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MTR1L_HUMAN
ID   MTR1L_HUMAN             Reviewed;         617 AA.
AC   Q13585; Q0VGG3; Q3ZAR0;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   03-AUG-2022, entry version 158.
DE   RecName: Full=Melatonin-related receptor;
DE   AltName: Full=G protein-coupled receptor 50;
DE   AltName: Full=H9;
GN   Name=GPR50;
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], AND VARIANTS 502-THR--HIS-505 DEL; ALA-532 AND
RP   VAL-606.
RC   TISSUE=Pituitary;
RX   PubMed=8647286; DOI=10.1016/0014-5793(96)00437-1;
RA   Reppert S.M., Weaver D.R., Ebisawa T., Mahle C.D., Kolakowski L.F. Jr.;
RT   "Cloning of a melatonin-related receptor from human pituitary.";
RL   FEBS Lett. 386:219-224(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS 502-THR--HIS-505 DEL AND ALA-532.
RC   TISSUE=Pituitary;
RA   Kaighin V.A., Martin A.L., Aronstam R.S.;
RL   Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS 502-THR--HIS-505 DEL;
RP   ALA-532 AND VAL-606.
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   SUBUNIT.
RX   PubMed=16778767; DOI=10.1038/sj.emboj.7601193;
RA   Levoye A., Dam J., Ayoub M.A., Guillaume J.L., Couturier C., Delagrange P.,
RA   Jockers R.;
RT   "The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor
RT   function through heterodimerization.";
RL   EMBO J. 25:3012-3023(2006).
RN   [5]
RP   VARIANTS 502THR--HIS505 DEL; ALA-528 AND ILE-606.
RX   PubMed=16436372; DOI=10.1194/jlr.m500338-jlr200;
RA   Bhattacharyya S., Luan J., Challis B., Keogh J., Montague C., Brennand J.,
RA   Morten J., Lowenbeim S., Jenkins S., Farooqi I.S., Wareham N.J.,
RA   O'Rahilly S.;
RT   "Sequence variants in the melatonin-related receptor gene (GPR50) associate
RT   with circulating triglyceride and HDL levels.";
RL   J. Lipid Res. 47:761-766(2006).
CC   -!- FUNCTION: Does not bind melatonin.
CC   -!- SUBUNIT: Homodimer, and heterodimer with MTNR1A and MTNR1B.
CC       {ECO:0000269|PubMed:16778767}.
CC   -!- INTERACTION:
CC       Q13585; P04731: MT1A; NbExp=3; IntAct=EBI-8550965, EBI-8045030;
CC       Q13585; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-8550965, EBI-10172590;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Hypothalamus and pituitary.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; U52219; AAC50614.1; -; mRNA.
DR   EMBL; EU432118; ABY87917.1; -; mRNA.
DR   EMBL; BC103696; AAI03697.1; -; mRNA.
DR   EMBL; BC105683; AAI05684.1; -; mRNA.
DR   EMBL; BC105684; AAI05685.1; -; mRNA.
DR   CCDS; CCDS44012.1; -.
DR   PIR; S70520; S70520.
DR   RefSeq; NP_004215.2; NM_004224.3.
DR   AlphaFoldDB; Q13585; -.
DR   SMR; Q13585; -.
DR   BioGRID; 114674; 57.
DR   IntAct; Q13585; 23.
DR   MINT; Q13585; -.
DR   STRING; 9606.ENSP00000218316; -.
DR   ChEMBL; CHEMBL3341577; -.
DR   iPTMnet; Q13585; -.
DR   PhosphoSitePlus; Q13585; -.
DR   BioMuta; GPR50; -.
DR   DMDM; 296439298; -.
DR   EPD; Q13585; -.
DR   jPOST; Q13585; -.
DR   MassIVE; Q13585; -.
DR   MaxQB; Q13585; -.
DR   PaxDb; Q13585; -.
DR   PeptideAtlas; Q13585; -.
DR   PRIDE; Q13585; -.
DR   ProteomicsDB; 59583; -.
DR   Antibodypedia; 7082; 305 antibodies from 34 providers.
DR   DNASU; 9248; -.
DR   Ensembl; ENST00000218316.4; ENSP00000218316.3; ENSG00000102195.10.
DR   GeneID; 9248; -.
DR   KEGG; hsa:9248; -.
DR   MANE-Select; ENST00000218316.4; ENSP00000218316.3; NM_004224.3; NP_004215.2.
DR   UCSC; uc010ntg.3; human.
DR   CTD; 9248; -.
DR   DisGeNET; 9248; -.
DR   GeneCards; GPR50; -.
