CNR1_MOUSE
ID CNR1_MOUSE Reviewed; 473 AA.
AC P47746; Q5SF33;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Cannabinoid receptor 1;
DE Short=CB-R;
DE Short=CB1;
DE AltName: Full=Brain-type cannabinoid receptor;
GN Name=Cnr1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=8777318; DOI=10.3109/10425179509020870;
RA Chakrabarti A., Onaivi E.S., Chaudhuri G.;
RT "Cloning and sequencing of a cDNA encoding the mouse brain-type cannabinoid
RT receptor protein.";
RL DNA Seq. 5:385-388(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8832654; DOI=10.1016/0304-3940(96)12792-0;
RA Ho B.Y., Zhao J.;
RT "Determination of the cannabinoid receptors in mouse x rat hybridoma NG108-
RT 15 cells and rat GH4C1 cells.";
RL Neurosci. Lett. 212:123-126(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=129/Sv;
RX PubMed=9888857; DOI=10.1126/science.283.5400.401;
RA Ledent C., Valverde O., Cossu G., Petitet F., Aubert J.F., Beslot F.,
RA Boehme G.A., Imperato A., Pedrazzini T., Roques B.P., Vassart G.,
RA Fratta W., Parmentier M.;
RT "Unresponsiveness to cannabinoids and reduced addictive effects of opiates
RT in CB1 receptor knockout mice.";
RL Science 283:401-404(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6 X CBA;
RX PubMed=15606779; DOI=10.1111/j.1432-1033.2004.04460.x;
RA McCaw E.A., Hu H., Gomez G.T., Hebb A.L., Kelly M.E., Denovan-Wright E.M.;
RT "Structure, expression and regulation of the cannabinoid receptor gene
RT (CB1) in Huntington's disease transgenic mice.";
RL Eur. J. Biochem. 271:4909-4920(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RA Bonner T.I.;
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yuan Z.-Q., Li L., Qiu B.-S., Song D.-K.;
RT "cDNA cloning and expression analysis of mouse cannabinoid receptor (CB1)
RT gene.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=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 [9]
RP TISSUE SPECIFICITY.
RX PubMed=10891614; DOI=10.1016/s0306-4522(00)00157-3;
RA Denovan-Wright E.M., Robertson H.A.;
RT "Cannabinoid receptor messenger RNA levels decrease in a subset of neurons
RT of the lateral striatum, cortex and hippocampus of transgenic Huntington's
RT disease mice.";
RL Neuroscience 98:705-713(2000).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY HIGH-FAT DIET, TISSUE
RP SPECIFICITY, DISRUPTION PHENOTYPE, AND INVOLVEMENT IN OBESITY.
RX PubMed=15864349; DOI=10.1172/jci200523057;
RA Osei-Hyiaman D., DePetrillo M., Pacher P., Liu J., Radaeva S., Batkai S.,
RA Harvey-White J., Mackie K., Offertaler L., Wang L., Kunos G.;
RT "Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid
RT synthesis and contributes to diet-induced obesity.";
RL J. Clin. Invest. 115:1298-1305(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426 AND SER-430, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION, AND POTENTIAL INVOLVEMENT IN OBESITY.
RX PubMed=22841573; DOI=10.1016/j.cmet.2012.07.002;
RA Tam J., Cinar R., Liu J., Godlewski G., Wesley D., Jourdan T., Szanda G.,
RA Mukhopadhyay B., Chedester L., Liow J.S., Innis R.B., Cheng K., Rice K.C.,
RA Deschamps J.R., Chorvat R.J., McElroy J.F., Kunos G.;
RT "Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by
RT reversing leptin resistance.";
RL Cell Metab. 16:167-179(2012).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY ENDOCANNABINOID ANANDAMIDE AND
RP HIGH-FAT DIET, AND INVOLVEMENT IN OBESITY.
