O95977 (S1PR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingosine 1-phosphate receptor 4
Short name=S1P receptor 4
Short name=S1P4

Alternative name(s):
Endothelial differentiation G-protein coupled receptor 6
Sphingosine 1-phosphate receptor Edg-6
Short name=S1P receptor Edg-6

Gene names

Name:	S1PR4
Synonyms:	EDG6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	384 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. May be involved in cell migration processes that are specific for lymphocytes. Ref.5 Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Specifically expressed in fetal and adult lymphoid and hematopoietic tissue as well as in lung. Considerable level of expression in adult and fetal spleen as well as adult peripheral leukocytes and lung. Lower expression in adult thymus, lymph node, bone marrow, and appendix as well as in fetal liver, thymus, and lung.
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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of phospholipase C activity Traceable author statement. Source: ProtInc elevation of cytosolic calcium ion concentration Traceable author statement. Source: ProtInc immune response Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	G-protein coupled receptor activity Traceable author statement. Source: ProtInc lipid binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 384

384

Sphingosine 1-phosphate receptor 4

PRO_0000069431

Regions

Topological domain

1 – 50

50

Extracellular By similarity

Transmembrane

51 – 71

21

Helical; Name=1; By similarity

Topological domain

72 – 84

13

Cytoplasmic By similarity

Transmembrane

85 – 105

21

Helical; Name=2; By similarity

Topological domain

106 – 117

12

Extracellular By similarity

Transmembrane

118 – 138

21

Helical; Name=3; By similarity

Topological domain

139 – 161

23

Cytoplasmic By similarity

Transmembrane

162 – 182

21

Helical; Name=4; By similarity

Topological domain

183 – 206

24

Extracellular By similarity

Transmembrane

207 – 227

21

Helical; Name=5; By similarity

Topological domain

228 – 252

25

Cytoplasmic By similarity

Transmembrane

253 – 273

21

Helical; Name=6; By similarity

Topological domain

274 – 288

15

Extracellular By similarity

Transmembrane

289 – 309

21

Helical; Name=7; By similarity

Topological domain

310 – 384

75

Cytoplasmic By similarity

Amino acid modifications

Lipidation

323

1

S-palmitoyl cysteine By similarity

Glycosylation

2

1

N-linked (GlcNAc...) Potential

Glycosylation

30

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

365

1

R → L.
Corresponds to variant rs3746072 [ dbSNP | Ensembl ].

VAR_022066

Secondary structure

1

.

.

.

.

.

384

Helix Strand Turn

Details...

Helix

108 – 111

4

Beta strand

113 – 116

4

Sequences

	Sequence		Length	Mass (Da)
	O95977 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 369A7BC56AB46A47	FASTA	384	41,623
	10 20 30 40 50 60 MNATGTPVAP ESCQQLAAGG HSRLIVLHYN HSGRLAGRGG PEDGGLGALR GLSVAASCLV 70 80 90 100 110 120 VLENLLVLAA ITSHMRSRRW VYYCLVNITL SDLLTGAAYL ANVLLSGART FRLAPAQWFL 130 140 150 160 170 180 REGLLFTALA ASTFSLLFTA GERFATMVRP VAESGATKTS RVYGFIGLCW LLAALLGMLP 190 200 210 220 230 240 LLGWNCLCAF DRCSSLLPLY SKRYILFCLV IFAGVLATIM GLYGAIFRLV QASGQKAPRP 250 260 270 280 290 300 AARRKARRLL KTVLMILLAF LVCWGPLFGL LLADVFGSNL WAQEYLRGMD WILALAVLNS 310 320 330 340 350 360 AVNPIIYSFR SREVCRAVLS FLCCGCLRLG MRGPGDCLAR AVEAHSGAST TDSSLRPRDS 370 380 FRGSRSLSFR MREPLSSISS VRSI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"EDG6, a novel G protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue." Graeler M.H., Bernhardt G., Lipp M. Genomics 53:164-169(1998) [PubMed: 9790765] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Dendritic cell.
[2]	"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 [LARGE SCALE MRNA].
[3]	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].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood.
[5]	"Edg-6 as a putative sphingosine 1-phosphate receptor coupling to Ca(2+) signaling pathway." Yamazaki Y., Kon J., Sato K., Tomura H., Sato M., Yoneya T., Okazaki H., Okajima F., Ohta H. Biochem. Biophys. Res. Commun. 268:583-589(2000) [PubMed: 10679247] [Abstract] Cited for: FUNCTION.
[6]	"Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6." Van Brocklyn J.R., Graeler M.H., Bernhardt G., Hobson J.P., Lipp M., Spiegel S. Blood 95:2624-2629(2000) [PubMed: 10753843] [Abstract] Cited for: FUNCTION.
[7]	"Peptide design and structural characterization of a GPCR loop mimetic." Pham T.-C.T., Kriwacki R.W., Parrill A.L. Biopolymers 86:298-310(2007) [PubMed: 17443712] [Abstract] Cited for: STRUCTURE BY NMR OF 105-122.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ000479 mRNA. Translation: CAA04118.1.
AY322537 Genomic DNA. Translation: AAP84350.1.
CH471139 Genomic DNA. Translation: EAW69336.1.
CH471139 Genomic DNA. Translation: EAW69337.1.
BC014970 mRNA. Translation: AAH14970.1.

IPI

IPI00021534.

RefSeq

NP_003766.1. NM_003775.3.

UniGene

Hs.662006.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DCO	NMR	-	A	105-118	[»]

ProteinModelPortal

O95977.

SMR

O95977. Positions 47-329.

ModBase

Search...

Protein-protein interaction databases

STRING

O95977.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

O95977.

Proteomic databases

PRIDE

O95977.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000246115; ENSP00000246115; ENSG00000125910.

GeneID

8698.

KEGG

hsa:8698.

UCSC

uc002lxg.1. human.

Organism-specific databases

CTD

8698.

GeneCards

GC19P003178.

H-InvDB

HIX0014635.

HGNC

HGNC:3170. S1PR4.

MIM

603751. gene.

neXtProt

NX_O95977.

PharmGKB

PA162402371.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14306.

GeneTree

ENSGT00590000082727.

HOGENOM

HBG714382.

HOVERGEN

HBG103071.

InParanoid

O95977.

OMA

FQRCSSL.

OrthoDB

EOG415GDR.

PhylomeDB

O95977.

Enzyme and pathway databases

Pathway_Interaction_DB

s1p_s1p4_pathway. S1P4 pathway.
s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

O95977.

Bgee

O95977.

CleanEx

HS_S1PR4.

Genevestigator

O95977.

GermOnline

ENSG00000125910. Homo sapiens.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR004064. EDG6_rcpt.
IPR017452. GPCR_Rhodpsn_supfam.
IPR004061. S1P_rcpt.
[Graphical view]

KO

K04293.

PANTHER

PTHR22750:SF13. EDG6_rcpt. 1 hit.

Pfam

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

PRINTS

PR01526. EDG6RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01523. S1PRECEPTOR.

PROSITE

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

ProtoNet

Search...

Other

NextBio

32617.

SOURCE

Search...

Entry information

Entry name

S1PR4_HUMAN

Accession

Primary (citable) accession number: O95977
Secondary accession number(s): D6W612

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 96 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.