F2RL3

Coagulation factor II (thrombin) receptor-like 3

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2ZPK, 3QDZ

Identifiers

Symbols

F2RL3 ; PAR4

External IDs

OMIM: 602779 MGI: 1298207 HomoloGene: 36148 IUPHAR: 350 ChEMBL: 4691 GeneCards: F2RL3 Gene

Gene ontology
Molecular function	• thrombin receptor activity
Cellular component	• extracellular region • plasma membrane • integral component of plasma membrane
Biological process	• signal transduction • phospholipase C-activating G-protein coupled receptor signaling pathway • blood coagulation • response to wounding • platelet activation • positive regulation of release of sequestered calcium ion into cytosol • platelet dense granule organization • thrombin receptor signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
16.89 – 16.89 Mb

Chr 8:
72.76 – 72.76 Mb

PubMed search

Protease-activated receptor 4 (PAR-4), also known as coagulation factor II (thrombin) receptor-like 3, is a protein that in humans is encoded by the F2RL3 gene.^[1]

Function

Coagulation factor II (thrombin) receptor-like 3 (F2RL3) is a member of the large family of 7-transmembrane-region receptors that couple to guanosine-nucleotide-binding proteins. F2RL3 is also a member of the protease-activated receptor family. F2RL3 is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. F2RL3 is activated by thrombin and trypsin.^[1]

References

1 2 "Entrez Gene: F2RL3 coagulation factor II (thrombin) receptor-like 3".

Leger AJ, Covic L, Kuliopulos A (2006). "Protease-activated receptors in cardiovascular diseases.". Circulation 114 (10): 1070–7. doi:10.1161/CIRCULATIONAHA.105.574830. PMID 16952995.
Xu WF, Andersen H, Whitmore TE; et al. (1998). "Cloning and characterization of human protease-activated receptor 4.". Proc. Natl. Acad. Sci. U.S.A. 95 (12): 6642–6. doi:10.1073/pnas.95.12.6642. PMC 22580. PMID 9618465.
Kahn ML, Zheng YW, Huang W; et al. (1998). "A dual thrombin receptor system for platelet activation.". Nature 394 (6694): 690–4. doi:10.1038/29325. PMID 9716134.
Kahn ML, Hammes SR, Botka C, Coughlin SR (1998). "Gene and locus structure and chromosomal localization of the protease-activated receptor gene family.". J. Biol. Chem. 273 (36): 23290–6. doi:10.1074/jbc.273.36.23290. PMID 9722561.
Kahn ML, Nakanishi-Matsui M, Shapiro MJ; et al. (1999). "Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin.". J. Clin. Invest. 103 (6): 879–87. doi:10.1172/JCI6042. PMC 408153. PMID 10079109.
Andersen H, Greenberg DL, Fujikawa K; et al. (1999). "Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity.". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11189–93. doi:10.1073/pnas.96.20.11189. PMC 18009. PMID 10500152.
Sambrano GR, Huang W, Faruqi T; et al. (2000). "Cathepsin G activates protease-activated receptor-4 in human platelets.". J. Biol. Chem. 275 (10): 6819–23. doi:10.1074/jbc.275.10.6819. PMID 10702240.
Nakanishi-Matsui M, Zheng YW, Sulciner DJ; et al. (2000). "PAR3 is a cofactor for PAR4 activation by thrombin.". Nature 404 (6778): 609–13. doi:10.1038/35007085. PMID 10766244.
Miike S, McWilliam AS, Kita H (2002). "Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2.". J. Immunol. 167 (11): 6615–22. doi:10.4049/jimmunol.167.11.6615. PMID 11714832.
Asokananthan N, Graham PT, Fink J; et al. (2002). "Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells.". J. Immunol. 168 (7): 3577–85. doi:10.4049/jimmunol.168.7.3577. PMID 11907122.
Henriksen RA, Hanks VK (2002). "PAR-4 agonist AYPGKF stimulates thromboxane production by human platelets.". Arterioscler. Thromb. Vasc. Biol. 22 (5): 861–6. doi:10.1161/01.ATV.0000014742.56572.25. PMID 12006403.
Covic L, Singh C, Smith H, Kuliopulos A (2003). "Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak syndrome.". Thromb. Haemost. 87 (4): 722–7. PMID 12008957.
Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Owen WG (2003). "PAR-3 is a low-affinity substrate, high affinity effector of thrombin.". Biochem. Biophys. Res. Commun. 305 (1): 166–8. doi:10.1016/S0006-291X(03)00732-0. PMID 12732212.
Adam F, Verbeuren TJ, Fauchère JL; et al. (2003). "Thrombin-induced platelet PAR4 activation: role of glycoprotein Ib and ADP.". J. Thromb. Haemost. 1 (4): 798–804. doi:10.1046/j.1538-7836.2003.00138.x. PMID 12871418.
Wu CC, Hwang TL, Liao CH; et al. (2004). "The role of PAR4 in thrombin-induced thromboxane production in human platelets.". Thromb. Haemost. 90 (2): 299–308. doi:10.1267/THRO03020299. PMID 12888878.
Kawai T, Akira S, Reed JC (2003). "ZIP kinase triggers apoptosis from nuclear PML oncogenic domains.". Mol. Cell. Biol. 23 (17): 6174–86. doi:10.1128/MCB.23.17.6174-6186.2003. PMC 180930. PMID 12917339.
Jacques SL, Kuliopulos A (2004). "Protease-activated receptor-4 uses dual prolines and an anionic retention motif for thrombin recognition and cleavage.". Biochem. J. 376 (Pt 3): 733–40. doi:10.1042/BJ20030954. PMC 1223816. PMID 13678420.
Han Y, Nurden A, Combrié R, Pasquet JM (2004). "Redistribution of glycoprotein Ib within platelets in response to protease-activated receptors 1 and 4: roles of cytoskeleton and calcium.". J. Thromb. Haemost. 1 (10): 2206–15. doi:10.1046/j.1538-7836.2003.00436.x. PMID 14521606.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

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F2RL3

Function

See also

References

Further reading