P51582 (P2RY4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
P2Y purinoceptor 4
Short name=P2Y4

Alternative name(s):
P2P
Uridine nucleotide receptor
Short name=UNR

Gene names

Name:	P2RY4
Synonyms:	NRU

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	365 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for UTP and UDP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. Not activated by ATP or ADP.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Pancreas.
Post-translational modification	Phosphorylation of Ser-333 and Ser-334 is a key step in agonist-dependent desensitization and loss of surface P2RY4. This phosphorylation does not involve PKC, nor other calcium activated kinases.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	elevation of cytosolic calcium ion concentration Traceable author statement Ref.2. Source: ProtInc phospholipase C-activating G-protein coupled receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc transepithelial chloride transport Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara basolateral plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: Compara G-protein coupled purinergic nucleotide receptor activity Inferred from electronic annotation. Source: InterPro UTP-activated nucleotide receptor activity Inferred from electronic annotation. Source: Compara uridine nucleotide receptor activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 365	365	P2Y purinoceptor 4		PRO_0000070020
Regions
	Topological domain	1 – 34	34	Extracellular Potential
	Transmembrane	35 – 61	27	Helical; Name=1; Potential
	Topological domain	62 – 72	11	Cytoplasmic Potential
	Transmembrane	73 – 95	23	Helical; Name=2; Potential
	Topological domain	96 – 112	17	Extracellular Potential
	Transmembrane	113 – 131	19	Helical; Name=3; Potential
	Topological domain	132 – 154	23	Cytoplasmic Potential
	Transmembrane	155 – 174	20	Helical; Name=4; Potential
	Topological domain	175 – 196	22	Extracellular Potential
	Transmembrane	197 – 222	26	Helical; Name=5; Potential
	Topological domain	223 – 246	24	Cytoplasmic Potential
	Transmembrane	247 – 269	23	Helical; Name=6; Potential
	Topological domain	270 – 287	18	Extracellular Potential
	Transmembrane	288 – 309	22	Helical; Name=7; Potential
	Topological domain	310 – 365	56	Cytoplasmic Potential
Amino acid modifications
	Modified residue	333	1	Phosphoserine Probable
	Modified residue	334	1	Phosphoserine Probable
	Disulfide bond	108 ↔ 185		By similarity
Natural variations
	Natural variant	168	1	V → M. Corresponds to variant rs1152186 [ dbSNP | Ensembl ].		VAR_011854
	Natural variant	178	1	N → T. Ref.2 Ref.5 Corresponds to variant rs1152187 [ dbSNP | Ensembl ].		VAR_011855
	Natural variant	191	1	P → L. Corresponds to variant rs1152188 [ dbSNP | Ensembl ].		VAR_011856
	Natural variant	234	1	S → A. Ref.2 Corresponds to variant rs3829709 [ dbSNP | Ensembl ].		VAR_049429
Experimental info
	Mutagenesis	243	1	S → A: No effect. Ref.6
	Mutagenesis	333 – 365	33	Missing: Abolishes agonist-induced phosphorylation. Prevents agonist-induced desensitization and loss of cell surface receptors. Ref.6
	Mutagenesis	333 – 359	27	SSLAL…SSCST → AALALVALPEDAACRWAAAP QDAACAA: Greatly reduces agonist-induced desensitization and loss of cell surface receptors. Ref.6
	Mutagenesis	333	1	S → A: Greatly reduces agonist-induced desensitization and loss of cell surface receptors; when associated with A-334 and A-339. Ref.6
	Mutagenesis	334	1	S → A: Greatly reduces agonist-induced desensitization and loss of cell surface receptors; when associated with A-333 and A-339. Ref.6
	Mutagenesis	339	1	S → A: Greatly reduces agonist-induced desensitization and loss of cell surface receptors; when associated with A-333 and A-334. Ref.6
	Mutagenesis	344 – 365	22	Missing: No effect on agonist-induced phosphorylation, no functional effect.
	Mutagenesis	356 – 365	10	Missing: No functional effect.
	Sequence conflict	86	1	L → V in AAC50347. Ref.2
	Sequence conflict	121	1	C → S in AAH96068. Ref.5
	Sequence conflict	247	1	I → V in AAH96069. Ref.5
	Sequence conflict	352	1	P → T in AAH96069. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P51582 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 23E0AFED3B7BDEED	FASTA	365	40,963
	10 20 30 40 50 60 MASTESSLLR SLGLSPGPGS SEVELDCWFD EDFKFILLPV SYAVVFVLGL GLNAPTLWLF 70 80 90 100 110 120 IFRLRPWDAT ATYMFHLALS DTLYVLSLPT LIYYYAAHNH WPFGTEICKF VRFLFYWNLY 130 140 150 160 170 180 CSVLFLTCIS VHRYLGICHP LRALRWGRPR LAGLLCLAVW LVVAGCLVPN LFFVTTSNKG 190 200 210 220 230 240 TTVLCHDTTR PEEFDHYVHF SSAVMGLLFG VPCLVTLVCY GLMARRLYQP LPGSAQSSSR 250 260 270 280 290 300 LRSLRTIAVV LTVFAVCFVP FHITRTIYYL ARLLEADCRV LNIVNVVYKV TRPLASANSC 310 320 330 340 350 360 LDPVLYLLTG DKYRRQLRQL CGGGKPQPRT AASSLALVSL PEDSSCRWAA TPQDSSCSTP RADRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional expression of a human uridine nucleotide receptor." Communi D., Pirotton S., Parmentier M., Boeynaems J.-M. J. Biol. Chem. 270:30849-30852(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Cloning, expression, and chromosomal localization of the human uridine nucleotide receptor gene." Nguyen T., Erb L., Weisman G.A., Marchese A., Heng H.H.Q., Garrad R.C., George S.R., Turner J.T., O'Dowd B.F. J. Biol. Chem. 270:30845-30848(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-178 AND ALA-234.
[3]	"Molecular cloning and characterization of a novel orphan receptor (P2P) expressed in human pancreas that shows high structural homology to the P2U purinoceptor." Stam N.J., Klomp J., van der Heuvel M., Olijve W. FEBS Lett. 384:260-264(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Pancreas.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-178.
[6]	"Differential regulation of the uridine nucleotide-activated P2Y4 and P2Y6 receptors. Ser-333 and Ser-334 in the carboxyl terminus are involved in agonist-dependent phosphorylation desensitization and internalization of the P2Y4 receptor." Brinson A.E., Harden T.K. J. Biol. Chem. 276:11939-11948(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-333 AND SER-334, MUTAGENESIS OF SER-243; SER-333; SER-334 AND SER-339.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X91852 Genomic DNA. Translation: CAA62963.1.
U40223 Genomic DNA. Translation: AAC50347.1.
X96597 Genomic DNA. Translation: CAA65415.1.
AL357752 Genomic DNA. Translation: CAI41492.1.
BC095503 mRNA. Translation: AAH95503.1.
BC096067 mRNA. Translation: AAH96067.1.
BC096068 mRNA. Translation: AAH96068.1.
BC096069 mRNA. Translation: AAH96069.1.
BC096070 mRNA. Translation: AAH96070.1.

