Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZ2SZB)

DOT Name	Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (MINDY4)
Synonyms	EC 3.4.19.12; Probable deubiquitinating enzyme MINDY-4
Gene Name	MINDY4
Related Disease	Acute erythroid leukemia ( ) Hydrocephalus ( ) Liver cirrhosis ( ) Matthew-Wood syndrome ( ) Meningioma ( ) Alzheimer disease ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Cervical cancer ( ) Cervical carcinoma ( ) Cholestasis ( ) Clear cell renal carcinoma ( ) Endometrial cancer ( ) Endometrial carcinoma ( ) Epithelial ovarian cancer ( ) Esophageal squamous cell carcinoma ( ) Glioblastoma multiforme ( ) Glioma ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Lung neoplasm ( ) Malignant mesothelioma ( ) Malignant pleural mesothelioma ( ) Mesothelioma ( ) Neoplasm ( ) OPTN-related open angle glaucoma ( ) Osteoarthritis ( ) Ovarian cancer ( ) Parkinson disease ( ) Prostate cancer ( ) Prostate carcinoma ( ) Renal cell carcinoma ( ) Cutaneous melanoma ( ) Hepatocellular carcinoma ( ) High blood pressure ( ) Breast cancer ( ) Breast carcinoma ( ) Nephropathy ( ) Adenocarcinoma ( ) Advanced cancer ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Melanoma ( ) Neuromyelitis optica ( ) Rheumatoid arthritis ( ) Squamous cell carcinoma ( ) Urolithiasis ( )
UniProt ID	MINY4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.4.19.12
Pfam ID	PF13898
Sequence	MDSLFVEEVAASLVREFLSRKGLKKTCVTMDQERPRSDLSINNRNDLRKVLHLEFLYKEN KAKENPLKTSLELITRYFLDHFGNTANNFTQDTPIPALSVPKKNNKVPSRCSETTLVNIY DLSDEDAGWRTSLSETSKARHDNLDGDVLGNFVSSKRPPHKSKPMQTVPGETPVLTSAWE KIDKLHSEPSLDVKRMGENSRPKSGLIVRGMMSGPIASSPQDSFHRHYLRRSSPSSSSTQ PQEESRKVPELFVCTQQDILASSNSSPSRTSLGQLSELTVERQKTTASSPPHLPSKRLPP WDRARPRDPSEDTPAVDGSTDTDRMPLKLYLPGGNSRMTQERLERAFKRQGSQPAPVRKN QLLPSDKVDGELGALRLEDVEDELIREEVILSPVPSVLKLQTASKPIDLSVAKEIKTLLF GSSFCCFNEEWKLQSFSFSNTASLKYGIVQNKGGPCGVLAAVQGCVLQKLLFEGDSKADC AQGLQPSDAHRTRCLVLALADIVWRAGGRERAVVALASRTQQFSPTGKYKADGVLETLTL HSLTCYEDLVTFLQQSIHQFEVGPYGCILLTLSAILSRSTELIRQDFDVPTSHLIGAHGY CTQELVNLLLTGKAVSNVFNDVVELDSGDGNITLLRGIAARSDIGFLSLFEHYNMCQVGC FLKTPRFPIWVVCSESHFSILFSLQPGLLRDWRTERLFDLYYYDGLANQQEQIRLTIDTT QTISEDTDNDLVPPLELCIRTKWKGASVNWNGSDPIL
Function	Probable hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute erythroid leukemia	DISZFC1O	Definitive	Biomarker	[1]
Hydrocephalus	DISIZUF7	Definitive	Biomarker	[2]
Liver cirrhosis	DIS4G1GX	Definitive	Genetic Variation	[3]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[4]
Meningioma	DISPT4TG	Definitive	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[8]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[8]
Cholestasis	DISDJJWE	Strong	Altered Expression	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[10]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[11]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[14]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[18]
Malignant mesothelioma	DISTHJGH	Strong	Genetic Variation	[19]
Malignant pleural mesothelioma	DIST2R60	Strong	Altered Expression	[20]
Mesothelioma	DISKWK9M	Strong	Altered Expression	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
OPTN-related open angle glaucoma	DISDR98A	Strong	Altered Expression	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[6]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[10]
Cutaneous melanoma	DIS3MMH9	moderate	Altered Expression	[25]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[26]
High blood pressure	DISY2OHH	moderate	Biomarker	[27]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[28]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[28]
Nephropathy	DISXWP4P	Disputed	Altered Expression	[29]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[30]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[31]
Colon cancer	DISVC52G	Limited	Biomarker	[32]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[32]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[33]
Melanoma	DIS1RRCY	Limited	Biomarker	[34]
Neuromyelitis optica	DISBFGKL	Limited	Biomarker	[35]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[36]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[30]
Urolithiasis	DISNFTKT	Limited	Genetic Variation	[37]
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⏷ Show the Full List of 49 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

4 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 Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (MINDY4).	[38]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (MINDY4).	[40]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (MINDY4).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (MINDY4).	[43]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (MINDY4).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (MINDY4).	[42]
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References

1	Induction of human aquaporin-1 gene by retinoic acid in human erythroleukemia HEL cells.Biochem Biophys Res Commun. 2002 May 10;293(3):913-7. doi: 10.1016/S0006-291X(02)00316-9.
