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P2X2

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Target id: 479

Nomenclature: P2X2

Family: P2X receptors

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 471 12q24.33 P2RX2 purinergic receptor P2X 2 18
Mouse 2 485 5 F P2rx2 purinergic receptor P2X, ligand-gated ion channel, 2 6
Rat 2 472 12q16 P2rx2 purinergic receptor P2X 2 2
Previous and Unofficial Names Click here for help
P2X purinoceptor 2 | purinergic receptor P2X, ligand gated ion channel, 2 | purinergic receptor P2X
Database Links Click here for help
Alphafold Q9UBL9 (Hs), P49653 (Rn)
CATH/Gene3D 2.60.490.10
ChEMBL Target CHEMBL2531 (Hs), CHEMBL2135 (Rn)
Ensembl Gene ENSG00000187848 (Hs), ENSMUSG00000029503 (Mm), ENSRNOG00000037456 (Rn)
Entrez Gene 22953 (Hs), 231602 (Mm), 114115 (Rn)
Human Protein Atlas ENSG00000187848 (Hs)
KEGG Gene hsa:22953 (Hs), mmu:231602 (Mm), rno:114115 (Rn)
OMIM 600844 (Hs)
Orphanet ORPHA330683 (Hs)
Pharos Q9UBL9 (Hs)
RefSeq Nucleotide NM_174873 (Hs), NM_170682 (Hs), NM_016318 (Hs), NM_170683 (Hs), NM_153400 (Mm), NM_053656 (Rn)
RefSeq Protein NP_777362 (Hs), NP_057402 (Hs), NP_733782 (Hs), NP_733783 (Hs), NP_700449 (Mm), NP_446108 (Rn)
UniProtKB Q9UBL9 (Hs), P49653 (Rn)
Wikipedia P2RX2 (Hs)
Natural/Endogenous Ligands Click here for help
ATP

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ATP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Agonist 5.8 pEC50 10
⤷ pEC50 5.8 (EC50 1.4x10-6 M) [10]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
NF770 Small molecule or natural product Hs Antagonist 7.0 – 8.0 pIC50 20
⤷ pIC50 7.0 – 8.0 [20]
NF778 Small molecule or natural product Hs Antagonist 7.0 – 8.0 pIC50 20
⤷ pIC50 7.0 – 8.0 [20]
PSB-10211 Small molecule or natural product Hs Antagonist ~7.0 pIC50 20
⤷ pIC50 ~7.0 [20]
suramin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 5.0 pIC50 11
⤷ pIC50 5.0 (IC50 1.04x10-5 M) [11]
View species-specific antagonist tables
Immunopharmacology Comments
P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [3,5].
Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  Human B cells express all P2 receptor subtypes.
References:  22
Tissue Distribution Click here for help
Retina
Expression level:  Medium
Species:  Mouse
Technique:  Immunohistochemistry, western blotting
References:  14
Carotid body
Expression level:  Medium
Species:  Rat
Technique:  Immunohistochemistry, RT-PCR
References:  21
Brain
Expression level:  Medium
Species:  Rat
Technique:  In situ hybridisation, IHC, RT-PCR
References:  7,15,19,26
Enteric nervous system
Expression level:  Medium
Species:  Rat
Technique:  Immunohistochemistry, RT-PCR, In situ hybridization.
References:  4,23,33
Taste buds
Expression level:  Low
Species:  Rat
Technique:  Immunohistochemistry
References:  1
Cochlea
Expression level:  Medium
Species:  Rat
Technique:  Immunohistochemistry
References:  9,12-13,32
Autonomic neurons, nerves
Expression level:  Medium
Species:  Rat
Technique:  Immunohistochemistry, RT-PCR, In situ hybridization.
References:  2,8,25,31
Sensory neurons
Expression level:  Medium
Species:  Rat
Technique:  Immunohistochemistry, IHC, in situ hybridisation
References:  17,27-31
Physiological Consequences of Altering Gene Expression Click here for help
Reduced pain related behaviour
Species:  Mouse
Tissue:  sensory neurons
Technique:  Gene knockout
References:  6
Reduced presynaptic facilitation onto a subpopulation of interneurons in the hippocampus
Species:  Mouse
Tissue:  Hippocampus
Technique:  Gene knockout
References:  16
Altered ventillatory responses to hypoxia
Species:  Mouse
Tissue:  whole animal work
Technique:  Gene knockout
References:  24
Reduced fast synaptic transmission in myenteric neurons
Species:  Mouse
Tissue:  Species Mouse myenteric plexus
Technique:  Gene knockout
References:  23
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Deafness, autosomal dominant 41; DFNA41
Synonyms: Autosomal dominant nonsyndromic deafness [Disease Ontology: DOID:0050564]
Autosomal dominant non-syndromic sensorineural deafness type DFNA [Orphanet: ORPHA90635]
Disease Ontology: DOID:0050564
OMIM: 608224
Orphanet: ORPHA90635
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  P2X2d
Amino acids:  497
Nucleotide accession:  NM_170683
Protein accession:  NP_733783
References:  18
Type:  Splice variant
Species:  Human
Description:  P2X2c
Amino acids:  447
Nucleotide accession:  NM_016318
Protein accession:  NP_057402
References:  18
Type:  Splice variant
Species:  Human
Description:  P2X2b
Amino acids:  404
Nucleotide accession:  NM_174873
Protein accession:  NP_777362
References:  18
General Comments
Although P2X2 is one of the most widely expressed P2X subunits in neurons, the complete knockout of P2X2 in mice produced relatively subtle effects [23]. These mice appear to display no overt CNS abnormalities, even though P2X2 is widely expressed in brain. Moreover, there are no examples of P2X2 receptor mediated fast ATP synaptic transmission in the brain. Overall, the function of P2X2 in brain requires further detailed evaluation.
The human P2X2 subunit exists as 6 alternatively spliced isoforms (A, which is tabulated above; B, NP_777362 - 404 aa; C, NP_057402 - 447 aa; D, NP_733783 - 497 aa; H, NP_777361 - 379 aa and I, NP_057402 - 447 aa).

