ID   PSYR_HUMAN              Reviewed;         337 AA.
AC   Q8IYL9; O75819;
DT   03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 161.
DE   RecName: Full=Psychosine receptor;
DE   AltName: Full=G-protein coupled receptor 65;
DE   AltName: Full=T-cell death-associated gene 8 protein;
GN   Name=GPR65; Synonyms=TDAG8;
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 [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX   PubMed=9655242; DOI=10.1089/dna.1998.17.493;
RA   Kyaw H., Zeng Z., Su K., Fan P., Shell B.K., Carter K.C., Li Y.;
RT   "Cloning, characterization, and mapping of human homolog of mouse T-cell
RT   death-associated gene.";
RL   DNA Cell Biol. 17:493-500(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Blood, and Brain;
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   [4]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=11309421; DOI=10.1083/jcb.153.2.429;
RA   Im D.-S., Heise C.E., Nguyen T., O'Dowd B.F., Lynch K.R.;
RT   "Identification of a molecular target of psychosine and its role in globoid
RT   cell formation.";
RL   J. Cell Biol. 153:429-434(2001).
RN   [5]
RP   CHARACTERIZATION OF VARIANT LEU-231, AND FUNCTION.
RX   PubMed=27287411; DOI=10.1016/j.immuni.2016.05.007;
RA   Lassen K.G., McKenzie C.I., Mari M., Murano T., Begun J., Baxt L.A.,
RA   Goel G., Villablanca E.J., Kuo S.Y., Huang H., Macia L., Bhan A.K.,
RA   Batten M., Daly M.J., Reggiori F., Mackay C.R., Xavier R.J.;
RT   "Genetic coding variant in GPR65 alters lysosomal pH and links lysosomal
RT   dysfunction with colitis risk.";
RL   Immunity 44:1392-1405(2016).
CC   -!- FUNCTION: Receptor for the glycosphingolipid psychosine (PSY) and
CC       several related glycosphingolipids (PubMed:11309421). Plays a role in
CC       immune response by maintaining lysosome function and supporting
CC       phagocytosis-mediated intracellular bacteria clearance
CC       (PubMed:27287411). May have a role in activation-induced cell death or
CC       differentiation of T-cells (By similarity).
CC       {ECO:0000250|UniProtKB:Q61038, ECO:0000269|PubMed:11309421,
CC       ECO:0000269|PubMed:27287411}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in thymus, spleen, lymph
CC       nodes, small intestine, lung, placenta and peripheral blood leukocytes.
CC       {ECO:0000269|PubMed:11309421, ECO:0000269|PubMed:9655242}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; U95218; AAC31794.1; -; Genomic_DNA.
DR   EMBL; AL157955; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC035633; AAH35633.1; -; mRNA.
DR   EMBL; BC071715; AAH71715.1; -; mRNA.
DR   CCDS; CCDS9879.1; -.
DR   RefSeq; NP_003599.2; NM_003608.3.
DR   AlphaFoldDB; Q8IYL9; -.
DR   SMR; Q8IYL9; -.
DR   BioGRID; 114052; 1.
DR   IntAct; Q8IYL9; 1.
DR   STRING; 9606.ENSP00000267549; -.
DR   BindingDB; Q8IYL9; -.
DR   ChEMBL; CHEMBL3714081; -.
DR   GlyCosmos; Q8IYL9; 3 sites, No reported glycans.
DR   GlyGen; Q8IYL9; 4 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8IYL9; -.
DR   PhosphoSitePlus; Q8IYL9; -.
DR   BioMuta; GPR65; -.
DR   DMDM; 37537957; -.
DR   MassIVE; Q8IYL9; -.
DR   PaxDb; 9606-ENSP00000267549; -.
DR   PeptideAtlas; Q8IYL9; -.
DR   ProteomicsDB; 71200; -.
DR   Antibodypedia; 13320; 241 antibodies from 30 providers.
DR   DNASU; 8477; -.
DR   Ensembl; ENST00000267549.5; ENSP00000267549.3; ENSG00000140030.6.
DR   GeneID; 8477; -.
DR   KEGG; hsa:8477; -.
DR   MANE-Select; ENST00000267549.5; ENSP00000267549.3; NM_003608.4; NP_003599.2.
DR   UCSC; uc001xvv.3; human.
