S1PR4_HUMAN
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 03-AUG-2022, entry version 172.
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 GlyGen; O95977; 2 sites.
DR iPTMnet; O95977; -.
DR PhosphoSitePlus; O95977; -.
DR SwissPalm; O95977; -.
DR BioMuta; S1PR4; -.
DR jPOST; O95977; -.
DR MassIVE; O95977; -.
DR PaxDb; O95977; -.
DR PeptideAtlas; O95977; -.
DR PRIDE; O95977; -.
DR ProteomicsDB; 51157; -.
DR Antibodypedia; 10967; 390 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 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; MLCWGPL; -.
DR OrthoDB; 981486at2759; -.
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; 12 hits in 1064 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 tissues.
DR Genevisible; O95977; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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 InterPro; IPR004064; EDG6_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR004061; S1P_rcpt.
DR PANTHER; PTHR22750:SF13; PTHR22750:SF13; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01526; EDG6RECEPTOR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01523; S1PRECEPTOR.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
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