References

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1. Bo X, Alavi A, Xiang Z, Oglesby I, Ford A, Burnstock G. (1999) Localization of ATP-gated P2X2 and P2X3 receptor immunoreactive nerves in rat taste buds. Neuroreport, 10 (5): 1107-11. [PMID:10321492]

2. Brake AJ, Wagenbach MJ, Julius D. (1994) New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature, 371 (6497): 519-23. [PMID:7523952]

3. Burnstock G, Boeynaems JM. (2014) Purinergic signalling and immune cells. Purinergic Signal, 10 (4): 529-64. [PMID:25352330]

4. Castelucci P, Robbins HL, Poole DP, Furness JB. (2002) The distribution of purine P2X(2) receptors in the guinea-pig enteric nervous system. Histochem Cell Biol, 117 (5): 415-22. [PMID:12029488]

5. Cekic C, Linden J. (2016) Purinergic regulation of the immune system. Nat Rev Immunol, 16 (3): 177-92. [PMID:26922909]

6. Cockayne DA, Dunn PM, Zhong Y, Rong W, Hamilton SG, Knight GE, Ruan HZ, Ma B, Yip P, Nunn P, McMahon SB, Burnstock G, Ford AP. (2005) P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol (Lond.), 567 (Pt 2): 621-39. [PMID:15961431]

7. Collo G, North RA, Kawashima E, Merlo-Pich E, Neidhart S, Surprenant A, Buell G. (1996) Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. J Neurosci, 16 (8): 2495-507. [PMID:8786426]

8. Dowling P, Ranson RN, Santer RM. (2006) Age-associated changes in distribution of the P2X2 receptor in the major pelvic ganglion of the male rat. Neurosci Lett, 404 (3): 320-3. [PMID:16969922]

9. Housley GD, Kanjhan R, Raybould NP, Greenwood D, Salih SG, Järlebark L, Burton LD, Setz VC, Cannell MB, Soeller C et al.. (1999) Expression of the P2X(2) receptor subunit of the ATP-gated ion channel in the cochlea: implications for sound transduction and auditory neurotransmission. J Neurosci, 19 (19): 8377-88. [PMID:10493739]

10. Jacobson KA, Ivanov AA, de Castro S, Harden TK, Ko H. (2009) Development of selective agonists and antagonists of P2Y receptors. Purinergic Signal, 5 (1): 75-89. [PMID:18600475]

11. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J Med Chem, 45 (19): 4057-93. [PMID:12213051]

12. Järlebark LE, Housley GD, Raybould NP, Vlajkovic S, Thorne PR. (2002) ATP-gated ion channels assembled from P2X2 receptor subunits in the mouse cochlea. Neuroreport, 13 (15): 1979-84. [PMID:12395104]

13. Järlebark LE, Housley GD, Thorne PR. (2000) Immunohistochemical localization of adenosine 5'-triphosphate-gated ion channel P2X(2) receptor subunits in adult and developing rat cochlea. J Comp Neurol, 421 (3): 289-301. [PMID:10813788]

14. Kaneda M, Ishii K, Morishima Y, Akagi T, Yamazaki Y, Nakanishi S, Hashikawa T. (2004) OFF-cholinergic-pathway-selective localization of P2X2 purinoceptors in the mouse retina. J Comp Neurol, 476 (1): 103-11. [PMID:15236470]