IPI

IPI00019403.

PIR

S68679.

RefSeq

NP_002556.1. NM_002565.3.

UniGene

Hs.673854.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2B6Q	model	-	A	1-365	[»]

ProteinModelPortal

P51582.

ModBase

Search...

Protein-protein interaction databases

IntAct

P51582. 1 interaction.

STRING

9606.ENSP00000363643.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P51582.

Polymorphism databases

DMDM

1709524.

Proteomic databases

PaxDb

P51582.

PRIDE

P51582.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374519; ENSP00000363643; ENSG00000186912.

GeneID

5030.

KEGG

hsa:5030.

UCSC

uc004dxz.1. human.

Organism-specific databases

CTD

5030.

GeneCards

GC0XM069478.

HGNC

HGNC:8542. P2RY4.

HPA

CAB022644.

MIM

300038. gene.

neXtProt

NX_P51582.

PharmGKB

PA32871.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG270952.

HOGENOM

HOG000231307.

HOVERGEN

HBG101120.

InParanoid

P51582.

KO

K04271.

OMA

YMFHLAL.

OrthoDB

EOG44J2JK.

PhylomeDB

P51582.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P51582.

Bgee

P51582.

CleanEx

HS_P2RY4.

Genevestigator

P51582.

GermOnline

ENSG00000186912. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002286. P2_purnocptor.
IPR000018. P2Y4_purnocptor.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00237. GPCRRHODOPSN.
PR01066. P2Y4PRNOCPTR.
PR01157. P2YPURNOCPTR.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P51582.

ChEMBL

CHEMBL2123.

GenomeRNAi

5030.

NextBio

19374.

SOURCE

Search...

Entry information

Entry name

P2RY4_HUMAN

Accession

Primary (citable) accession number: P51582
Secondary accession number(s): Q4VBB7 , Q4VBB8, Q502W2, Q5JT22

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 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.