ID   S1PR4_HUMAN             Reviewed;         384 AA.
AC   O95977; D6W612;
DT   16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=Sphingosine 1-phosphate receptor 4;
DE            Short=S1P receptor 4;
DE            Short=S1P4;
DE   AltName: Full=Endothelial differentiation G-protein coupled receptor 6;
DE   AltName: Full=Sphingosine 1-phosphate receptor Edg-6;
DE            Short=S1P receptor Edg-6;
GN   Name=S1PR4; Synonyms=EDG6;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Dendritic cell;
RX   PubMed=9790765; DOI=10.1006/geno.1998.5491;
RA   Graeler M.H., Bernhardt G., Lipp M.;
RT   "EDG6, a novel G protein-coupled receptor related to receptors for
RT   bioactive lysophospholipids, is specifically expressed in lymphoid
RT   tissue.";
RL   Genomics 53:164-169(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT   "cDNA clones of human proteins involved in signal transduction sequenced by
RT   the Guthrie cDNA resource center (www.cdna.org).";
RL   Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Blood;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   FUNCTION.
RX   PubMed=10679247; DOI=10.1006/bbrc.2000.2162;
RA   Yamazaki Y., Kon J., Sato K., Tomura H., Sato M., Yoneya T., Okazaki H.,
RA   Okajima F., Ohta H.;
RT   "Edg-6 as a putative sphingosine 1-phosphate receptor coupling to Ca(2+)
RT   signaling pathway.";
RL   Biochem. Biophys. Res. Commun. 268:583-589(2000).
RN   [6]
RP   FUNCTION.
RX   PubMed=10753843;
RA   Van Brocklyn J.R., Graeler M.H., Bernhardt G., Hobson J.P., Lipp M.,
RA   Spiegel S.;
RT   "Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor
RT   EDG-6.";
RL   Blood 95:2624-2629(2000).
RN   [7]
RP   STRUCTURE BY NMR OF 105-122.
RX   PubMed=17443712; DOI=10.1002/bip.20745;
RA   Pham T.-C.T., Kriwacki R.W., Parrill A.L.;
RT   "Peptide design and structural characterization of a GPCR loop mimetic.";
RL   Biopolymers 86:298-310(2007).
CC   -!- FUNCTION: Receptor for the lysosphingolipid sphingosine 1-phosphate
CC       (S1P). S1P is a bioactive lysophospholipid that elicits diverse
CC       physiological effect on most types of cells and tissues. May be
CC       involved in cell migration processes that are specific for lymphocytes.
CC       {ECO:0000269|PubMed:10679247, ECO:0000269|PubMed:10753843}.
CC   -!- INTERACTION:
CC       O95977; P57678: GEMIN4; NbExp=3; IntAct=EBI-12194739, EBI-356700;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Specifically expressed in fetal and adult lymphoid
CC       and hematopoietic tissue as well as in lung. Considerable level of
CC       expression in adult and fetal spleen as well as adult peripheral
CC       leukocytes and lung. Lower expression in adult thymus, lymph node, bone
CC       marrow, and appendix as well as in fetal liver, thymus, and lung.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; AJ000479; CAA04118.1; -; mRNA.
DR   EMBL; AY322537; AAP84350.1; -; Genomic_DNA.
DR   EMBL; CH471139; EAW69336.1; -; Genomic_DNA.
DR   EMBL; CH471139; EAW69337.1; -; Genomic_DNA.
DR   EMBL; BC014970; AAH14970.1; -; mRNA.
DR   CCDS; CCDS12105.1; -.
DR   RefSeq; NP_003766.1; NM_003775.3.
DR   PDB; 2DCO; NMR; -; A=105-118.
DR   PDBsum; 2DCO; -.
DR   AlphaFoldDB; O95977; -.
DR   SMR; O95977; -.
DR   BioGRID; 114243; 157.
DR   CORUM; O95977; -.
DR   IntAct; O95977; 3.
DR   STRING; 9606.ENSP00000246115; -.
DR   BindingDB; O95977; -.
DR   ChEMBL; CHEMBL3230; -.
DR   DrugBank; DB08868; Fingolimod.
DR   DrugCentral; O95977; -.
DR   GuidetoPHARMACOLOGY; 278; -.
DR   GlyCosmos; O95977; 2 sites, No reported glycans.
DR   GlyGen; O95977; 2 sites.
DR   iPTMnet; O95977; -.
DR   PhosphoSitePlus; O95977; -.
DR   SwissPalm; O95977; -.
DR   BioMuta; S1PR4; -.
DR   jPOST; O95977; -.
DR   MassIVE; O95977; -.
DR   PaxDb; 9606-ENSP00000246115; -.