15. Kanjhan R, Housley GD, Burton LD, Christie DL, Kippenberger A, Thorne PR, Luo L, Ryan AF. (1999) Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system. J Comp Neurol, 407 (1): 11-32. [PMID:10213185]

16. Khakh BS, Gittermann D, Cockayne DA, Jones A. (2003) ATP modulation of excitatory synapses onto interneurons. J Neurosci, 23 (19): 7426-37. [PMID:12917379]

17. Kobayashi K, Fukuoka T, Yamanaka H, Dai Y, Obata K, Tokunaga A, Noguchi K. (2005) Differential expression patterns of mRNAs for P2X receptor subunits in neurochemically characterized dorsal root ganglion neurons in the rat. J Comp Neurol, 481 (4): 377-90. [PMID:15593340]

18. Lynch KJ, Touma E, Niforatos W, Kage KL, Burgard EC, van Biesen T, Kowaluk EA, Jarvis MF. (1999) Molecular and functional characterization of human P2X(2) receptors. Mol Pharmacol, 56 (6): 1171-81. [PMID:10570044]

19. Masin M, Kerschensteiner D, Dümke K, Rubio ME, Soto F. (2006) Fe65 interacts with P2X2 subunits at excitatory synapses and modulates receptor function. J Biol Chem, 281 (7): 4100-8. [PMID:16330549]

20. North RA, Jarvis MF. (2013) P2X receptors as drug targets. Mol Pharmacol, 83 (4): 759-69. [PMID:23253448]

21. Prasad M, Fearon IM, Zhang M, Laing M, Vollmer C, Nurse CA. (2001) Expression of P2X2 and P2X3 receptor subunits in rat carotid body afferent neurones: role in chemosensory signalling. J Physiol (Lond.), 537 (Pt 3): 667-77. [PMID:11744746]

22. Przybyła T, Sakowicz-Burkiewicz M, Pawełczyk T. (2018) Purinergic signaling in B cells. Acta Biochim Pol, 65 (1): 1-7. [PMID:29360885]

23. Ren J, Bian X, DeVries M, Schnegelsberg B, Cockayne DA, Ford AP, Galligan JJ. (2003) P2X2 subunits contribute to fast synaptic excitation in myenteric neurons of the mouse small intestine. J Physiol (Lond.), 552 (Pt 3): 809-21. [PMID:12937291]

24. Rong W, Gourine AV, Cockayne DA, Xiang Z, Ford AP, Spyer KM, Burnstock G. (2003) Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. J Neurosci, 23 (36): 11315-21. [PMID:14672995]

25. Ruan HZ, Burnstock G. (2004) P2X2 and P2X3 receptor expression in the gallbladder of the guinea pig. Auton Neurosci, 111 (2): 89-96. [PMID:15182738]

26. Rubio ME, Soto F. (2001) Distinct Localization of P2X receptors at excitatory postsynaptic specializations. J Neurosci, 21 (2): 641-53. [PMID:11160443]

27. Simon J, Kidd EJ, Smith FM, Chessell IP, Murrell-Lagnado R, Humphrey PP, Barnard EA. (1997) Localization and functional expression of splice variants of the P2X2 receptor. Mol Pharmacol, 52 (2): 237-48. [PMID:9271346]

28. Staikopoulos V, Sessle BJ, Furness JB, Jennings EA. (2007) Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons. Neuroscience, 144 (1): 208-16. [PMID:17110047]

29. Vulchanova L, Arvidsson U, Riedl M, Wang J, Buell G, Surprenant A, North RA, Elde R. (1996) Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry. Proc Natl Acad Sci USA, 93 (15): 8063-7. [PMID:8755603]

30. Vulchanova L, Riedl MS, Shuster SJ, Buell G, Surprenant A, North RA, Elde R. (1997) Immunohistochemical study of the P2X2 and P2X3 receptor subunits in rat and monkey sensory neurons and their central terminals. Neuropharmacology, 36 (9): 1229-42. [PMID:9364478]

31. Xiang Z, Bo X, Burnstock G. (1998) Localization of ATP-gated P2X receptor immunoreactivity in rat sensory and sympathetic ganglia. Neurosci Lett, 256 (2): 105-8. [PMID:9853714]

32. Xiang Z, Bo X, Burnstock G. (1999) P2X receptor immunoreactivity in the rat cochlea, vestibular ganglion and cochlear nucleus. Hear Res, 128 (1-2): 190-6. [PMID:10082298]

33. Xiang Z, Burnstock G. (2004) P2X2 and P2X3 purinoceptors in the rat enteric nervous system. Histochem Cell Biol, 121 (3): 169-79. [PMID:14767775]

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