PSYR_HUMAN
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 03-AUG-2022, entry version 153.
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 GlyGen; Q8IYL9; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IYL9; -.
DR PhosphoSitePlus; Q8IYL9; -.
DR BioMuta; GPR65; -.
DR DMDM; 37537957; -.
DR PaxDb; Q8IYL9; -.
DR PeptideAtlas; Q8IYL9; -.
DR PRIDE; Q8IYL9; -.
DR ProteomicsDB; 71200; -.
DR Antibodypedia; 13320; 223 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 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; ENSGT01050000244810; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q8IYL9; -.
DR OMA; GRSDMWN; -.
DR OrthoDB; 987208at2759; -.
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 BioGRID-ORCS; 8477; 10 hits in 1074 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 tissues.
DR ExpressionAtlas; Q8IYL9; baseline and differential.
DR Genevisible; Q8IYL9; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0031532; P:actin cytoskeleton reorganization; 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:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled 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 InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR005464; Psych_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01649; PSYCHOSINER.
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 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
