Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAM7JTR)

• DOT Name: Integrin alpha-V (ITGAV)
• Synonyms: Vitronectin receptor; Vitronectin receptor subunit alpha; CD antigen CD51
• Gene Name: ITGAV
• UniProt ID: ITAV_HUMAN
• PDB ID: 1JV2 ; 1L5G ; 1M1X ; 1U8C ; 3IJE ; 4G1E ; 4G1M ; 4MMX ; 4MMY ; 4MMZ ; 4O02 ; 4UM8 ; 4UM9 ; 5FFG ; 5FFO ; 5NEM ; 5NER ; 5NET ; 5NEU ; 6AVQ ; 6AVR ; 6AVU ; 6DJP ; 6MK0 ; 6MSL ; 6MSU ; 6NAJ ; 6OM1 ; 6OM2 ; 6UJA ; 6UJB ; 6UJC ; 7Y1T ; 8TCF ; 8TCG
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF20806 ; PF00357
• Sequence:
  MAFPPRRRLRLGPRGLPLLLSGLLLPLCRAFNLDVDSPAEYSGPEGSYFGFAVDFFVPSA
  SSRMFLLVGAPKANTTQPGIVEGGQVLKCDWSSTRRCQPIEFDATGNRDYAKDDPLEFKS
  HQWFGASVRSKQDKILACAPLYHWRTEMKQEREPVGTCFLQDGTKTVEYAPCRSQDIDAD
  GQGFCQGGFSIDFTKADRVLLGGPGSFYWQGQLISDQVAEIVSKYDPNVYSIKYNNQLAT
  RTAQAIFDDSYLGYSVAVGDFNGDGIDDFVSGVPRAARTLGMVYIYDGKNMSSLYNFTGE
  QMAAYFGFSVAATDINGDDYADVFIGAPLFMDRGSDGKLQEVGQVSVSLQRASGDFQTTK
  LNGFEVFARFGSAIAPLGDLDQDGFNDIAIAAPYGGEDKKGIVYIFNGRSTGLNAVPSQI
  LEGQWAARSMPPSFGYSMKGATDIDKNGYPDLIVGAFGVDRAILYRARPVITVNAGLEVY
  PSILNQDNKTCSLPGTALKVSCFNVRFCLKADGKGVLPRKLNFQVELLLDKLKQKGAIRR
  ALFLYSRSPSHSKNMTISRGGLMQCEELIAYLRDESEFRDKLTPITIFMEYRLDYRTAAD
  TTGLQPILNQFTPANISRQAHILLDCGEDNVCKPKLEVSVDSDQKKIYIGDDNPLTLIVK
  AQNQGEGAYEAELIVSIPLQADFIGVVRNNEALARLSCAFKTENQTRQVVCDLGNPMKAG
  TQLLAGLRFSVHQQSEMDTSVKFDLQIQSSNLFDKVSPVVSHKVDLAVLAAVEIRGVSSP
  DHVFLPIPNWEHKENPETEEDVGPVVQHIYELRNNGPSSFSKAMLHLQWPYKYNNNTLLY
  ILHYDIDGPMNCTSDMEINPLRIKISSLQTTEKNDTVAGQGERDHLITKRDLALSEGDIH
  TLGCGVAQCLKIVCQVGRLDRGKSAILYVKSLLWTETFMNKENQNHSYSLKSSASFNVIE
  FPYKNLPIEDITNSTLVTTNVTWGIQPAPMPVPVWVIILAVLAGLLLLAVLVFVMYRMGF
  FKRVRPPQEEQEREQLQPHENGEGNSET
• Function: The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 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. ITGAV:ITGB3 and ITGAV:ITGB6 act as receptors for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1. Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) 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. ITGAV:ITGB3 acts as a receptor for CD40LG. ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP ; (Microbial infection) Integrin ITGAV:ITGB5 acts as a receptor for Adenovirus type C; (Microbial infection) Integrin ITGAV:ITGB5 and ITGAV:ITGB3 act as receptors for Coxsackievirus A9 and B1; (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8; (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for herpes simplex 1/HHV-1; (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Human parechovirus 1; (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus; (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
• KEGG Pathway:
  Phagosome (hsa04145)
  Efferocytosis (hsa04148)
  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)
  Thyroid hormone sig.ling pathway (hsa04919)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Small cell lung cancer (hsa05222)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Elastic fibre formation (R-HSA-1566948)
  PECAM1 interactions (R-HSA-210990)
  Molecules associated with elastic fibres (R-HSA-2129379)
  Integrin cell surface interactions (R-HSA-216083)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  Laminin interactions (R-HSA-3000157)
  Syndecan interactions (R-HSA-3000170)
  ECM proteoglycans (R-HSA-3000178)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  Signal transduction by L1 (R-HSA-445144)
  Neutrophil degranulation (R-HSA-6798695)
  Cross-presentation of particulate exogenous antigens (phagosomes) (R-HSA-1236973)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Integrin alpha-V (ITGAV) affects the response to substance of Fluorouracil.	[30]
Urokinase	DM0GOUD	Approved	Integrin alpha-V (ITGAV) increases the Chromosomal abnormalities and abnormal gene carriers ADR of Urokinase.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Integrin alpha-V (ITGAV).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Integrin alpha-V (ITGAV).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Integrin alpha-V (ITGAV).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Integrin alpha-V (ITGAV).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Integrin alpha-V (ITGAV).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Integrin alpha-V (ITGAV).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Integrin alpha-V (ITGAV).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Integrin alpha-V (ITGAV).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Integrin alpha-V (ITGAV).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Integrin alpha-V (ITGAV).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Integrin alpha-V (ITGAV).	[11]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Integrin alpha-V (ITGAV).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Integrin alpha-V (ITGAV).	[13]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Integrin alpha-V (ITGAV).	[14]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Integrin alpha-V (ITGAV).	[15]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Integrin alpha-V (ITGAV).	[16]
Epinephrine	DM3KJBC	Approved	Epinephrine increases the expression of Integrin alpha-V (ITGAV).	[17]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Integrin alpha-V (ITGAV).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Integrin alpha-V (ITGAV).	[19]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Integrin alpha-V (ITGAV).	[20]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Integrin alpha-V (ITGAV).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Integrin alpha-V (ITGAV).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Integrin alpha-V (ITGAV).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Integrin alpha-V (ITGAV).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Integrin alpha-V (ITGAV).	[25]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Integrin alpha-V (ITGAV).	[26]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Integrin alpha-V (ITGAV).	[27]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Integrin alpha-V (ITGAV).	[28]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Integrin alpha-V (ITGAV).	[29]

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