Q99572 (P2RX7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
P2X purinoceptor 7
Short name=P2X7

Alternative name(s):
ATP receptor
P2Z receptor
Purinergic receptor

Gene names

Name:

P2RX7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	595 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for ATP that acts as a ligand-gated ion channel. Responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells.
Subunit structure	Forms homo- or heteropolymers. Interacts with LAMA3, ITGB2, ACTB, ACTN4, SVIL, MPP3, HSPA1, HSPCB, HSPA8, PIK230 and PTPRB. Ref.5
Subcellular location	Membrane; Multi-pass membrane protein.
Post-translational modification	Phosphorylation results in its inactivation. ADP-ribosylation at Arg-125 is necessary and sufficient to activate P2RX7 and gate the channel By similarity.
Sequence similarities	Belongs to the P2X receptor family.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Ionic channel Ligand-gated ion channel Receptor
PTM	ADP-ribosylation Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of innate immune response Traceable author statement. Source: Reactome bleb assembly Inferred from sequence or structural similarity. Source: BHF-UCL innate immune response Traceable author statement. Source: Reactome membrane depolarization Inferred from direct assay Ref.1. Source: BHF-UCL negative regulation of MAPKKK cascade Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of bone resorption Inferred from sequence or structural similarity. Source: BHF-UCL pore complex assembly Inferred from direct assay Ref.1. Source: BHF-UCL positive regulation of bone mineralization Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of calcium ion transport into cytosol Inferred from direct assay Ref.1. Source: BHF-UCL positive regulation of cytolysis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cytoskeleton organization Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of interleukin-1 beta secretion Inferred from direct assay. Source: BHF-UCL regulation of apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL regulation of killing of cells of other organism Non-traceable author statement. Source: BHF-UCL regulation of sodium ion transport Inferred from sequence or structural similarity. Source: BHF-UCL response to ATP Inferred from direct assay Ref.1. Source: BHF-UCL sensory perception of pain Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular component	bleb Inferred from sequence or structural similarity. Source: BHF-UCL cytoplasm Inferred from sequence or structural similarity. Source: BHF-UCL integral to plasma membrane Inferred by curator Ref.1. Source: BHF-UCL
Molecular function	ATP binding Inferred by curator Ref.1. Source: BHF-UCL extracellular ATP-gated cation channel activity Inferred from direct assay Ref.1. Source: BHF-UCL lipopolysaccharide binding Inferred from sequence or structural similarity. Source: BHF-UCL protein homodimerization activity Non-traceable author statement. Source: BHF-UCL purinergic nucleotide receptor activity Inferred from direct assay Ref.1. Source: BHF-UCL receptor binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-1753251,EBI-375543
GRB2	P62993	1	EBI-1753251,EBI-401755
NCK1	P16333	1	EBI-1753251,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 595	595	P2X purinoceptor 7		PRO_0000161560
Regions
	Topological domain	1 – 25	25	Cytoplasmic Potential
	Transmembrane	26 – 46	21	Helical; Name=1; Potential
	Topological domain	47 – 334	288	Extracellular Potential
	Transmembrane	335 – 355	21	Helical; Name=2; Potential
	Topological domain	356 – 595	240	Cytoplasmic Potential
Amino acid modifications
	Modified residue	125	1	ADP-ribosylarginine By similarity
	Modified residue	133	1	ADP-ribosylarginine By similarity
	Modified residue	343	1	Phosphotyrosine Ref.5
	Glycosylation	187	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	202	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	213	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	241	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	284	1	N-linked (GlcNAc...) Ref.6
Natural variations
	Natural variant	25	1	N → S in a colorectal cancer sample; somatic mutation. Ref.8		VAR_036444
	Natural variant	76	1	V → A. Corresponds to variant rs17525809 [ dbSNP | Ensembl ].		VAR_057665
	Natural variant	150	1	G → R. Corresponds to variant rs28360447 [ dbSNP | Ensembl ].		VAR_057666
	Natural variant	155	1	Y → H. Ref.1 Ref.2 Ref.4 Corresponds to variant rs208294 [ dbSNP | Ensembl ].		VAR_019649
