S1PR5_HUMAN
ID S1PR5_HUMAN Reviewed; 398 AA.
AC Q9H228; Q6NW11;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Sphingosine 1-phosphate receptor 5;
DE Short=S1P receptor 5;
DE Short=S1P5;
DE AltName: Full=Endothelial differentiation G-protein-coupled receptor 8;
DE AltName: Full=Sphingosine 1-phosphate receptor Edg-8;
DE Short=S1P receptor Edg-8;
GN Name=S1PR5; Synonyms=EDG8;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Lymphocyte;
RX PubMed=12427546; DOI=10.1016/s0167-4781(02)00529-8;
RA Kothapalli R., Kusmartseva I., Loughran T.P. Jr.;
RT "Characterization of a human sphingosine-1-phosphate receptor gene (S1P5)
RT and its differential expression in LGL leukemia.";
RL Biochim. Biophys. Acta 1579:117-123(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=11705398; DOI=10.1021/bi011606i;
RA Im D.-S., Clemens J., Macdonald T.L., Lynch K.R.;
RT "Characterization of the human and mouse sphingosine 1-phosphate receptor,
RT S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate
RT receptors.";
RL Biochemistry 40:14053-14060(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "Isolation of complete coding sequence for endothelial differentiation,
RT sphingolipid GPCR 8 (EDG8).";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12044878; DOI=10.1016/s0014-5793(02)02775-8;
RA Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.;
RT "Identification of G protein-coupled receptor genes from the human genome
RT sequence.";
RL FEBS Lett. 520:97-101(2002).
RN [6]
RP ERRATUM OF PUBMED:12044878.
RA Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.;
RL FEBS Lett. 523:257-257(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin;
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 [9]
RP TISSUE SPECIFICITY.
RX PubMed=12234605; DOI=10.1016/s0006-2952(02)01289-3;
RA Niedernberg A., Scherer C.R., Busch A.E., Kostenis E.;
RT "Comparative analysis of human and rat S1P(5) (edg8): differential
RT expression profiles and sensitivities to antagonists.";
RL Biochem. Pharmacol. 64:1243-1250(2002).
RN [10]
RP DEVELOPMENTAL STAGE, AND POSSIBLE FUNCTION.
RX PubMed=15530552; DOI=10.1016/j.acthis.2004.08.002;
RA Ulfig N., Briese M.;
RT "Evidence for the presence of the sphingosine-1-phosphate receptor Edg-8 in
RT human radial glial fibers.";
RL Acta Histochem. 106:373-378(2004).
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. Is coupled to
CC both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins (By
CC similarity). May play a regulatory role in the transformation of radial
CC glial cells into astrocytes and may affect proliferative activity of
CC these cells. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9H228; P48165: GJA8; NbExp=3; IntAct=EBI-2564169, EBI-17458373;
CC Q9H228; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-2564169, EBI-17280858;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H228-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H228-2; Sequence=VSP_013369, VSP_013370;
CC -!- TISSUE SPECIFICITY: Widely expressed in the brain, most prominently in
CC the corpus callosum, which is predominantly white matter. Detected in
CC spleen, peripheral blood leukocytes, placenta, lung, aorta and fetal
CC spleen. Low-level signal detected in many tissue extracts.
CC Overexpressed in leukemic large granular lymphocytes. Isoform 1 is
CC predominantly expressed in peripheral tissues. Isoform 2 is expressed
CC in brain, spleen and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:11705398, ECO:0000269|PubMed:12234605,
CC ECO:0000269|PubMed:12427546}.
CC -!- DEVELOPMENTAL STAGE: At 24 weeks of gestation, fragments of radial
CC glial fibers are positive within the cortical plate and subplate of
CC allocortical areas. These positive fragments often appear enlarged as
CC varicosities and some of them terminate at blood vessels. Between 28
CC and 30 weeks of gestation, all iso- and allocortical areas contain
CC immunolabeled radial glial fibers revealing curvature next to sulci.
CC After 32 weeks of gestation, radial glial fibers gradually disappear;
CC instead positive transitional stages between radial glia and astrocytes
CC were found. {ECO:0000269|PubMed:15530552}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF331840; AAL57041.1; -; mRNA.
DR EMBL; AK074661; BAC11119.1; -; mRNA.
DR EMBL; AF317676; AAG38113.1; -; Genomic_DNA.
DR EMBL; AY262689; AAP20653.1; -; Genomic_DNA.
DR EMBL; AB083602; BAB89315.1; -; Genomic_DNA.
DR EMBL; AC011461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034703; AAH34703.1; -; mRNA.
DR EMBL; BC067781; AAH67781.1; -; mRNA.
DR CCDS; CCDS12240.1; -. [Q9H228-1]
DR RefSeq; NP_001159687.1; NM_001166215.1. [Q9H228-1]
DR RefSeq; NP_110387.1; NM_030760.4. [Q9H228-1]
DR PDB; 7EW1; EM; 3.40 A; A=1-344.
DR PDBsum; 7EW1; -.
DR AlphaFoldDB; Q9H228; -.
DR SMR; Q9H228; -.
DR BioGRID; 119793; 17.
DR CORUM; Q9H228; -.
DR IntAct; Q9H228; 10.
DR MINT; Q9H228; -.
DR STRING; 9606.ENSP00000328472; -.
DR BindingDB; Q9H228; -.
DR ChEMBL; CHEMBL2274; -.
DR DrugBank; DB08868; Fingolimod.
DR DrugBank; DB12612; Ozanimod.
DR DrugBank; DB12371; Siponimod.
DR DrugCentral; Q9H228; -.
DR GuidetoPHARMACOLOGY; 279; -.
DR GlyGen; Q9H228; 1 site.
DR iPTMnet; Q9H228; -.
DR PhosphoSitePlus; Q9H228; -.
