MTR1B_HUMAN
ID MTR1B_HUMAN Reviewed; 362 AA.
AC P49286;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Melatonin receptor type 1B;
DE Short=Mel-1B-R;
DE Short=Mel1b receptor;
GN Name=MTNR1B;
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 TISSUE SPECIFICITY.
RX PubMed=7568007; DOI=10.1073/pnas.92.19.8734;
RA Reppert S.M., Godson C., Mahle C.D., Weaver D.R., Slaugenhaupt S.A.,
RA Gusella J.F.;
RT "Molecular characterization of a second melatonin receptor expressed in
RT human retina and brain: the Mel1b melatonin receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:8734-8738(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-24 AND PHE-66.
RX PubMed=10696804; DOI=10.1016/s0304-3940(99)00981-7;
RA Ebisawa T., Uchiyama M., Kajimura N., Kamei Y., Shibui K., Kim K., Kudo Y.,
RA Iwase T., Sugishita M., Jodoi T., Ikeda M., Ozeki Y., Watanabe T.,
RA Sekimoto M., Katoh M., Yamada N., Toyoshima R., Okawa M., Takahashi K.,
RA Yamauchi T.;
RT "Genetic polymorphisms of human melatonin 1b receptor gene in circadian
RT rhythm sleep disorders and controls.";
RL Neurosci. Lett. 280:29-32(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JAN-2004) 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 INTERACTION WITH GPR61; GPR62 AND GPR135.
RX PubMed=28827538; DOI=10.1038/s41598-017-08996-7;
RA Oishi A., Karamitri A., Gerbier R., Lahuna O., Ahmad R., Jockers R.;
RT "Orphan GPR61, GPR62 and GPR135 receptors and the melatonin MT2 receptor
RT reciprocally modulate their signaling functions.";
RL Sci. Rep. 7:8990-8990(2017).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 35-340 IN COMPLEX WITH MELATONIN
RP ANALOG, AND DISULFIDE BOND.
RX PubMed=31019305; DOI=10.1038/s41586-019-1144-0;
RA Johansson L.C., Stauch B., McCorvy J.D., Han G.W., Patel N., Huang X.P.,
RA Batyuk A., Gati C., Slocum S.T., Li C., Grandner J.M., Hao S.,
RA Olsen R.H.J., Tribo A.R., Zaare S., Zhu L., Zatsepin N.A., Weierstall U.,
RA Yous S., Stevens R.C., Liu W., Roth B.L., Katritch V., Cherezov V.;
RT "XFEL structures of the human MT2 melatonin receptor reveal the basis of
RT subtype selectivity.";
RL Nature 569:289-292(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 -!- SUBUNIT: Interacts with GPR61, GPR62 and GPR135 (PubMed:28827538).
CC {ECO:0000269|PubMed:28827538}.
CC -!- INTERACTION:
CC P49286; P28335: HTR2C; NbExp=3; IntAct=EBI-1188341, EBI-994141;
CC P49286; P48039: MTNR1A; NbExp=2; IntAct=EBI-1188341, EBI-1188238;
CC P49286; O76081: RGS20; NbExp=2; IntAct=EBI-1188341, EBI-1052678;
CC P49286; Q14669: TRIP12; NbExp=3; IntAct=EBI-1188341, EBI-308443;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in retina and less in brain and
CC hippocampus. {ECO:0000269|PubMed:7568007}.
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; U25341; AAC50612.1; -; mRNA.
DR EMBL; AB033598; BAA92315.1; -; Genomic_DNA.
DR EMBL; AY521019; AAS00461.1; -; mRNA.
DR EMBL; BC069163; AAH69163.1; -; mRNA.
DR CCDS; CCDS8290.1; -.
DR PIR; I38990; I38990.
DR RefSeq; NP_005950.1; NM_005959.3.
DR RefSeq; XP_011541141.1; XM_011542839.2.
DR PDB; 6ME6; X-ray; 2.80 A; A/B=35-340.
DR PDB; 6ME7; X-ray; 3.20 A; A/B=35-340.
DR PDB; 6ME8; X-ray; 3.10 A; A/B=35-340.
DR PDB; 6ME9; X-ray; 3.30 A; A/B=35-340.
DR PDB; 7VH0; EM; 3.46 A; A=1-362.
DR PDBsum; 6ME6; -.
DR PDBsum; 6ME7; -.
DR PDBsum; 6ME8; -.
DR PDBsum; 6ME9; -.
DR PDBsum; 7VH0; -.
DR AlphaFoldDB; P49286; -.
DR SMR; P49286; -.
DR BioGRID; 110640; 198.
DR CORUM; P49286; -.
DR IntAct; P49286; 204.
DR MINT; P49286; -.
DR STRING; 9606.ENSP00000257068; -.
DR BindingDB; P49286; -.
DR ChEMBL; CHEMBL1946; -.
DR DrugBank; DB06594; Agomelatine.
DR DrugBank; DB01065; Melatonin.
DR DrugBank; DB00980; Ramelteon.
DR DrugBank; DB02709; Resveratrol.
DR DrugBank; DB09071; Tasimelteon.
DR DrugBank; DB15133; Tepotinib.
DR DrugCentral; P49286; -.
DR GuidetoPHARMACOLOGY; 288; -.
DR GlyGen; P49286; 1 site.
DR BioMuta; MTNR1B; -.
DR DMDM; 1346548; -.
DR PaxDb; P49286; -.
