P21453 (S1PR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingosine 1-phosphate receptor 1
Short name=S1P receptor 1
Short name=S1P1

Alternative name(s):
Endothelial differentiation G-protein coupled receptor 1
Sphingosine 1-phosphate receptor Edg-1
Short name=S1P receptor Edg-1
CD_antigen=CD363

Gene names

Name:	S1PR1
Synonyms:	CHEDG1, EDG1

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	382 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. This inducible epithelial cell G-protein-coupled receptor may be involved in the processes that regulate the differentiation of endothelial cells. Seems to be coupled to the G(i) subclass of heteromeric G proteins. Ref.10 Ref.13
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Endothelial cells, and to a lesser extent, in vascular smooth muscle cells, fibroblasts, melanocytes, and cells of epithelioid origin.
Induction	By the tumor promoter phorbol 12-myristate 13-acetate (PMA) in the presence of cycloheximide.
Post-translational modification	S1P-induced endothelial cell migration requires the PKB/AKT1-mediated phosphorylation of the third intracellular loop at the Thr-236 residue.
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 Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara angiogenesis Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara cell adhesion Traceable author statement PubMed 10555146Ref.10. Source: ProtInc elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Inferred from electronic annotation. Source: Compara endothelial cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of stress fiber assembly Inferred from electronic annotation. Source: Compara neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of Ras GTPase activity Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from electronic annotation. Source: Compara positive regulation of positive chemotaxis Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of cell adhesion Inferred from electronic annotation. Source: Compara sphingosine-1-phosphate signaling pathway Inferred from electronic annotation. Source: GOC transmission of nerve impulse Inferred from electronic annotation. Source: Compara
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.9. Source: ProtInc sphingolipid binding Inferred from electronic annotation. Source: Compara 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 – 382

382

Sphingosine 1-phosphate receptor 1

PRO_0000069412

Regions

Topological domain

1 – 46

46

Extracellular By similarity

Transmembrane

47 – 71

25

Helical; Name=1; By similarity

Topological domain

72 – 78

7

Cytoplasmic By similarity

Transmembrane

79 – 107

29

Helical; Name=2; By similarity

Topological domain

108 – 121

14

Extracellular By similarity

Transmembrane

122 – 140

19

Helical; Name=3; By similarity

Topological domain

141 – 159

19

Cytoplasmic By similarity

Transmembrane

160 – 185

26

Helical; Name=4; By similarity

Topological domain

186 – 201

16

Extracellular By similarity

Transmembrane

202 – 222

21

Helical; Name=5; By similarity

Topological domain

223 – 255

33

Cytoplasmic By similarity

Transmembrane

256 – 277

22

Helical; Name=6; By similarity

Topological domain

278 – 293

16

Extracellular By similarity

Transmembrane

294 – 314

21

Helical; Name=7; By similarity

Topological domain

315 – 382

68

Cytoplasmic By similarity

Amino acid modifications

Modified residue

236

1

Phosphothreonine; by PKB/AKT1 Ref.12

Modified residue

353

1

Phosphoserine Potential

Lipidation

328

1

S-palmitoyl cysteine By similarity

Glycosylation

30

1

N-linked (GlcNAc...) Potential

Glycosylation

36

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

15

1

S → L.
Corresponds to variant rs4987250 [ dbSNP | Ensembl ].

VAR_046158

Natural variant

115

1

A → T.
Corresponds to variant rs11542632 [ dbSNP | Ensembl ].

VAR_046159

Natural variant

332

1

P → R.
Corresponds to variant rs7549921 [ dbSNP | Ensembl ].

VAR_046160

Experimental info

Mutagenesis

120

1

R → A: Drastically reduced affinity for sphingosine 1-phosphate. Ref.3

Mutagenesis

121

1

E → A: Drastically reduced affinity for sphingosine 1-phosphate. Ref.3

Mutagenesis

121

1

E → Q: Slight activation of the receptor at maximal ligand concentration. Ref.3

Mutagenesis

236

1

T → A: Acts as a dominant negative GPCR and inhibits S1P-induced Rac activation, chemotaxis, and angiogenesis. Ref.12

Mutagenesis

292

1

R → A or V: Drastically reduced affinity for sphingosine 1-phosphate. Ref.3

Sequence conflict

250 – 252

3

KSL → NV in AAA52336. Ref.1

Sequence conflict

250 – 252

3

KSL → NV in AAC51905. Ref.2

Secondary structure

1

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382

Helix Strand Turn

Details...

