F2RL2

Coagulation factor II (thrombin) receptor-like 2

Identifiers

F2RL2 ; PAR-3; PAR3

External IDs

OMIM: 601919 MGI: 1298208 HomoloGene: 36151 IUPHAR: 349 ChEMBL: 5477 GeneCards: F2RL2 Gene

Gene ontology
Molecular function	• phosphatidylinositol phospholipase C activity • protein binding • thrombin receptor activity
Cellular component	• extracellular region • plasma membrane • integral component of plasma membrane • apical plasma membrane
Biological process	• blood coagulation • response to wounding • platelet activation • 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 5:
76.62 – 76.62 Mb

Chr 13:
95.7 – 95.7 Mb

PubMed search

Protease activated receptor 3 (PAR-3) also known as coagulation factor II receptor-like 2 (F2RL2) and thrombin receptor-like 2, is a protein that in humans is encoded by the F2RL2 gene.

Function

Coagulation factor II (thrombin) receptor-like 2 (F2RL2) is a member of the large family of 7-transmembrane receptors that couple to G proteins. F2RL2 is also a member of the protease-activated receptor family and activated by thrombin. F2RL2 is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. F2RL2 is a cofactor for F2RL3 activation by thrombin. It mediates thrombin-triggered phosphoinositide hydrolysis and is expressed in a variety of tissues.^[1]

References

↑ "Entrez Gene: F2RL2 coagulation factor II (thrombin) receptor-like 2".

Hollenberg MD, Compton SJ (2002). "International Union of Pharmacology. XXVIII. Proteinase-activated receptors.". Pharmacol. Rev. 54 (2): 203–17. doi:10.1124/pr.54.2.203. PMID 12037136.
Ishihara H, Connolly AJ, Zeng D; et al. (1997). "Protease-activated receptor 3 is a second thrombin receptor in humans.". Nature 386 (6624): 502–6. doi:10.1038/386502a0. PMID 9087410.
Schmidt VA, Nierman WC, Maglott DR; et al. (1998). "The human proteinase-activated receptor-3 (PAR-3) gene. Identification within a Par gene cluster and characterization in vascular endothelial cells and platelets.". J. Biol. Chem. 273 (24): 15061–8. doi:10.1074/jbc.273.24.15061. PMID 9614115.
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.
Guyonnet Dupérat V, Jacquelin B, Boisseau P; et al. (1998). "Protease-activated receptor genes are clustered on 5q13". Blood 92 (1): 25–31. PMID 9639495.
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.
Hauck RW, Schulz C, Schömig A; et al. (1999). "alpha-Thrombin stimulates contraction of human bronchial rings by activation of protease-activated receptors". Am. J. Physiol. 277 (1 Pt 1): L22–9. PMID 10409227.
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.
O'Brien PJ, Prevost N, Molino M; et al. (2000). "Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1". J. Biol. Chem. 275 (18): 13502–9. doi:10.1074/jbc.275.18.13502. PMID 10788464.
Cumashi A, Ansuini H, Celli N; et al. (2001). "Neutrophil proteases can inactivate human PAR3 and abolish the co-receptor function of PAR3 on murine platelets". Thromb. Haemost. 85 (3): 533–8. PMID 11307827.
Sambrano GR, Weiss EJ, Zheng YW; et al. (2001). "Role of thrombin signalling in platelets in haemostasis and thrombosis". Nature 413 (6851): 74–8. doi:10.1038/35092573. PMID 11544528.
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.
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.
Even-Ram SC, Grisaru-Granovsky S, Pruss D; et al. (2003). "The pattern of expression of protease-activated receptors (PARs) during early trophoblast development". J. Pathol. 200 (1): 47–52. doi:10.1002/path.1338. PMID 12692840.
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.
Tanaka N, Morita T, Nezu A; et al. (2003). "Thrombin-induced Ca2+ mobilization in human gingival fibroblasts is mediated by protease-activated receptor-1 (PAR-1)". Life Sci. 73 (3): 301–10. doi:10.1016/S0024-3205(03)00269-8. PMID 12757837.

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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F2RL2

Function

See also

References

Further reading