Protein Domain : P2X purinoreceptor 7, intracellular domain IPR046815

Type	Domain
Description	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 [ ]. 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 [ , ]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. 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.This entry represents the intracellular domain found at the C-terminal domain of P2X7 (also known as P2Z receptor). P2X7 receptor has different functional properties from those of P2X1-P2X6. Key properties of the current produced are little rectification or desensitisation, and strong potentiation of responses when the concentration of extracellular Ca2 and/or Mg2 are reduced. It is also found to be relatively insensitive to ATP. In certain studies, prolonged activation of expressed P2X7 receptors causes cell permeabilization, and lysis. This domain is critical for the receptor to initiate apoptosis and not undergo desensitization. It shows a globular structure and is shaped like a wedge with three β-strands forming an antiparallel β-sheet followed by eight α-helices separated by loops that form a helical bundle [ ].
Short Name	P2RX7_C