PAR3 Membrane Protein Introduction

Introduction of PAR3

PAR3, also known as coagulation factor II receptor-like 2 (F2RL2) or thrombin receptor-like 2, is a protein of 374 amino acids and has approximately 42.5 kDa molecular mass. In humans, it is encoded by the gene F2RL2 located at the chromosome 5q13.3. PAR3 belongs to the protease-activated receptor (PAR) family, a subfamily of seven transmembrane G protein-coupled receptor, and is activated by thrombin.

Basic Information of PAR3
Protein Name	Proteinase-activated receptor 3
Gene Name	PAR3
Aliases	Baz, ASIP, PAR3, PARD-3, PARD3A, SE2-5T2, PPP1R118, SE2-5L16, SE2-5LT1, PAR3alpha
Organism	Homo sapiens (Human)
UniProt ID	O00254
Transmembrane Times	7
Length (aa)	374
Sequence	MKALIFAAAGLLLLLPTFCQSGMENDTNNLAKPTLPIKTFRGAPPNSFEEFPFSALEGWT GATITVKIKCPEESASHLHVKNATMGYLTSSLSTKLIPAIYLLVFVVGVPANAVTLWMLF FRTRSICTTVFYTNLAIADFLFCVTLPFKIAYHLNGNNWVFGEVLCRATTVIFYGNMYCS ILLLACISINRYLAIVHPFTYRGLPKHTYALVTCGLVWATVFLYMLPFFILKQEYYLVQP DITTCHDVHNTCESSSPFQLYYFISLAFFGFLIPFVLIIYCYAAIIRTLNAYDHRWLWYV KASLLILVIFTICFAPSNIILIIHHANYYYNNTDGLYFIYLIALCLGSLNSCLDPFLYFL MSKTRNHSTAYLTK

Function of PAR3 Membrane Protein

This protein functions as a cofactor involved in the thrombin-mediated cleavage and activation of the PAR family member proteinase-activated receptor (PAR4). This receptor coupled to G proteins stimulates thrombin-triggered phosphoinositide hydrolysis and is found in many different tissues. PAR3 protein products play an important role in hemostasis and thrombosis and alternate splicing of it can lead to multiple transcript variants encoding diverse isoforms.

Fig.1 Structures of murine thrombin in complex with fragments of murine PAR3. (Bah, 2007)

Application of PAR3 Membrane Protein in Literature

Hapak S. M., et al. PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization. Cell Mol Life Sci. 2018. PubMed ID: 29696344

This article aimed to discuss the diverse signaling mechanisms and effector functions which have been linked to PAR3, PAR6, together with aPKC during the establishment of neuronal polarity.
Vorhagen S., et al. Shared and independent functions of aPKCλ and Par3 in skin tumorigenesis. Oncogene. 2018. PubMed ID: 29789715

The data from authors indicated that Par3 and aPKCλ cooperate to facilitate skin tumor initiation and progression, likely via sustaining survival, growth, and inflammatory signaling.
Renschler F. A., et al. Structural basis for the interaction between the cell polarity proteins Par3 and Par6. Sci Signal. 2018, 11(517). PubMed ID: 29440511.

This article revealed that Par3 can potentially recruit two Par6 proteins meanwhile, which may promote the assembly of polarity protein networks by the interaction of multivalent PDZ domain.
Yeo M. K., et al. Decreased Expression of the Polarity Regulatory PAR Complex Predicts Poor Prognosis of the Patients with Colorectal Adenocarcinoma. Transl Oncol. 2018, 11(1): 109-115. PubMed ID: 29220829

The results of this paper suggested that the down-expression of PKCζs is an independent poor prognostic and metastatic factor for the colorectal adenocarcinoma (CRAC).
Vanlandewijck M., et al. The protein kinase SIK downregulates the polarity protein Par3. Oncotarget. 2017, 9(5): 5716-5735. PubMed ID: 29464029

The bioinformatic and biochemical evidence provided by the researchers showed that SIK has potential to phosphorylate the polarity complex protein of Par3, a well-established regulator of tight junction assembly.

PAR3 Preparation Options

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Reference

Bah A, et al. (2007). Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4. Proc Natl Acad Sci U S A. 104(28), 11603-8.

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