ID   MTR1A_HUMAN             Reviewed;         350 AA.
AC   P48039; A0AVC5; B0M0L2;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   04-NOV-2026, entry version 202.
DE   RecName: Full=Melatonin receptor type 1A;
DE            Short=Mel-1A-R;
DE            Short=Mel1a receptor;
GN   Name=MTNR1A;
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].
RX   PubMed=7946354; DOI=10.1016/0896-6273(94)90055-8;
RA   Reppert S.M., Weaver D.R., Ebisawa T.;
RT   "Cloning and characterization of a mammalian melatonin receptor that
RT   mediates reproductive and circadian responses.";
RL   Neuron 13:1177-1185(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-54 AND VAL-157.
RC   TISSUE=Leukocyte;
RX   PubMed=10471411; DOI=10.1006/bbrc.1999.1308;
RA   Ebisawa T., Kajimura N., Uchiyama M., Katoh M., Sekimoto M., Watanabe T.,
RA   Ozeki Y., Ikeda M., Jodoi T., Sugishita M., Iwase T., Kamei Y., Kim K.,
RA   Shibui K., Kudo Y., Yamada N., Toyoshima R., Okawa M., Takahashi K.,
RA   Yamauchi T.;
RT   "Alleic variants of human melatonin 1a receptor: function and prevalence in
RT   subjects with circadian rhythm sleep disorders.";
RL   Biochem. Biophys. Res. Commun. 262:832-837(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Hippocampus;
RA   Huang Y.-H., Kaighin V.A., Martin A.L., Aronstam R.S.;
RL   Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH MELATONIN ANALOG, AND DISULFIDE BOND.
RX   PubMed=31019306; DOI=10.1038/s41586-019-1141-3;
RA   Stauch B., Johansson L.C., McCorvy J.D., Patel N., Han G.W., Huang X.P.,
RA   Gati C., Batyuk A., Slocum S.T., Ishchenko A., Brehm W., White T.A.,
RA   Michaelian N., Madsen C., Zhu L., Grant T.D., Grandner J.M., Shiriaeva A.,
RA   Olsen R.H.J., Tribo A.R., Yous S., Stevens R.C., Weierstall U.,
RA   Katritch V., Roth B.L., Liu W., Cherezov V.;
RT   "Structural basis of ligand recognition at the human MT1 melatonin
RT   receptor.";
RL   Nature 569:284-288(2019).
CC   -!- FUNCTION: High affinity receptor for melatonin. Likely to mediate the
CC       reproductive and circadian actions of melatonin. The activity of this
CC       receptor is mediated by pertussis toxin sensitive G proteins that
CC       inhibit adenylate cyclase activity. Possibly involved in sleep
CC       induction, by melatonin activation of the potassium channel KCNMA1/BK
CC       and the dissociation of G-beta and G-gamma subunits, thereby decreasing
CC       synaptic transmission (By similarity). {ECO:0000250|UniProtKB:Q61184}.
