Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH6C0WU)

DOT Name Tetraspanin-33 (TSPAN33)
Synonyms Tspan-33; Penumbra; hPen; Proerythroblast new membrane
Gene Name TSPAN33
Related Disease
Androgen insensitivity syndrome ( )
Brain infarction ( )
Oral lichen planus ( )
Subarachnoid hemorrhage ( )
Advanced cancer ( )
Atrial fibrillation ( )
Autoimmune disease ( )
B-cell lymphoma ( )
B-cell neoplasm ( )
Cerebral infarction ( )
Depression ( )
Drug dependence ( )
Juvenile hyaline fibromatosis ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma ( )
Migraine disorder ( )
Migraine with aura ( )
Neoplasm ( )
Neuromyelitis optica ( )
Non-small-cell lung cancer ( )
Osteoglophonic dwarfism ( )
Systemic lupus erythematosus ( )
Breast cancer ( )
Breast carcinoma ( )
Glioblastoma multiforme ( )
Small-cell lung cancer ( )
Stroke ( )
Acute myelogenous leukaemia ( )
Anemia ( )
High blood pressure ( )
Myelodysplastic syndrome ( )
Type-1 diabetes ( )
Type-1/2 diabetes ( )
UniProt ID
TSN33_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00335
Sequence
MARRPRAPAASGEEFSFVSPLVKYLLFFFNMLFWVISMVMVAVGVYARLMKHAEAALACL
AVDPAILLIVVGVLMFLLTFCGCIGSLRENICLLQTFSLCLTAVFLLQLAAGILGFVFSD
KARGKVSEIINNAIVHYRDDLDLQNLIDFGQKKFSCCGGISYKDWSQNMYFNCSEDNPSR
ERCSVPYSCCLPTPDQAVINTMCGQGMQAFDYLEASKVIYTNGCIDKLVNWIHSNLFLLG
GVALGLAIPQLVGILLSQILVNQIKDQIKLQLYNQQHRADPWY
Function
Part of TspanC8 subgroup, composed of 6 members that interact with the transmembrane metalloprotease ADAM10. This interaction is required for ADAM10 exit from the endoplasmic reticulum and for enzymatic maturation and trafficking to the cell surface as well as substrate specificity. Different TspanC8/ADAM10 complexes have distinct substrates. Plays an important role in normal erythropoiesis. It has a role in the differentiation of erythroid progenitors. Negatively regulates ligand-induced Notch activity probably by regulating ADAM10 activity. Mediates docking of ADAM10 to zonula adherens by interacting with ADAM10 and, in a PDZD11-dependent manner, with the zonula adherens protein PLEKHA7.
Tissue Specificity Predominantly expressed in erythroblasts.
Reactome Pathway
Amyloid fiber formation (R-HSA-977225 )

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Androgen insensitivity syndrome DISUZBBO Definitive Biomarker [1]
Brain infarction DISPPGYK Definitive Biomarker [2]
Oral lichen planus DISVEAJA Definitive Biomarker [3]
Subarachnoid hemorrhage DISI7I8Y Definitive Biomarker [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Atrial fibrillation DIS15W6U Strong Genetic Variation [6]
Autoimmune disease DISORMTM Strong Biomarker [7]
B-cell lymphoma DISIH1YQ Strong Altered Expression [7]
B-cell neoplasm DISVY326 Strong Biomarker [7]
Cerebral infarction DISR1WNP Strong Biomarker [8]
Depression DIS3XJ69 Strong Biomarker [9]
Drug dependence DIS9IXRC Strong Biomarker [10]
Juvenile hyaline fibromatosis DISQP8V9 Strong Biomarker [11]
Lung cancer DISCM4YA Strong Biomarker [12]
Lung carcinoma DISTR26C Strong Biomarker [12]
Lymphoma DISN6V4S Strong Altered Expression [7]
Migraine disorder DISFCQTG Strong Genetic Variation [13]
Migraine with aura DISDM7I8 Strong Biomarker [14]
Neoplasm DISZKGEW Strong Altered Expression [15]
Neuromyelitis optica DISBFGKL Strong Biomarker [16]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [12]
Osteoglophonic dwarfism DISVSNPT Strong Altered Expression [17]
Systemic lupus erythematosus DISI1SZ7 Strong Altered Expression [7]
Breast cancer DIS7DPX1 moderate Biomarker [18]
Breast carcinoma DIS2UE88 moderate Biomarker [18]
