Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBCH21D)

• DOT Name: Integrin alpha-3 (ITGA3)
• Synonyms: CD49 antigen-like family member C; FRP-2; Galactoprotein B3; GAPB3; VLA-3 subunit alpha; CD antigen CD49c
• Gene Name: ITGA3
• Related Disease:
  Narcolepsy
  Pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome
  Adenocarcinoma
  Bladder cancer
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Craniosynostosis
  Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive
  Esophageal adenocarcinoma
  Focal segmental glomerulosclerosis
  Gastric cancer
  Glioblastoma multiforme
  Glomerulonephritis
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Intrahepatic cholangiocarcinoma
  Malignant glioma
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Nephrotic syndrome
  Prostate cancer
  Prostate carcinoma
  Skin disease
  Squamous cell carcinoma
  Stomach cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Thyroid tumor
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bone osteosarcoma
  Colorectal carcinoma
  Glioma
  Meningioma
  Osteosarcoma
  Pulmonary disease
  Advanced cancer
  Epidermolysis bullosa
  Familial nephrotic syndrome
  Myocardial infarction
  Nasopharyngeal carcinoma
  Neoplasm
  Neuroblastoma
  Pancreatic cancer
• UniProt ID: ITA3_HUMAN
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF20806
• Sequence:
  MGPGPSRAPRAPRLMLCALALMVAAGGCVVSAFNLDTRFLVVKEAGNPGSLFGYSVALHR
  QTERQQRYLLLAGAPRELAVPDGYTNRTGAVYLCPLTAHKDDCERMNITVKNDPGHHIIE
  DMWLGVTVASQGPAGRVLVCAHRYTQVLWSGSEDQRRMVGKCYVRGNDLELDSSDDWQTY
  HNEMCNSNTDYLETGMCQLGTSGGFTQNTVYFGAPGAYNWKGNSYMIQRKEWDLSEYSYK
  DPEDQGNLYIGYTMQVGSFILHPKNITIVTGAPRHRHMGAVFLLSQEAGGDLRRRQVLEG
  SQVGAYFGSAIALADLNNDGWQDLLVGAPYYFERKEEVGGAIYVFMNQAGTSFPAHPSLL
  LHGPSGSAFGLSVASIGDINQDGFQDIAVGAPFEGLGKVYIYHSSSKGLLRQPQQVIHGE
  KLGLPGLATFGYSLSGQMDVDENFYPDLLVGSLSDHIVLLRARPVINIVHKTLVPRPAVL
  DPALCTATSCVQVELCFAYNQSAGNPNYRRNITLAYTLEADRDRRPPRLRFAGSESAVFH
  GFFSMPEMRCQKLELLLMDNLRDKLRPIIISMNYSLPLRMPDRPRLGLRSLDAYPILNQA
  QALENHTEVQFQKECGPDNKCESNLQMRAAFVSEQQQKLSRLQYSRDVRKLLLSINVTNT
  RTSERSGEDAHEALLTLVVPPALLLSSVRPPGACQANETIFCELGNPFKRNQRMELLIAF
  EVIGVTLHTRDLQVQLQLSTSSHQDNLWPMILTLLVDYTLQTSLSMVNHRLQSFFGGTVM
  GESGMKTVEDVGSPLKYEFQVGPMGEGLVGLGTLVLGLEWPYEVSNGKWLLYPTEITVHG
  NGSWPCRPPGDLINPLNLTLSDPGDRPSSPQRRRRQLDPGGGQGPPPVTLAAAKKAKSET
  VLTCATGRAHCVWLECPIPDAPVVTNVTVKARVWNSTFIEDYRDFDRVRVNGWATLFLRT
  SIPTINMENKTTWFSVDIDSELVEELPAEIELWLVLVAVGAGLLLLGLIILLLWKCGFFK
  RARTRALYEAKRQKAEMKSQPSETERLTDDY
• Function: Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration; (Microbial infection) Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression.
• Tissue Specificity: Isoform 1 is widely expressed. Isoform 2 is expressed in brain and heart. In brain, both isoforms are exclusively expressed on vascular smooth muscle cells, whereas in heart isoform 1 is strongly expressed on vascular smooth muscle cells, isoform 2 is detected only on endothelial vein cells.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Hematopoietic cell lineage (hsa04640)
  Regulation of actin cytoskeleton (hsa04810)
  Cytoskeleton in muscle cells (hsa04820)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Integrin cell surface interactions (R-HSA-216083)
  Laminin interactions (R-HSA-3000157)
  MET activates PTK2 signaling (R-HSA-8874081)
  Basigin interactions (R-HSA-210991)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[1]
Pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome	DIS3CFDL	Definitive	Autosomal recessive	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[6]
Craniosynostosis	DIS6J405	Strong	Altered Expression	[7]
Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive	DISZRA6Y	Strong	Biomarker	[8]
Esophageal adenocarcinoma	DISODWFP	Strong	Altered Expression	[9]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Altered Expression	[10]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[12]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[13]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[14]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[16]
Malignant glioma	DISFXKOV	Strong	Biomarker	[17]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[19]
Nephrotic syndrome	DISSPSC2	Strong	Genetic Variation	[20]
Prostate cancer	DISF190Y	Strong	Altered Expression	[21]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[21]
Skin disease	DISDW8R6	Strong	Genetic Variation	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[23]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[24]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[24]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[24]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[24]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[25]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	moderate	Genetic Variation	[26]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[27]
Glioma	DIS5RPEH	moderate	Biomarker	[17]
Meningioma	DISPT4TG	moderate	Biomarker	[28]
Osteosarcoma	DISLQ7E2	moderate	Genetic Variation	[26]
Pulmonary disease	DIS6060I	Disputed	Genetic Variation	[29]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[30]
Epidermolysis bullosa	DISVOTZQ	Limited	Biomarker	[31]
Familial nephrotic syndrome	DISADF8G	Limited	Genetic Variation	[20]
Myocardial infarction	DIS655KI	Limited	Biomarker	[32]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[33]
Neoplasm	DISZKGEW	Limited	Biomarker	[34]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[35]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[34]