	Natural variant	270	1	R → C. Corresponds to variant rs16950860 [ dbSNP | Ensembl ].		VAR_057667
	Natural variant	270	1	R → H. Ref.1 Ref.4 Corresponds to variant rs7958311 [ dbSNP | Ensembl ].		VAR_019648
	Natural variant	276	1	R → H. Corresponds to variant rs7958316 [ dbSNP | Ensembl ].		VAR_057668
	Natural variant	307	1	R → Q. Corresponds to variant rs28360457 [ dbSNP | Ensembl ].		VAR_057669
	Natural variant	348	1	A → T. Ref.2 Corresponds to variant rs1718119 [ dbSNP | Ensembl ].		VAR_057670
	Natural variant	357	1	T → S. Corresponds to variant rs2230911 [ dbSNP | Ensembl ].		VAR_019650
	Natural variant	430	1	P → R. Corresponds to variant rs10160951 [ dbSNP | Ensembl ].		VAR_057671
	Natural variant	433	1	A → V. Corresponds to variant rs28360459 [ dbSNP | Ensembl ].		VAR_057672
	Natural variant	460	1	Q → R. Corresponds to variant rs2230912 [ dbSNP | Ensembl ].		VAR_019651
	Natural variant	496	1	E → A in a polymorphism that results in a loss of function. Ref.7 Corresponds to variant rs3751143 [ dbSNP | Ensembl ].		VAR_019652
	Natural variant	521	1	H → Q. Corresponds to variant rs2230913 [ dbSNP | Ensembl ].		VAR_057673
	Natural variant	522	1	V → I. Corresponds to variant rs34219304 [ dbSNP | Ensembl ].		VAR_057674
	Natural variant	574	1	R → L in a colorectal cancer sample; somatic mutation. Ref.8		VAR_036445
	Natural variant	578	1	R → Q. Corresponds to variant rs28360460 [ dbSNP | Ensembl ].		VAR_057675
Experimental info
	Mutagenesis	187	1	N → A: Alters cell surface expression. Ref.6
	Sequence conflict	481	1	S → R in CAA73360. Ref.2
	Sequence conflict	568	1	N → I in CAA70755. Ref.1
	Sequence conflict	568	1	N → I in CAA73360. Ref.2
	Sequence conflict	568	1	N → I in AAH11913. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q99572 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 584C17E81D29C899	FASTA	595	68,586
	10 20 30 40 50 60 MPACCSCSDV FQYETNKVTR IQSMNYGTIK WFFHVIIFSY VCFALVSDKL YQRKEPVISS 70 80 90 100 110 120 VHTKVKGIAE VKEEIVENGV KKLVHSVFDT ADYTFPLQGN SFFVMTNFLK TEGQEQRLCP 130 140 150 160 170 180 EYPTRRTLCS SDRGCKKGWM DPQSKGIQTG RCVVYEGNQK TCEVSAWCPI EAVEEAPRPA 190 200 210 220 230 240 LLNSAENFTV LIKNNIDFPG HNYTTRNILP GLNITCTFHK TQNPQCPIFR LGDIFRETGD 250 260 270 280 290 300 NFSDVAIQGG IMGIEIYWDC NLDRWFHHCR PKYSFRRLDD KTTNVSLYPG YNFRYAKYYK 310 320 330 340 350 360 ENNVEKRTLI KVFGIRFDIL VFGTGGKFDI IQLVVYIGST LSYFGLAAVF IDFLIDTYSS 370 380 390 400 410 420 NCCRSHIYPW CKCCQPCVVN EYYYRKKCES IVEPKPTLKY VSFVDESHIR MVNQQLLGRS 430 440 450 460 470 480 LQDVKGQEVP RPAMDFTDLS RLPLALHDTP PIPGQPEEIQ LLRKEATPRS RDSPVWCQCG 490 500 510 520 530 540 SCLPSQLPES HRCLEELCCR KKPGACITTS ELFRKLVLSR HVLQFLLLYQ EPLLALDVDS 550 560 570 580 590 TNSRLRHCAY RCYATWRFGS QDMADFANLP SCCRWRIRKE FPKSEGQYSG FKSPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA." Rassendren F., Buell G.N., Virginio C., Collo G., North R.A., Surprenant A. J. Biol. Chem. 272:5482-5486(1997) [PubMed: 9038151] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-155 AND HIS-270. Tissue: Brain.
[2]	"Gene structure and chromosomal localization of the human P2X7 receptor." Buell G.N., Talabot F., Gos A., Lorenz J., Lai E., Morris M.A., Antonarakis S.E. Recept. Channels 5:347-354(1998) [PubMed: 9826911] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-155 AND THR-348.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS HIS-155 AND HIS-270. Tissue: Skin.
[5]	"Proteomic and functional evidence for a P2X7 receptor signalling complex." Kim M., Jiang L.H., Wilson H.L., North R.A., Surprenant A. EMBO J. 20:6347-6358(2001) [PubMed: 11707406] [Abstract] Cited for: PHOSPHORYLATION AT TYR-343, INTERACTION WITH LAMA3; ITGB2; ACTB; ACTN4; SVIL; MPP3; HSPA1; HSPCB; HSPA8; PIK230 AND PTPRB.
[6]	"Mutation of putative N-linked GLycosylation sites on the human nucleotide receptor P2X7 reveals a key residue important for receptor function." Lenertz L.Y., Wang Z., Guadarrama A., Hill L.M., Gavala M.L., Bertics P.J. Biochemistry 49:4611-4619(2010) [PubMed: 20450227] [Abstract] Cited for: GLYCOSYLATION AT ASN-187; ASN-202; ASN-213; ASN-241 AND ASN-284, MUTAGENESIS OF ASN-187.
[7]	"A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor." Gu B.J., Zhang W., Worthington R.A., Sluyter R., Dao-Ung P., Petrou S., Barden J.A., Wiley J.S. J. Biol. Chem. 276:11135-11142(2001) [PubMed: 11150303] [Abstract] Cited for: VARIANT ALA-496.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-25 AND LEU-574.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

