Table 1

Proteinase-activated receptors

IUPHAR recommended namePAR1 PAR2 PAR3 PAR4
IUPHAR receptor code2.1:PAR:1:PAR1:HUMAN:002.1:PAR:2:PAR2:HUMAN:002.1:PAR:3:PAR:3:HUMAN:002.1:PAR:4:PAR:4:HUMAN:00
Alternate designatorsThrombin receptorTrypsin receptorThrombin receptorThrombin receptor
Receptor variantsF240S mutation (h)
Amino acid composition425 aa (h)1-a 397 aa (h)374 aa (h)385 aa (h)
Agonist proteinases
Thrombin > trypsin
Thrombin ≅ trypsin
Cathepsin G; factors VIIa/X
Trypsin, tryptase, trypsin 2, matriptase/MT-serine protease 1
Factor Xa/TF/VIIa, Der p3, Der p9
Thrombin ≫ trypsin > factor
Proteases cleavage but receptor does not generate a calcium signal
Thrombin ≅ Trypsin Cathepsin G; factors VIIa/X
Inactivating proteinasesCathepsin G, proteinase 3, elastase, plasmin, chymaseUnknownUnknownUnknown
Tethered ligand sequencesSFLLR (h), SFFLR (m,r)SLIGKV (h), SLIGRL (m,r)TFRGAP (h), SFNGGP (m)GYPGQV (h), GYPGKF (m)
Subtype selective peptide agonistsTFRIFD1-b SLIGKV-NH2, SLIGRL-NH2 GYPGKF-NH2 1-c
Antagonists Trans-cinnamoyl-parafluoro-Phe-paraguanidino-Phe-Leu-Arg-Arg-NH2 1-d
Mercaptopropionyl-Phe-Cha-Arg-Lys-Pro-Lys-Pro-Asn-Asp-Lys-NH2 1-f TRANS-cinnamoyl-YPGKF-NH2 1-e
Non-peptide antagonists: RWJ56110 and RWJ58259
Signal transduction mechanismsGq/11 (increased IP3/DAG); Gi; G12/13 1-g None known— g
Gene/chromosomeF2R/5q13 (h)F2RL1/5q13 (h)F2RL2/5q13 (h)F2RL3/19p12 (h)
F2R/13D2 (m)F2RL1/13D2 (m)F2RL2/13D2 (m)F2RL3/8B3.3 (m)
NCBI accession no. M62424 (h) U34038 (h) U92971(h) AF080214, AF055917 (h)
L03529 (m) Z48043(m) U92972 (m) AF080215 (m)
M81642 (r) U61373(r)
  • 1-a  The IUPHAR receptor code is provided for each human (h) PAR, but not for murine (m), or rat (r) PARs.

  • 1-b  TFRIFD is the Xenopusthrombin receptor tethered ligand domain (the human PAR1tethered ligand domain sequence, SFLLRN, activates both PAR1 and PAR2 receptors).

  • 1-c  AYPGKF is 10 times more potent than the natural human (GYPGQV) or murine (GYPGKF) tethered ligand sequences, which are also PAR4 selective.

  • 1-d  May also act at PAR2 as agonist; also designated BMS 200261.

  • 1-e  Validated only in rat platelets.

  • 1-f  Antagonizes PAR1; acts as an agonist at PAR2.

  • 1-g  Stimulates phosphositide turnover through an uncharacterized G protein, probably Gq/11; Gi interactions with PAR2 not evaluated; PAR4 believed not to interact with Gi.