2	Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus.Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3515-3526. doi: 10.1016/j.bbadis.2018.08.006. Epub 2018 Aug 8.
3	Influence of aquaporin-1 gene polymorphism on water retention in liver cirrhosis.Scand J Gastroenterol. 2011 Oct;46(10):1267-74. doi: 10.3109/00365521.2011.603161. Epub 2011 Jul 27.
4	AQP1 and AQP3 Expression are Associated With Severe Symptoms and Poor-prognosis of the Pancreatic Ductal Adenocarcinoma.Appl Immunohistochem Mol Morphol. 2019 Jan;27(1):40-47. doi: 10.1097/PAI.0000000000000523.
5	Atypical cystic meningioma overexpressing AQP1 in early infancy: case report with literature review.Acta Paediatr. 2008 Aug;97(8):1145-9. doi: 10.1111/j.1651-2227.2008.00877.x. Epub 2008 May 21.
6	Expression of Aquaporin 1 and Aquaporin 4 in the Temporal Neocortex of Patients with Parkinson's Disease.Brain Pathol. 2017 Mar;27(2):160-168. doi: 10.1111/bpa.12369. Epub 2016 Apr 6.
7	Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.Am J Physiol Heart Circ Physiol. 2017 Nov 1;313(5):H1063-H1073. doi: 10.1152/ajpheart.00651.2016. Epub 2017 Jul 21.
8	Decreased expression of aquaporin 1 correlates with clinicopathological features of patients with cervical cancer.Onco Targets Ther. 2019 Apr 23;12:2843-2851. doi: 10.2147/OTT.S194650. eCollection 2019.
9	Improved hepatic MRP2/ABCC2 transport activity in LPS-induced cholestasis by aquaporin-1 gene transfer.Biochimie. 2019 Oct;165:179-182. doi: 10.1016/j.biochi.2019.07.027. Epub 2019 Aug 1.
10	Transcript levels of aquaporin 1 and carbonic anhydrase IV as predictive indicators for prognosis of renal cell carcinoma patients after nephrectomy.Int J Cancer. 1998 Feb 20;79(1):1-7. doi: 10.1002/(sici)1097-0215(19980220)79:1<1::aid-ijc1>3.0.co;2-5.
11	Aquaporin-1 plays a crucial role in estrogen-induced tubulogenesis of vascular endothelial cells.J Clin Endocrinol Metab. 2013 Apr;98(4):E672-82. doi: 10.1210/jc.2012-4081. Epub 2013 Feb 28.
12	Different Prognostic Implications of Aquaporin-1 and Aquaporin-5 Expression among Different Histological Types of Ovarian Carcinoma.Pathol Oncol Res. 2020 Jan;26(1):263-271. doi: 10.1007/s12253-018-0456-y. Epub 2018 Jul 19.
13	Aquaporin 1 suppresses apoptosis and affects prognosis in esophageal squamous cell carcinoma.Oncotarget. 2018 Jul 6;9(52):29957-29974. doi: 10.18632/oncotarget.25722. eCollection 2018 Jul 6.
14	Association of aquaporin? with tumor migration, invasion and vasculogenic mimicry in glioblastoma multiforme.Mol Med Rep. 2018 Feb;17(2):3206-3211. doi: 10.3892/mmr.2017.8265. Epub 2017 Dec 12.
15	Regulation and function of aquaporin-1 in glioma cells.Neoplasia. 2007 Sep;9(9):777-87. doi: 10.1593/neo.07454.
16	Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma.Interact Cardiovasc Thorac Surg. 2017 Dec 1;25(6):856-861. doi: 10.1093/icvts/ivx202.
17	Aquaporin 1 promotes the proliferation and migration of lung cancer cell invitro.Oncol Rep. 2015 Sep;34(3):1440-8. doi: 10.3892/or.2015.4107. Epub 2015 Jul 3.
18	Berberine and cinnamaldehyde together prevent lung carcinogenesis.Oncotarget. 2017 Aug 7;8(44):76385-76397. doi: 10.18632/oncotarget.20059. eCollection 2017 Sep 29.
