTEKEVQQWYKGFIKDCPSGQLDAAGFQKIYKQFFPFGD
PTKFATFVFNVFDENKDGRIEFSEFIQALSVTSRGTLDEKLRWAFKLYDLDNDGYITRNE
MLDIVDAIYQMVGNTVELPEEENTPEKRVDRIFAMMDKNADGKLTLQEFQEGSKADPSIV
QALSLYDGLV
Function
Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin. Stimulates PI4KB kinase activity. Involved in long-term synaptic plasticity through its interaction with PICK1. May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autism DISV4V1Z Definitive Biomarker [1]
Bipolar disorder DISAM7J2 Definitive Biomarker [2]
Wolfram syndrome DISN16XW Definitive Biomarker [3]
X-linked intellectual disability DISYJBY3 Definitive Biomarker [4]
Alzheimer disease DISF8S70 Strong Genetic Variation [5]
Cerebral infarction DISR1WNP Strong Biomarker [6]
Cognitive impairment DISH2ERD Strong Biomarker [7]
Depression DIS3XJ69 Strong Biomarker [8]
Fragile X syndrome DISE8W3A Strong Biomarker [9]
Lung squamous cell carcinoma DISXPIBD Strong Altered Expression [10]
Mental disorder DIS3J5R8 Strong Biomarker [11]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [11]
Obesity DIS47Y1K Strong Biomarker [11]
Substance abuse DIS327VW Strong Altered Expression [12]
Anxiety disorder DISBI2BT Limited Biomarker [13]
Arrhythmia DISFF2NI Limited Biomarker [14]
Breast cancer DIS7DPX1 Limited Biomarker [15]
Breast carcinoma DIS2UE88 Limited Biomarker [15]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Altered Expression [16]
Cocaine addiction DISHTRXG Limited Biomarker [17]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [16]
Liver cancer DISDE4BI Limited Altered Expression [16]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [18]
Neoplasm DISZKGEW Limited Biomarker [16]
Nervous system disease DISJ7GGT Limited Biomarker [2]
Neuroblastoma DISVZBI4 Limited Altered Expression [19]
Schizophrenia DISSRV2N Limited Biomarker [2]
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⏷ Show the Full List of 27 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Neuronal calcium sensor 1 (NCS1). [20]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Neuronal calcium sensor 1 (NCS1). [21]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Neuronal calcium sensor 1 (NCS1). [22]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Neuronal calcium sensor 1 (NCS1). [23]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Neuronal calcium sensor 1 (NCS1). [24]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Neuronal calcium sensor 1 (NCS1). [25]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Neuronal calcium sensor 1 (NCS1). [26]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Neuronal calcium sensor 1 (NCS1). [27]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Neuronal calcium sensor 1 (NCS1). [28]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Neuronal calcium sensor 1 (NCS1). [29]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Neuronal calcium sensor 1 (NCS1). [30]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Neuronal calcium sensor 1 (NCS1). [31]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Neuronal calcium sensor 1 (NCS1). [32]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Neuronal calcium sensor 1 (NCS1). [33]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Neuronal calcium sensor 1 (NCS1). [34]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Neuronal calcium sensor 1 (NCS1). [35]
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⏷ Show the Full List of 15 Drug(s)

References

1 The Complex Conformational Dynamics of Neuronal Calcium Sensor-1: A Single Molecule Perspective.Front Mol Neurosci. 2018 Dec 17;11:468. doi: 10.3389/fnmol.2018.00468. eCollection 2018.
2 Current Understanding of the Role of Neuronal Calcium Sensor 1 in Neurological Disorders.Mol Neurobiol. 2019 Sep;56(9):6080-6094. doi: 10.1007/s12035-019-1497-2. Epub 2019 Feb 4.
3 ER-mitochondria cross-talk is regulated by the Ca(2+) sensor NCS1 and is impaired in Wolfram syndrome.Sci Signal. 2018 Oct 23;11(553):eaaq1380. doi: 10.1126/scisignal.aaq1380.
