Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4NUHWB)

DOT Name Caspase recruitment domain-containing protein 16 (CARD16)
Synonyms Caspase recruitment domain-only protein 1; CARD-only protein 1; Caspase-1 inhibitor COP; Pseudo interleukin-1 beta converting enzyme; Pseudo-ICE; Pseudo-IL1B-converting enzyme
Gene Name CARD16
Related Disease
Acute coronary syndrome ( )
Adenocarcinoma ( )
B-cell lymphoma ( )
Breast cancer ( )
Hematologic disease ( )
Hepatitis C virus infection ( )
Huntington disease ( )
Multiple sclerosis ( )
Non-small-cell lung cancer ( )
Parkinson disease ( )
Peripheral arterial disease ( )
Relapsing-remitting multiple sclerosis ( )
Scleroderma ( )
Systemic sclerosis ( )
Amyotrophic lateral sclerosis ( )
Gastric cancer ( )
Spinal muscular atrophy ( )
Stomach cancer ( )
Lymphoma ( )
Malaria ( )
Nasopharyngeal carcinoma ( )
Neoplasm ( )
UniProt ID
CAR16_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00619
Sequence
MADKVLKEKRKLFIHSMGEGTINGLLDELLQTRVLNQEEMEKVKRENATVMDKTRALIDS
VIPKGAQACQICITYICEEDSYLAETLGLSAALQAVQDNPAMPTCSSPEGRIKLCFLEDA
QRIWKQKLQRCHVQNTIIKWSERYTSGSFEMQWLFLRTNFIERFWRNILLLPLHKGSLYP
RIPGLGKELQTGTHKLS
Function
Caspase inhibitor. Acts as a regulator of procaspase-1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation. Inhibits the release of IL1B in response to LPS in monocytes. Also induces NF-kappa-B activation during the pro-inflammatory cytokine response. Also able to inhibit CASP1-mediated neuronal cell death, TNF-alpha, hypoxia-, UV-, and staurosporine-mediated cell death but not ER stress-mediated cell death. Acts by preventing activation of caspases CASP1 and CASP4, possibly by preventing the interaction between CASP1 and RIPK2.
Tissue Specificity Widely expressed. Expressed at higher level in placenta, spleen, lymph node and bone marrow. Weakly or not expressed in thymus.
KEGG Pathway
NOD-like receptor sig.ling pathway (hsa04621 )

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute coronary syndrome DIS7DYEW Strong Genetic Variation [1]
Adenocarcinoma DIS3IHTY Strong Biomarker [2]
B-cell lymphoma DISIH1YQ Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Biomarker [4]
Hematologic disease DIS9XD9A Strong Genetic Variation [5]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [6]
Huntington disease DISQPLA4 Strong Genetic Variation [7]
Multiple sclerosis DISB2WZI Strong Biomarker [8]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [9]
Parkinson disease DISQVHKL Strong Biomarker [10]
Peripheral arterial disease DIS78WFB Strong Genetic Variation [11]
Relapsing-remitting multiple sclerosis DISSXFCF Strong Biomarker [12]
Scleroderma DISVQ342 Strong Biomarker [13]
Systemic sclerosis DISF44L6 Strong Biomarker [13]
Amyotrophic lateral sclerosis DISF7HVM moderate Biomarker [14]
Gastric cancer DISXGOUK moderate Biomarker [15]
Spinal muscular atrophy DISTLKOB moderate Biomarker [16]
Stomach cancer DISKIJSX moderate Biomarker [15]
Lymphoma DISN6V4S Limited Biomarker [17]
Malaria DISQ9Y50 Limited Biomarker [18]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [19]
Neoplasm DISZKGEW Limited Biomarker [20]
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⏷ Show the Full List of 22 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [21]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [22]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [23]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [24]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [25]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [26]
Triclosan DMZUR4N Approved Triclosan increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [27]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [28]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [29]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [30]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [31]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Caspase recruitment domain-containing protein 16 (CARD16). [28]
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⏷ Show the Full List of 12 Drug(s)
1 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 affects the methylation of Caspase recruitment domain-containing protein 16 (CARD16). [32]
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References

