Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTERIU75)

DOT Name Sarcolipin (SLN)
Gene Name SLN
Related Disease
Adult glioblastoma ( )
Arthritis ( )
Brucellosis ( )
Glioblastoma multiforme ( )
Invasive breast carcinoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cardiac failure ( )
Cardiomyopathy ( )
Cervical cancer ( )
Cervical carcinoma ( )
Classic Hodgkin lymphoma ( )
Congestive heart failure ( )
Coronary atherosclerosis ( )
Cytomegalovirus infection ( )
Impulse control disorder ( )
Long QT syndrome ( )
Lung adenocarcinoma ( )
Mental disorder ( )
Metabolic disorder ( )
Myocardial infarction ( )
Myocardial ischemia ( )
Myopathy ( )
Obesity ( )
Onychomycosis ( )
Triple negative breast cancer ( )
Tuberculosis ( )
Duchenne muscular dystrophy ( )
Head-neck squamous cell carcinoma ( )
Atrial fibrillation ( )
Cutaneous melanoma ( )
Ductal breast carcinoma in situ ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Leukemia ( )
Marfan syndrome ( )
Melanoma ( )
Neoplasm ( )
UniProt ID
SARCO_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1JDM
Pfam ID
PF05366
Sequence
MGINTRELFLNFTIVLITVILMWLLVRSYQY
Function
Reversibly inhibits the activity of ATP2A1 and ATP2A2 in sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in muscle. Required for muscle-based, non-shivering thermogenesis.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )
Reactome Pathway
Ion transport by P-type ATPases (R-HSA-936837 )
Ion homeostasis (R-HSA-5578775 )

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Definitive Biomarker [1]
Arthritis DIST1YEL Definitive Genetic Variation [2]
Brucellosis DISEAYGH Definitive Biomarker [3]
Glioblastoma multiforme DISK8246 Definitive Biomarker [1]
Invasive breast carcinoma DISANYTW Definitive Biomarker [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Alzheimer disease DISF8S70 Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Breast neoplasm DISNGJLM Strong Biomarker [8]
Cardiac failure DISDC067 Strong Altered Expression [9]
Cardiomyopathy DISUPZRG Strong Altered Expression [10]
Cervical cancer DISFSHPF Strong Biomarker [11]
Cervical carcinoma DIST4S00 Strong Biomarker [11]
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [12]
Congestive heart failure DIS32MEA Strong Altered Expression [9]
Coronary atherosclerosis DISKNDYU Strong Altered Expression [13]
Cytomegalovirus infection DISCEMGC Strong Biomarker [14]
Impulse control disorder DISRIYJ5 Strong Biomarker [15]
Long QT syndrome DISMKWS3 Strong Biomarker [16]
Lung adenocarcinoma DISD51WR Strong Biomarker [5]
Mental disorder DIS3J5R8 Strong Biomarker [17]
Metabolic disorder DIS71G5H Strong Biomarker [18]
Myocardial infarction DIS655KI Strong Biomarker [19]
Myocardial ischemia DISFTVXF Strong Altered Expression [13]
Myopathy DISOWG27 Strong Altered Expression [20]
Obesity DIS47Y1K Strong Biomarker [21]
Onychomycosis DISE4C4D Strong Biomarker [22]
Triple negative breast cancer DISAMG6N Strong Biomarker [23]
Tuberculosis DIS2YIMD Strong Biomarker [24]
Duchenne muscular dystrophy DISRQ3NV moderate Biomarker [25]
Head-neck squamous cell carcinoma DISF7P24 moderate Biomarker [26]
Atrial fibrillation DIS15W6U Limited Altered Expression [9]
Cutaneous melanoma DIS3MMH9 Limited Biomarker [27]
Ductal breast carcinoma in situ DISLCJY7 Limited Biomarker [28]
Endometrial cancer DISW0LMR Limited Biomarker [29]
Endometrial carcinoma DISXR5CY Limited Biomarker [29]
Leukemia DISNAKFL Limited Altered Expression [30]
Marfan syndrome DISVEUWZ Limited Biomarker [31]
Melanoma DIS1RRCY Limited Biomarker [27]
Neoplasm DISZKGEW Limited Genetic Variation [4]
------------------------------------------------------------------------------------
⏷ Show the Full List of 41 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Sarcolipin (SLN). [32]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Sarcolipin (SLN). [33]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Sarcolipin (SLN). [34]
Triclosan DMZUR4N Approved Triclosan increases the expression of Sarcolipin (SLN). [35]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Sarcolipin (SLN). [36]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Sarcolipin (SLN). [39]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Sarcolipin (SLN). [40]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Sarcolipin (SLN). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Sarcolipin (SLN). [38]
------------------------------------------------------------------------------------

References

1 Preparation and investigation of indirubin-loaded SLN nanoparticles and their anti-cancer effects on human glioblastoma U87MG cells.Cell Biol Int. 2019 Jan;43(1):2-11. doi: 10.1002/cbin.11037.
