Cnr1
entrez
12801
canonical
uniprot
P47746
canonical
ensembl
ENSMUSG00000044288
resolver
ensp
ENSMUSP00000055797
resolver
ensp
ENSMUSP00000081787
resolver
ensp
ENSMUSP00000217002
resolver
ensp
ENSMUSP00000217004
resolver
ensp
ENSMUSP00000217005
resolver
ensp
ENSMUSP00000217007
resolver
ensp
ENSMUSP00000217008
resolver
ensp
ENSMUSP00000217009
resolver
ensp
ENSMUSP00000217012
resolver
enst
ENSMUST00000057188
resolver
enst
ENSMUST00000084736
resolver
genesymbol
Cnr1
resolver
uniprot
A0A385KNU8
resolver
uniprot
Q5SF33
resolver
uniprot_entry
A0A385KNU8_MOUSE
resolver
uniprot_entry
CNR1_MOUSE
resolver
uniprot_sec
Q5SF33
resolver
activity_regulation
ACTIVITY REGULATION: Hemopressin, a peptide derived from hemoglobin subunit alpha (HBA1 and/or HBA2), acts as an antagonist peptide: hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and subsequent signaling. {ECO:0000250|UniProtKB:P21554}.
uniprot
proteins
amino_acid_sequence
MKSILDGLADTTFRTITTDLLYVGSNDIQYEDIKGDMASKLGYFPQKFPLTSFRGSPFQEKMTAGDNSPLVPAGDTTNITEFYNKSLSSFKENEDNIQCGENFMDMECFMILNPSQQLAIAVLSLTLGTFTVLENLLVLCVILHSRSLRCRPSYHFIGSLAVADLLGSVIFVYSFVDFHVFHRKDSPNVFLFKLGGVTASFTASVGSLFLTAIDRYISIHRPLAYKRIVTRPKAVVAFCLMWTIAIVIAVLPLLGWNCKKLQSVCSDIFPLIDETYLMFWIGVTSVLLLFIVYAYMYILWKAHSHAVRMIQRGTQKSIIIHTSEDGKVQVTRPDQARMDIRLAKTLVLILVVLIICWGPLLAIMVYDVFGKMNKLIKTVFAFCSMLCLLNSTVNPIIYALRSKDLRHAFRSMFPSCEGTAQPLDNSMGDSDCLHKHANNTASMHRAAESCIKSTVKIAKVTMSVSTDTSAEAL
uniprot
proteins
disease_involvement
DISEASE: Note=May contribute to the development of diet-induced obesity and several obesity-associated features, such as dyslipidemia and liver steatosis, regulating peripheral lipogenesis, energy expenditure and feeding behavior. In the liver, mediates cannabinoid-induced de novo lipogenesis and reduces fatty acid catabolism (PubMed:15864349, PubMed:21987372). In muscles, affects energy expenditure through mitochondrial metabolism (PubMed:22841573, PubMed:26671069). Induces leptin production by adipocytes and reduces LRP2-mediated leptin clearance in the kidney. The resulting hyperleptinemia causes resistance to the anorexic and weight-reducing effects of leptin (PubMed:22841573). In response to cannabinoids, drives the release of orexigenic beta-endorphin from hypothalamic POMC neurons, hence promoting food intake (PubMed:25707796). The use of peripherally-restricted inverse agonists in diet-induced obese mice reduces appetite, body weight, hepatic steatosis, and insulin resistance (PubMed:22841573). {ECO:0000269|PubMed:15864349, ECO:0000269|PubMed:21987372, ECO:0000269|PubMed:22841573, ECO:0000269|PubMed:25707796, ECO:0000269|PubMed:26671069}.