CC   -!- INTERACTION:
CC       P48039; Q02410: APBA1; NbExp=2; IntAct=EBI-1188238, EBI-368690;
CC       P48039; Q99767: APBA2; NbExp=2; IntAct=EBI-1188238, EBI-81711;
CC       P48039; P27797: CALR; NbExp=3; IntAct=EBI-1188238, EBI-1049597;
CC       P48039; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1188238, EBI-3867333;
CC       P48039; Q12959: DLG1; NbExp=3; IntAct=EBI-1188238, EBI-357481;
CC       P48039; Q92796: DLG3; NbExp=3; IntAct=EBI-1188238, EBI-80440;
CC       P48039; P78352: DLG4; NbExp=3; IntAct=EBI-1188238, EBI-80389;
CC       P48039; Q68DX3: FRMPD2; NbExp=3; IntAct=EBI-1188238, EBI-53993476;
CC       P48039; A4D2P6: GRID2IP; NbExp=2; IntAct=EBI-1188238, EBI-15893226;
CC       P48039; Q9Y3R0: GRIP1; NbExp=5; IntAct=EBI-1188238, EBI-5349621;
CC       P48039; Q9C0E4: GRIP2; NbExp=5; IntAct=EBI-1188238, EBI-949557;
CC       P48039; Q14005: IL16; NbExp=2; IntAct=EBI-1188238, EBI-2831580;
CC       P48039; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-1188238, EBI-11749135;
CC       P48039; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-1188238, EBI-739832;
CC       P48039; Q8N448: LNX2; NbExp=2; IntAct=EBI-1188238, EBI-2340947;
CC       P48039; Q96QZ7: MAGI1; NbExp=2; IntAct=EBI-1188238, EBI-924464;
CC       P48039; Q86UL8: MAGI2; NbExp=5; IntAct=EBI-1188238, EBI-311035;
CC       P48039; O75970: MPDZ; NbExp=4; IntAct=EBI-1188238, EBI-821405;
CC       P48039; P49286: MTNR1B; NbExp=2; IntAct=EBI-1188238, EBI-1188341;
CC       P48039; Q86UT5: NHERF4; NbExp=2; IntAct=EBI-1188238, EBI-8744528;
CC       P48039; Q8NI35: PATJ; NbExp=9; IntAct=EBI-1188238, EBI-724390;
CC       P48039; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-1188238, EBI-349819;
CC       P48039; Q12923: PTPN13; NbExp=2; IntAct=EBI-1188238, EBI-355227;
CC       P48039; O60894: RAMP1; NbExp=3; IntAct=EBI-1188238, EBI-962893;
CC       P48039; O60895: RAMP2; NbExp=3; IntAct=EBI-1188238, EBI-9009040;
CC       P48039; O60896: RAMP3; NbExp=3; IntAct=EBI-1188238, EBI-720447;
CC       P48039; O76081: RGS20; NbExp=6; IntAct=EBI-1188238, EBI-1052678;
CC       P48039; Q14160: SCRIB; NbExp=3; IntAct=EBI-1188238, EBI-357345;
CC       P48039; Q07157: TJP1; NbExp=2; IntAct=EBI-1188238, EBI-79553;
CC       P48039; P57088: TMEM33; NbExp=3; IntAct=EBI-1188238, EBI-1048629;
CC       P48039; Q9P202: WHRN; NbExp=3; IntAct=EBI-1188238, EBI-310886;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed in hypophyseal pars tuberalis and
CC       hypothalamic suprachiasmatic nuclei (SCN). Hippocampus.
CC   -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Melatonin receptor entry;
CC       URL="https://en.wikipedia.org/wiki/Melatonin_receptor";
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DR   EMBL; U14108; AAB17720.1; -; mRNA.
DR   EMBL; AB029933; BAA85303.1; -; Genomic_DNA.
DR   EMBL; EU432127; ABY87926.1; -; mRNA.
DR   EMBL; BC074946; AAH74946.1; -; mRNA.
DR   EMBL; BC074947; AAH74947.1; -; mRNA.
DR   EMBL; BC126297; AAI26298.1; -; mRNA.
DR   EMBL; BC126299; AAI26300.1; -; mRNA.
DR   CCDS; CCDS3848.1; -.
DR   PIR; I38848; I38848.
DR   RefSeq; NP_005949.1; NM_005958.4.
DR   PDB; 6ME2; X-ray; 2.80 A; A=12-325.
DR   PDB; 6ME3; X-ray; 2.90 A; A=12-325.
DR   PDB; 6ME4; X-ray; 3.20 A; A=12-325.
DR   PDB; 6ME5; X-ray; 3.20 A; A=12-325.
DR   PDB; 6PS8; X-ray; 3.30 A; A=12-218, A=228-325.
DR   PDB; 7DB6; EM; 3.30 A; D=1-340.
DR   PDB; 7VGY; EM; 3.10 A; A=1-350.
DR   PDB; 7VGZ; EM; 3.30 A; B=1-350.
DR   AlphaFoldDB; P48039; -.
DR   EMDB; EMD-30627; -.
DR   EMDB; EMD-31980; -.