2 Preclinical Explorative Assessment of Celecoxib-Based Biocompatible Lipidic Nanocarriers for the Management of CFA-Induced Rheumatoid Arthritis in Wistar Rats.AAPS PharmSciTech. 2018 Oct;19(7):3187-3198. doi: 10.1208/s12249-018-1148-3. Epub 2018 Aug 24.
3 Doxycycline-encapsulated solid lipid nanoparticles for the enhanced antibacterial potential to treat the chronic brucellosis and preventing its relapse: in vivo study.Ann Clin Microbiol Antimicrob. 2019 Nov 9;18(1):33. doi: 10.1186/s12941-019-0333-x.
4 Dynamic contrast-enhanced and diffusion-weighted MRI of invasive breast cancer for the prediction of sentinel lymph node status.J Magn Reson Imaging. 2020 Feb;51(2):615-626. doi: 10.1002/jmri.26865. Epub 2019 Jul 16.
5 Toward stimulating apoptosis in human lung adenocarcinoma cells by novel nano-carmofur compound treatment.Anticancer Drugs. 2021 Jun 1;32(6):657-663. doi: 10.1097/CAD.0000000000000720.
6 Improvement of memory deficits in the rat model of Alzheimer's disease by erythropoietin-loaded solid lipid nanoparticles.Neurobiol Learn Mem. 2019 Dec;166:107082. doi: 10.1016/j.nlm.2019.107082. Epub 2019 Sep 5.
7 Axillary Dissection vs. no Axillary Dissection in Breast Cancer Patients With Positive Sentinel Lymph Node: A Single Institution Experience.In Vivo. 2019 Nov-Dec;33(6):1941-1947. doi: 10.21873/invivo.11689.
8 Sentinel lymph node biopsy following previous axillary surgery in recurrent breast cancer.Eur J Surg Oncol. 2019 Oct;45(10):1835-1838. doi: 10.1016/j.ejso.2019.05.016. Epub 2019 May 16.
9 Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca2+ uptake in human atrial fibrillation.Biochem Biophys Res Commun. 2011 Jun 24;410(1):97-101. doi: 10.1016/j.bbrc.2011.05.113. Epub 2011 May 25.
10 Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and associated cardiomyopathy in mice.Nat Commun. 2017 Oct 20;8(1):1068. doi: 10.1038/s41467-017-01146-7.
11 SLN biopsy in cervical cancer patients with tumors larger than 2cm and 4cm.Gynecol Oncol. 2018 Mar;148(3):456-460. doi: 10.1016/j.ygyno.2018.01.001. Epub 2018 Feb 1.
12 Curcumin formulated in solid lipid nanoparticles has enhanced efficacy in Hodgkin's lymphoma in mice.Arch Biochem Biophys. 2018 Jun 15;648:12-19. doi: 10.1016/j.abb.2018.04.012. Epub 2018 Apr 18.
13 Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology.J Mol Cell Cardiol. 2007 Aug;43(2):215-22. doi: 10.1016/j.yjmcc.2007.05.009. Epub 2007 May 18.
14 Protein and DNA evidences of HCMV infection in primary breast cancer tissues and metastatic sentinel lymph nodes.Cancer Biomark. 2018;21(4):769-780. doi: 10.3233/CBM-170409.
15 Skin targeting of resveratrol utilizing solid lipid nanoparticle-engrossed gel for chemically induced irritant contact dermatitis.Drug Deliv Transl Res. 2017 Feb;7(1):37-52. doi: 10.1007/s13346-016-0350-7.