RX PubMed=21987372; DOI=10.1002/hep.24733;
RA Jourdan T., Demizieux L., Gresti J., Djaouti L., Gaba L., Verges B.,
RA Degrace P.;
RT "Antagonism of peripheral hepatic cannabinoid receptor-1 improves liver
RT lipid metabolism in mice: evidence from cultured explants.";
RL Hepatology 55:790-799(2012).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND TOPOLOGY.
RX PubMed=22388959; DOI=10.1038/nn.3053;
RA Benard G., Massa F., Puente N., Lourenco J., Bellocchio L., Soria-Gomez E.,
RA Matias I., Delamarre A., Metna-Laurent M., Cannich A., Hebert-Chatelain E.,
RA Mulle C., Ortega-Gutierrez S., Martin-Fontecha M., Klugmann M.,
RA Guggenhuber S., Lutz B., Gertsch J., Chaouloff F., Lopez-Rodriguez M.L.,
RA Grandes P., Rossignol R., Marsicano G.;
RT "Mitochondrial CB(1) receptors regulate neuronal energy metabolism.";
RL Nat. Neurosci. 15:558-564(2012).
RN [15]
RP FUNCTION, AND INDUCTION BY ENDOCANNABINOID ANANDAMIDE AND IL1B.
RX PubMed=23955712; DOI=10.1038/nm.3265;
RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J.,
RA Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P.,
RA Kunos G.;
RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by
RT endocannabinoids mediates beta cell loss in type 2 diabetes.";
RL Nat. Med. 19:1132-1140(2013).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25869131; DOI=10.1074/jbc.m115.646885;
RA Palomba L., Silvestri C., Imperatore R., Morello G., Piscitelli F.,
RA Martella A., Cristino L., Di Marzo V.;
RT "Negative regulation of leptin-induced reactive oxygen species (ROS)
RT formation by cannabinoid CB1 receptor activation in hypothalamic neurons.";
RL J. Biol. Chem. 290:13669-13677(2015).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN
RP OBESITY.
RX PubMed=25707796; DOI=10.1038/nature14260;
RA Koch M., Varela L., Kim J.G., Kim J.D., Hernandez-Nuno F., Simonds S.E.,
RA Castorena C.M., Vianna C.R., Elmquist J.K., Morozov Y.M., Rakic P.,
RA Bechmann I., Cowley M.A., Szigeti-Buck K., Dietrich M.O., Gao X.B.,
RA Diano S., Horvath T.L.;
RT "Hypothalamic POMC neurons promote cannabinoid-induced feeding.";
RL Nature 519:45-50(2015).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN
RP OBESITY.
RX PubMed=26671069; DOI=10.1371/journal.pone.0145244;
RA Arrabal S., Lucena M.A., Canduela M.J., Ramos-Uriarte A., Rivera P.,
RA Serrano A., Pavon F.J., Decara J., Vargas A., Baixeras E.,
RA Martin-Rufian M., Marquez J., Fernandez-Llebrez P., De Roos B., Grandes P.,
RA Rodriguez de Fonseca F., Suarez J.;
RT "Pharmacological blockade of cannabinoid CB1 receptors in diet-induced
RT obesity regulates mitochondrial dihydrolipoamide dehydrogenase in muscle.";
RL PLoS ONE 10:E0145244-E0145244(2015).
RN [19]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=27826249; DOI=10.3389/fphys.2016.00476;
RA Mendizabal-Zubiaga J., Melser S., Benard G., Ramos A., Reguero L.,
RA Arrabal S., Elezgarai I., Gerrikagoitia I., Suarez J.,
RA Rodriguez De Fonseca F., Puente N., Marsicano G., Grandes P.;
RT "Cannabinoid CB1 receptors are localized in striated muscle mitochondria
RT and regulate mitochondrial respiration.";
RL Front. Physiol. 7:476-476(2016).
RN [20]
RP FUNCTION, INTERACTION WITH G PROTEIN ALPHA SUBUNITS, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF 1-MET--TYR-22.