DR   HGNC; HGNC:4506; GPR50.
DR   HPA; ENSG00000102195; Tissue enriched (pituitary).
DR   MIM; 300207; gene.
DR   neXtProt; NX_Q13585; -.
DR   OpenTargets; ENSG00000102195; -.
DR   PharmGKB; PA28895; -.
DR   VEuPathDB; HostDB:ENSG00000102195; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00940000160515; -.
DR   HOGENOM; CLU_468199_0_0_1; -.
DR   InParanoid; Q13585; -.
DR   OMA; GHHKSVF; -.
DR   OrthoDB; 907115at2759; -.
DR   PhylomeDB; Q13585; -.
DR   TreeFam; TF331693; -.
DR   PathwayCommons; Q13585; -.
DR   SignaLink; Q13585; -.
DR   BioGRID-ORCS; 9248; 10 hits in 697 CRISPR screens.
DR   GeneWiki; GPR50; -.
DR   GenomeRNAi; 9248; -.
DR   Pharos; Q13585; Tbio.
DR   PRO; PR:Q13585; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q13585; protein.
DR   Bgee; ENSG00000102195; Expressed in adenohypophysis and 39 other tissues.
DR   Genevisible; Q13585; HS.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0008502; F:melatonin receptor activity; IEA:InterPro.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR002280; Mel_rcpt_1X.
DR   InterPro; IPR000025; Melatonin_rcpt.
DR   PANTHER; PTHR24228:SF56; PTHR24228:SF56; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01151; MELATONIN1XR.
DR   PRINTS; PR00857; MELATONINR.
DR   SMART; SM01381; 7TM_GPCR_Srsx; 1.
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   Cell membrane; Disulfide bond; G-protein coupled receptor; Membrane;
KW   Receptor; Reference proteome; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..617
FT                   /note="Melatonin-related receptor"
FT                   /id="PRO_0000069878"
FT   TOPO_DOM        1..30
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        31..51
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        52..64
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        65..85
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        86..103
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        104..124
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        125..143
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        144..164
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        165..188
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        189..209
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        210..239
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        240..260
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        261..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..617
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          340..438
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          464..596
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        340..355
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        388..409
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        476..504
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        101..178
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VARIANT         502..505
FT                   /note="Missing (lower fasting circulating triglyceride
FT                   levels)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8647286, ECO:0000269|Ref.2"
FT                   /id="VAR_062254"
FT   VARIANT         532
FT                   /note="T -> A (higher fasting circulating triglyceride
FT                   levels; dbSNP:rs561077)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8647286, ECO:0000269|Ref.2"
FT                   /id="VAR_062255"
FT   VARIANT         606
FT                   /note="I -> V (higher fasting circulating triglyceride
FT                   levels; dbSNP:rs13440581)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8647286"
FT                   /id="VAR_062256"
FT   CONFLICT        320
FT                   /note="S -> P (in Ref. 1; AAC50614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        448
FT                   /note="A -> G (in Ref. 1; AAC50614)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   617 AA;  67369 MW;  A0B73A7ACE1053BB CRC64;
     MGPTLAVPTP YGCIGCKLPQ PEYPPALIIF MFCAMVITIV VDLIGNSMVI LAVTKNKKLR
     NSGNIFVVSL SVADMLVAIY PYPLMLHAMS IGGWDLSQLQ CQMVGFITGL SVVGSIFNIV
     AIAINRYCYI CHSLQYERIF SVRNTCIYLV ITWIMTVLAV LPNMYIGTIE YDPRTYTCIF
     NYLNNPVFTV TIVCIHFVLP LLIVGFCYVR IWTKVLAARD PAGQNPDNQL AEVRNFLTMF
     VIFLLFAVCW CPINVLTVLV AVSPKEMAGK IPNWLYLAAY FIAYFNSCLN AVIYGLLNEN
     FRREYWTIFH AMRHPIIFFS GLISDIREMQ EARTLARARA HARDQAREQD RAHACPAVEE
     TPMNVRNVPL PGDAAAGHPD RASGHPKPHS RSSSAYRKSA STHHKSVFSH SKAASGHLKP
     VSGHSKPASG HPKSATVYPK PASVHFKADS VHFKGDSVHF KPDSVHFKPA SSNPKPITGH
     HVSAGSHSKS AFSAATSHPK PTTGHIKPAT SHAEPTTADY PKPATTSHPK PTAADNPELS
     ASHCPEIPAI AHPVSDDSDL PESASSPAAG PTKPAASQLE SDTIADLPDP TVVTTSTNDY
     HDVVVIDVED DPDEMAV
 
 
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