16 The variation of the sarcolipin gene (SLN) in atrial fibrillation, long QT syndrome and sudden arrhythmic death syndrome.Clin Chim Acta. 2007 Jan;375(1-2):87-91. doi: 10.1016/j.cca.2006.06.020. Epub 2006 Jun 22.
17 Lipid nanoparticles for administration of poorly water soluble neuroactive drugs.Biomed Microdevices. 2017 Sep;19(3):44. doi: 10.1007/s10544-017-0188-x.
18 Sarcolipin Signaling Promotes Mitochondrial Biogenesis and Oxidative Metabolism in Skeletal Muscle.Cell Rep. 2018 Sep 11;24(11):2919-2931. doi: 10.1016/j.celrep.2018.08.036.
19 RGD modified and PEGylated lipid nanoparticles loaded with puerarin: Formulation, characterization and protective effects on acute myocardial ischemia model.Biomed Pharmacother. 2017 May;89:297-304. doi: 10.1016/j.biopha.2017.02.029. Epub 2017 Feb 24.
20 Sarcolipin deletion exacerbates soleus muscle atrophy and weakness in phospholamban overexpressing mice.PLoS One. 2017 Mar 9;12(3):e0173708. doi: 10.1371/journal.pone.0173708. eCollection 2017.
21 Phospholamban deficiency does not alter skeletal muscle SERCA pumping efficiency or predispose mice to diet-induced obesity.Am J Physiol Endocrinol Metab. 2019 Mar 1;316(3):E432-E442. doi: 10.1152/ajpendo.00288.2018. Epub 2019 Jan 2.
22 SLN- and NLC-encapsulating antifungal agents: skin drug delivery and their unexplored potential for treating onychomycosis.Curr Pharm Des. 2017 Nov 14. doi: 10.2174/1381612823666171115112745. Online ahead of print.
23 Predicting Non-sentinel Lymph Node Metastases in Patients with a Positive Sentinel Lymph Node After Neoadjuvant Chemotherapy.Ann Surg Oncol. 2018 Oct;25(10):2867-2874. doi: 10.1245/s10434-018-6578-3. Epub 2018 Jun 28.
24 Newly synthesized surfactants for surface mannosylation of respirable SLN assemblies to target macrophages in tuberculosis therapy.Drug Deliv Transl Res. 2019 Feb;9(1):298-310. doi: 10.1007/s13346-018-00607-w.
25 Sarcolipin overexpression impairs myogenic differentiation in Duchenne muscular dystrophy.Am J Physiol Cell Physiol. 2019 Oct 1;317(4):C813-C824. doi: 10.1152/ajpcell.00146.2019. Epub 2019 Jul 31.
26 Sentinel Lymph Node-Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model.Mol Cancer Ther. 2019 Aug;18(8):1430-1438. doi: 10.1158/1535-7163.MCT-18-1372. Epub 2019 Jun 6.
27 Correlation of Tumor Burden in Sentinel Lymph Nodes with Tumor Burden in Nonsentinel Lymph Nodes and Survival in Cutaneous Melanoma.Clin Cancer Res. 2019 Dec 15;25(24):7585-7593. doi: 10.1158/1078-0432.CCR-19-1194. Epub 2019 Sep 30.
28 Sentinel lymph node biopsy in low risk settings.Am J Surg. 2017 Sep;214(3):489-494. doi: 10.1016/j.amjsurg.2017.03.006. Epub 2017 Mar 15.
29 The utility of sentinel lymph node mapping in the management of endometrial atypical hyperplasia.Gynecol Oncol. 2018 Mar;148(3):485-490. doi: 10.1016/j.ygyno.2017.12.026. Epub 2017 Dec 28.
30 Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models.Emerg Microbes Infect. 2019;8(1):1108-1121. doi: 10.1080/22221751.2019.1637072.
31 Marfan Syndrome Variability: Investigation of the Roles of Sarcolipin and Calcium as Potential Transregulator of FBN1 Expression.Genes (Basel). 2018 Aug 21;9(9):421. doi: 10.3390/genes9090421.
32 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.
33 Atrial-like Engineered Heart Tissue: An In?Vitro Model of the Human Atrium. Stem Cell Reports. 2018 Dec 11;11(6):1378-1390. doi: 10.1016/j.stemcr.2018.10.008. Epub 2018 Nov 8.
34 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
35 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
36 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
37 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.
38 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
39 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.
40 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.