DR PeptideAtlas; P49286; -.
DR PRIDE; P49286; -.
DR Antibodypedia; 17799; 337 antibodies from 33 providers.
DR DNASU; 4544; -.
DR Ensembl; ENST00000257068.3; ENSP00000257068.2; ENSG00000134640.3.
DR GeneID; 4544; -.
DR KEGG; hsa:4544; -.
DR MANE-Select; ENST00000257068.3; ENSP00000257068.2; NM_005959.5; NP_005950.1.
DR UCSC; uc001pdk.2; human.
DR CTD; 4544; -.
DR DisGeNET; 4544; -.
DR GeneCards; MTNR1B; -.
DR HGNC; HGNC:7464; MTNR1B.
DR HPA; ENSG00000134640; Group enriched (brain, placenta).
DR MalaCards; MTNR1B; -.
DR MIM; 600804; gene.
DR neXtProt; NX_P49286; -.
DR OpenTargets; ENSG00000134640; -.
DR PharmGKB; PA31268; -.
DR VEuPathDB; HostDB:ENSG00000134640; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000162341; -.
DR HOGENOM; CLU_009579_3_3_1; -.
DR InParanoid; P49286; -.
DR OMA; RLFFQDT; -.
DR OrthoDB; 1011028at2759; -.
DR PhylomeDB; P49286; -.
DR TreeFam; TF331693; -.
DR PathwayCommons; P49286; -.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P49286; -.
DR SIGNOR; P49286; -.
DR BioGRID-ORCS; 4544; 7 hits in 1067 CRISPR screens.
DR GeneWiki; Melatonin_receptor_1B; -.
DR GenomeRNAi; 4544; -.
DR Pharos; P49286; Tclin.
DR PRO; PR:P49286; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P49286; protein.
DR Bgee; ENSG00000134640; Expressed in islet of Langerhans and 34 other tissues.
DR ExpressionAtlas; P49286; baseline and differential.
DR Genevisible; P49286; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0008502; F:melatonin receptor activity; TAS:ProtInc.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
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:0042593; P:glucose homeostasis; IMP:BHF-UCL.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:1902260; P:negative regulation of delayed rectifier potassium channel activity; IEA:Ensembl.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0051970; P:negative regulation of transmission of nerve impulse; IEA:Ensembl.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; IEA:Ensembl.
DR GO; GO:0051971; P:positive regulation of transmission of nerve impulse; IEA:Ensembl.
DR GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0098908; P:regulation of neuronal action potential; IEA:Ensembl.
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..362
FT /note="Melatonin receptor type 1B"
FT /id="PRO_0000069870"
FT TOPO_DOM 1..42
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..63
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..115
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 116..136
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..200
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..274
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 275..287
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 175
FT /ligand="melatonin"
FT /ligand_id="ChEBI:CHEBI:16796"
FT /evidence="ECO:0000269|PubMed:31019305,
FT ECO:0007744|PDB:6ME6"
FT BINDING 194
FT /ligand="melatonin"
FT /ligand_id="ChEBI:CHEBI:16796"
FT /evidence="ECO:0000269|PubMed:31019305,
FT ECO:0007744|PDB:6ME6"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 113..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:31019305, ECO:0007744|PDB:6ME6"
FT VARIANT 24
FT /note="G -> E (in dbSNP:rs8192552)"
FT /evidence="ECO:0000269|PubMed:10696804"
FT /id="VAR_009262"
FT VARIANT 66
FT /note="L -> F (in dbSNP:rs370338802)"
FT /evidence="ECO:0000269|PubMed:10696804"
FT /id="VAR_009263"
FT VARIANT 231
FT /note="R -> H (in dbSNP:rs8192553)"
FT /id="VAR_049421"
FT HELIX 39..67
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:6ME6"
FT TURN 73..76
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 77..91
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 93..102
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 111..143
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 145..150
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 156..172
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 175..178
FT /evidence="ECO:0007829|PDB:6ME6"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:6ME6"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:6ME6"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 198..207
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 210..229
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 246..276
FT /evidence="ECO:0007829|PDB:6ME6"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 281..284
FT /evidence="ECO:0007829|PDB:6ME8"
FT HELIX 287..299
FT /evidence="ECO:0007829|PDB:6ME6"
FT TURN 300..303
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 304..311
FT /evidence="ECO:0007829|PDB:6ME6"
FT HELIX 313..327
FT /evidence="ECO:0007829|PDB:6ME6"
SQ SEQUENCE 362 AA; 40188 MW; EECD78649DD79121 CRC64;
MSENGSFANC CEAGGWAVRP GWSGAGSARP SRTPRPPWVA PALSAVLIVT TAVDVVGNLL
VILSVLRNRK LRNAGNLFLV SLALADLVVA FYPYPLILVA IFYDGWALGE EHCKASAFVM
GLSVIGSVFN ITAIAINRYC YICHSMAYHR IYRRWHTPLH ICLIWLLTVV ALLPNFFVGS
LEYDPRIYSC TFIQTASTQY TAAVVVIHFL LPIAVVSFCY LRIWVLVLQA RRKAKPESRL
CLKPSDLRSF LTMFVVFVIF AICWAPLNCI GLAVAINPQE MAPQIPEGLF VTSYLLAYFN
SCLNAIVYGL LNQNFRREYK RILLALWNPR HCIQDASKGS HAEGLQSPAP PIIGVQHQAD
AL
