Q9H228 (S1PR5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingosine 1-phosphate receptor 5
Short name=S1P receptor 5
Short name=S1P5

Alternative name(s):
Endothelial differentiation G-protein-coupled receptor 8
Sphingosine 1-phosphate receptor Edg-8
Short name=S1P receptor Edg-8

Gene names

Name:	S1PR5
Synonyms:	EDG8

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	398 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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. Is coupled to both the G(i/0)alpha and G12 subclass of heteromeric G-proteins By similarity. May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells. Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Widely expressed in the brain, most prominently in the corpus callosum, which is predominantly white matter. Detected in spleen, peripheral blood leukocytes, placenta, lung, aorta and fetal spleen. Low-level signal detected in many tissue extracts. Overexpressed in leukemic large granular lymphocytes. Isoform 1 is predominantly expressed in peripheral tissues. Isoform 2 is expressed in brain, spleen and peripheral blood leukocytes. Ref.1 Ref.3 Ref.9
Developmental stage	At 24 weeks of gestation, fragments of radial glial fibers are positive within the cortical plate and subplate of allocortical areas. These positive fragments often appear enlarged as varicosities and some of them terminate at blood vessels. Between 28 and 30 weeks of gestation, all iso- and allocortical areas contain immunolabeled radial glial fibers revealing curvature next to sulci. After 32 weeks of gestation, radial glial fibers gradually disappear; instead positive transitional stages between radial glia and astrocytes were found. Ref.10
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of neuron differentiation Inferred from electronic annotation. Source: Compara sphingosine-1-phosphate signaling pathway Inferred from electronic annotation. Source: GOC
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	sphingosine-1-phosphate receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H228-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9H228-2)

The sequence of this isoform differs from the canonical sequence as follows:
     214-310: RIYCQVRANA...LNPIIYTLTN → LAGLAAHAQR...EWLPAVGERG
     311-398: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 398	398	Sphingosine 1-phosphate receptor 5		PRO_0000069436
Regions
	Topological domain	1 – 40	40	Extracellular By similarity
	Transmembrane	41 – 61	21	Helical; Name=1; By similarity
	Topological domain	62 – 70	9	Cytoplasmic By similarity
	Transmembrane	71 – 91	21	Helical; Name=2; By similarity
	Topological domain	92 – 111	20	Extracellular By similarity
	Transmembrane	112 – 132	21	Helical; Name=3; By similarity
	Topological domain	133 – 151	19	Cytoplasmic By similarity
	Transmembrane	152 – 172	21	Helical; Name=4; By similarity
	Topological domain	173 – 192	20	Extracellular By similarity
	Transmembrane	193 – 213	21	Helical; Name=5; By similarity
	Topological domain	214 – 252	39	Cytoplasmic By similarity
	Transmembrane	253 – 273	21	Helical; Name=6; By similarity
	Topological domain	274 – 287	14	Extracellular By similarity
	Transmembrane	288 – 308	21	Helical; Name=7; By similarity
	Topological domain	309 – 398	90	Cytoplasmic By similarity
Amino acid modifications
	Lipidation	323	1	S-palmitoyl cysteine By similarity
	Glycosylation	20	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	214 – 310	97	RIYCQ…YTLTN → LAGLAAHAQRGAPGLCGMLG PPHPAAVARRGVPGAHLSCT PAGRSLPGTGHGQLTSEPHH LHAHQPRPAPRAPAPGLLRT PLLRQRPEWLPAVGERG in isoform 2.		VSP_013369
	Alternative sequence	311 – 398	88	Missing in isoform 2.		VSP_013370
	Natural variant	318	1	L → Q. Corresponds to variant rs35483143 [ dbSNP | Ensembl ].		VAR_033466

