Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXTW2I4)

DOT Name Calpain-8 (CAPN8)
Synonyms EC 3.4.22.53; New calpain 2; nCL-2; Stomach-specific M-type calpain
Gene Name CAPN8
Related Disease
Lung adenocarcinoma ( )
CLN2 Batten disease ( )
Coeliac disease ( )
Lysosomal storage disease ( )
Neuronal ceroid lipofuscinosis ( )
UniProt ID
CAN8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2NQA
EC Number
3.4.22.53
Pfam ID
PF01067 ; PF00648
Sequence
MAAQAAGVSRQRAATQGLGSNQNALKYLGQDFKTLRQQCLDSGVLFKDPEFPACPSALGY
KDLGPGSPQTQGIIWKRPTELCPSPQFIVGGATRTDICQGGLGDCWLLAAIASLTLNEEL
LYRVVPRDQDFQENYAGIFHFQFWQYGEWVEVVIDDRLPTKNGQLLFLHSEQGNEFWSAL
LEKAYAKLNGCYEALAGGSTVEGFEDFTGGISEFYDLKKPPANLYQIIRKALCAGSLLGC
SIDVSSAAEAEAITSQKLVKSHAYSVTGVEEVNFQGHPEKLIRLRNPWGEVEWSGAWSDD
APEWNHIDPRRKEELDKKVEDGEFWMSLSDFVRQFSRLEICNLSPDSLSSEEVHKWNLVL
FNGHWTRGSTAGGCQNYPATYWTNPQFKIRLDEVDEDQEESIGEPCCTVLLGLMQKNRRW
RKRIGQGMLSIGYAVYQVPKELESHTDAHLGRDFFLAYQPSARTSTYVNLREVSGRARLP
PGEYLVVPSTFEPFKDGEFCLRVFSEKKAQALEIGDVVAGNPYEPHPSEVDQEDDQFRRL
FEKLAGKDSEITANALKILLNEAFSKRTDIKFDGFNINTCREMISLLDSNGTGTLGAVEF
KTLWLKIQKYLEIYWETDYNHSGTIDAHEMRTALRKAGFTLNSQVQQTIALRYACSKLGI
NFDSFVACMIRLETLFKLFSLLDEDKDGMVQLSLAEWLCCVLV
Function
Calcium-regulated non-lysosomal thiol-protease. Involved in membrane trafficking in the gastric surface mucus cells (pit cells) and may involve the membrane trafficking of mucus cells via interactions with coat protein. Proteolytically cleaves the beta-subunit of coatomer complex.
Tissue Specificity Stomach.
Reactome Pathway
Degradation of the extracellular matrix (R-HSA-1474228 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung adenocarcinoma DISD51WR Definitive Biomarker [1]
CLN2 Batten disease DISZC5YB Limited Biomarker [2]
Coeliac disease DISIY60C Limited Biomarker [3]
Lysosomal storage disease DIS6QM6U Limited Genetic Variation [2]
Neuronal ceroid lipofuscinosis DIS9A4K4 Limited Genetic Variation [2]
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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 decreases the methylation of Calpain-8 (CAPN8). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Calpain-8 (CAPN8). [8]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Calpain-8 (CAPN8). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Calpain-8 (CAPN8). [6]
Malathion DMXZ84M Approved Malathion decreases the expression of Calpain-8 (CAPN8). [7]
Permethrin DMZ0Q1G Approved Permethrin decreases the expression of Calpain-8 (CAPN8). [7]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Calpain-8 (CAPN8). [9]
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References

1 Mucin mRNA expression in lung adenocarcinoma cell lines and tissues.Oncology. 1996 Mar-Apr;53(2):118-26. doi: 10.1159/000227547.
2 Batten disease: biochemical and molecular characterization revealing novel PPT1 and TPP1 gene mutations in Indian patients.BMC Neurol. 2018 Dec 12;18(1):203. doi: 10.1186/s12883-018-1206-1.
3 Celiac disease biomarkers identified by transcriptome analysis of small intestinal biopsies.Cell Mol Life Sci. 2018 Dec;75(23):4385-4401. doi: 10.1007/s00018-018-2898-5. Epub 2018 Aug 10.
4 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.
5 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.
6 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
7 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
8 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.
9 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.