Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2VIZQ)

• DTT Name: ITGAV messenger RNA (ITGAV mRNA)
• Synonyms: Vitronectin receptor subunit alpha (mRNA); Vitronectin receptor alpha subunit (mRNA); Vitronectin receptor (mRNA); VTNR (mRNA); VNRA (mRNA); MSK8 (mRNA); CD51 antigen (mRNA); CD51 (mRNA)
• Gene Name: ITGAV
• DTT Type: Clinical trial target; [1]
• BioChemical Class: mRNA target
• UniProt ID: ITAV_HUMAN
• TTD ID: T87259
• 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 a receptor 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.
• KEGG Pathway:
  Phagosome (hsa04145)
  PI3K-Akt signaling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Cell adhesion molecules (hsa04514)
  Regulation of actin cytoskeleton (hsa04810)
  Thyroid hormone signaling 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 DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TV-1102	DM28M6I	Multiple sclerosis	8A40	Phase 2	[1]

References

• [1] Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.