ATP P2X receptor-like
IPR059116
Definition
This entry represents all P2X receptors subtypes (P2X1 through P2X7), including five P2X-like proteins (P2XA-E) present in Dictyostelium discoideum and some P2X-like ion channels from green algae e.g. Ostreococcus tauri. P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis. Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional PMID:29631184. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines. Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo [[cite:PMID:10414359], [cite:PMID:12270951]]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation PMID:29631184. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies. P2X receptors in Dictyostelium discoideum are a unique group of ion channels with properties distinct from their vertebrate counterparts. The Dictyostelium genome encodes five P2X-like proteins (P2XA-E) that share sequence similarity with the vertebrate P2X receptors [[cite:PMID:19833731], [cite:PMID:23740252]]. Unlike P2X receptors in vertebrates, which are typically found on the plasma membrane, Dictyostelium P2X receptors are localised to intracellular organelles, such as tubules and bladders of the contractile vacuole, an organelle responsible for osmoregulation in the cell PMID:23740252. Four of the five proteins (P2XA, P2XB, P2XD, and P2XE) function as ATP-gated cation channels PMID:23740252. P2XC does not form a functional channel and cannot be activated by ATP. P2X receptor in green algae have been functionally identified, particularly in the species Ostreococcus tauri [[cite:PMID:19015952], [cite:PMID:18381285]]. These proteins form functional channels that are activated by ATP, but not by other nucleotides. P2X receptor from Ostreococcus tauri has a different cation permeability profile compared to mammalian P2X receptors, notably a low relative calcium permeability due to substitution of an asparagine residue for a typically conserved aspartate in the receptor's transmembrane domain PMID:18381285. The existence of P2X receptors in green algae indicates that the molecular system for ATP-gated ion channel activity evolved over 1 billion years ago, before the divergence of animals and plants.
7 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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