Details of Drug Off-Target (DOT)

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

• DOT Name: Transport and Golgi organization protein 1 homolog (MIA3)
• Synonyms: TANGO1; C219-reactive peptide; D320; Melanoma inhibitory activity protein 3
• Gene Name: MIA3
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Cardiovascular disease
  Colorectal carcinoma
  Coronary atherosclerosis
  Hepatocellular carcinoma
  Odontochondrodysplasia 2 with hearing loss and diabetes
  Rheumatoid arthritis
  Age-related macular degeneration
  Coronary heart disease
  Melanoma
  Myocardial infarction
  Neoplasm
• UniProt ID: TGO1_HUMAN
• PDB ID: 5KYN; 5KYU; 5KYW; 7R3M
• Pfam ID: PF07653
• Sequence:
  MAAAPGLLVWLLVLRLPWRVPGQLDPSTGRRFSEHKLCADDECSMLMYRGEALEDFTGPD
  CRFVNFKKGDPVYVYYKLARGWPEVWAGSVGRTFGYFPKDLIQVVHEYTKEELQVPTDET
  DFVCFDGGRDDFHNYNVEELLGFLELYNSAATDSEKAVEKTLQDMEKNPELSKEREPEPE
  PVEANSEESDSVFSENTEDLQEQFTTQKHHSHANSQANHAQGEQASFESFEEMLQDKLKV
  PESENNKTSNSSQVSNEQDKIDAYKLLKKEMTLDLKTKFGSTADALVSDDETTRLVTSLE
  DDFDEELDTEYYAVGKEDEENQEDFDELPLLTFTDGEDMKTPAKSGVEKYPTDKEQNSNE
  EDKVQLTVPPGIKNDDKNILTTWGDTIFSIVTGGEETRDTMDLESSSSEEEKEDDDDALV
  PDSKQGKPQSATDYSDPDNVDDGLFIVDIPKTNNDKEVNAEHHIKGKGRGVQESKRGLVQ
  DKTELEDENQEGMTVHSSVHSNNLNSMPAAEKGKDTLKSAYDDTENDLKGAAIHISKGML
  HEEKPGEQILEGGSESESAQKAAGNQMNDRKIQQESLGSAPLMGDDHPNASRDSVEGDAL
  VNGAKLHTLSVEHQREELKEELVLKTQNQPRFSSPDEIDLPRELEDEVPILGRNLPWQQE
  RDVAATASKQMSEKIRLSEGEAKEDSLDEEFFHHKAMQGTEVGQTDQTDSTGGPAFLSKV
  EEDDYPSEELLEDENAINAKRSKEKNPGNQGRQFDVNLQVPDRAVLGTIHPDPEIEESKQ
  ETSMILDSEKTSETAAKGVNTGGREPNTMVEKERPLADKKAQRPFERSDFSDSIKIQTPE
  LGEVFQNKDSDYLKNDNPEEHLKTSGLAGEPEGELSKEDHENTEKYMGTESQGSAAAEPE
  DDSFHWTPHTSVEPGHSDKREDLLIISSFFKEQQSLQRFQKYFNVHELEALLQEMSSKLK
  SAQQESLPYNMEKVLDKVFRASESQILSIAEKMLDTRVAENRDLGMNENNIFEEAAVLDD
  IQDLIYFVRYKHSTAEETATLVMAPPLEEGLGGAMEEMQPLHEDNFSREKTAELNVQVPE
  EPTHLDQRVIGDTHASEVSQKPNTEKDLDPGPVTTEDTPMDAIDANKQPETAAEEPASVT
  PLENAILLIYSFMFYLTKSLVATLPDDVQPGPDFYGLPWKPVFITAFLGIASFAIFLWRT
  VLVVKDRVYQVTEQQISEKLKTIMKENTELVQKLSNYEQKIKESKKHVQETRKQNMILSD
  EAIKYKDKIKTLEKNQEILDDTAKNLRVMLESEREQNVKNQDLISENKKSIEKLKDVISM
  NASEFSEVQIALNEAKLSEEKVKSECHRVQEENARLKKKKEQLQQEIEDWSKLHAELSEQ
  IKSFEKSQKDLEVALTHKDDNINALTNCITQLNLLECESESEGQNKGGNDSDELANGEVG
  GDRNEKMKNQIKQMMDVSRTQTAISVVEEDLKLLQLKLRASVSTKCNLEDQVKKLEDDRN
  SLQAAKAGLEDECKTLRQKVEILNELYQQKEMALQKKLSQEEYERQEREHRLSAADEKAV
  SAAEEVKTYKRRIEEMEDELQKTERSFKNQIATHEKKAHENWLKARAAERAIAEEKREAA
  NLRHKLLELTQKMAMLQEEPVIVKPMPGKPNTQNPPRRGPLSQNGSFGPSPVSGGECSPP
  LTVEPPVRPLSATLNRRDMPRSEFGSVDGPLPHPRWSAEASGKPSPSDPGSGTATMMNSS
  SRGSSPTRVLDEGKVNMAPKGPPPFPGVPLMSTPMGGPVPPPIRYGPPPQLCGPFGPRPL
  PPPFGPGMRPPLGLREFAPGVPPGRRDLPLHPRGFLPGHAPFRPLGSLGPREYFIPGTRL
  PPPTHGPQEYPPPPAVRDLLPSGSRDEPPPASQSTSQDCSQALKQSP
• Function: Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum. Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES.
• Tissue Specificity: Broadly expressed, except in bone marrow and peripheral blood mononuclear cells. Down-regulated in melanoma tissue.
• Reactome Pathway:
  Cargo concentration in the ER (R-HSA-5694530)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Odontochondrodysplasia 2 with hearing loss and diabetes	DISM1SQI	Strong	Autosomal recessive	[7]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[8]
Age-related macular degeneration	DIS0XS2C	moderate	Genetic Variation	[9]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[10]
Melanoma	DIS1RRCY	Limited	Altered Expression	[11]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[12]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]

