Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP4HSHG)

• DOT Name: Integrin beta-8 (ITGB8)
• Gene Name: ITGB8
• UniProt ID: ITB8_HUMAN
• PDB ID: 6DJP; 6OM1; 6OM2; 6UJA; 6UJB; 6UJC; 7Y1T; 8TCF
• Pfam ID: PF07974 ; PF00362 ; PF17205
• Sequence:
  MCGSALAFFTAAFVCLQNDRRGPASFLWAAWVFSLVLGLGQGEDNRCASSNAASCARCLA
  LGPECGWCVQEDFISGGSRSERCDIVSNLISKGCSVDSIEYPSVHVIIPTENEINTQVTP
  GEVSIQLRPGAEANFMLKVHPLKKYPVDLYYLVDVSASMHNNIEKLNSVGNDLSRKMAFF
  SRDFRLGFGSYVDKTVSPYISIHPERIHNQCSDYNLDCMPPHGYIHVLSLTENITEFEKA
  VHRQKISGNIDTPEGGFDAMLQAAVCESHIGWRKEAKRLLLVMTDQTSHLALDSKLAGIV
  VPNDGNCHLKNNVYVKSTTMEHPSLGQLSEKLIDNNINVIFAVQGKQFHWYKDLLPLLPG
  TIAGEIESKAANLNNLVVEAYQKLISEVKVQVENQVQGIYFNITAICPDGSRKPGMEGCR
  NVTSNDEVLFNVTVTMKKCDVTGGKNYAIIKPIGFNETAKIHIHRNCSCQCEDNRGPKGK
  CVDETFLDSKCFQCDENKCHFDEDQFSSESCKSHKDQPVCSGRGVCVCGKCSCHKIKLGK
  VYGKYCEKDDFSCPYHHGNLCAGHGECEAGRCQCFSGWEGDRCQCPSAAAQHCVNSKGQV
  CSGRGTCVCGRCECTDPRSIGRFCEHCPTCYTACKENWNCMQCLHPHNLSQAILDQCKTS
  CALMEQQHYVDQTSECFSSPSYLRIFFIIFIVTFLIGLLKVLIIRQVILQWNSNKIKSSS
  DYRVSASKKDKLILQSVCTRAVTYRREKPEEIKMDISKLNAHETFRCNF
• Function: Integrin alpha-V:beta-8 (ITGAV:ITGB8) is a receptor for fibronectin. It recognizes the sequence R-G-D in its ligands. Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation on the surface of activated regulatory T-cells (Tregs) (Probable). Required during vasculogenesis.
• Tissue Specificity: Placenta, kidney, brain, ovary, uterus and in several transformed cells. Transiently expressed in 293 human embryonic kidney cells.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Cell adhesion molecules (hsa04514)
  Regulation of actin cytoskeleton (hsa04810)
  Cytoskeleton in muscle cells (hsa04820)
  Human papillomavirus infection (hsa05165)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Integrin cell surface interactions (R-HSA-216083)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  Molecules associated with elastic fibres (R-HSA-2129379)

Molecular Interaction Atlas (MIA) of This DOT

20 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 Integrin beta-8 (ITGB8).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integrin beta-8 (ITGB8).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Integrin beta-8 (ITGB8).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Integrin beta-8 (ITGB8).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Integrin beta-8 (ITGB8).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Integrin beta-8 (ITGB8).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Integrin beta-8 (ITGB8).	[7]
Progesterone	DMUY35B	Approved	Progesterone affects the expression of Integrin beta-8 (ITGB8).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Integrin beta-8 (ITGB8).	[9]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Integrin beta-8 (ITGB8).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Integrin beta-8 (ITGB8).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Integrin beta-8 (ITGB8).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Integrin beta-8 (ITGB8).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Integrin beta-8 (ITGB8).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Integrin beta-8 (ITGB8).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Integrin beta-8 (ITGB8).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Integrin beta-8 (ITGB8).	[16]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Integrin beta-8 (ITGB8).	[17]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Integrin beta-8 (ITGB8).	[18]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol decreases the expression of Integrin beta-8 (ITGB8).	[19]

References

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• [2] 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.
• [3] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [4] 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.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [7] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [8] Perfluorooctanoic acid alters progesterone activity in human endometrial cells and induces reproductive alterations in young women. Chemosphere. 2020 Mar;242:125208. doi: 10.1016/j.chemosphere.2019.125208. Epub 2019 Oct 24.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] 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.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [18] Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.
• [19] Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo. J Gastrointest Surg. 2012 Jun;16(6):1136-43. doi: 10.1007/s11605-012-1869-7. Epub 2012 Mar 27.