DR   AGR; HGNC:4517; -.
DR   CTD; 8477; -.
DR   DisGeNET; 8477; -.
DR   GeneCards; GPR65; -.
DR   HGNC; HGNC:4517; GPR65.
DR   HPA; ENSG00000140030; Tissue enhanced (bone marrow, lymphoid tissue).
DR   MIM; 604620; gene.
DR   neXtProt; NX_Q8IYL9; -.
DR   OpenTargets; ENSG00000140030; -.
DR   PharmGKB; PA28909; -.
DR   VEuPathDB; HostDB:ENSG00000140030; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT01100000263537; -.
DR   HOGENOM; CLU_009579_8_2_1; -.
DR   InParanoid; Q8IYL9; -.
DR   OMA; ICNQKVY; -.
DR   OrthoDB; 4329413at2759; -.
DR   PhylomeDB; Q8IYL9; -.
DR   TreeFam; TF331803; -.
DR   PathwayCommons; Q8IYL9; -.
DR   Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR   Reactome; R-HSA-416476; G alpha (q) signalling events.
DR   SignaLink; Q8IYL9; -.
DR   SIGNOR; Q8IYL9; -.
DR   BioGRID-ORCS; 8477; 12 hits in 1155 CRISPR screens.
DR   GeneWiki; GPR65; -.
DR   GenomeRNAi; 8477; -.
DR   Pharos; Q8IYL9; Tbio.
DR   PRO; PR:Q8IYL9; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; Q8IYL9; Protein.
DR   Bgee; ENSG00000140030; Expressed in leukocyte and 113 other cell types or tissues.
DR   ExpressionAtlas; Q8IYL9; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IDA:BHF-UCL.
DR   GO; GO:0090630; P:activation of GTPase activity; IDA:BHF-UCL.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IBA:GO_Central.
DR   GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:BHF-UCL.
DR   GO; GO:0010447; P:response to acidic pH; IDA:BHF-UCL.
DR   CDD; cd15365; 7tmA_GPR65_TDAG8; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR005464; Psych_rcpt.
DR   PANTHER; PTHR24234:SF11; G PROTEIN-COUPLED RECEPTOR 65; 1.
DR   PANTHER; PTHR24234; LYSOPHOSPHATIDIC ACID RECEPTOR 5/SPHINGOSYLPHOSPHORYLCHOLINE RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01649; PSYCHOSINER.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; Q8IYL9; HS.
PE   1: Evidence at protein level;
KW   Apoptosis; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW   Glycoprotein; Membrane; Receptor; Reference proteome; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..337
FT                   /note="Psychosine receptor"
FT                   /id="PRO_0000070087"
FT   TOPO_DOM        1..15
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        16..36
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        37..50
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        51..71
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        72..89
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        90..110
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        111..129
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        130..150
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        151..180
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        181..201
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        202..227
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        228..248
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        249..273
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        274..294
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        295..337
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        2
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        166
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        87..170
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VARIANT         231
FT                   /note="I -> L (increased lysosomal pH; increased lipid
FT                   droplets accumulation; dbSNP:rs3742704)"
FT                   /id="VAR_022064"
FT   CONFLICT        43
FT                   /note="A -> P (in Ref. 1; AAC31794)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        97
FT                   /note="N -> K (in Ref. 1; AAC31794)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        130
FT                   /note="F -> I (in Ref. 1; AAC31794)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   337 AA;  39333 MW;  CFDBF217291C0FA2 CRC64;
     MNSTCIEEQH DLDHYLFPIV YIFVIIVSIP ANIGSLCVSF LQAKKESELG IYLFSLSLSD
     LLYALTLPLW IDYTWNKDNW TFSPALCKGS AFLMYMNFYS STAFLTCIAV DRYLAVVYPL
     KFFFLRTRRF ALMVSLSIWI LETIFNAVML WEDETVVEYC DAEKSNFTLC YDKYPLEKWQ
     INLNLFRTCT GYAIPLVTIL ICNRKVYQAV RHNKATENKE KKRIIKLLVS ITVTFVLCFT
     PFHVMLLIRC ILEHAVNFED HSNSGKRTYT MYRITVALTS LNCVADPILY CFVTETGRYD
     MWNILKFCTG RCNTSQRQRK RILSVSTKDT MELEVLE
//