PAR4 Membrane Protein Introduction

Introduction of PAR4

PAR4, also referred to coagulation factor II receptor-like 3 (F2RL3) or thrombin receptor-like 3, is a type I receptor protein of 41 kDa that encoded by the chromosome 19p13.11. It has 385 amino acids and belongs to the protease-activated receptor (PAR) subfamily. Other members of PAR family include PAR1, 2 and 3, and among them, PAR1 and PAR3 can be activated by thrombin, PAR2 and PAR4 by several serine proteases. PAR4 is also a component of the G-protein-coupled receptor (GPCR) family.

Basic Information of PAR4
Protein Name	Proteinase-activated receptor 4
Gene Name	PAR4
Aliases	F2RL3, F2R Like Thrombin Or Trypsin Receptor 3, Coagulation Factor II (Thrombin) Receptor-Like 3, F2R Like Thrombin/Trypsin Receptor 3, Thrombin Receptor-Like 3
Organism	Homo sapiens (Human)
UniProt ID	Q96RI0
Transmembrane Times	7
Length (aa)	385
Sequence	MWGRLLLWPLVLGFSLSGGTQTPSVYDESGSTGGGDDSTPSILPAPRGYPGQVCANDSDT LELPDSSRALLLGWVPTRLVPALYGLVLVVGLPANGLALWVLATQAPRLPSTMLLMNLAA ADLLLALALPPRIAYHLRGQRWPFGEAACRLATAALYGHMYGSVLLLAAVSLDRYLALVH PLRARALRGRRLALGLCMAAWLMAAALALPLTLQRQTFRLARSDRVLCHDALPLDAQASH WQPAFTCLALLGCFLPLLAMLLCYGATLHTLAASGRRYGHALRLTAVVLASAVAFFVPSN LLLLLHYSDPSPSAWGNLYGAYVPSLALSTLNSCVDPFIYYYVSAEFRDKVRAGLFQRSP GDTVASKASAEGGSRGMGTHSSLLQ

Function of PAR4 Membrane Protein

This protein is identified as a low-affinity thrombin receptor and plays pathophysiological a role in inflammation, blood coagulation, and response to pain. In humans, PAR4 has been discovered highly expressed in lots of tissues, such as the lung, testis, pancreas, thyroid, and small intestine. There is reported that hypomethylation at this gene may be correlated with lung cancer in patients.

Fig.1 Protein structure of PAR4.

Application of PAR4 Membrane Protein in Literature

Morikawa Y., et al. Protease-activated receptor-4 (PAR4) variant influences on platelet reactivity induced by PAR4-activating peptide through altered Ca²⁺ mobilization and ERK phosphorylation in healthy Japanese subjects. Thromb Res. 2018, 162: 44-52. PubMed ID: 29289806

The data of this report demonstrated that PAR4-AP-induced platelet reactivity among PAR4 rs773902 is correlated with the changed intensity of Ca²⁺ mobilization and ERK (Extracellular-signal-regulated kinase) activation.
Rwibasira R. G., et al. Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy. Int J Mol Sci. 2018, 19(2). PubMed ID: 29443899

This review summarized the PAR4 characteristics, including structure, activation mechanism, and role in the pathophysiology of diseases, as well as the connection of PAR4 targeting for improved cardiac protection. In all, this paper highlights the importance of PAR4 antagonists and its promising application in different cardiovascular diseases (CVDs).
French S. L., et al. Perinatal lethality of Par4^-/- mice delivered by primiparous dams reveals spontaneous bleeding in mice without platelet thrombin receptor function. Platelets. 2018, 29(2): 196-198. PubMed ID: 28960148

The study provided the first testification of spontaneous bleeding in Par4^-/- mice, suggested that a dam's first litter offers more hemostatic challenge than followed litters, and revealed a vital role for platelets-and more particularly thrombin-induced platelet activation in hemostasis during these traumatic births.
Wang W., et al. Endogenous H2S sensitizes the PAR4-induced bladder pain. Am J Physiol Renal Physiol. 2018, 314(6): F1077-F1086. PubMed ID: 29357418

This article uncovered that the endogenous H2S produced by cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) caused about hyperalgesia mediated via MIF in mice with PAR4-induced bladder pain, without resulting in bladder injury and altering micturition behavior.
Lu D., et al. miR-17-3P regulates the proliferation and survival of colon cancer cells by targeting Par4. Mol Med Rep. 2018, 17(1): 618-623. PubMed ID: 29115593

The authors of this paper presented a study demonstrating that miR-17-3P is significant in colorectal cancer (CRC) cell survival through targeting Par4, which indicates a novel finding regarding CRC progressions in humans.

PAR4 Preparation Options

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