Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT28UK84)

• DOT Name: Integrin beta-4 (ITGB4)
• Synonyms: GP150; CD antigen CD104
• Gene Name: ITGB4
• Related Disease:
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Glioblastoma multiforme
  Junctional epidermolysis bullosa with pyloric atresia
  Neoplasm
  Arteriosclerosis
  Atherosclerosis
  Breast neoplasm
  Cardiovascular disease
  Epidermolysis bullosa
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Junctional epidermolysis bullosa
  Junctional epidermolysis bullosa Herlitz type
  Junctional epidermolysis bullosa, non-Herlitz type
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate neoplasm
  Schizophrenia
  Squamous cell carcinoma
  Stomach cancer
  Carcinoma
  Clouston syndrome
  Colon cancer
  Colon carcinoma
  Ectodermal dysplasia
  Triple negative breast cancer
  Aplasia cutis congenita
  Epidermolysis bullosa simplex 5C, with pyloric atresia
  Generalized junctional epidermolysis bullosa non-Herlitz type
  Localized junctional epidermolysis bullosa, non-Herlitz type
  Asthma
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Epidermolysis bullosa simplex 1C, localized
  Pancreatic cancer
• UniProt ID: ITB4_HUMAN
• PDB ID: 1QG3; 2YRZ; 3F7P; 3F7Q; 3F7R; 3FQ4; 3FSO; 3H6A; 4Q58; 4WTW; 4WTX; 6GVK; 6GVL
• Pfam ID: PF03160 ; PF07974 ; PF00041 ; PF18372 ; PF07965 ; PF00362 ; PF17205
• Sequence:
  MAGPRPSPWARLLLAALISVSLSGTLANRCKKAPVKSCTECVRVDKDCAYCTDEMFRDRR
  CNTQAELLAAGCQRESIVVMESSFQITEETQIDTTLRRSQMSPQGLRVRLRPGEERHFEL
  EVFEPLESPVDLYILMDFSNSMSDDLDNLKKMGQNLARVLSQLTSDYTIGFGKFVDKVSV
  PQTDMRPEKLKEPWPNSDPPFSFKNVISLTEDVDEFRNKLQGERISGNLDAPEGGFDAIL
  QTAVCTRDIGWRPDSTHLLVFSTESAFHYEADGANVLAGIMSRNDERCHLDTTGTYTQYR
  TQDYPSVPTLVRLLAKHNIIPIFAVTNYSYSYYEKLHTYFPVSSLGVLQEDSSNIVELLE
  EAFNRIRSNLDIRALDSPRGLRTEVTSKMFQKTRTGSFHIRRGEVGIYQVQLRALEHVDG
  THVCQLPEDQKGNIHLKPSFSDGLKMDAGIICDVCTCELQKEVRSARCSFNGDFVCGQCV
  CSEGWSGQTCNCSTGSLSDIQPCLREGEDKPCSGRGECQCGHCVCYGEGRYEGQFCEYDN
  FQCPRTSGFLCNDRGRCSMGQCVCEPGWTGPSCDCPLSNATCIDSNGGICNGRGHCECGR
  CHCHQQSLYTDTICEINYSAIHPGLCEDLRSCVQCQAWGTGEKKGRTCEECNFKVKMVDE
  LKRAEEVVVRCSFRDEDDDCTYSYTMEGDGAPGPNSTVLVHKKKDCPPGSFWWLIPLLLL
  LLPLLALLLLLCWKYCACCKACLALLPCCNRGHMVGFKEDHYMLRENLMASDHLDTPMLR
  SGNLKGRDVVRWKVTNNMQRPGFATHAASINPTELVPYGLSLRLARLCTENLLKPDTREC
  AQLRQEVEENLNEVYRQISGVHKLQQTKFRQQPNAGKKQDHTIVDTVLMAPRSAKPALLK
  LTEKQVEQRAFHDLKVAPGYYTLTADQDARGMVEFQEGVELVDVRVPLFIRPEDDDEKQL
  LVEAIDVPAGTATLGRRLVNITIIKEQARDVVSFEQPEFSVSRGDQVARIPVIRRVLDGG
  KSQVSYRTQDGTAQGNRDYIPVEGELLFQPGEAWKELQVKLLELQEVDSLLRGRQVRRFH
  VQLSNPKFGAHLGQPHSTTIIIRDPDELDRSFTSQMLSSQPPPHGDLGAPQNPNAKAAGS
  RKIHFNWLPPSGKPMGYRVKYWIQGDSESEAHLLDSKVPSVELTNLYPYCDYEMKVCAYG
  AQGEGPYSSLVSCRTHQEVPSEPGRLAFNVVSSTVTQLSWAEPAETNGEITAYEVCYGLV
  NDDNRPIGPMKKVLVDNPKNRMLLIENLRESQPYRYTVKARNGAGWGPEREAIINLATQP
  KRPMSIPIIPDIPIVDAQSGEDYDSFLMYSDDVLRSPSGSQRPSVSDDTGCGWKFEPLLG
  EELDLRRVTWRLPPELIPRLSASSGRSSDAEAPHGPPDDGGAGGKGGSLPRSATPGPPGE
  HLVNGRMDFAFPGSTNSLHRMTTTSAAAYGTHLSPHVPHRVLSTSSTLTRDYNSLTRSEH
  SHSTTLPRDYSTLTSVSSHDSRLTAGVPDTPTRLVFSALGPTSLRVSWQEPRCERPLQGY
  SVEYQLLNGGELHRLNIPNPAQTSVVVEDLLPNHSYVFRVRAQSQEGWGREREGVITIES
  QVHPQSPLCPLPGSAFTLSTPSAPGPLVFTALSPDSLQLSWERPRRPNGDIVGYLVTCEM
  AQGGGPATAFRVDGDSPESRLTVPGLSENVPYKFKVQARTTEGFGPEREGIITIESQDGG
  PFPQLGSRAGLFQHPLQSEYSSITTTHTSATEPFLVDGLTLGAQHLEAGGSLTRHVTQEF
  VSRTLTTSGTLSTHMDQQFFQT
• Function: Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling. ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling.
• Tissue Specificity: Integrin alpha-6/beta-4 is predominantly expressed by epithelia. Isoform beta-4D is also expressed in colon and placenta. Isoform beta-4E is also expressed in epidermis, lung, duodenum, heart, spleen and stomach.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  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:
  Laminin interactions (R-HSA-3000157)
  Syndecan interactions (R-HSA-3000170)
  Type I hemidesmosome assembly (R-HSA-446107)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[2]
Junctional epidermolysis bullosa with pyloric atresia	DIS5QMS0	Definitive	Autosomal recessive	[4]
Neoplasm	DISZKGEW	Definitive	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[5]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[5]
Epidermolysis bullosa	DISVOTZQ	Strong	Genetic Variation	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Junctional epidermolysis bullosa	DISJRXWU	Strong	Genetic Variation	[14]
Junctional epidermolysis bullosa Herlitz type	DIS6X2W8	Strong	Genetic Variation	[15]
Junctional epidermolysis bullosa, non-Herlitz type	DISQM23S	Strong	Autosomal recessive	[16]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Lung neoplasm	DISVARNB	Strong	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[19]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[21]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Carcinoma	DISH9F1N	moderate	Biomarker	[22]
Clouston syndrome	DISZRYX4	moderate	Biomarker	[23]
Colon cancer	DISVC52G	moderate	Altered Expression	[22]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[22]
Ectodermal dysplasia	DISLRS4M	moderate	Biomarker	[23]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[24]
Aplasia cutis congenita	DISMDAYM	Supportive	Autosomal dominant	[25]
Epidermolysis bullosa simplex 5C, with pyloric atresia	DIS15AFN	Supportive	Autosomal recessive	[26]
Generalized junctional epidermolysis bullosa non-Herlitz type	DISSD3MX	Supportive	Autosomal recessive	[27]
Localized junctional epidermolysis bullosa, non-Herlitz type	DIS1UMS1	Supportive	Autosomal recessive	[26]
Asthma	DISW9QNS	Limited	Biomarker	[28]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[29]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[29]
Colorectal carcinoma	DIS5PYL0	Limited	Posttranslational Modification	[30]
Epidermolysis bullosa simplex 1C, localized	DISQCPMC	Limited	Unknown	[7]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[31]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Integrin beta-4 (ITGB4) decreases the response to substance of Arsenic trioxide.	[56]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Integrin beta-4 (ITGB4).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Integrin beta-4 (ITGB4).	[51]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Integrin beta-4 (ITGB4).	[52]