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 Transport and Golgi organization protein 1 homolog (MIA3).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transport and Golgi organization protein 1 homolog (MIA3).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transport and Golgi organization protein 1 homolog (MIA3).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transport and Golgi organization protein 1 homolog (MIA3).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transport and Golgi organization protein 1 homolog (MIA3).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transport and Golgi organization protein 1 homolog (MIA3).	[20]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Transport and Golgi organization protein 1 homolog (MIA3).	[21]

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 Transport and Golgi organization protein 1 homolog (MIA3).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transport and Golgi organization protein 1 homolog (MIA3).	[19]

References

• [1] Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia.Br J Cancer. 2017 Sep 5;117(6):1215-1223. doi: 10.1038/bjc.2017.240. Epub 2017 Jul 25.
• [2] Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer.Breast Cancer Res. 2016 Feb 16;18(1):21. doi: 10.1186/s13058-016-0682-8.
• [3] The Mediterranean diet reduces the genetic risk of chromosome 9p21 for myocardial infarction in an Asian population community cohort.Sci Rep. 2019 Dec 5;9(1):18405. doi: 10.1038/s41598-019-54938-w.
• [4] MicroRNA-222 influences migration and invasion through MIA3 in colorectal cancer.Cancer Cell Int. 2017 Aug 29;17:78. doi: 10.1186/s12935-017-0447-1. eCollection 2017.
• [5] Identification of a molecular signaling gene-gene regulatory network between GWAS susceptibility genes ADTRP and MIA3/TANGO1 for coronary artery disease.Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1640-1653. doi: 10.1016/j.bbadis.2017.03.010. Epub 2017 Mar 21.
• [6] Reduced expression of TANGO in colon and hepatocellular carcinomas.Oncol Rep. 2007 Oct;18(4):885-91.
• [7] Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance?. J Oral Pathol Med. 2005 Aug;34(7):444-6. doi: 10.1111/j.1600-0714.2005.00318.x.
• [8] Association study of MIA3 rs17465637 polymorphism with cardiovascular disease in rheumatoid arthritis patients.DNA Cell Biol. 2012 Aug;31(8):1412-7. doi: 10.1089/dna.2012.1672. Epub 2012 May 11.
• [9] Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration.Sci Rep. 2016 Jul 4;6:29046. doi: 10.1038/srep29046.
• [10] Effect of Coronary Artery Disease risk SNPs on serum cytokine levels and cytokine imbalance in Premature Coronary Artery Disease.Cytokine. 2019 Oct;122:154060. doi: 10.1016/j.cyto.2017.05.013. Epub 2017 Jul 10.
• [11] The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer.Pathol Int. 2018 May;68(5):278-286. doi: 10.1111/pin.12672. Epub 2018 Apr 14.
• [12] A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.Nat Genet. 2015 Oct;47(10):1121-1130. doi: 10.1038/ng.3396. Epub 2015 Sep 7.
• [13] 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.
• [14] 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.
• [15] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [16] 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.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] 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.
• [19] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [20] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [21] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.