P2RX6 Membrane Protein Introduction

Introduction of P2RX6

P2X purinoceptor 6 (P2RX6), also known as Purinergic receptor P2X-like 1 (P2RXL1), is encoded by human P2RX6 gene, which is mapped to chromosome 22q11.21. P2RX6 is detected in several brain regions and in the spinal cord. Except for the nervous system, P2RX6 is also expressed in skeletal muscle and spleen, and some other tissues. P2RX6 shares the typical structure of P2X receptors, including 2 transmembrane domains, a segment resembling the H5 region of voltage-gated potassium channels, 3 N-glycosylation sites, and 11 conserved cysteine residues.

Basic Information of P2RX6
Protein Name	P2X purinoceptor 6
Gene Name	P2RX6
Aliases	P2X6, P2XM, Purinergic receptor P2X-like 1
Organism	Homo sapiens (Human)
UniProt ID	O15547
Transmembrane Times	2
Length (aa)	441
Sequence	MCPQLAGAGSMGSPGATTGWGLLDYKTEKYVMTRNWRVGALQRLLQFGIVVYVVGWALLAKKGYQERDLEPQFSIITKLKGVSVTQIKELGNRLWDVADFVKPPQGENVFFLVTNFLVTPAQVQGRCPEHPSVPLANCWVDEDCPEGEGGTHSHGVKTGQCVVFNGTHRTCEIWSWCPVESGVVPSRPLLAQAQNFTLFIKNTVTFSKFNFSKSNALETWDPTYFKHCRYEPQFSPYCPVFRIGDLVAKAGGTFEDLALLGGSVGIRVHWDCDLDTGDSGCWPHYSFQLQEKSYNFRTATHWWEQPGVEARTLLKLYGIRFDILVTGQAGKFGLIPTAVTLGTGAAWLGVVTFFCDLLLLYVDREAHFYWRTKYEEAKAPKATANSVWRELALASQARLAECLRRSSAPAPTATAAGSQTQTPGWPCPSSDTHLPTHSGSL

Function of P2RX6 Membrane Protein

Unlike other members of P2X purinoceptor family, the functions of P2RX6 is still unknown clearly. But as a member of ATP-gated P2X receptor cation channel family, P2RX6 also the permeation of cation and its activity is regulated by the binding of extracellular adenosine 5'-triphosphate. Regulated by p53, P2RX6 may play a significant role in the proliferation and/or differentiation of skeletal muscle cells and its altered expression may be involved in the development of some sarcomas. It is reported that P2RX6 is involved in VE-cadherin at the adherens junctions of human umbilical vein endothelial cells. Generally, P2RX6 cannot assemble into functional homomeric channels by itself, and it often co-assembles with other P2RX subtypes. It is documented that heteromeric P2RX4/P2RX6 channels can be blocked effectively by suramin and be activated by low micromolar αβ-methylene-ATP.

Fig.1 Schematic Representation of P2RX6 Structure.

Application of P2RX6 Membrane Protein in Literature

de Baaij J.H., et al. P2X6 Knockout Mice Exhibit Normal Electrolyte Homeostasis. PLoS One. 2016, 11(6): e0156803. PubMed ID: 27254077

This article suggests that purinergic signaling via P2RX6 is not apparently associated with the mediation of renal electrolyte handling under normal physiological conditions.
Díaz-Hernández J.I., et al. Age-related nuclear translocation of P2X6 subunit modifies splicing activity interacting with splicing factor 3A1. PLoS One. 2015, 10(4): e0123121. PubMed ID: 25874565

This article shows that P2RX6 subunit interacts with the splicing factor 3A1 in vivo inside the nucleus, which finally leads to a reduction of the mRNA splicing activity.
Padilla K., et al. Differential gene expression patterns and colocalization of ATP-gated P2X6/P2X4 ion channels during rat small intestine ontogeny. Gene Expr Patterns. 2016, 21(2): 81-8. PubMed ID: 27545450

This article demonstrates that P2RX6 and P2RX4 gene expression levels are decreased during the embryonic-perinatal transition, whereas both receptors increase their gene expression levels from ages P17 to P30 (suckling-weaning transition), suggesting that purinergic receptors may be involved in intestinal maturation, which is associated with age.
Chen L., et al. Differential expression of ATP-gated P2X receptors in DRG between chronic neuropathic pain and visceralgia rat models. Purinergic Signal. 2016, 12(1): 79-87. PubMed ID: 26531254

This article suggests that in addition to P2X2/3 heteromeric, other P2X subunits may also be able to generate heteromeric channel, such as P2X4/6 and/or P2X4/7 in visceral pain and P2X1/5 and/or P2X2/5 in neuropathic pain.
García-Alcocer G., et al. Distribution of the purinegic receptors P2X(4) and P2X(6) during rat gut development. Neurosci Lett. 2012, 509(2): 92-5. PubMed ID: 22230887

This article concludes that P2RX4 and P2RX6 gene are expressed in the gut from birth and that they are differentially distributed among different regions.

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