1 NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes: Genome-Wide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO).Circ Cardiovasc Genet. 2015 Jun;8(3):498-506. doi: 10.1161/CIRCGENETICS.114.000724. Epub 2015 Mar 6.
2 COP1 is downregulated in renal cell carcinoma (RCC) and inhibits the migration of RCC ACHN cells invitro.Mol Med Rep. 2016 Aug;14(2):1371-8. doi: 10.3892/mmr.2016.5373. Epub 2016 Jun 7.
3 Tel-eVax: a genetic vaccine targeting telomerase for treatment of canine lymphoma.J Transl Med. 2018 Dec 11;16(1):349. doi: 10.1186/s12967-018-1738-6.
4 Multiple susceptibility loci for radiation-induced mammary tumorigenesis in F2[Dahl S x R]-intercross rats.PLoS One. 2013 Aug 14;8(8):e72143. doi: 10.1371/journal.pone.0072143. eCollection 2013.
5 Inherited hematological disorders due to defects in coat protein (COP)II complex.Am J Hematol. 2013 Feb;88(2):135-40. doi: 10.1002/ajh.23292. Epub 2012 Jul 5.
6 Hepatitis C virus replication and Golgi function in brefeldin a-resistant hepatoma-derived cells.PLoS One. 2013 Sep 18;8(9):e74491. doi: 10.1371/journal.pone.0074491. eCollection 2013.
7 Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 activation in Huntington's disease.J Neurosci. 2005 Dec 14;25(50):11645-54. doi: 10.1523/JNEUROSCI.4181-05.2005.
8 Release of interleukin-10 and neurotrophic factors in the choroid plexus: possible inductors of neurogenesis following copolymer-1 immunization after cerebral ischemia.Neural Regen Res. 2018 Oct;13(10):1743-1752. doi: 10.4103/1673-5374.238615.
9 Combination of platelet count and lymphocyte to monocyte ratio is a prognostic factor in patients undergoing surgery for non-small cell lung cancer.Oncotarget. 2017 Jun 1;8(42):73198-73207. doi: 10.18632/oncotarget.18336. eCollection 2017 Sep 22.
10 Postural control deficit during sit-to-walk in patients with Parkinson's disease and freezing of gait.Gait Posture. 2018 Mar;61:325-330. doi: 10.1016/j.gaitpost.2018.01.032. Epub 2018 Feb 2.
11 Gait deficiencies associated with peripheral artery disease are different than chronic obstructive pulmonary disease.Gait Posture. 2017 Sep;57:258-264. doi: 10.1016/j.gaitpost.2017.06.018. Epub 2017 Jun 27.
12 Glatiramer Acetate: from Bench to Bed and Back.Isr Med Assoc J. 2019 Mar;21(3):151-157.
13 Identification of the mouse beta'-COP Golgi component as a spermatocyte autoantigen in scleroderma and mapping of its gene Copb2 to mouse chromosome 9.Cytogenet Cell Genet. 1999;87(3-4):201-4. doi: 10.1159/000015467.
14 Limited effects of glatiramer acetate in the high-copy number hSOD1-G93A mouse model of ALS.Exp Neurol. 2007 Aug;206(2):288-95. doi: 10.1016/j.expneurol.2007.05.007. Epub 2007 May 18.
15 Combination of platelet count and neutrophil-lymphocyte ratio as a prognostic marker to predict chemotherapeutic response and survival in metastatic advanced gastric cancer.Biomark Med. 2017 Oct 26. doi: 10.2217/bmm-2016-0288. Online ahead of print.
16 Interaction between alpha-COP and SMN ameliorates disease phenotype in a mouse model of spinal muscular atrophy.Biochem Biophys Res Commun. 2019 Jun 25;514(2):530-537. doi: 10.1016/j.bbrc.2019.04.176. Epub 2019 May 3.
17 Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia.Curr Probl Cancer. 2017 Nov-Dec;41(6):419-425. doi: 10.1016/j.currproblcancer.2017.09.001. Epub 2017 Sep 23.
18 Characterisation of a delta-COP homologue in the malaria parasite, Plasmodium falciparum.Mol Biochem Parasitol. 2002 Aug 7;123(1):11-21. doi: 10.1016/s0166-6851(02)00117-2.
19 Pretreatment combination of platelet counts and neutrophil-lymphocyte ratio predicts survival of nasopharyngeal cancer patients receiving intensity-modulated radiotherapy.Onco Targets Ther. 2017 May 26;10:2751-2760. doi: 10.2147/OTT.S137000. eCollection 2017.
20 Self-Templated Stepwise Synthesis of Monodispersed Nanoscale Metalated Covalent Organic Polymers for In Vivo Bioimaging and Photothermal Therapy.Chem Asian J. 2017 Sep 5;12(17):2183-2188. doi: 10.1002/asia.201700796. Epub 2017 Aug 2.
21 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.
22 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.
23 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.
24 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
25 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.
26 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.
27 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
28 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
29 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
30 A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
31 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
32 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.