DR   EMDB; EMD-31981; -.
DR   MDRepo; P48039; -.
DR   SMR; P48039; -.
DR   BioGRID; 110639; 235.
DR   CORUM; P48039; -.
DR   ELM; P48039; -.
DR   FunCoup; P48039; 638.
DR   IntAct; P48039; 305.
DR   NDEx; IQUERY-CP-MTNR1A; 5 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000302811; -.
DR   BindingDB; P48039; -.
DR   ChEMBL; CHEMBL1945; -.
DR   DrugBank; DB06594; Agomelatine.
DR   DrugBank; DB01065; Melatonin.
DR   DrugBank; DB08190; N-[2-(2-iodo-5-methoxy-1H-indol-3-yl)ethyl]acetamide.
DR   DrugBank; DB04275; N-acetylserotonin.
DR   DrugBank; DB12288; Piromelatine.
DR   DrugBank; DB00980; Ramelteon.
DR   DrugBank; DB02709; Resveratrol.
DR   DrugBank; DB09071; Tasimelteon.
DR   DrugBank; DB16909; TIK-301.
DR   DrugCentral; P48039; -.
DR   GuidetoPHARMACOLOGY; 287; -.
DR   TCDB; 9.A.14.1.3; the g-protein-coupled receptor (gpcr) family.
DR   GlyCosmos; P48039; 2 sites, No reported glycans.
DR   GlyGen; P48039; 2 sites.
DR   iPTMnet; P48039; -.
DR   BioMuta; MTNR1A; -.
DR   DMDM; 1346544; -.
DR   PaxDb; 9606-ENSP00000302811; -.
DR   Antibodypedia; 29126; 371 antibodies from 37 providers.
DR   DNASU; 4543; -.
DR   Ensembl; ENST00000307161.5; ENSP00000302811.5; ENSG00000168412.7.
DR   Ensembl; ENST00000703170.1; ENSP00000515216.1; ENSG00000168412.7.
DR   GeneID; 4543; -.
DR   KEGG; hsa:4543; -.
DR   MANE-Select; ENST00000307161.5; ENSP00000302811.5; NM_005958.4; NP_005949.1.
DR   UCSC; uc003izd.2; human.
DR   AGR; HGNC:7463; -.
DR   ClinPGx; PA31267; -.
DR   CTD; 4543; -.
DR   DisGeNET; 4543; -.
DR   GeneCards; MTNR1A; -.
DR   HGNC; HGNC:7463; MTNR1A.
DR   HPA; ENSG00000168412; Tissue enhanced (kidney).
DR   MIM; 600665; gene.
DR   OpenTargets; ENSG00000168412; -.
DR   VEuPathDB; HostDB:ENSG00000168412; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00940000160321; -.
DR   HOGENOM; CLU_009579_3_3_1; -.
DR   InParanoid; P48039; -.
DR   OMA; AHCQISG; -.
DR   OrthoDB; 10044919at2759; -.
DR   PAN-GO; P48039; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; P48039; -.
DR   PathwayCommons; P48039; -.
DR   Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; P48039; -.
DR   SIGNOR; P48039; -.
DR   Agora; ENSG00000168412; -.
DR   BioGRID-ORCS; 4543; 8 hits in 1161 CRISPR screens.
DR   GeneWiki; Melatonin_receptor_1A; -.
DR   GenomeRNAi; 4543; -.
DR   Pharos; P48039; Tclin.
DR   PRO; PR:P48039; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P48039; protein.
DR   Bgee; ENSG00000168412; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 31 other cell types or tissues.
DR   GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0043235; C:signaling receptor complex; IDA:BHF-UCL.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0042562; F:hormone binding; IPI:BHF-UCL.
DR   GO; GO:0008502; F:melatonin receptor activity; IDA:BHF-UCL.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0007623; P:circadian rhythm; TAS:ProtInc.
DR   GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR   GO; GO:0007617; P:mating behavior; TAS:ProtInc.