Glioblastoma multiforme DISK8246 moderate Biomarker [19]
Small-cell lung cancer DISK3LZD moderate Altered Expression [20]
Stroke DISX6UHX moderate Biomarker [21]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [22]
Anemia DISTVL0C Limited Biomarker [22]
High blood pressure DISY2OHH Limited Biomarker [23]
Myelodysplastic syndrome DISYHNUI Limited Genetic Variation [22]
Type-1 diabetes DIS7HLUB Limited Genetic Variation [24]
Type-1/2 diabetes DISIUHAP Limited Biomarker [25]
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⏷ Show the Full List of 34 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 increases the expression of Tetraspanin-33 (TSPAN33). [26]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Tetraspanin-33 (TSPAN33). [27]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Tetraspanin-33 (TSPAN33). [28]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Tetraspanin-33 (TSPAN33). [29]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Tetraspanin-33 (TSPAN33). [30]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Tetraspanin-33 (TSPAN33). [31]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Tetraspanin-33 (TSPAN33). [32]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Tetraspanin-33 (TSPAN33). [27]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tetraspanin-33 (TSPAN33). [33]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Tetraspanin-33 (TSPAN33). [34]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Tetraspanin-33 (TSPAN33). [35]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Tetraspanin-33 (TSPAN33). [36]
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⏷ Show the Full List of 12 Drug(s)

References

1 Perfusion Changes of Unexplained Early Neurological Deterioration After Reperfusion Therapy.Transl Stroke Res. 2020 Apr;11(2):195-203. doi: 10.1007/s12975-019-00723-w. Epub 2019 Aug 28.
2 Neuroprotective Action of Human Wharton's Jelly-Derived Mesenchymal Stromal Cell Transplants in a Rodent Model of Stroke.Cell Transplant. 2018 Nov;27(11):1603-1612. doi: 10.1177/0963689718802754. Epub 2018 Oct 4.
3 Identification of the key genes implicated in the transformation of OLP to OSCC using RNA-sequencing.Oncol Rep. 2017 Apr;37(4):2355-2365. doi: 10.3892/or.2017.5487. Epub 2017 Mar 2.
4 Amplitude Instability of Somatosensory Evoked Potentials as an Indicator of Delayed Cerebral Ischemia in a Case of Subarachnoid Hemorrhage.Clin EEG Neurosci. 2019 May;50(3):205-209. doi: 10.1177/1550059418804915. Epub 2018 Oct 3.
5 Penicisulfuranol A, a novel C-terminal inhibitor disrupting molecular chaperone function of Hsp90 independent of ATP binding domain.Biochem Pharmacol. 2019 May;163:404-415. doi: 10.1016/j.bcp.2019.03.012. Epub 2019 Mar 8.
6 Unilateral Acute Renal Artery Embolism: An Index Case of Successful Mechanical Aspiration Thrombectomy With Use of Penumbra Indigo Aspiration System and a Review of the Literature.Vasc Endovascular Surg. 2018 Jul;52(5):391-394. doi: 10.1177/1538574418764052. Epub 2018 Mar 19.
7 TSPAN33 is a novel marker of activated and malignant B cells.Clin Immunol. 2013 Dec;149(3):388-99. doi: 10.1016/j.clim.2013.08.005. Epub 2013 Aug 15.
8 FCPR03, a novel phosphodiesterase 4 inhibitor, alleviates cerebral ischemia/reperfusion injury through activation of the AKT/GSK3/ -catenin signaling pathway.Biochem Pharmacol. 2019 May;163:234-249. doi: 10.1016/j.bcp.2019.02.023. Epub 2019 Feb 21.
9 Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis Lecture.Stroke. 2003 Jan;34(1):214-23. doi: 10.1161/01.str.0000048846.09677.62.
