CNR1
entrez
1268
canonical
uniprot
P21554
canonical
ensembl
ENSG00000118432
resolver
ensp
ENSP00000358513
resolver
ensp
ENSP00000412192
resolver
ensp
ENSP00000420188
resolver
ensp
ENSP00000446702
resolver
ensp
ENSP00000552463
resolver
ensp
ENSP00000552464
resolver
ensp
ENSP00000552465
resolver
ensp
ENSP00000552466
resolver
ensp
ENSP00000552467
resolver
ensp
ENSP00000552468
resolver
ensp
ENSP00000552469
resolver
ensp
ENSP00000588548
resolver
ensp
ENSP00000588549
resolver
ensp
ENSP00000588550
resolver
ensp
ENSP00000621446
resolver
genesymbol
CNR1
resolver
genesymbol_syn
CNR
resolver
hgnc
HGNC:2159
resolver
uniprot
B2R9T4
resolver
uniprot
E1P512
resolver
uniprot
Q13949
resolver
uniprot
Q495Z0
resolver
uniprot
Q4PLI4
resolver
uniprot
Q4VBM6
resolver
uniprot
Q5JVL5
resolver
uniprot
Q5UB37
resolver
uniprot
Q9UNN0
resolver
uniprot
V5KA96
resolver
uniprot_entry
CNR1_HUMAN
resolver
uniprot_entry
V5KA96_HUMAN
resolver
uniprot_sec
B2R9T4
resolver
uniprot_sec
E1P512
resolver
uniprot_sec
Q13949
resolver
uniprot_sec
Q495Z0
resolver
uniprot_sec
Q4PLI4
resolver
uniprot_sec
Q4VBM6
resolver
uniprot_sec
Q5JVL5
resolver
uniprot_sec
Q5UB37
resolver
uniprot_sec
Q9UNN0
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:0000269|PubMed:18077343}.
uniprot
proteins
amino_acid_sequence
MKSILDGLADTTFRTITTDLLYVGSNDIQYEDIKGDMASKLGYFPQKFPLTSFRGSPFQEKMTAGDNPQLVPADQVNITEFYNKSLSSFKENEENIQCGENFMDIECFMVLNPSQQLAIAVLSLTLGTFTVLENLLVLCVILHSRSLRCRPSYHFIGSLAVADLLGSVIFVYSFIDFHVFHRKDSRNVFLFKLGGVTASFTASVGSLFLTAIDRYISIHRPLAYKRIVTRPKAVVAFCLMWTIAIVIAVLPLLGWNCEKLQSVCSDIFPHIDETYLMFWIGVTSVLLLFIVYAYMYILWKAHSHAVRMIQRGTQKSIIIHTSEDGKVQVTRPDQARMDIRLAKTLVLILVVLIICWGPLLAIMVYDVFGKMNKLIKTVFAFCSMLCLLNSTVNPIIYALRSKDLRHAFRSMFPSCEGTAQPLDNSMGDSDCLHKHANNAASVHRAAESCIKSTVKIAKVTMSVSTDTSAEAL
uniprot
proteins
disease_involvement
DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:18177726}. Note=The protein represented in this entry may be involved in disease pathogenesis. 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. CNR1 inverse agonists have been shown to reduce body weight and improve metabolic abnormalities in obese subjects, although adverse neuropsychiatric effects, including anxiety, irritability, and depressed mood, halted their therapeutic development (PubMed:18177726). In obese mice, peripherally restricted CNR1 inverse agonists have been shown to normalize metabolic abnormalities, including insulin resistance and fatty liver, and to reverse leptin resistance. {ECO:0000269|PubMed:18177726}.; DISEASE: Note=Dysfunction of the endogenous cannabinoid system including CNR1 has been implicated in the pathogenesis of a number of central nervous system disorders, including Huntington disease, Parkinson disease, and Alzheimer disease (PubMed:32549916). In post-mortem brains from Huntington disease patients, a progressive CNR1 loss has been observed in the caudate nucleus, putamen, and substantia nigra pars reticulata, and altered expression and abnormal endocannabinoid levels precede motor symptoms in a disease mouse model (PubMed:10828533, PubMed:19524019, PubMed:8255419). In Parkinson disease, low CNR1 expression in mid-superior frontal gyrus and mid-cingulate cortex has been associated with poor mind, poor executive functioning and poor episode memory, while patients with more severe visuospatial dysfunction showed decreased receptor availability in the precuneus, mid-cingulate, supplementary motor cortex, inferior orbitofrontal gyrus and thalamus (PubMed:31342135). In an animal model for Alzheimer disease, CNR1 heterozygous deletion has been associated with decreased levels of postsynaptic density protein 95 (DLG4/PSD95) and accelerated memory impairment, suggesting synaptic dysfunction and a crucial role for CNR1 in the progression of disease symptoms (PubMed:10828533, PubMed:19524019, PubMed:30096288, PubMed:31342135, PubMed:8255419). {ECO:0000269|PubMed:10828533, ECO:0000269|PubMed:19524019, ECO:0000269|PubMed:30096288, ECO:0000269|PubMed:31342135, ECO:0000269|PubMed:32549916, ECO:0000269|PubMed:8255419}.