RX PubMed=27828947; DOI=10.1038/nature20127;
RA Hebert-Chatelain E., Desprez T., Serrat R., Bellocchio L., Soria-Gomez E.,
RA Busquets-Garcia A., Pagano Zottola A.C., Delamarre A., Cannich A.,
RA Vincent P., Varilh M., Robin L.M., Terral G., Garcia-Fernandez M.D.,
RA Colavita M., Mazier W., Drago F., Puente N., Reguero L., Elezgarai I.,
RA Dupuy J.W., Cota D., Lopez-Rodriguez M.L., Barreda-Gomez G., Massa F.,
RA Grandes P., Benard G., Marsicano G.;
RT "A cannabinoid link between mitochondria and memory.";
RL Nature 539:555-559(2016).
CC -!- FUNCTION: G-protein coupled receptor for cannabinoids, including
CC endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also
CC called anandamide or AEA) and 2-arachidonoylglycerol (2-AG)
CC (PubMed:9888857, PubMed:22388959). Mediates many cannabinoid-induced
CC effects, acting, among others, on food intake, memory loss,
CC gastrointestinal motility, catalepsy, ambulatory activity, anxiety,
CC chronic pain (PubMed:9888857, PubMed:27828947). Signaling typically
CC involves reduction in cyclic AMP (PubMed:8832654, PubMed:27828947). In
CC the hypothalamus, may have a dual effect on mitochondrial respiration
CC depending upon the agonist dose and possibly upon the cell type.
CC Increases respiration at low doses, while decreases respiration at high
CC doses (PubMed:25707796, PubMed:27828947). At high doses, CNR1 signal
CC transduction involves G-protein alpha-i protein activation and
CC subsequent inhibition of mitochondrial soluble adenylate cyclase,
CC decrease in cyclic AMP concentration, inhibition of protein kinase A
CC (PKA)-dependent phosphorylation of specific subunits of the
CC mitochondrial electron transport system, including NDUFS2
CC (PubMed:27828947). In the hypothalamus, inhibits leptin-induced
CC reactive oxygen species (ROS) formation and mediates cannabinoid-
CC induced increase in SREBF1 and FASN gene expression (PubMed:25869131).
CC In response to cannabinoids, drives the release of orexigenic beta-
CC endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-
CC MSH, from hypothalamic POMC neurons, hence promoting food intake
CC (PubMed:25707796). In the hippocampus, regulates cellular respiration
CC and energy production in response to cannabinoids. Involved in
CC cannabinoid-dependent depolarization-induced suppression of inhibition
CC (DSI), a process in which depolarization of CA1 postsynaptic pyramidal
CC neurons mobilizes eCBs, which retrogradely activate presynaptic CB1
CC receptors, transiently decreasing GABAergic inhibitory
CC neurotransmission (PubMed:22388959). Also reduces excitatory synaptic
CC transmission (PubMed:27828947). In superior cervical ganglions and
CC cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+)
CC channels in a constitutive, as well as agonist-dependent manner (By
CC similarity). In cerebral vascular smooth muscle cells, cannabinoid-
CC induced inhibition of voltage-gated Ca(2+) channels leads to
CC vasodilation and decreased vascular tone (By similarity). Induces
CC leptin production in adipocytes and reduces LRP2-mediated leptin
CC clearance in the kidney, hence participating in hyperleptinemia
CC (PubMed:22841573). In adipose tissue, CNR1 signaling leads to increased
CC expression of SREBF1, ACACA and FASN genes (PubMed:15864349). In the
CC liver, activation by endocannabinoids leads to increased de novo
CC lipogenesis and reduced fatty acid catabolism, associated with
CC increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN
CC genes (PubMed:15864349, PubMed:21987372). May also affect de novo
CC cholesterol synthesis and HDL-cholesteryl ether uptake
CC (PubMed:21987372). Peripherally modulates energy metabolism. In high