DR BioMuta; S1PR5; -.
DR DMDM; 62510663; -.
DR MassIVE; Q9H228; -.
DR MaxQB; Q9H228; -.
DR PaxDb; Q9H228; -.
DR PeptideAtlas; Q9H228; -.
DR PRIDE; Q9H228; -.
DR ProteomicsDB; 80479; -. [Q9H228-1]
DR ProteomicsDB; 80480; -. [Q9H228-2]
DR Antibodypedia; 12897; 409 antibodies from 37 providers.
DR DNASU; 53637; -.
DR Ensembl; ENST00000333430.6; ENSP00000328472.3; ENSG00000180739.15. [Q9H228-1]
DR Ensembl; ENST00000439028.3; ENSP00000416915.2; ENSG00000180739.15. [Q9H228-1]
DR GeneID; 53637; -.
DR KEGG; hsa:53637; -.
DR MANE-Select; ENST00000333430.6; ENSP00000328472.3; NM_030760.5; NP_110387.1.
DR UCSC; uc002mot.2; human. [Q9H228-1]
DR CTD; 53637; -.
DR DisGeNET; 53637; -.
DR GeneCards; S1PR5; -.
DR HGNC; HGNC:14299; S1PR5.
DR HPA; ENSG00000180739; Tissue enhanced (brain).
DR MIM; 605146; gene.
DR neXtProt; NX_Q9H228; -.
DR OpenTargets; ENSG00000180739; -.
DR PharmGKB; PA162402378; -.
DR VEuPathDB; HostDB:ENSG00000180739; -.
DR eggNOG; ENOG502QSWN; Eukaryota.
DR GeneTree; ENSGT01050000244887; -.
DR HOGENOM; CLU_047979_1_0_1; -.
DR InParanoid; Q9H228; -.
DR OMA; LVLHYNY; -.
DR OrthoDB; 981486at2759; -.
DR PhylomeDB; Q9H228; -.
DR TreeFam; TF330052; -.
DR PathwayCommons; Q9H228; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-419408; Lysosphingolipid and LPA receptors.
DR SignaLink; Q9H228; -.
DR SIGNOR; Q9H228; -.
DR BioGRID-ORCS; 53637; 18 hits in 1068 CRISPR screens.
DR ChiTaRS; S1PR5; human.
DR GeneWiki; S1PR5; -.
DR GenomeRNAi; 53637; -.
DR Pharos; Q9H228; Tclin.
DR PRO; PR:Q9H228; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H228; protein.
DR Bgee; ENSG00000180739; Expressed in granulocyte and 133 other tissues.
DR ExpressionAtlas; Q9H228; baseline and differential.
DR Genevisible; Q9H228; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0038036; F:sphingosine-1-phosphate receptor activity; IEA:InterPro.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR GO; GO:0045664; P:regulation of neuron differentiation; IEA:Ensembl.
DR InterPro; IPR005386; EDG8_S1P_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR004061; S1P_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01561; EDG8RECEPTOR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01523; S1PRECEPTOR.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..398
FT /note="Sphingosine 1-phosphate receptor 5"
FT /id="PRO_0000069436"
FT TOPO_DOM 1..40
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 41..61
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 62..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 71..91
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 92..111
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 112..132
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 133..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 152..172
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 173..192
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 193..213
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 214..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..287
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 288..308
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 309..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 329..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 360..386
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 381
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JKM5"
FT LIPID 323
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 214..310
FT /note="RIYCQVRANARRLPARPGTAGTTSTRARRKPRSLALLRTLSVVLLAFVACWG
FT PLFLLLLLDVACPARTCPVLLQADPFLGLAMANSLLNPIIYTLTN -> LAGLAAHAQR
FT GAPGLCGMLGPPHPAAVARRGVPGAHLSCTPAGRSLPGTGHGQLTSEPHHLHAHQPRPA
FT PRAPAPGLLRTPLLRQRPEWLPAVGERG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013369"
FT VAR_SEQ 311..398
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013370"
FT VARIANT 318
FT /note="L -> Q (in dbSNP:rs35483143)"
FT /id="VAR_033466"
FT HELIX 15..22
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 38..62
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 70..95
FT /evidence="ECO:0007829|PDB:7EW1"
FT TURN 98..102
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 105..138
FT /evidence="ECO:0007829|PDB:7EW1"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 147..165
FT /evidence="ECO:0007829|PDB:7EW1"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:7EW1"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:7EW1"
FT STRAND 184..190
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 191..222
FT /evidence="ECO:0007829|PDB:7EW1"
FT TURN 223..225
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 243..246
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 248..274
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 289..301
FT /evidence="ECO:0007829|PDB:7EW1"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:7EW1"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:7EW1"
SQ SEQUENCE 398 AA; 41775 MW; 34ADC6C40D8250BF CRC64;
MESGLLRPAP VSEVIVLHYN YTGKLRGARY QPGAGLRADA VVCLAVCAFI VLENLAVLLV
LGRHPRFHAP MFLLLGSLTL SDLLAGAAYA ANILLSGPLT LKLSPALWFA REGGVFVALT
ASVLSLLAIA LERSLTMARR GPAPVSSRGR TLAMAAAAWG VSLLLGLLPA LGWNCLGRLD
ACSTVLPLYA KAYVLFCVLA FVGILAAICA LYARIYCQVR ANARRLPARP GTAGTTSTRA
RRKPRSLALL RTLSVVLLAF VACWGPLFLL LLLDVACPAR TCPVLLQADP FLGLAMANSL
LNPIIYTLTN RDLRHALLRL VCCGRHSCGR DPSGSQQSAS AAEASGGLRR CLPPGLDGSF
SGSERSSPQR DGLDTSGSTG SPGAPTAART LVSEPAAD