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 34ADC6C40D8250BF	FASTA	398	41,775
	10 20 30 40 50 60 MESGLLRPAP VSEVIVLHYN YTGKLRGARY QPGAGLRADA VVCLAVCAFI VLENLAVLLV 70 80 90 100 110 120 LGRHPRFHAP MFLLLGSLTL SDLLAGAAYA ANILLSGPLT LKLSPALWFA REGGVFVALT 130 140 150 160 170 180 ASVLSLLAIA LERSLTMARR GPAPVSSRGR TLAMAAAAWG VSLLLGLLPA LGWNCLGRLD 190 200 210 220 230 240 ACSTVLPLYA KAYVLFCVLA FVGILAAICA LYARIYCQVR ANARRLPARP GTAGTTSTRA 250 260 270 280 290 300 RRKPRSLALL RTLSVVLLAF VACWGPLFLL LLLDVACPAR TCPVLLQADP FLGLAMANSL 310 320 330 340 350 360 LNPIIYTLTN RDLRHALLRL VCCGRHSCGR DPSGSQQSAS AAEASGGLRR CLPPGLDGSF 370 380 390 SGSERSSPQR DGLDTSGSTG SPGAPTAART LVSEPAAD
	Isoform 2 [UniParc]. Checksum: 906D2B43EC85A8AB	FASTA	310	32,279
	10 20 30 40 50 60 MESGLLRPAP VSEVIVLHYN YTGKLRGARY QPGAGLRADA VVCLAVCAFI VLENLAVLLV 70 80 90 100 110 120 LGRHPRFHAP MFLLLGSLTL SDLLAGAAYA ANILLSGPLT LKLSPALWFA REGGVFVALT 130 140 150 160 170 180 ASVLSLLAIA LERSLTMARR GPAPVSSRGR TLAMAAAAWG VSLLLGLLPA LGWNCLGRLD 190 200 210 220 230 240 ACSTVLPLYA KAYVLFCVLA FVGILAAICA LYALAGLAAH AQRGAPGLCG MLGPPHPAAV 250 260 270 280 290 300 ARRGVPGAHL SCTPAGRSLP GTGHGQLTSE PHHLHAHQPR PAPRAPAPGL LRTPLLRQRP 310 EWLPAVGERG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a human sphingosine-1-phosphate receptor gene (S1P5) and its differential expression in LGL leukemia." Kothapalli R., Kusmartseva I., Loughran T.P. Jr. Biochim. Biophys. Acta 1579:117-123(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Lymphocyte.
[2]	"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] (ISOFORM 1). Tissue: Mammary gland.
[3]	"Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors." Im D.-S., Clemens J., Macdonald T.L., Lynch K.R. Biochemistry 40:14053-14060(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[4]	"Isolation of complete coding sequence for endothelial differentiation, sphingolipid GPCR 8 (EDG8)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Identification of G protein-coupled receptor genes from the human genome sequence." Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S. FEBS Lett. 520:97-101(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Erratum Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S. FEBS Lett. 523:257-257(2002)
[7]	"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].
[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] (ISOFORMS 1 AND 2). Tissue: Skin.
[9]	"Comparative analysis of human and rat S1P(5) (edg8): differential expression profiles and sensitivities to antagonists." Niedernberg A., Scherer C.R., Busch A.E., Kostenis E. Biochem. Pharmacol. 64:1243-1250(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Evidence for the presence of the sphingosine-1-phosphate receptor Edg-8 in human radial glial fibers." Ulfig N., Briese M. Acta Histochem. 106:373-378(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE, POSSIBLE FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF331840 mRNA. Translation: AAL57041.1. AK074661 mRNA. Translation: BAC11119.1. AF317676 Genomic DNA. Translation: AAG38113.1. AY262689 Genomic DNA. Translation: AAP20653.1. AB083602 Genomic DNA. Translation: BAB89315.1. AC011461 Genomic DNA. No translation available. BC034703 mRNA. Translation: AAH34703.1. BC067781 mRNA. Translation: AAH67781.1.
IPI	IPI00006152. IPI00432841.
RefSeq	NP_001159687.1. NM_001166215.1. NP_110387.1. NM_030760.4.
UniGene	Hs.501561.
3D structure databases
ProteinModelPortal	Q9H228.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H228. 1 interaction.
STRING	9606.ENSP00000328472.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9H228.
Polymorphism databases
DMDM	62510663.
Proteomic databases
PaxDb	Q9H228.
PRIDE	Q9H228.
Protocols and materials databases
DNASU	53637.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000333430; ENSP00000328472; ENSG00000180739. ENST00000439028; ENSP00000416915; ENSG00000180739.
GeneID	53637.
KEGG	hsa:53637.
UCSC	uc002mot.2. human.
Organism-specific databases
CTD	53637.
GeneCards	GC19M010626.
H-InvDB	HIX0174397.
HGNC	HGNC:14299. S1PR5.
HPA	HPA029683.
MIM	605146. gene.
neXtProt	NX_Q9H228.
PharmGKB	PA162402378.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG135858.
HOGENOM	HOG000233501.
HOVERGEN	HBG103071.
InParanoid	Q9H228.
KO	K04295.
OMA	PIIYTFT.
OrthoDB	EOG4PNXHD.
PhylomeDB	Q9H228.
Enzyme and pathway databases
Pathway_Interaction_DB	s1p_s1p4_pathway. S1P4 pathway. s1p_s1p5_pathway. S1P5 pathway. s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q9H228.
CleanEx	HS_S1PR5.
Genevestigator	Q9H228.
GermOnline	ENSG00000180739. Homo sapiens.
Family and domain databases
InterPro	IPR005386. EDG8_S1P_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR004061. S1P_rcpt. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR01561. EDG8RECEPTOR. 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	Q9H228.
ChEMBL	CHEMBL2274.
GenomeRNAi	53637.
NextBio	56120.
SOURCE	Search...

Entry information

Entry name

S1PR5_HUMAN

Accession

Primary (citable) accession number: Q9H228
Secondary accession number(s): Q6NW11

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 102 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.