CC carbohydrate diet-induced obesity, may decrease the expression of
CC mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as
CC well as that of selected glucose/ pyruvate metabolic enzymes, hence
CC affecting energy expenditure through mitochondrial metabolism
CC (PubMed:26671069). In response to cannabinoid anandamide, elicits a
CC pro-inflammatory response in macrophages, which involves NLRP3
CC inflammasome activation and IL1B and IL18 secretion. In macrophages
CC infiltrating pancreatic islets, this process may participate in the
CC progression of type-2 diabetes and associated loss of pancreatic beta-
CC cells (PubMed:23955712). {ECO:0000250|UniProtKB:O02777,
CC ECO:0000250|UniProtKB:P21554, ECO:0000269|PubMed:15864349,
CC ECO:0000269|PubMed:21987372, ECO:0000269|PubMed:22388959,
CC ECO:0000269|PubMed:22841573, ECO:0000269|PubMed:23955712,
CC ECO:0000269|PubMed:25707796, ECO:0000269|PubMed:25869131,
CC ECO:0000269|PubMed:26671069, ECO:0000269|PubMed:27828947,
CC ECO:0000269|PubMed:8832654, ECO:0000269|PubMed:9888857}.
CC -!- ACTIVITY REGULATION: Hemopressin, a peptide derived from hemoglobin
CC subunit alpha (HBA1 and/or HBA2), acts as an antagonist peptide:
CC hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and
CC subsequent signaling. {ECO:0000250|UniProtKB:P21554}.
CC -!- SUBUNIT: Interacts (via C-terminus) with CNRIP1 (By similarity).
CC Associates with G protein alpha subunits, including G(i) alpha-1/GNAI1,
CC G(i) alpha-3/GNAI3 and G(o)-alpha/GNAO1; palmitoylation is important
CC for interaction with GNAI3 and GNAO1 (PubMed:27828947).
CC {ECO:0000250|UniProtKB:P21554, ECO:0000269|PubMed:27828947}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15864349,
CC ECO:0000269|PubMed:25707796, ECO:0000269|PubMed:27828947}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P21554}. Mitochondrion outer
CC membrane {ECO:0000269|PubMed:22388959, ECO:0000269|PubMed:25707796,
CC ECO:0000269|PubMed:26671069, ECO:0000269|PubMed:27826249,
CC ECO:0000269|PubMed:27828947}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P20272}. Presynapse
CC {ECO:0000250|UniProtKB:P20272}. Note=In CA1 hippocampal neurons, 15.5%
CC of total protein is localized in mitochondria (PubMed:22388959). Found
CC on presynaptic axon terminals in some GABAergic neurons in the
CC somatosensory cortex (By similarity). In striated muscles,
CC predominantly located in mitochondria (PubMed:27826249). Unexpectedly,
CC in the mitochondria, the C-terminus is located in the mitochondrial
CC intermembrane space, a compartment topologically considered as
CC extracellular. In canonical seven-transmembrane G-protein coupled
CC receptors, the C-terminus is cytosolic (PubMed:22388959).
CC {ECO:0000250|UniProtKB:P20272, ECO:0000269|PubMed:22388959,
CC ECO:0000269|PubMed:27826249}.
CC -!- TISSUE SPECIFICITY: Expressed in brain neurons (at protein level)
CC (PubMed:22388959). Detected throughout the striatum, cortex and
CC hippocampus, with highest levels in the lateral striatum
CC (PubMed:15606779, PubMed:10891614, PubMed:22388959). In rostral brain
CC regions, high expression levels in the dorsal lateral striatum, while
CC in the caudal brain regions, high levels are observed in the ventral
CC lateral striatum (PubMed:10891614). Expressed in neurons
CC (PubMed:10891614). In the hypothalamus, expressed in both GABAergic and
CC glutamatergic presynaptic terminals of POMC neurons (at protein level)
CC (PubMed:25869131, PubMed:25707796). Expressed in striated muscles,
CC including skeletal muscles (gastrocnemius and rectus abdominis) and
CC myocardium (at protein level) (PubMed:26671069, PubMed:27826249).