uniprot
proteins
function
FUNCTION: G protein-coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723, PubMed:27768894, PubMed:27851727, PubMed:35637350). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP (PubMed:1718258, PubMed:21895628, PubMed:27768894). 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. 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. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. 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. 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. Also reduces excitatory synaptic transmission (By similarity). 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 (PubMed:17895407). 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. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (By similarity). 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. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism (By similarity). 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 (By similarity). In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion (By similarity). 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:P47746, ECO:0000269|PubMed:15620723, ECO:0000269|PubMed:1718258, ECO:0000269|PubMed:17895407, ECO:0000269|PubMed:21895628, ECO:0000269|PubMed:23955712, ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727, ECO:0000269|PubMed:35637350}.; FUNCTION: [Isoform 1]: Binds both 2-arachidonoylglycerol (2-AG) and anandamide. {ECO:0000269|PubMed:15620723}.; FUNCTION: [Isoform 2]: Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 2 in assays measuring GTP binding to membranes. {ECO:0000269|PubMed:15620723}.; FUNCTION: [Isoform 3]: Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 3 in assays measuring GTP binding to membranes. {ECO:0000269|PubMed:15620723}.
uniprot
proteins
mass_dalton
52858
uniprot
proteins
mutagenesis
MUTAGEN 155; /note="F->V: Enhanced G(i) signaling activation ability."; /evidence="ECO:0000269|PubMed:35637350"; MUTAGEN 155; /note="F->W: Reduced agonist-induced receptor activation."; /evidence="ECO:0000269|PubMed:35637350"; MUTAGEN 210; /note="T->A: 7-fold lower affinity for a synthetic agonist, CP55940, possibly due the stabilization of an inactive conformation."; /evidence="ECO:0000269|PubMed:27851727"; MUTAGEN 341..342; /note="LA->AL: Loss of activity, when assayed for GNAI1 GTPase stimulatory activity."; /evidence="ECO:0000269|PubMed:12237474"; MUTAGEN 415; /note="C->A: Loss of palmitoylation, marked loss of association with lipid rafts on the plasma membrane and loss of activity, when assayed for downstream GTP-binding and reduction in cAMP levels."; /evidence="ECO:0000269|PubMed:21895628
uniprot
proteins
post_translational_modification
PTM: Palmitoylation at Cys-415 is important for recruitment at plasma membrane and lipid rafts and association with G protein alpha subunits. {ECO:0000269|PubMed:21895628}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10828533
uniprot
proteins
pubmed
12237474
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15620723
uniprot
proteins
pubmed
1718258
uniprot
proteins
pubmed
17895407
uniprot
proteins
pubmed
18077343
uniprot
proteins
pubmed
18177726
uniprot
proteins
pubmed
19524019
uniprot
proteins
pubmed
21895628
uniprot
proteins
pubmed
2263478
uniprot
proteins
pubmed
23955712
uniprot
proteins
pubmed
27768894
uniprot
proteins
pubmed
27851727
uniprot
proteins
pubmed
30096288
uniprot
proteins
pubmed
31342135
uniprot
proteins
pubmed
32549916
uniprot
proteins
pubmed
35637350
uniprot
proteins
pubmed
7876112
uniprot
proteins
pubmed
8255419
uniprot
proteins
sequence_length
472
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21895628}; Multi-pass membrane protein {ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727}. Membrane raft {ECO:0000269|PubMed:21895628}. Mitochondrion outer membrane {ECO:0000250|UniProtKB:P47746}. Cell projection, axon {ECO:0000250|UniProtKB:P20272}. Presynapse {ECO:0000250|UniProtKB:P20272}. Note=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 (By similarity). Found on presynaptic axon terminals in some GABAergic neurons in the somatosensory cortex (By similarity). {ECO:0000250|UniProtKB:P20272, ECO:0000250|UniProtKB:P47746}.
uniprot
proteins
transmembrane_region
TRANSMEM 117..142; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727"; TRANSMEM 155..175; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727"; TRANSMEM 188..212; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727"; TRANSMEM 233..255; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727"; TRANSMEM 274..299; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727"; TRANSMEM 345..365; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727"; TRANSMEM 378..399; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727
uniprot
proteins