Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3RCI67)

• DOT Name: Integrin alpha-5 (ITGA5)
• Synonyms: CD49 antigen-like family member E; Fibronectin receptor subunit alpha; Integrin alpha-F; VLA-5; CD antigen CD49e
• Gene Name: ITGA5
• UniProt ID: ITA5_HUMAN
• PDB ID: 3VI3; 3VI4; 4WJK; 4WK0; 4WK2; 4WK4; 7NWL; 7NXD
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF20806
• Sequence:
  MGSRTPESPLHAVQLRWGPRRRPPLLPLLLLLLPPPPRVGGFNLDAEAPAVLSGPPGSFF
  GFSVEFYRPGTDGVSVLVGAPKANTSQPGVLQGGAVYLCPWGASPTQCTPIEFDSKGSRL
  LESSLSSSEGEEPVEYKSLQWFGATVRAHGSSILACAPLYSWRTEKEPLSDPVGTCYLST
  DNFTRILEYAPCRSDFSWAAGQGYCQGGFSAEFTKTGRVVLGGPGSYFWQGQILSATQEQ
  IAESYYPEYLINLVQGQLQTRQASSIYDDSYLGYSVAVGEFSGDDTEDFVAGVPKGNLTY
  GYVTILNGSDIRSLYNFSGEQMASYFGYAVAATDVNGDGLDDLLVGAPLLMDRTPDGRPQ
  EVGRVYVYLQHPAGIEPTPTLTLTGHDEFGRFGSSLTPLGDLDQDGYNDVAIGAPFGGET
  QQGVVFVFPGGPGGLGSKPSQVLQPLWAASHTPDFFGSALRGGRDLDGNGYPDLIVGSFG
  VDKAVVYRGRPIVSASASLTIFPAMFNPEERSCSLEGNPVACINLSFCLNASGKHVADSI
  GFTVELQLDWQKQKGGVRRALFLASRQATLTQTLLIQNGAREDCREMKIYLRNESEFRDK
  LSPIHIALNFSLDPQAPVDSHGLRPALHYQSKSRIEDKAQILLDCGEDNICVPDLQLEVF
  GEQNHVYLGDKNALNLTFHAQNVGEGGAYEAELRVTAPPEAEYSGLVRHPGNFSSLSCDY
  FAVNQSRLLVCDLGNPMKAGASLWGGLRFTVPHLRDTKKTIQFDFQILSKNLNNSQSDVV
  SFRLSVEAQAQVTLNGVSKPEAVLFPVSDWHPRDQPQKEEDLGPAVHHVYELINQGPSSI
  SQGVLELSCPQALEGQQLLYVTRVTGLNCTTNHPINPKGLELDPEGSLHHQQKREAPSRS
  SASSGPQILKCPEAECFRLRCELGPLHQQESQSLQLHFRVWAKTFLQREHQPFSLQCEAV
  YKALKMPYRILPRQLPQKERQVATAVQWTKAEGSYGVPLWIIILAILFGLLLLGLLIYIL
  YKLGFFKRSLPYGTAMEKAQLKPPATSDA
• Function: Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. ITGA5:ITGB1 acts as a receptor for fibronectin (FN1) and mediates R-G-D-dependent cell adhesion to FN1. ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling. ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling ; (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human metapneumovirus; (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human parvovirus B19; (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
• Tissue Specificity: Expressed in placenta (at protein level).
• KEGG Pathway:
  Virion - Herpesvirus (hsa03266)
  Phagosome (hsa04145)
  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)
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)
  Pertussis (hsa05133)
  Yersinia infection (hsa05135)
  Human papillomavirus infection (hsa05165)
  Herpes simplex virus 1 infection (hsa05168)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Fibronectin matrix formation (R-HSA-1566977)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Integrin cell surface interactions (R-HSA-216083)
  Signal transduction by L1 (R-HSA-445144)
  RUNX2 regulates genes involved in cell migration (R-HSA-8941332)
  GPER1 signaling (R-HSA-9634597)
  Elastic fibre formation (R-HSA-1566948)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Integrin alpha-5 (ITGA5) affects the response to substance of Topotecan.	[30]

33 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-5 (ITGA5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Integrin alpha-5 (ITGA5).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integrin alpha-5 (ITGA5).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Integrin alpha-5 (ITGA5).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Integrin alpha-5 (ITGA5).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Integrin alpha-5 (ITGA5).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Integrin alpha-5 (ITGA5).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Integrin alpha-5 (ITGA5).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Integrin alpha-5 (ITGA5).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Integrin alpha-5 (ITGA5).	[4]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Integrin alpha-5 (ITGA5).	[11]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Integrin alpha-5 (ITGA5).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Integrin alpha-5 (ITGA5).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Integrin alpha-5 (ITGA5).	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Integrin alpha-5 (ITGA5).	[15]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Integrin alpha-5 (ITGA5).	[16]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Integrin alpha-5 (ITGA5).	[17]
Tetracycline	DMZA017	Approved	Tetracycline increases the expression of Integrin alpha-5 (ITGA5).	[18]
Diazepam	DM08E9O	Approved	Diazepam increases the expression of Integrin alpha-5 (ITGA5).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Integrin alpha-5 (ITGA5).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Integrin alpha-5 (ITGA5).	[21]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Integrin alpha-5 (ITGA5).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Integrin alpha-5 (ITGA5).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Integrin alpha-5 (ITGA5).	[24]
HSDB-41	DMR8VJA	Preclinical	HSDB-41 increases the expression of Integrin alpha-5 (ITGA5).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Integrin alpha-5 (ITGA5).	[25]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Integrin alpha-5 (ITGA5).	[26]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Integrin alpha-5 (ITGA5).	[27]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Integrin alpha-5 (ITGA5).	[9]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Integrin alpha-5 (ITGA5).	[28]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Integrin alpha-5 (ITGA5).	[23]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Integrin alpha-5 (ITGA5).	[23]
BROMODEOXYURIDINE	DM0D7LA	Investigative	BROMODEOXYURIDINE increases the expression of Integrin alpha-5 (ITGA5).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Integrin alpha-5 (ITGA5).	[6]

References

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