CC Expressed in the liver, with highest levels in Kupffer cells and lower
CC levels in endothelial cells as well as hepatocytes, particularly in
CC perivascular areas (at protein level) (PubMed:15864349,
CC PubMed:21987372). The hepatic expression level is up-regulated in obese
CC mice compared to lean animals (PubMed:21987372).
CC {ECO:0000269|PubMed:10891614, ECO:0000269|PubMed:15606779,
CC ECO:0000269|PubMed:15864349, ECO:0000269|PubMed:21987372,
CC ECO:0000269|PubMed:22388959, ECO:0000269|PubMed:25707796,
CC ECO:0000269|PubMed:25869131, ECO:0000269|PubMed:26671069,
CC ECO:0000269|PubMed:27826249}.
CC -!- INDUCTION: Up-regulated by endocannabinoid anandamide/AEA
CC (PubMed:21987372, PubMed:23955712). Down-regulated by IL1B
CC (PubMed:23955712). Up-regulated in the liver of animals on a high-fat
CC diet compared to regular diet (PubMed:15864349, PubMed:21987372).
CC {ECO:0000269|PubMed:15864349, ECO:0000269|PubMed:21987372,
CC ECO:0000269|PubMed:23955712}.
CC -!- PTM: Palmitoylation at Cys-416 is important for recruitment at both
CC plasma membrane and lipid rafts and association with G protein alpha
CC subunits. {ECO:0000250|UniProtKB:P20272}.
CC -!- DISEASE: Note=May contribute to the development of diet-induced obesity
CC and several obesity-associated features, such as dyslipidemia and liver
CC steatosis, regulating peripheral lipogenesis, energy expenditure and
CC feeding behavior. In the liver, mediates cannabinoid-induced de novo
CC lipogenesis and reduces fatty acid catabolism (PubMed:15864349,
CC PubMed:21987372). In muscles, affects energy expenditure through
CC mitochondrial metabolism (PubMed:22841573, PubMed:26671069). Induces
CC leptin production by adipocytes and reduces LRP2-mediated leptin
CC clearance in the kidney. The resulting hyperleptinemia causes
CC resistance to the anorexic and weight-reducing effects of leptin
CC (PubMed:22841573). In response to cannabinoids, drives the release of
CC orexigenic beta-endorphin from hypothalamic POMC neurons, hence
CC promoting food intake (PubMed:25707796). The use of peripherally-
CC restricted inverse agonists in diet-induced obese mice reduces
CC appetite, body weight, hepatic steatosis, and insulin resistance
CC (PubMed:22841573). {ECO:0000269|PubMed:15864349,
CC ECO:0000269|PubMed:21987372, ECO:0000269|PubMed:22841573,
CC ECO:0000269|PubMed:25707796, ECO:0000269|PubMed:26671069}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype, although mutant mice
CC present a mild impairment in the adaptation to new environment. Mutant
CC mice do not respond to cannabinoids, such as anandamide. The acute
CC effects of opiates are not affected, but the reinforcing properties of
CC morphine and the severity of the withdrawal syndrome are strongly
CC reduced (PubMed:9888857). On high-fat diet, mutant mice remain lean,
CC their metabolic and hormonal profile are unchanged, and they do not
CC develop fatty liver, despite having caloric intake similar to that of
CC wild-type mice (PubMed:15864349). {ECO:0000269|PubMed:15864349,
CC ECO:0000269|PubMed:9888857}.
CC -!- MISCELLANEOUS: High-fat diet also increases the hepatic levels of CNR1
CC ligand anandamide, but not that of 2-arachidonoylglycerol.
