P46093 (GPR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein coupled receptor 4

Alternative name(s):
G-protein coupled receptor 19

Gene names

Name:	GPR4
Synonyms:	GPR19

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	362 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Proton-sensing receptor coupled to several G-proteins, including G(s), G13 and G(q)/G11 proteins, leading to cAMP production. Ref.9 Ref.11 Ref.12
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence AAA63180.1 differs from that shown. Reason: Frameshift at position 347.

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 Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 362	362	G-protein coupled receptor 4		PRO_0000069512
Regions
	Topological domain	1 – 17	17	Extracellular Potential
	Transmembrane	18 – 42	25	Helical; Name=1; Potential
	Topological domain	43 – 54	12	Cytoplasmic Potential
	Transmembrane	55 – 76	22	Helical; Name=2; Potential
	Topological domain	77 – 91	15	Extracellular Potential
	Transmembrane	92 – 113	22	Helical; Name=3; Potential
	Topological domain	114 – 132	19	Cytoplasmic Potential
	Transmembrane	133 – 154	22	Helical; Name=4; Potential
	Topological domain	155 – 179	25	Extracellular Potential
	Transmembrane	180 – 201	22	Helical; Name=5; Potential
	Topological domain	202 – 224	23	Cytoplasmic Potential
	Transmembrane	225 – 245	21	Helical; Name=6; Potential
	Topological domain	246 – 263	18	Extracellular Potential
	Transmembrane	264 – 284	21	Helical; Name=7; Potential
	Topological domain	285 – 362	78	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	3	1	N-linked (GlcNAc...) Potential
	Glycosylation	164	1	N-linked (GlcNAc...) Potential
	Disulfide bond	90 ↔ 168		By similarity
Natural variations
	Natural variant	295	1	S → N. Corresponds to variant rs36012326 [ dbSNP | Ensembl ].		VAR_049390
Experimental info
	Sequence conflict	57	1	M → L in AAA79061. Ref.3
	Sequence conflict	69	1	T → S in AAA79061. Ref.3
	Sequence conflict	130	1	R → C in AAH67535. Ref.8
	Sequence conflict	255	1	P → L in BAF83387. Ref.5
	Sequence conflict	337	1	A → V in AAA79061. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P46093 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 6C75D97C36204541	FASTA	362	40,982
	10 20 30 40 50 60 MGNHTWEGCH VDSRVDHLFP PSLYIFVIGV GLPTNCLALW AAYRQVQQRN ELGVYLMNLS 70 80 90 100 110 120 IADLLYICTL PLWVDYFLHH DNWIHGPGSC KLFGFIFYTN IYISIAFLCC ISVDRYLAVA 130 140 150 160 170 180 HPLRFARLRR VKTAVAVSSV VWATELGANS APLFHDELFR DRYNHTFCFE KFPMEGWVAW 190 200 210 220 230 240 MNLYRVFVGF LFPWALMLLS YRGILRAVRG SVSTERQEKA KIKRLALSLI AIVLVCFAPY 250 260 270 280 290 300 HVLLLSRSAI YLGRPWDCGF EERVFSAYHS SLAFTSLNCV ADPILYCLVN EGARSDVAKA 310 320 330 340 350 360 LHNLLRFLAS DKPQEMANAS LTLETPLTSK RNSTAKAMTG SWAATPPSQG DQVQLKMLPP AQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of three novel human genes encoding G protein-coupled receptors." Heiber M., Docherty J.M., Shah G., Nguyen T., Cheng R., Heng H.H.Q., Marchese A., Tsui L.-C., Shi X., George S.R., O'Dowd B.F. DNA Cell Biol. 14:25-35(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Isolation of a novel G protein-coupled receptor (GPR4) localized to chromosome 19q13.3." Mahadevan M.S., Baird S., Bailly J.E., Shutler G.G., Sabourin L.A., Tsilfidis C., Neville C.E., Narang M., Korneluk R.G. Genomics 30:84-88(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue." An S., Tsai C., Goetzl E.J. FEBS Lett. 375:121-124(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[6]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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].
[9]	"Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4." Zhu K., Baudhuin L.M., Hong G., Williams F.S., Cristina K.L., Kabarowski J.H., Witte O.N., Xu Y. J. Biol. Chem. 276:41325-41335(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY FUNCTION.
[10]	Erratum Zhu K., Baudhuin L.M., Hong G., Williams F.S., Cristina K.L., Kabarowski J.H., Witte O.N., Xu Y. J. Biol. Chem. 280:43280-43280(2005) Cited for: RETRACTION.
[11]	"Proton-sensing G-protein-coupled receptors." Ludwig M.-G., Vanek M., Guerini D., Gasser J.A., Jones C.E., Junker U., Hofstetter H., Wolf R.M., Seuwen K. Nature 425:93-98(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Previously postulated 'ligand-independent' signaling of GPR4 is mediated through proton-sensing mechanisms." Tobo M., Tomura H., Mogi C., Wang J.Q., Liu J.P., Komachi M., Damirin A., Kimura T., Murata N., Kurose H., Sato K., Okajima F. Cell. Signal. 19:1745-1753(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L36148 Genomic DNA. Translation: AAA63180.1. Frameshift. U21051 Genomic DNA. Translation: AAA98457.1. U35399 mRNA. Translation: AAA79061.1. EU432116 mRNA. Translation: ABY87915.1. AK290698 mRNA. Translation: BAF83387.1. AC011480 Genomic DNA. No translation available. CH471126 Genomic DNA. Translation: EAW57368.1. BC067535 mRNA. Translation: AAH67535.1. BC067536 mRNA. Translation: AAH67536.1.
IPI	IPI00004347.
PIR	A57641. I53033. S68207.
RefSeq	NP_005273.1. NM_005282.2.
UniGene	Hs.17170.
3D structure databases
ProteinModelPortal	P46093.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000319744.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	1708027.
Proteomic databases
PaxDb	P46093.
PRIDE	P46093.
Protocols and materials databases
DNASU	2828.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323040; ENSP00000319744; ENSG00000177464.
GeneID	2828.
KEGG	hsa:2828.
UCSC	uc002pcm.3. human.
Organism-specific databases
CTD	2828.
GeneCards	GC19M046093.
HGNC	HGNC:4497. GPR4.
HPA	HPA014278.
MIM	600551. gene.
neXtProt	NX_P46093.
PharmGKB	PA28886.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG149070.
HOGENOM	HOG000004801.
HOVERGEN	HBG096696.
InParanoid	P46093.
KO	K04312.
OMA	NHTFCFE.
OrthoDB	EOG4MCX0G.
PhylomeDB	P46093.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	P46093.
CleanEx	HS_GPR19. HS_GPR4.
Genevestigator	P46093.
GermOnline	ENSG00000177464. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR002276. GPR4_orph. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01147. GPR4RECEPTOR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2828.
NextBio	11159.
SOURCE	Search...

Entry information

Entry name

GPR4_HUMAN

Accession

Primary (citable) accession number: P46093
Secondary accession number(s): A8K3T3, B0M0K1, Q6NWM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 107 of the entry and version 2 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.