29 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 alpha-3 (ITGA3).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Integrin alpha-3 (ITGA3).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Integrin alpha-3 (ITGA3).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integrin alpha-3 (ITGA3).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Integrin alpha-3 (ITGA3).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Integrin alpha-3 (ITGA3).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Integrin alpha-3 (ITGA3).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Integrin alpha-3 (ITGA3).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Integrin alpha-3 (ITGA3).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Integrin alpha-3 (ITGA3).	[45]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Integrin alpha-3 (ITGA3).	[45]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Integrin alpha-3 (ITGA3).	[46]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Integrin alpha-3 (ITGA3).	[47]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Integrin alpha-3 (ITGA3).	[48]
Selenium	DM25CGV	Approved	Selenium increases the expression of Integrin alpha-3 (ITGA3).	[49]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Integrin alpha-3 (ITGA3).	[50]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Integrin alpha-3 (ITGA3).	[51]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Integrin alpha-3 (ITGA3).	[52]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Integrin alpha-3 (ITGA3).	[53]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Integrin alpha-3 (ITGA3).	[54]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Integrin alpha-3 (ITGA3).	[55]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Integrin alpha-3 (ITGA3).	[56]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Integrin alpha-3 (ITGA3).	[57]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Integrin alpha-3 (ITGA3).	[49]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Integrin alpha-3 (ITGA3).	[58]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Integrin alpha-3 (ITGA3).	[60]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Integrin alpha-3 (ITGA3).	[61]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Integrin alpha-3 (ITGA3).	[62]
Manganese	DMKT129	Investigative	Manganese increases the expression of Integrin alpha-3 (ITGA3).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Integrin alpha-3 (ITGA3).	[59]

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