DR   PeptideAtlas; O95977; -.
DR   ProteomicsDB; 51157; -.
DR   Antibodypedia; 10967; 421 antibodies from 37 providers.
DR   DNASU; 8698; -.
DR   Ensembl; ENST00000246115.5; ENSP00000246115.3; ENSG00000125910.6.
DR   GeneID; 8698; -.
DR   KEGG; hsa:8698; -.
DR   MANE-Select; ENST00000246115.5; ENSP00000246115.3; NM_003775.4; NP_003766.1.
DR   UCSC; uc002lxg.4; human.
DR   AGR; HGNC:3170; -.
DR   CTD; 8698; -.
DR   DisGeNET; 8698; -.
DR   GeneCards; S1PR4; -.
DR   HGNC; HGNC:3170; S1PR4.
DR   HPA; ENSG00000125910; Tissue enhanced (bone marrow, lymphoid tissue).
DR   MIM; 603751; gene.
DR   neXtProt; NX_O95977; -.
DR   OpenTargets; ENSG00000125910; -.
DR   PharmGKB; PA162402371; -.
DR   VEuPathDB; HostDB:ENSG00000125910; -.
DR   eggNOG; ENOG502QQUE; Eukaryota.
DR   GeneTree; ENSGT01050000244887; -.
DR   HOGENOM; CLU_047979_1_1_1; -.
DR   InParanoid; O95977; -.
DR   OMA; PAHWFLR; -.
DR   OrthoDB; 4607247at2759; -.
DR   PhylomeDB; O95977; -.
DR   TreeFam; TF330052; -.
DR   PathwayCommons; O95977; -.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-419408; Lysosphingolipid and LPA receptors.
DR   SignaLink; O95977; -.
DR   SIGNOR; O95977; -.
DR   BioGRID-ORCS; 8698; 15 hits in 1144 CRISPR screens.
DR   EvolutionaryTrace; O95977; -.
DR   GeneWiki; S1PR4; -.
DR   GenomeRNAi; 8698; -.
DR   Pharos; O95977; Tclin.
DR   PRO; PR:O95977; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O95977; Protein.
DR   Bgee; ENSG00000125910; Expressed in granulocyte and 125 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0008289; F:lipid binding; TAS:ProtInc.
DR   GO; GO:0038036; F:sphingosine-1-phosphate receptor activity; IEA:InterPro.
DR   GO; GO:0007202; P:activation of phospholipase C activity; TAS:ProtInc.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; TAS:ProtInc.
DR   GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR004064; EDG6_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR004061; S1P_rcpt.
DR   PANTHER; PTHR22750; G-PROTEIN COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR22750:SF13; SPHINGOSINE 1-PHOSPHATE RECEPTOR 4; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR01526; EDG6RECEPTOR.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01523; S1PRECEPTOR.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; O95977; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; G-protein coupled receptor; Glycoprotein;
KW   Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..384
FT                   /note="Sphingosine 1-phosphate receptor 4"
FT                   /id="PRO_0000069431"
FT   TOPO_DOM        1..50
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        51..71
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        72..84
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        85..105
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        106..117
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        118..138
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        139..161
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        162..182
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        183..206
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        207..227
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        228..252
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        253..273
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        274..288
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        289..309
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        310..384
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   LIPID           323
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        2
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        30
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         365
FT                   /note="R -> L (in dbSNP:rs3746072)"
FT                   /id="VAR_022066"
FT   HELIX           108..111
FT                   /evidence="ECO:0007829|PDB:2DCO"
FT   STRAND          113..116
FT                   /evidence="ECO:0007829|PDB:2DCO"
SQ   SEQUENCE   384 AA;  41623 MW;  369A7BC56AB46A47 CRC64;
     MNATGTPVAP ESCQQLAAGG HSRLIVLHYN HSGRLAGRGG PEDGGLGALR GLSVAASCLV
     VLENLLVLAA ITSHMRSRRW VYYCLVNITL SDLLTGAAYL ANVLLSGART FRLAPAQWFL
     REGLLFTALA ASTFSLLFTA GERFATMVRP VAESGATKTS RVYGFIGLCW LLAALLGMLP
     LLGWNCLCAF DRCSSLLPLY SKRYILFCLV IFAGVLATIM GLYGAIFRLV QASGQKAPRP
     AARRKARRLL KTVLMILLAF LVCWGPLFGL LLADVFGSNL WAQEYLRGMD WILALAVLNS
     AVNPIIYSFR SREVCRAVLS FLCCGCLRLG MRGPGDCLAR AVEAHSGAST TDSSLRPRDS
     FRGSRSLSFR MREPLSSISS VRSI
//