MTR1A_HUMAN
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 03-AUG-2022, entry version 183.
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 (2.80 ANGSTROMS) OF 12-325 IN COMPLEX WITH MELATONIN
RP 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.
CC -!- INTERACTION:
CC P48039; P27797: CALR; NbExp=3; IntAct=EBI-1188238, EBI-1049597;
CC P48039; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1188238, EBI-3867333;
CC P48039; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-1188238, EBI-11749135;
CC P48039; P49286: MTNR1B; NbExp=2; IntAct=EBI-1188238, EBI-1188341;
CC P48039; O76081: RGS20; NbExp=6; IntAct=EBI-1188238, EBI-1052678;
CC P48039; P57088: TMEM33; NbExp=3; IntAct=EBI-1188238, EBI-1048629;
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; 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 PDBsum; 6ME2; -.
DR PDBsum; 6ME3; -.
DR PDBsum; 6ME4; -.
DR PDBsum; 6ME5; -.
DR PDBsum; 7DB6; -.
DR PDBsum; 7VGY; -.
DR PDBsum; 7VGZ; -.
DR AlphaFoldDB; P48039; -.
DR SMR; P48039; -.
DR BioGRID; 110639; 231.
DR CORUM; P48039; -.
DR ELM; P48039; -.
DR IntAct; P48039; 224.
DR MINT; P48039; -.
DR STRING; 9606.ENSP00000302811; -.
DR BindingDB; P48039; -.
DR ChEMBL; CHEMBL1945; -.
DR DrugBank; DB06594; Agomelatine.
DR DrugBank; DB01065; Melatonin.
DR DrugBank; DB00980; Ramelteon.
DR DrugBank; DB02709; Resveratrol.
DR DrugBank; DB09071; Tasimelteon.
DR DrugCentral; P48039; -.
DR GuidetoPHARMACOLOGY; 287; -.
DR TCDB; 9.A.14.1.3; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P48039; 2 sites.
DR iPTMnet; P48039; -.
DR BioMuta; MTNR1A; -.
DR DMDM; 1346544; -.
DR PaxDb; P48039; -.
DR PeptideAtlas; P48039; -.
DR PRIDE; P48039; -.
DR Antibodypedia; 29126; 352 antibodies from 33 providers.
DR DNASU; 4543; -.
DR Ensembl; ENST00000307161.5; ENSP00000302811.5; ENSG00000168412.6.
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 CTD; 4543; -.
DR DisGeNET; 4543; -.
DR GeneCards; MTNR1A; -.
DR HGNC; HGNC:7463; MTNR1A.
DR HPA; ENSG00000168412; Tissue enhanced (brain, intestine, kidney, testis).
DR MIM; 600665; gene.
DR neXtProt; NX_P48039; -.
DR OpenTargets; ENSG00000168412; -.
DR PharmGKB; PA31267; -.
DR VEuPathDB; HostDB:ENSG00000168412; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000160321; -.
DR HOGENOM; CLU_009579_3_3_1; -.
DR InParanoid; P48039; -.
DR OMA; KPDNNPR; -.
DR OrthoDB; 1011028at2759; -.
DR PhylomeDB; P48039; -.
DR TreeFam; TF331693; -.
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 BioGRID-ORCS; 4543; 8 hits in 1078 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 palpebral conjunctiva and 31 other tissues.
DR Genevisible; P48039; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C: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:0097159; F:organic cyclic compound binding; IPI: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; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
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 InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002278; Mel_1A/1B_rcpt.
DR InterPro; IPR000025; Melatonin_rcpt.
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 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:7DB6"
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..195
FT /evidence="ECO:0007829|PDB:6ME2"
FT HELIX 197..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