uniprot
proteins
function
FUNCTION: G protein-coupled receptor for cannabinoids, including endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG) (PubMed:22388959, PubMed:9888857). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain (PubMed:27828947, PubMed:9888857). Signaling typically involves reduction in cyclic AMP (PubMed:27828947, PubMed:8832654). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses (PubMed:25707796, PubMed:27828947). At high doses, CNR1 signal transduction involves G protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2 (PubMed:27828947). In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression (PubMed:25869131). In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake (PubMed:25707796). In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission (PubMed:22388959). Also reduces excitatory synaptic transmission (PubMed:27828947). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner (By similarity). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia (PubMed:22841573). In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (PubMed:15864349). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes (PubMed:15864349, PubMed:21987372). May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake (PubMed:21987372). Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (PubMed:26671069). In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells (PubMed:23955712). {ECO:0000250|UniProtKB:O02777, ECO:0000250|UniProtKB:P21554, ECO:0000269|PubMed:15864349, ECO:0000269|PubMed:21987372, ECO:0000269|PubMed:22388959, ECO:0000269|PubMed:22841573, ECO:0000269|PubMed:23955712, ECO:0000269|PubMed:25707796, ECO:0000269|PubMed:25869131, ECO:0000269|PubMed:26671069, ECO:0000269|PubMed:27828947, ECO:0000269|PubMed:8832654, ECO:0000269|PubMed:9888857}.
uniprot
proteins
mass_dalton
52831
uniprot
proteins
mutagenesis
MUTAGEN 2..23; /note="Missing: Loss of mitochondrial localization. Loss of cannabinoid-induced reduction of respiration, mitochondrial mobility, synaptic transmission and memory formation. No effect on MAPK/ERK signaling, nor on G protein activation."; /evidence="ECO:0000269|PubMed:27828947
uniprot
proteins
post_translational_modification
PTM: Palmitoylation at Cys-416 is important for recruitment at both plasma membrane and lipid rafts and association with G protein alpha subunits. {ECO:0000250|UniProtKB:P20272}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10891614
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15606779
uniprot
proteins
pubmed
15864349
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21987372
uniprot
proteins
pubmed
22388959
uniprot
proteins
pubmed
22841573
uniprot
proteins
pubmed
23955712
uniprot
proteins
pubmed
25707796
uniprot
proteins
pubmed
25869131
uniprot
proteins
pubmed
26671069
uniprot
proteins
pubmed
27826249
uniprot
proteins
pubmed
27828947
uniprot
proteins
pubmed
8777318
uniprot
proteins
pubmed
8832654
uniprot
proteins
pubmed
9888857
uniprot
proteins
sequence_length
473
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15864349, ECO:0000269|PubMed:25707796, ECO:0000269|PubMed:27828947}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P21554}. Mitochondrion outer membrane {ECO:0000269|PubMed:22388959, ECO:0000269|PubMed:25707796, ECO:0000269|PubMed:26671069, ECO:0000269|PubMed:27826249, ECO:0000269|PubMed:27828947}. Cell projection, axon {ECO:0000250|UniProtKB:P20272}. Presynapse {ECO:0000250|UniProtKB:P20272}. Note=In CA1 hippocampal neurons, 15.5% of total protein is localized in mitochondria (PubMed:22388959). Found on presynaptic axon terminals in some GABAergic neurons in the somatosensory cortex (By similarity). In striated muscles, predominantly located in mitochondria (PubMed:27826249). Unexpectedly, in the mitochondria, the C-terminus is located in the mitochondrial intermembrane space, a compartment topologically considered as extracellular. In canonical seven-transmembrane G protein-coupled receptors, the C-terminus is cytosolic (PubMed:22388959). {ECO:0000250|UniProtKB:P20272, ECO:0000269|PubMed:22388959, ECO:0000269|PubMed:27826249}.
uniprot
proteins
transmembrane_region
TRANSMEM 122..142; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P21554"; TRANSMEM 156..176; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P21554"; TRANSMEM 189..209; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P21554"; TRANSMEM 234..254; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P21554"; TRANSMEM 279..299; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P21554"; TRANSMEM 346..366; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P21554"; TRANSMEM 379..399; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P21554
uniprot
proteins