P2RX4

General Information

Full gene name:purinergic receptor P2X, ligand-gated ion channel, 4 Entrez Gene ID:5025 Location:12q24.32 Synonyms:P2X4, P2X4R Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP	Distance (bp)	Direction
rs7957197	186978	upstream

NCBI Summary

The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel with high calcium permeability. The main pharmacological distinction between the members of the purinoceptor family is the relative sensitivity to the antagonists suramin and PPADS. The product of this gene has the lowest sensitivity for these antagonists. Multiple alternatively spliced transcript variants, some protein-coding and some not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

OMIM

OMIM ID:`OMIM ID 600846 `_

NCBI Phenotypes

No phenotypes found linked to this gene.

Gene Ontology

• positive regulation of nitric oxide biosynthetic process
• plasma membrane
• vasodilation
• protein homodimerization activity
• regulation of sodium ion transport
• zinc ion binding
• response to stress
• sensory perception of pain
• positive regulation of calcium-mediated signaling
• cadherin binding
• terminal button
• cell junction
• response to ATP
• negative regulation of cardiac muscle hypertrophy
• positive regulation of prostaglandin secretion
• drug binding
• endothelial cell activation
• positive regulation of calcium ion transport into cytosol
• copper ion binding
• regulation of cardiac muscle contraction
• apical part of cell
• ATP binding
• membrane
• regulation of blood pressure
• integral to plasma membrane
• regulation of action potential in neuron
• membrane depolarization
• regulation of excitatory postsynaptic membrane potential
• calcium ion transport
• nitric oxide biosynthetic process
• positive regulation of calcium ion transport
• neuronal cell body
• protein homooligomerization
• perinuclear region of cytoplasm
• postsynaptic density
• response to fluid shear stress
• extracellular ATP-gated cation channel activity
• tissue homeostasis
• receptor binding
• signal transduction
• purinergic nucleotide receptor signaling pathway
• relaxation of cardiac muscle
• regulation of apoptotic process
• purinergic nucleotide receptor activity
• transport

KEGG Pathways

• Neuroactive ligand-receptor interaction
• Calcium signaling pathway

GeneRIFs

• This review discusses the need to reinterpret the assumed "go-it alone" function of the P2X7 receptor in light of convincing biochemical and electrophysiological evidence for the existence of P2X4/P2X7 heteromeric receptors. [PMID 17895406]
• We have identified a distinct subpopulation of P2X4-positive macrophages infiltrating the dystrophic fibres. These cells were absent from normal muscle and rarely present in the dystrophic muscle taken before and after the onset of degeneration. [PMID 15006691]
• P2X4 receptor-specific residues contribute to the ivermectin effects on channel deactivation [PMID 16949036]
• The Tyr315>Cys mutation (rs28360472) reduced the peak amplitude of the ATP-induced inward current. In Victorian Family Heart Study participants, 1 minor allele increased pulse pressure by 2.84 mm Hg. [PMID 22068874]
• in human parotid acinar cells, in addition to modulation of Ca(2+) release, Ca(2+) influx through P2X(4)R may constitute a further locus for the synergistic effects of Ca(2+) and PKA activation. [PMID 15262999]
• Observational study of gene-disease association. (HuGE Navigator) [PMID 19913121]
• Owing to their favorable diameters and equivalent spacing, the lateral portals split the task of ion supply threefold and minimize an ion’s diffusive path before it succumbs to transmembrane electrochemical gradients [PMID 21808018]
• This study presents a picture whereby P2X(4)R become functional in response to initial phagocytic stimuli but return to a non-functional state during sustained activation by classical macrophage activation. [PMID 19283779]
• Allosteric modulation of Ca2+ flux in ligand-gated cation channel (P2X4) by actions on lateral portals [PMID 22219189]
• Results show that P2X4 and P2X6 receptors are associated with VE-cadherin at HUVEC adherens junctions. [PMID 12088286]
• Affinity Capture-Western [PMID 12088286]
• Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [PMID 20628086]
• Main role for P2X(4) receptor in nucleotide-induced apoptosis in human mesangial cells, indicating a relevant role for purinergic signaling in regulating death rate in these cells. [PMID 17264311]
• analysis of molecular shape, architecture, and size of P2X4 receptors [PMID 18635539]
• Transcripts of five different isoforms of P2X4 receptors are expressed in human liver cells indicating that they represent an important component of the purinergic signaling complex in HCV induced liver pathogenesis. [PMID 21899776]
• Results suggest that amyloid beta(1-42)-induced synaptic dysfunction and neuronal death may involve perturbations in P2X4 purinergic receptors. [PMID 19562525]
• Studies indicate that P2X1, P2X2, and P2X4 receptors are detected in preglomerular microvessels. [PMID 21768526]
• we have identified an extracellular signaling pathway where Tbeta4 increases cell surface ATP levels via ATP synthase and have shown further that ATP-responsive P2X4 receptor is required for Tbeta4-induced cell migration [PMID 21106936]
• Increased contractility likely underlies survival benefit from P2X4 receptor overexpression. [PMID 15130891]
• P2X(4) and P2X(7) receptors are expressed by human osteoblast-like cells. P2X(7) receptor is mainly responsible for pore formation although P2X(4) receptors may also be involved. [PMID 19226284]
• Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP [PMID 20699225]
• T-cell receptor stimulation results in the translocation of P2X1 and P2X4 receptors and pannexin-1 hemichannels to the immune synapse. [PMID 20660288]
• INF-gamma selectively increases P2X4-receptor gene expression, leading to an up-regulation of purinergic signaling in vascular endothelial cells. [PMID 18678988]
• wild-type desensitization properties requires an aromatic moiety at position 374 and an amino rather than a guanidino group at position 373 [PMID 16533808]
• support a common site of ATP action at P2X receptors and suggest that non-conserved residues also play a regulatory role in agonist action [PMID 18487206]
• These data have identified the first transcription factor involved in P2X receptor expression. [PMID 19953327]
• shear stress stimulates pulmonary artery endothelial cells to release ATP, which activates Ca2+ influx via P2X4 receptors. [PMID 12714321]
• Data confirmed the presence of functional P2X1, P2X4 and P2X7 receptors in LAD2 cells and HLMCs. [PMID 19552691]