DR   FunFam; 1.20.1070.10:FF:000056; Melatonin receptor type 1A; 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; IPR002278; Mel_1A/1B_rcpt.
DR   InterPro; IPR000025; Melatonin_rcpt.
DR   PANTHER; PTHR24228; B2 BRADYKININ RECEPTOR/ANGIOTENSIN II RECEPTOR; 1.
DR   PANTHER; PTHR24228:SF53; MELATONIN RECEPTOR TYPE 1A; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01149; MELATONIN1AR.
DR   PRINTS; PR00857; MELATONINR.
DR   SMART; SM01381; 7TM_GPCR_Srsx; 1.
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.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; G protein-coupled receptor;
KW   Glycoprotein; Membrane; Receptor; Reference proteome; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..350
FT                   /note="Melatonin receptor type 1A"
FT                   /id="PRO_0000069862"
FT   TOPO_DOM        1..29
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        30..50
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        51..63
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        64..84
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        85..102
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        103..123
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        124..142
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        143..163
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        164..187
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        188..208
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        209..240
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        241..261
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        262..274
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        275..295
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        296..350
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   BINDING         162
FT                   /ligand="melatonin"
FT                   /ligand_id="ChEBI:CHEBI:16796"
FT                   /evidence="ECO:0000269|PubMed:31019306,
FT                   ECO:0007744|PDB:6ME3"
FT   BINDING         181
FT                   /ligand="melatonin"
FT                   /ligand_id="ChEBI:CHEBI:16796"
FT                   /evidence="ECO:0000269|PubMed:31019306,
FT                   ECO:0007744|PDB:6ME3"
FT   CARBOHYD        4
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        10
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        100..177
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT                   ECO:0000269|PubMed:31019306, ECO:0007744|PDB:6ME2"
FT   VARIANT         54
FT                   /note="R -> W (exhibits significantly reduced B(max) and
FT                   slightly enhanced affinity; dbSNP:rs1800885)"
FT                   /evidence="ECO:0000269|PubMed:10471411"
FT                   /id="VAR_009260"
FT   VARIANT         157
FT                   /note="A -> V (similar binding characteristics compared to
FT                   wild-type; dbSNP:rs1800884)"
FT                   /evidence="ECO:0000269|PubMed:10471411"
FT                   /id="VAR_009261"
FT   VARIANT         212
FT                   /note="I -> T (in dbSNP:rs7654853)"
FT                   /id="VAR_049420"
FT   HELIX           24..54
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   TURN            56..58
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           61..63
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           64..78
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           80..90
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           96..134
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           135..138
FT                   /evidence="ECO:0007829|PDB:7VGY"
FT   HELIX           144..159
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           161..165
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   STRAND          168..171
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   TURN            172..175
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   STRAND          176..179
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   TURN            181..183
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           185..192
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           193..197
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           198..218
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   TURN            229..231
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           235..263
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           265..271
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           274..286
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           287..289
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           290..298
FT                   /evidence="ECO:0007829|PDB:6ME2"
FT   HELIX           300..312
FT                   /evidence="ECO:0007829|PDB:6ME2"
SQ   SEQUENCE   350 AA;  39375 MW;  DF7C67111D2386ED CRC64;
     MQGNGSALPN ASQPVLRGDG ARPSWLASAL ACVLIFTIVV DILGNLLVIL SVYRNKKLRN
     AGNIFVVSLA VADLVVAIYP YPLVLMSIFN NGWNLGYLHC QVSGFLMGLS VIGSIFNITG
     IAINRYCYIC HSLKYDKLYS SKNSLCYVLL IWLLTLAAVL PNLRAGTLQY DPRIYSCTFA
     QSVSSAYTIA VVVFHFLVPM IIVIFCYLRI WILVLQVRQR VKPDRKPKLK PQDFRNFVTM
     FVVFVLFAIC WAPLNFIGLA VASDPASMVP RIPEWLFVAS YYMAYFNSCL NAIIYGLLNQ
     NFRKEYRRII VSLCTARVFF VDSSNDVADR VKWKPSPLMT NNNVVKVDSV
//