CC {ECO:0000269|PubMed:15864349}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U17985; AAA57202.1; -; mRNA.
DR EMBL; U40709; AAA91176.1; -; mRNA.
DR EMBL; Y18374; CAB42647.1; -; Genomic_DNA.
DR EMBL; AY522555; AAS91801.1; -; Genomic_DNA.
DR EMBL; AY522554; AAS91800.1; -; mRNA.
DR EMBL; U22948; AAA64413.1; -; Genomic_DNA.
DR EMBL; AF153345; AAD34624.1; -; mRNA.
DR EMBL; AK139417; BAE24003.1; -; mRNA.
DR EMBL; BC070447; AAH70447.1; -; mRNA.
DR EMBL; BC079564; AAH79564.1; -; mRNA.
DR CCDS; CCDS18025.1; -.
DR RefSeq; NP_031752.1; NM_007726.3.
DR RefSeq; XP_006537654.1; XM_006537591.2.
DR RefSeq; XP_006537655.1; XM_006537592.3.
DR RefSeq; XP_006537656.1; XM_006537593.3.
DR RefSeq; XP_006537657.1; XM_006537594.2.
DR RefSeq; XP_006537658.1; XM_006537595.2.
DR RefSeq; XP_017175428.1; XM_017319939.1.
DR AlphaFoldDB; P47746; -.
DR SMR; P47746; -.
DR BioGRID; 198793; 1.
DR IntAct; P47746; 5.
DR STRING; 10090.ENSMUSP00000055797; -.
DR BindingDB; P47746; -.
DR ChEMBL; CHEMBL3037; -.
DR DrugCentral; P47746; -.
DR GuidetoPHARMACOLOGY; 56; -.
DR GlyGen; P47746; 2 sites.
DR iPTMnet; P47746; -.
DR PhosphoSitePlus; P47746; -.
DR SwissPalm; P47746; -.
DR MaxQB; P47746; -.
DR PaxDb; P47746; -.
DR PeptideAtlas; P47746; -.
DR PRIDE; P47746; -.
DR ProteomicsDB; 285519; -.
DR Antibodypedia; 3355; 571 antibodies from 41 providers.
DR DNASU; 12801; -.
DR Ensembl; ENSMUST00000057188; ENSMUSP00000055797; ENSMUSG00000044288.
DR Ensembl; ENSMUST00000084736; ENSMUSP00000081787; ENSMUSG00000044288.
DR GeneID; 12801; -.
DR KEGG; mmu:12801; -.
DR UCSC; uc008sfw.1; mouse.
DR CTD; 1268; -.
DR MGI; MGI:104615; Cnr1.
DR VEuPathDB; HostDB:ENSMUSG00000044288; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234510; -.
DR HOGENOM; CLU_009579_7_0_1; -.
DR InParanoid; P47746; -.
DR OMA; CMMWAIS; -.
DR OrthoDB; 822074at2759; -.
DR PhylomeDB; P47746; -.
DR TreeFam; TF330052; -.
DR Reactome; R-MMU-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 12801; 4 hits in 71 CRISPR screens.
DR PRO; PR:P47746; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P47746; protein.
DR Bgee; ENSMUSG00000044288; Expressed in cerebellum lobe and 175 other tissues.
DR ExpressionAtlas; P47746; baseline and differential.
DR Genevisible; P47746; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IDA:MGI.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR GO; GO:0004949; F:cannabinoid receptor activity; IMP:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0099635; F:voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels; IDA:SynGO.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; ISO:MGI.
DR GO; GO:0007413; P:axonal fasciculation; IMP:MGI.
DR GO; GO:0038171; P:cannabinoid signaling pathway; IMP:SynGO.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IPI:MGI.
DR GO; GO:0007611; P:learning or memory; ISO:MGI.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0045759; P:negative regulation of action potential; ISO:MGI.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISO:MGI.