19	Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment.Radiol Oncol. 2019 Mar 3;53(1):96-104. doi: 10.2478/raon-2019-0009.
20	Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report.Int J Mol Sci. 2018 Feb 28;19(3):685. doi: 10.3390/ijms19030685.
21	Aquaporin-1 expression in fluoro-edenite-induced mesothelioma effusions: An approach by cell-block procedure.Cytopathology. 2018 Oct;29(5):455-460. doi: 10.1111/cyt.12583. Epub 2018 Jul 23.
22	Increased aquaporin-1 levels in lens epithelial cells with primary angle-closure glaucoma.Int J Ophthalmol. 2017 Jul 18;10(7):1101-1105. doi: 10.18240/ijo.2017.07.13. eCollection 2017.
23	Aquaporin 1 (AQP1) expression in experimentally induced osteoarthritic knee menisci: an in vivo and in vitro study.Tissue Cell. 2013 Apr;45(2):145-52. doi: 10.1016/j.tice.2012.10.004. Epub 2012 Nov 17.
24	Overexpression of Aquaporin-1 is a Prognostic Factor for Biochemical Recurrence in Prostate Adenocarcinoma.Pathol Oncol Res. 2017 Jan;23(1):189-196. doi: 10.1007/s12253-016-0145-7. Epub 2016 Nov 5.
25	Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma.Pathol Oncol Res. 2020 Jan;26(1):405-410. doi: 10.1007/s12253-018-0513-6. Epub 2018 Oct 30.
26	The association between aquaporin-1 expression, microvessel density and the clinicopathological features of hepatocellular carcinoma.Oncol Lett. 2017 Dec;14(6):7077-7084. doi: 10.3892/ol.2017.7106. Epub 2017 Sep 29.
27	Aqp-1 Gene Knockout Attenuates Hypoxic Pulmonary Hypertension of Mice.Arterioscler Thromb Vasc Biol. 2019 Jan;39(1):48-62. doi: 10.1161/ATVBAHA.118.311714.
28	Decreased miR-320 expression is associated with breast cancer progression, cell migration, and invasiveness via targeting Aquaporin 1.Acta Biochim Biophys Sin (Shanghai). 2018 May 1;50(5):473-480. doi: 10.1093/abbs/gmy023.
29	Aquaporin expression in normal human kidney and in renal disease.J Am Soc Nephrol. 2003 Oct;14(10):2581-7. doi: 10.1097/01.asn.0000089566.28106.f6.
30	Relationship of aquaporin 1, 3, and 5 expression in lung cancer cells to cellular differentiation, invasive growth, and metastasis potential.Hum Pathol. 2011 May;42(5):669-78. doi: 10.1016/j.humpath.2010.07.022. Epub 2011 Jan 15.
31	Combined pharmacological administration of AQP1 ion channel blocker AqB011 and water channel blocker Bacopaside II amplifies inhibition of colon cancer cell migration.Sci Rep. 2019 Sep 2;9(1):12635. doi: 10.1038/s41598-019-49045-9.
32	FAM188B enhances cell survival via interaction with USP7.Cell Death Dis. 2018 May 24;9(6):633. doi: 10.1038/s41419-018-0650-6.
33	Reduced aquaporin-1 transcript expression in colorectal carcinoma is associated with promoter hypermethylation.Epigenetics. 2019 Feb;14(2):158-170. doi: 10.1080/15592294.2019.1580112. Epub 2019 Feb 20.
34	Aquaporin-1 inhibition reduces metastatic formation in a mouse model of melanoma.J Cell Mol Med. 2018 Feb;22(2):904-912. doi: 10.1111/jcmm.13378. Epub 2017 Oct 17.
35	Predictive Value of Serum Antibodies and Point Mutations of AQP4, AQP1 and MOG in A Cohort of Spanish Patients with Neuromyelitis Optica Spectrum Disorders.Int J Mol Sci. 2019 Nov 19;20(22):5810. doi: 10.3390/ijms20225810.
36	Therapeutic effect of acetazolamide, an aquaporin 1 inhibitor, on adjuvant-induced arthritis in rats by inhibiting NF-B signal pathway.Immunopharmacol Immunotoxicol. 2018 Apr;40(2):117-125. doi: 10.1080/08923973.2017.1417998. Epub 2018 Jan 5.
37	Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population.J Am Soc Nephrol. 2019 May;30(5):855-864. doi: 10.1681/ASN.2018090942. Epub 2019 Apr 11.
38	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
39	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
40	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.
41	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.
42	Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
43	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.