PubMed Articles

Recent articles:

• Samways DS et al. “Allosteric modulation of Ca2+ flux in ligand-gated cation channel (P2X4) by actions on lateral portals.” J Biol Chem. 2012 Mar 2;287(10):7594-602. PMID 22219189
• Stokes L et al. “A loss-of-function polymorphism in the human P2X4 receptor is associated with increased pulse pressure.” Hypertension. 2011 Dec;58(6):1086-92. PMID 22068874
• Manzoor S et al. “Identification of ionotrophic purinergic receptors in Huh-7 cells and their response towards structural proteins of HCV genotype 3a.” Virol J. 2011 Sep 8;8:431. PMID 21899776
• Guan Z et al. “Role of adenosine 5’-triphosphate in regulating renal microvascular function and in hypertension.” Hypertension. 2011 Sep;58(3):333-40. PMID 21768526
• Samways DS et al. “Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors).” Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13800-5. PMID 21808018
• Freeman KW et al. “Regenerative protein thymosin beta-4 is a novel regulator of purinergic signaling.” FASEB J. 2011 Mar;25(3):907-15. PMID 21106936
• Woehrle T et al. “Pannexin-1 hemichannel-mediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synapse.” Blood. 2010 Nov 4;116(18):3475-84. PMID 20660288
• Allsopp RC et al. “Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP: chimeras and point mutants identify intracellular amino-terminal residues involved in lipid regulation of P2X1 receptors.” J Biol Chem. 2010 Oct 22;285(43):32770-7. PMID 20699225
• Bailey SD et al. “Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.” Diabetes Care. 2010 Oct;33(10):2250-3. PMID 20628086
• Gu BJ et al. “Identification of the promoter region of the P2RX4 gene.” Mol Biol Rep. 2010 Oct;37(7):3369-76. PMID 19953327

Top Pubmed articles linked to gene P2RX4 matching any search term:

• Manzoor S et al. “Identification of ionotrophic purinergic receptors in Huh-7 cells and their response towards structural proteins of HCV genotype 3a.” Virol J. 2011 Sep 8;8:431. PMID 21899776
• Bailey SD et al. “Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.” Diabetes Care. 2010 Oct;33(10):2250-3. PMID 20628086
• Emmett DS et al. “Characterization of ionotrophic purinergic receptors in hepatocytes.” Hepatology. 2008 Feb;47(2):698-705. PMID 18027885
• Inoue K et al. “[Involvement of microglia in neuropathic pain signalling].” Brain Nerve. 2007 Jul;59(7):739-46. PMID 17663145
• Inoue K et al. “ATP receptors of microglia involved in pain.” Novartis Found Symp. 2006;276:263-72; discussion 273-81. PMID 16805436
• Wilson SG et al. “Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort.” Eur J Hum Genet. 2006 Mar;14(3):340-8. PMID 16391564
• Tsuda M et al. “Neuropathic pain and spinal microglia: a big problem from molecules in “small” glia.” Trends Neurosci. 2005 Feb;28(2):101-7. PMID 15667933
• Iwai N et al. “Genetic analysis of 22 candidate genes for hypertension in the Japanese population.” J Hypertens. 2004 Jun;22(6):1119-26. PMID 15167446