Q99500 (S1PR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingosine 1-phosphate receptor 3
Short name=S1P receptor 3
Short name=S1P3

Alternative name(s):
Endothelial differentiation G-protein coupled receptor 3
Sphingosine 1-phosphate receptor Edg-3
Short name=S1P receptor Edg-3

Gene names

Name:	S1PR3
Synonyms:	EDG3

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	378 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis. Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in all tissues, but most abundantly in heart, placenta, kidney, and liver.
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	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara anatomical structure morphogenesis Traceable author statement PubMed 10555146. Source: ProtInc cytokine production Inferred from electronic annotation. Source: Compara elevation of cytosolic calcium ion concentration Traceable author statement Ref.2. Source: ProtInc inflammatory response Traceable author statement PubMed 8649355. Source: ProtInc positive regulation of cell proliferation Traceable author statement Ref.9. Source: ProtInc regulation of interleukin-1 beta production Inferred from electronic annotation. Source: Compara sphingosine-1-phosphate signaling pathway Inferred from electronic annotation. Source: GOC
Cellular_component	integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement PubMed 10555146. Source: ProtInc lipid binding Traceable author statement Ref.2. Source: ProtInc sphingosine-1-phosphate receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 378	378	Sphingosine 1-phosphate receptor 3		PRO_0000069421
Regions
	Topological domain	1 – 40	40	Extracellular By similarity
	Transmembrane	41 – 65	25	Helical; Name=1; By similarity
	Topological domain	66 – 72	7	Cytoplasmic By similarity
	Transmembrane	73 – 101	29	Helical; Name=2; By similarity
	Topological domain	102 – 115	14	Extracellular By similarity
	Transmembrane	116 – 134	19	Helical; Name=3; By similarity
	Topological domain	135 – 153	19	Cytoplasmic By similarity
	Transmembrane	154 – 179	26	Helical; Name=4; By similarity
	Topological domain	180 – 195	16	Extracellular By similarity
	Transmembrane	196 – 216	21	Helical; Name=5; By similarity
	Topological domain	217 – 243	27	Cytoplasmic By similarity
	Transmembrane	244 – 265	22	Helical; Name=6; By similarity
	Topological domain	266 – 281	16	Extracellular By similarity
	Transmembrane	282 – 302	21	Helical; Name=7; By similarity
	Topological domain	303 – 378	76	Cytoplasmic By similarity
Amino acid modifications
	Glycosylation	15	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	243	1	R → Q. Corresponds to variant rs34075341 [ dbSNP | Ensembl ].		VAR_033465
Experimental info
	Sequence conflict	359	1	A → D in CAA58744. Ref.1
	Sequence conflict	359	1	A → D in AAC51906. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q99500 [UniParc]. Last modified February 16, 2004. Version 2. Checksum: 79A00300968F439F	FASTA	378	42,250
	10 20 30 40 50 60 MATALPPRLQ PVRGNETLRE HYQYVGKLAG RLKEASEGST LTTVLFLVIC SFIVLENLMV 70 80 90 100 110 120 LIAIWKNNKF HNRMYFFIGN LALCDLLAGI AYKVNILMSG KKTFSLSPTV WFLREGSMFV 130 140 150 160 170 180 ALGASTCSLL AIAIERHLTM IKMRPYDANK RHRVFLLIGM CWLIAFTLGA LPILGWNCLH 190 200 210 220 230 240 NLPDCSTILP LYSKKYIAFC ISIFTAILVT IVILYARIYF LVKSSSRKVA NHNNSERSMA 250 260 270 280 290 300 LLRTVVIVVS VFIACWSPLF ILFLIDVACR VQACPILFKA QWFIVLAVLN SAMNPVIYTL 310 320 330 340 350 360 ASKEMRRAFF RLVCNCLVRG RGARASPIQP ALDPSRSKSS SSNNSSHSPK VKEDLPHTAP 370 SSCIMDKNAA LQNGIFCN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the novel human G protein-coupled receptor (GPCR) gene mapped on chromosome 9." Yamaguchi F., Tokuda M., Hatase O., Brenner S. Biochem. Biophys. Res. Commun. 227:608-614(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[2]	"Identification of cDNAs encoding two G protein-coupled receptors for lysosphingolipids." An S., Bleu T., Huang W., Hallmark O.G., Coughlin S.R., Goetzl E.J. FEBS Lett. 417:279-282(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: Testis.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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]. Tissue: Placenta.
[8]	"Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5." Ancellin N., Hla T. J. Biol. Chem. 274:18997-19002(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHARMACOLOGICAL CHARACTERIZATION.
[9]	"Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5." An S., Zheng Y., Bleu T. J. Biol. Chem. 275:288-296(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Evidence for Edg-3 receptor-mediated activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes." Himmel H.M., Meyer Zu Heringdorf D., Graf E., Dobrev D., Kortner A., Schueler S., Jakobs K.H., Ravens U. Mol. Pharmacol. 58:449-454(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SPHINGOSINE 1-PHOSPHATE ACTIVATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X83864 Genomic DNA. Translation: CAA58744.1. AF022139 mRNA. Translation: AAC51906.1. AY322540 Genomic DNA. Translation: AAP84353.1. AK312798 mRNA. Translation: BAG35658.1. AL772202 Genomic DNA. Translation: CAI16743.1. CH471089 Genomic DNA. Translation: EAW62758.1. BC060827 mRNA. Translation: AAH60827.1. BC069579 mRNA. Translation: AAH69579.1.
IPI	IPI00015983.
PIR	JC5245.
RefSeq	NP_005217.2. NM_005226.3.
UniGene	Hs.585118.
3D structure databases
ProteinModelPortal	Q99500.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000350878.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q99500.
Polymorphism databases
DMDM	42560554.
Proteomic databases
PaxDb	Q99500.
PRIDE	Q99500.
Protocols and materials databases
DNASU	1903.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000358157; ENSP00000350878; ENSG00000213694. ENST00000375846; ENSP00000365006; ENSG00000213694.
GeneID	1903.
KEGG	hsa:1903.
UCSC	uc004aqe.3. human.
Organism-specific databases
CTD	1903.
GeneCards	GC09P091606.
HGNC	HGNC:3167. S1PR3.
MIM	601965. gene.
neXtProt	NX_Q99500.
PharmGKB	PA162402362.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG148018.
HOGENOM	HOG000233501.
HOVERGEN	HBG103071.
InParanoid	Q99500.
KO	K04290.
OMA	LPDCSTI.
OrthoDB	EOG4SXNCQ.
PhylomeDB	Q99500.
Enzyme and pathway databases
Pathway_Interaction_DB	s1p_s1p3_pathway. S1P3 pathway. s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q99500.
CleanEx	HS_S1PR3.
Genevestigator	Q99500.
GermOnline	ENSG00000186354. Homo sapiens.
Family and domain databases
InterPro	IPR004062. EDG3_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR004061. S1P_rcpt. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR01524. EDG3RECEPTOR. PR00237. GPCRRHODOPSN. PR01523. S1PRECEPTOR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q99500.
ChEMBL	CHEMBL3892.
GenomeRNAi	1903.
NextBio	7753.
SOURCE	Search...

Entry information

Entry name

S1PR3_HUMAN

Accession

Primary (citable) accession number: Q99500
Secondary accession number(s): Q5SQD8, Q7Z5I2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 16, 2004
Last modified:	May 1, 2013
This is version 116 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.