Molecule Information

General Information of the Molecule (ID: Mol01888)

• Name: Integrin subunit beta 3 (ITGB3) ,Homo sapiens
• Synonyms: ITGB3; GP3A
• Molecule Type: Protein
• Gene Name: ITGB3
• Gene ID: 3690
• Location: chr17:47,253,827-47,313,743[+]
• Sequence:
  MRARPRPRPLWATVLALGALAGVGVGGPNICTTRGVSSCQQCLAVSPMCAWCSDEALPLG
  SPRCDLKENLLKDNCAPESIEFPVSEARVLEDRPLSDKGSGDSSQVTQVSPQRIALRLRP
  DDSKNFSIQVRQVEDYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFG
  AFVDKPVSPYMYISPPEALENPCYDMKTTCLPMFGYKHVLTLTDQVTRFNEEVKKQSVSR
  NRDAPEGGFDAIMQATVCDEKIGWRNDASHLLVFTTDAKTHIALDGRLAGIVQPNDGQCH
  VGSDNHYSASTTMDYPSLGLMTEKLSQKNINLIFAVTENVVNLYQNYSELIPGTTVGVLS
  MDSSNVLQLIVDAYGKIRSKVELEVRDLPEELSLSFNATCLNNEVIPGLKSCMGLKIGDT
  VSFSIEAKVRGCPQEKEKSFTIKPVGFKDSLIVQVTFDCDCACQAQAEPNSHRCNNGNGT
  FECGVCRCGPGWLGSQCECSEEDYRPSQQDECSPREGQPVCSQRGECLCGQCVCHSSDFG
  KITGKYCECDDFSCVRYKGEMCSGHGQCSCGDCLCDSDWTGYYCNCTTRTDTCMSSNGLL
  CSGRGKCECGSCVCIQPGSYGDTCEKCPTCPDACTFKKECVECKKFDRGALHDENTCNRY
  CRDEIESVKELKDTGKDAVNCTYKNEDDCVVRFQYYEDSSGKSILYVVEEPECPKGPDIL
  VVLLSVMGAILLIGLAALLIWKLLITIHDRKEFAKFEEERARAKWDTANNPLYKEATSTF
  TNITYRGT
• Function: Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts 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 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. In brain, plays a role in synaptic transmission and plasticity. Involved in the regulation of the serotonin neurotransmission, is required to localize to specific compartments within the synapse the serotonin receptor SLC6A4 and for an appropriate reuptake of serotonin. Controls excitatory synaptic strength by regulating GRIA2-containing AMPAR endocytosis, which affects AMPAR abundance and composition. ITGAV:ITGB3 act as a receptor for CD40LG.
• Uniprot ID: ITB3_HUMAN
• Ensembl ID: ENSG00000259207
• HGNC ID: HGNC:6156

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Clopidogrel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hypo-attenuated leaflet thickening [1]

• Resistant Disease: Hypo-attenuated leaflet thickening [ICD-11: BD10.2]
• Resistant Drug: Clopidogrel
• Molecule Alteration: SNP; rs5918
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01).

References

• Ref 1: Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement .J Thromb Thrombolysis. 2018 Apr;45(3):463-465. doi: 10.1007/s11239-018-1636-z. 10.1007/s11239-018-1636-z