10 Neuropeptide PEN and Its Receptor GPR83: Distribution, Signaling, and Regulation.ACS Chem Neurosci. 2019 Apr 17;10(4):1884-1891. doi: 10.1021/acschemneuro.8b00559. Epub 2019 Feb 21.
11 Electrical Stimulation of the Mesencephalic Locomotor Region Attenuates Neuronal Loss and Cytokine Expression in the Perifocal Region of Photothrombotic Stroke in Rats.Int J Mol Sci. 2019 May 11;20(9):2341. doi: 10.3390/ijms20092341.
12 Bone Marrow and Tumor Radiomics at (18)F-FDG PET/CT: Impact on Outcome Prediction in Non-Small Cell Lung Cancer.Radiology. 2019 Nov;293(2):451-459. doi: 10.1148/radiol.2019190357. Epub 2019 Sep 17.
13 Stroke progression and clinical outcome in ischemic stroke patients with a history of migraine.Int J Stroke. 2019 Dec;14(9):946-955. doi: 10.1177/1747493019851288. Epub 2019 May 27.
14 Vulnerability to Infarction During Cerebral Ischemia in Migraine Sufferers.Stroke. 2018 Mar;49(3):573-578. doi: 10.1161/STROKEAHA.118.020554. Epub 2018 Feb 19.
15 Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo.J Med Chem. 2019 Mar 14;62(5):2708-2719. doi: 10.1021/acs.jmedchem.8b02036. Epub 2019 Feb 28.
16 Unique neuromyelitis optica pathology produced in nave rats by intracerebral administration of NMO-IgG.Acta Neuropathol. 2014 Apr;127(4):539-51. doi: 10.1007/s00401-013-1204-8. Epub 2013 Nov 5.
17 Role of acute-phase protein ORM in a mice model of ischemic stroke.J Cell Physiol. 2019 Nov;234(11):20533-20545. doi: 10.1002/jcp.28653. Epub 2019 Apr 26.
18 The influence of socio-cultural factors on breast cancer screening behaviors in Lagos, Nigeria.Ethn Health. 2019 Jul;24(5):544-559. doi: 10.1080/13557858.2017.1348489. Epub 2017 Jul 5.
19 Classification of subpopulations of cells within human primary brain tumors by single cell gene expression profiling.Neurochem Res. 2015 Feb;40(2):336-52. doi: 10.1007/s11064-014-1431-y. Epub 2014 Sep 24.
20 Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer.Mol Cancer Ther. 2019 Nov;18(11):1926-1936. doi: 10.1158/1535-7163.MCT-19-0022.
21 Expression of Histone Deacetylases HDAC1 and HDAC2 and Their Role in Apoptosis in the Penumbra Induced by Photothrombotic Stroke.Mol Neurobiol. 2020 Jan;57(1):226-238. doi: 10.1007/s12035-019-01772-w. Epub 2019 Sep 6.
22 Penumbra encodes a novel tetraspanin that is highly expressed in erythroid progenitors and promotes effective erythropoiesis.Blood. 2007 Apr 15;109(8):3244-52. doi: 10.1182/blood-2006-09-046672. Epub 2006 Dec 7.
23 'I believe high blood pressure can kill me:' using the PEN-3 Cultural Model to understand patients' perceptions of an intervention to control hypertension in Ghana.Ethn Health. 2019 Apr;24(3):257-270. doi: 10.1080/13557858.2017.1346178. Epub 2017 Jul 4.
24 Factors Affecting Self-Care Performance in Adolescents with Type I Diabetes According to the PEN-3 Cultural Model.Int J Endocrinol Metab. 2018 Sep 18;16(4):e62582. doi: 10.5812/ijem.62582. eCollection 2018 Oct.
25 Clinical Outcome After Mechanical Thrombectomy in Patients with Diabetes with Major Ischemic Stroke of the Anterior Circulation.World Neurosurg. 2018 Dec;120:e212-e220. doi: 10.1016/j.wneu.2018.08.032. Epub 2018 Aug 16.
26 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
27 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.
28 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
29 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
30 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
31 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
32 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
33 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.
34 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.
35 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
36 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.