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Integrin beta-4 (ITGB4).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integrin beta-4 (ITGB4).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Integrin beta-4 (ITGB4).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Integrin beta-4 (ITGB4).	[36]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Integrin beta-4 (ITGB4).	[37]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Integrin beta-4 (ITGB4).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Integrin beta-4 (ITGB4).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Integrin beta-4 (ITGB4).	[40]
Marinol	DM70IK5	Approved	Marinol increases the expression of Integrin beta-4 (ITGB4).	[41]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Integrin beta-4 (ITGB4).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Integrin beta-4 (ITGB4).	[34]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Integrin beta-4 (ITGB4).	[43]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Integrin beta-4 (ITGB4).	[44]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of Integrin beta-4 (ITGB4).	[45]
Epanova	DMHEAGL	Approved	Epanova increases the expression of Integrin beta-4 (ITGB4).	[46]
Ofloxacin	DM0VQN3	Approved	Ofloxacin decreases the expression of Integrin beta-4 (ITGB4).	[47]
Clarithromycin	DM4M1SG	Approved	Clarithromycin decreases the expression of Integrin beta-4 (ITGB4).	[47]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Integrin beta-4 (ITGB4).	[48]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Integrin beta-4 (ITGB4).	[49]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Integrin beta-4 (ITGB4).	[50]
Roxithromycin	DMVMIK2	Withdrawn from market	Roxithromycin decreases the expression of Integrin beta-4 (ITGB4).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Integrin beta-4 (ITGB4).	[53]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Integrin beta-4 (ITGB4).	[54]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Integrin beta-4 (ITGB4).	[55]

References

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