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Protein

Sphingosine 1-phosphate receptor 4

Gene

S1PR4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: ProtInc
  2. lipid binding Source: ProtInc
  3. sphingosine-1-phosphate receptor activity Source: InterPro

GO - Biological processi

  1. activation of phospholipase C activity Source: ProtInc
  2. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
  3. G-protein coupled receptor signaling pathway Source: ProtInc
  4. immune response Source: ProtInc
  5. positive regulation of cytosolic calcium ion concentration Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_18365. Lysosphingolipid and LPA receptors.
REACT_19231. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
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 namesi
Name:S1PR4
Synonyms:EDG6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:3170. S1PR4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5050ExtracellularBy similarityAdd
BLAST
Transmembranei51 – 7121Helical; Name=1By similarityAdd
BLAST
Topological domaini72 – 8413CytoplasmicBy similarityAdd
BLAST
Transmembranei85 – 10521Helical; Name=2By similarityAdd
BLAST
Topological domaini106 – 11712ExtracellularBy similarityAdd
BLAST
Transmembranei118 – 13821Helical; Name=3By similarityAdd
BLAST
Topological domaini139 – 16123CytoplasmicBy similarityAdd
BLAST
Transmembranei162 – 18221Helical; Name=4By similarityAdd
BLAST
Topological domaini183 – 20624ExtracellularBy similarityAdd
BLAST
Transmembranei207 – 22721Helical; Name=5By similarityAdd
BLAST
Topological domaini228 – 25225CytoplasmicBy similarityAdd
BLAST
Transmembranei253 – 27321Helical; Name=6By similarityAdd
BLAST
Topological domaini274 – 28815ExtracellularBy similarityAdd
BLAST
Transmembranei289 – 30921Helical; Name=7By similarityAdd
BLAST
Topological domaini310 – 38475CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162402371.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 384384Sphingosine 1-phosphate receptor 4PRO_0000069431Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi2 – 21N-linked (GlcNAc...)Sequence Analysis
Glycosylationi30 – 301N-linked (GlcNAc...)Sequence Analysis
Lipidationi323 – 3231S-palmitoyl cysteineBy similarity

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiO95977.
PRIDEiO95977.

PTM databases

PhosphoSiteiO95977.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiO95977.
CleanExiHS_S1PR4.
GenevestigatoriO95977.

Organism-specific databases

HPAiHPA060601.

Interactioni

Protein-protein interaction databases

BioGridi114243. 2 interactions.
STRINGi9606.ENSP00000246115.

Structurei

Secondary structure

1
384
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi108 – 1114Combined sources
Beta strandi113 – 1164Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DCONMR-A105-118[»]
ProteinModelPortaliO95977.
SMRiO95977. Positions 24-319.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95977.

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG150569.
GeneTreeiENSGT00760000118804.
HOGENOMiHOG000233501.
HOVERGENiHBG103071.
InParanoidiO95977.
KOiK04293.
OMAiRANGQKA.
OrthoDBiEOG708W0B.
PhylomeDBiO95977.
TreeFamiTF330052.

Family and domain databases

InterProiIPR004064. EDG6_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004061. S1P_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF13. PTHR22750:SF13. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01526. EDG6RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01523. S1PRECEPTOR.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O95977-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNATGTPVAP ESCQQLAAGG HSRLIVLHYN HSGRLAGRGG PEDGGLGALR
60 70 80 90 100
GLSVAASCLV VLENLLVLAA ITSHMRSRRW VYYCLVNITL SDLLTGAAYL
110 120 130 140 150
ANVLLSGART FRLAPAQWFL REGLLFTALA ASTFSLLFTA GERFATMVRP
160 170 180 190 200
VAESGATKTS RVYGFIGLCW LLAALLGMLP LLGWNCLCAF DRCSSLLPLY
210 220 230 240 250
SKRYILFCLV IFAGVLATIM GLYGAIFRLV QASGQKAPRP AARRKARRLL
260 270 280 290 300
KTVLMILLAF LVCWGPLFGL LLADVFGSNL WAQEYLRGMD WILALAVLNS
310 320 330 340 350
AVNPIIYSFR SREVCRAVLS FLCCGCLRLG MRGPGDCLAR AVEAHSGAST
360 370 380
TDSSLRPRDS FRGSRSLSFR MREPLSSISS VRSI
Length:384
Mass (Da):41,623
Last modified:May 1, 1999 - v1
Checksum:i369A7BC56AB46A47
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti365 – 3651R → L.
Corresponds to variant rs3746072 [ dbSNP | Ensembl ].
VAR_022066

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12105.1.
RefSeqiNP_003766.1. NM_003775.3.
UniGeneiHs.662006.

Genome annotation databases

EnsembliENST00000246115; ENSP00000246115; ENSG00000125910.
GeneIDi8698.
KEGGihsa:8698.
UCSCiuc002lxg.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12105.1.
RefSeqiNP_003766.1. NM_003775.3.
UniGeneiHs.662006.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DCONMR-A105-118[»]
ProteinModelPortaliO95977.
SMRiO95977. Positions 24-319.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114243. 2 interactions.
STRINGi9606.ENSP00000246115.

Chemistry

BindingDBiO95977.
ChEMBLiCHEMBL2363041.
GuidetoPHARMACOLOGYi278.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiO95977.

Proteomic databases

PaxDbiO95977.
PRIDEiO95977.

Protocols and materials databases

DNASUi8698.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246115; ENSP00000246115; ENSG00000125910.
GeneIDi8698.
KEGGihsa:8698.
UCSCiuc002lxg.3. human.

Organism-specific databases

CTDi8698.
GeneCardsiGC19P003178.
H-InvDBHIX0174310.
HGNCiHGNC:3170. S1PR4.
HPAiHPA060601.
MIMi603751. gene.
neXtProtiNX_O95977.
PharmGKBiPA162402371.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG150569.
GeneTreeiENSGT00760000118804.
HOGENOMiHOG000233501.
HOVERGENiHBG103071.
InParanoidiO95977.
KOiK04293.
OMAiRANGQKA.
OrthoDBiEOG708W0B.
PhylomeDBiO95977.
TreeFamiTF330052.

Enzyme and pathway databases

ReactomeiREACT_18365. Lysosphingolipid and LPA receptors.
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

EvolutionaryTraceiO95977.
GeneWikiiS1PR4.
GenomeRNAii8698.
NextBioi32617.
PROiO95977.
SOURCEiSearch...

Gene expression databases

BgeeiO95977.
CleanExiHS_S1PR4.
GenevestigatoriO95977.

Family and domain databases

InterProiIPR004064. EDG6_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004061. S1P_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF13. PTHR22750:SF13. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01526. EDG6RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01523. S1PRECEPTOR.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 105-122.

Entry informationi

Entry nameiS1PR4_HUMAN
AccessioniPrimary (citable) accession number: O95977
Secondary accession number(s): D6W612
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: May 1, 1999
Last modified: January 7, 2015
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.