Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4EZB2)

• DTT Name: Platelet endothelial cell adhesion molecule (PECAM1)
• Synonyms: PECAM-1; PECA1; GPIIA'; EndoCAM; ECAM; CD31 antigen; CD31
• Gene Name: PECAM1
• DTT Type: Literature-reported target; [1]
• UniProt ID: PECA1_HUMAN
• TTD ID: T89056
• Sequence:
  MQPRWAQGATMWLGVLLTLLLCSSLEGQENSFTINSVDMKSLPDWTVQNGKNLTLQCFAD
  VSTTSHVKPQHQMLFYKDDVLFYNISSMKSTESYFIPEVRIYDSGTYKCTVIVNNKEKTT
  AEYQVLVEGVPSPRVTLDKKEAIQGGIVRVNCSVPEEKAPIHFTIEKLELNEKMVKLKRE
  KNSRDQNFVILEFPVEEQDRVLSFRCQARIISGIHMQTSESTKSELVTVTESFSTPKFHI
  SPTGMIMEGAQLHIKCTIQVTHLAQEFPEIIIQKDKAIVAHNRHGNKAVYSVMAMVEHSG
  NYTCKVESSRISKVSSIVVNITELFSKPELESSFTHLDQGERLNLSCSIPGAPPANFTIQ
  KEDTIVSQTQDFTKIASKSDSGTYICTAGIDKVVKKSNTVQIVVCEMLSQPRISYDAQFE
  VIKGQTIEVRCESISGTLPISYQLLKTSKVLENSTKNSNDPAVFKDNPTEDVEYQCVADN
  CHSHAKMLSEVLRVKVIAPVDEVQISILSSKVVESGEDIVLQCAVNEGSGPITYKFYREK
  EGKPFYQMTSNATQAFWTKQKASKEQEGEYYCTAFNRANHASSVPRSKILTVRVILAPWK
  KGLIAVVIIGVIIALLIIAAKCYFLRKAKAKQMPVEMSRPAVPLLNSNNEKMSDPNMEAN
  SHYGHNDDVRNHAMKPINDNKEPLNSDVQYTEVQVSSAESHKDLGKKDTETVYSEVRKAV
  PDAVESRYSRTEGSLDGT
• Function: Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes. Trans-homophilic interaction may play a role in endothelial cell-cell adhesion via cell junctions. Heterophilic interaction with CD177 plays a role in transendothelial migration of neutrophils. Homophilic ligation of PECAM1 prevents macrophage-mediated phagocytosis of neighboring viable leukocytes by transmitting a detachment signal. Promotes macrophage-mediated phagocytosis of apoptotic leukocytes by tethering them to the phagocytic cells; PECAM1-mediated detachment signal appears to be disabled in apoptotic leukocytes. Modulates bradykinin receptor BDKRB2 activation. Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in endothelial cells. Induces susceptibility to atherosclerosis. Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Leukocyte transendothelial migration (hsa04670)
  Malaria (hsa05144)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  PECAM1 interactions (R-HSA-210990)
  Integrin cell surface interactions (R-HSA-216083)
  Platelet sensitization by LDL (R-HSA-432142)
  Neutrophil degranulation (R-HSA-6798695)
  Platelet degranulation (R-HSA-114608)

References

• [1] Biomarkers of eosinophil involvement in allergic and eosinophilic diseases: review of phenotypic and serum markers including a novel assay to quantify levels of soluble Siglec-8. J Immunol Methods. 2012 Sep 28;383(1-2):39-46.