4 IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis.Hum Mol Genet. 2003 Jun 15;12(12):1415-25. doi: 10.1093/hmg/ddg147.
5 Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
6 Electroacupuncture Alleviates Brain Damage Through Targeting of Neuronal Calcium Sensor 1 by miR-191a-5p After Ischemic Stroke.Rejuvenation Res. 2017 Dec;20(6):492-505. doi: 10.1089/rej.2017.1920. Epub 2017 Jul 17.
7 Mice lacking neuronal calcium sensor-1 show social and cognitive deficits.Behav Brain Res. 2020 Mar 2;381:112420. doi: 10.1016/j.bbr.2019.112420. Epub 2019 Dec 9.
8 Incident Chronic Spinal Pain and Depressive Disorders: Data From the National Comorbidity Survey.J Pain. 2019 Apr;20(4):481-488. doi: 10.1016/j.jpain.2018.11.002. Epub 2018 Nov 22.
9 Deciphering the Inhibition of the Neuronal Calcium Sensor 1 and the Guanine Exchange Factor Ric8a with a Small Phenothiazine Molecule for the Rational Generation of Therapeutic Synapse Function Regulators.J Med Chem. 2018 Jul 26;61(14):5910-5921. doi: 10.1021/acs.jmedchem.8b00088. Epub 2018 Jul 17.
10 Involvement of dual-strand of the miR-144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma.Cancer Sci. 2019 Jan;110(1):420-432. doi: 10.1111/cas.13853. Epub 2018 Dec 6.
11 NCS-1 Deficiency Is Associated With Obesity and Diabetes Type 2 in Mice.Front Mol Neurosci. 2019 Apr 3;12:78. doi: 10.3389/fnmol.2019.00078. eCollection 2019.
12 NCS-1 is a regulator of calcium signaling in health and disease.Biochim Biophys Acta Mol Cell Res. 2018 Nov;1865(11 Pt B):1660-1667. doi: 10.1016/j.bbamcr.2018.05.005. Epub 2018 May 8.
13 When Emotional Pain Becomes Physical: Adverse Childhood Experiences, Pain, and the Role of Mood and Anxiety Disorders.J Clin Psychol. 2017 Oct;73(10):1403-1428. doi: 10.1002/jclp.22444. Epub 2017 Mar 22.
14 Emerging Roles of Neuronal Ca(2+) Sensor-1 in Cardiac and Neuronal Tissues: A Mini Review.Front Mol Neurosci. 2019 Mar 4;12:56. doi: 10.3389/fnmol.2019.00056. eCollection 2019.
15 NCS-1 expression is higher in basal breast cancers and regulates calcium influx and cytotoxic responses to doxorubicin.Mol Oncol. 2020 Jan;14(1):87-104. doi: 10.1002/1878-0261.12589. Epub 2019 Nov 11.
16 Hepatocellular Carcinoma Outcome Is Predicted by Expression of Neuronal Calcium Sensor 1.Cancer Epidemiol Biomarkers Prev. 2018 Sep;27(9):1091-1100. doi: 10.1158/1055-9965.EPI-18-0167. Epub 2018 May 22.
17 Neuronal calcium sensor-1 and cocaine addiction: a genetic association study in African-Americans and European Americans.Neurosci Lett. 2012 Nov 30;531(1):46-51. doi: 10.1016/j.neulet.2012.09.014. Epub 2012 Sep 20.
18 Neuronal calcium sensor 1 (NCS1) promotes motility and metastatic spread of breast cancer cells in vitro and in vivo.FASEB J. 2019 Apr;33(4):4802-4813. doi: 10.1096/fj.201802004R. Epub 2018 Dec 28.
19 Inhibition of paclitaxel-induced decreases in calcium signaling.J Biol Chem. 2012 Nov 2;287(45):37907-16. doi: 10.1074/jbc.M112.385070. Epub 2012 Sep 17.
20 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.
21 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
22 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
23 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.
24 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
25 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
26 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.
27 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
28 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
29 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
30 Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
31 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
32 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
33 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
34 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.
35 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.