P2X receptor entry

Wikipedia

P2RX7 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y09561 mRNA. Translation: CAA70755.1. Y12851 , Y12852, Y12853, Y12854, Y12855 Genomic DNA. Translation: CAA73360.1. Z98941 Genomic DNA. No translation available. BC011913 mRNA. Translation: AAH11913.1.
IPI	IPI00293328.
UniGene	Hs.729169.
3D structure databases
ProteinModelPortal	Q99572.
SMR	Q99572. Positions 27-356.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99572. 3 interactions.
MINT	MINT-3972963.
STRING	Q99572.
Protein family/group databases
TCDB	1.A.7.1.3. ATP-gated P2X receptor cation channel (P2X Receptor) family.
PTM databases
PhosphoSite	Q99572.
Polymorphism databases
DMDM	296439282.
Proteomic databases
PRIDE	Q99572.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261826; ENSP00000261826; ENSG00000089041.
Organism-specific databases
GeneCards	GC12P121570.
HGNC	HGNC:8537. P2RX7.
HPA	HPA034967. HPA034968.
MIM	602566. gene.
neXtProt	NX_Q99572.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13847.
GeneTree	ENSGT00390000016028.
HOGENOM	HBG713324.
HOVERGEN	HBG053086.
InParanoid	Q99572.
OMA	QKTCEVS.
OrthoDB	EOG4DJJWD.
PhylomeDB	Q99572.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q99572.
Bgee	Q99572.
CleanEx	HS_P2RX7.
Genevestigator	Q99572.
GermOnline	ENSG00000089041. Homo sapiens.
Family and domain databases
InterPro	IPR003050. P2X7_purnocptor. IPR001429. P2X_purnocptor. [Graphical view]
PANTHER	PTHR10125. ATP_P2X_rcpt. 1 hit. PTHR10125:SF13. PTHR10125:SF13. 1 hit.
Pfam	PF00864. P2X_receptor. 1 hit. [Graphical view]
PRINTS	PR01314. P2X7RECEPTOR. PR01307. P2XRECEPTOR.
TIGRFAMs	TIGR00863. P2X. 1 hit.
PROSITE	PS01212. P2X_RECEPTOR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	19358.
SOURCE	Search...

Entry information

Entry name

P2RX7_HUMAN

Accession

Primary (citable) accession number: Q99572
Secondary accession number(s): O14991, Q96EV7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 18, 2010
Last modified:	January 25, 2012
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.