DR GO; GO:0033602; P:negative regulation of dopamine secretion; ISO:MGI.
DR GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; ISO:MGI.
DR GO; GO:0043271; P:negative regulation of ion transport; ISO:MGI.
DR GO; GO:0033004; P:negative regulation of mast cell activation; ISO:MGI.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0014063; P:negative regulation of serotonin secretion; ISO:MGI.
DR GO; GO:0002866; P:positive regulation of acute inflammatory response to antigenic stimulus; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:MGI.
DR GO; GO:0031622; P:positive regulation of fever generation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0060259; P:regulation of feeding behavior; ISO:MGI.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:MGI.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISO:MGI.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR GO; GO:0060405; P:regulation of penile erection; ISO:MGI.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISO:MGI.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISO:MGI.
DR GO; GO:0042220; P:response to cocaine; ISO:MGI.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0043278; P:response to morphine; ISO:MGI.
DR GO; GO:0035094; P:response to nicotine; ISO:MGI.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0098921; P:retrograde trans-synaptic signaling by endocannabinoid; IDA:SynGO.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0099553; P:trans-synaptic signaling by endocannabinoid, modulating synaptic transmission; IMP:SynGO.
DR InterPro; IPR000810; Canbinoid_rcpt_1.
DR InterPro; IPR002230; Cnbnoid_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR22750:SF47; PTHR22750:SF47; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PIRSF; PIRSF037995; Cnoid_rcpt_1; 1.
DR PRINTS; PR00522; CANABINOID1R.
DR PRINTS; PR00362; CANNABINOIDR.
DR PRINTS; PR00237; GPCRRHODOPSN.
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; Cell projection; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Obesity; Palmitate; Phosphoprotein; Receptor; Reference proteome; Synapse;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..473
FT /note="Cannabinoid receptor 1"
FT /id="PRO_0000069316"
FT TOPO_DOM 1..121
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 143..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 177..188
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 210..233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 255..278
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 300..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 346..366
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 367..378
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 379..399
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 400..473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT REGION 2..23
FT /note="Required for mitochondrial localization"
FT /evidence="ECO:0000269|PubMed:27828947"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT LIPID 416
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 2..23
FT /note="Missing: Loss of mitochondrial localization. Loss of
FT cannabinoid-induced reduction of respiration, mitochondrial
FT mobility, synaptic transmission and memory formation. No
FT effect on MAPK/ERK signaling, nor on G protein activation."
FT /evidence="ECO:0000269|PubMed:27828947"
FT CONFLICT 9
FT /note="A -> G (in Ref. 1; AAA57202)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="S -> R (in Ref. 1; AAA57202)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="T -> R (in Ref. 1; AAA57202)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 473 AA; 52831 MW; E504168191CB6429 CRC64;
MKSILDGLAD TTFRTITTDL LYVGSNDIQY EDIKGDMASK LGYFPQKFPL TSFRGSPFQE
KMTAGDNSPL VPAGDTTNIT EFYNKSLSSF KENEDNIQCG ENFMDMECFM ILNPSQQLAI
AVLSLTLGTF TVLENLLVLC VILHSRSLRC RPSYHFIGSL AVADLLGSVI FVYSFVDFHV
FHRKDSPNVF LFKLGGVTAS FTASVGSLFL TAIDRYISIH RPLAYKRIVT RPKAVVAFCL
MWTIAIVIAV LPLLGWNCKK LQSVCSDIFP LIDETYLMFW IGVTSVLLLF IVYAYMYILW
KAHSHAVRMI QRGTQKSIII HTSEDGKVQV TRPDQARMDI RLAKTLVLIL VVLIICWGPL
LAIMVYDVFG KMNKLIKTVF AFCSMLCLLN STVNPIIYAL RSKDLRHAFR SMFPSCEGTA
QPLDNSMGDS DCLHKHANNT ASMHRAAESC IKSTVKIAKV TMSVSTDTSA EAL