Helix

23 – 31

9

Helix

36 – 39

4

Helix

42 – 72

31

Helix

74 – 76

3

Helix

79 – 104

26

Helix

106 – 109

4

Helix

114 – 146

33

Helix

158 – 176

19

Turn

177 – 181

5

Helix

188 – 190

3

Beta strand

193 – 195

3

Helix

200 – 231

32

Helix

253 – 280

28

Turn

284 – 286

3

Turn

289 – 291

3

Helix

294 – 302

9

Helix

303 – 305

3

Helix

307 – 314

8

Helix

316 – 323

8

Sequences

	Sequence		Length	Mass (Da)
	P21453 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: 0CCE8685A5E1BAD2	FASTA	382	42,811
	10 20 30 40 50 60 MGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII 70 80 90 100 110 120 LENIFVLLTI WKTKKFHRPM YYFIGNLALS DLLAGVAYTA NLLLSGATTY KLTPAQWFLR 130 140 150 160 170 180 EGSMFVALSA SVFSLLAIAI ERYITMLKMK LHNGSNNFRL FLLISACWVI SLILGGLPIM 190 200 210 220 230 240 GWNCISALSS CSTVLPLYHK HYILFCTTVF TLLLLSIVIL YCRIYSLVRT RSRRLTFRKN 250 260 270 280 290 300 ISKASRSSEK SLALLKTVII VLSVFIACWA PLFILLLLDV GCKVKTCDIL FRAEYFLVLA 310 320 330 340 350 360 VLNSGTNPII YTLTNKEMRR AFIRIMSCCK CPSGDSAGKF KRPIIAGMEF SRSKSDNSSH 370 380 PQKDEGDNPE TIMSSGNVNS SS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors." Hla T., Maciag T. J. Biol. Chem. 265:9308-9313(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Umbilical vein endothelial cell.
[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: Lung.
[3]	"Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate." Parrill A.L., Wang D., Bautista D.L., Van Brocklyn J.R., Lorincz Z., Fischer D.J., Baker D.L., Liliom K., Spiegel S., Tigyi G. J. Biol. Chem. 275:39379-39384(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF ARG-120; GLU-121 AND ARG-292.
[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: Substantia nigra.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [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 (SEP-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]. Tissue: Lung.
[9]	"The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway." Lee M.-J., Evans M., Hla T. J. Biol. Chem. 271:11272-11279(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHARMACOLOGICAL CHARACTERIZATION.
[10]	"Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1." Lee M.-J., Van Brocklyn J.R., Thangada S., Liu C.H., Hand A.R., Menzeleev R., Spiegel S., Hla T. Science 279:1552-1555(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"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.
[12]	"Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis." Lee M.-J., Thangada S., Paik J.-H., Sapkota G.P., Ancellin N., Chae S.-S., Wu M., Morales-Ruiz M., Sessa W.C., Alessi D.R., Hla T. Mol. Cell 8:693-704(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-236, MUTAGENESIS OF THR-236.
[13]	"Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility." Hobson J.P., Rosenfeldt H.M., Barak L.S., Olivera A., Poulton S., Caron M.G., Milstien S., Spiegel S. Science 291:1800-1803(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M31210 mRNA. Translation: AAA52336.1.
AF022137 mRNA. Translation: AAC51905.1.
AF233365 mRNA. Translation: AAF43420.1.
AK312493 mRNA. Translation: BAG35395.1.
CR541786 mRNA. Translation: CAG46585.1.
CR542269 mRNA. Translation: CAG47065.1.
AL109741 Genomic DNA. Translation: CAI21861.1.
CH471097 Genomic DNA. Translation: EAW72927.1.
CH471097 Genomic DNA. Translation: EAW72928.1.
BC018650 mRNA. Translation: AAH18650.1.

IPI

IPI00015343.

PIR

A35300.

RefSeq

NP_001391.2. NM_001400.4.

UniGene

Hs.154210.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3V2W	X-ray	3.35	A	2-326	[»]
3V2Y	X-ray	2.80	A	2-326	[»]

ProteinModelPortal

P21453.

ModBase

Search...

Protein-protein interaction databases

IntAct

P21453. 2 interactions.

STRING

9606.ENSP00000305416.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P21453.

Polymorphism databases

DMDM

205371820.

Proteomic databases

PaxDb

P21453.

PRIDE

P21453.

Protocols and materials databases

DNASU

1901.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000305352; ENSP00000305416; ENSG00000170989.

GeneID

1901.

KEGG

hsa:1901.

UCSC

uc001dud.2. human.

Organism-specific databases

CTD

1901.

GeneCards

GC01P101702.

HGNC

HGNC:3165. S1PR1.

HPA

CAB010104.

MIM

601974. gene.

neXtProt

NX_P21453.

PharmGKB

PA162402344.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG148018.

HOGENOM

HOG000233501.

HOVERGEN

HBG103071.

InParanoid

P21453.

KO

K04288.

OrthoDB

EOG418BNR.

PhylomeDB

P21453.

Enzyme and pathway databases

Pathway_Interaction_DB

fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
pdgfrbpathway. PDGFR-beta signaling pathway.
s1p_s1p1_pathway. S1P1 pathway.
s1p_s1p3_pathway. S1P3 pathway.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P21453.

Bgee

P21453.

CleanEx

HS_S1PR1.

Genevestigator

P21453.

GermOnline

ENSG00000170989. Homo sapiens.

Family and domain databases

InterPro

IPR000987. EDG1_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004061. S1P_rcpt.
[Graphical view]

Pfam

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

PRINTS

PR00642. EDG1RECEPTOR.
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

P21453.

ChEMBL

CHEMBL4333.

GenomeRNAi

1901.

NextBio

7743.

SOURCE

Search...

Entry information

Entry name

S1PR1_HUMAN

Accession

Primary (citable) accession number: P21453
Secondary accession number(s): D3DT66, Q9BYY4, Q9NYN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	September 2, 2008
Last modified:	May 1, 2013
This is version 130 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.