Cannabinoid receptor 1

Details

Name
Cannabinoid receptor 1
Kind
protein
Synonyms
  • CANN6
  • CB-R
  • CB1
  • CNR
Gene Name
CNR1
UniProtKB Entry
P21554Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000122|Cannabinoid receptor 1
MKSILDGLADTTFRTITTDLLYVGSNDIQYEDIKGDMASKLGYFPQKFPLTSFRGSPFQE
KMTAGDNPQLVPADQVNITEFYNKSLSSFKENEENIQCGENFMDIECFMVLNPSQQLAIA
VLSLTLGTFTVLENLLVLCVILHSRSLRCRPSYHFIGSLAVADLLGSVIFVYSFIDFHVF
HRKDSRNVFLFKLGGVTASFTASVGSLFLTAIDRYISIHRPLAYKRIVTRPKAVVAFCLM
WTIAIVIAVLPLLGWNCEKLQSVCSDIFPHIDETYLMFWIGVTSVLLLFIVYAYMYILWK
AHSHAVRMIQRGTQKSIIIHTSEDGKVQVTRPDQARMDIRLAKTLVLILVVLIICWGPLL
AIMVYDVFGKMNKLIKTVFAFCSMLCLLNSTVNPIIYALRSKDLRHAFRSMFPSCEGTAQ
PLDNSMGDSDCLHKHANNAASVHRAAESCIKSTVKIAKVTMSVSTDTSAEAL
Number of residues
472
Molecular Weight
52857.365
Theoretical pI
8.25
GO Classification
Functions
G protein-coupled receptor activity / identical protein binding
Processes
adenylate cyclase-activating G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / negative regulation of serotonin secretion / regulation of metabolic process / regulation of presynaptic cytosolic calcium ion concentration / retrograde trans-synaptic signaling by endocannabinoid / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission
Components
actin cytoskeleton / cytoplasm / GABA-ergic synapse / glutamatergic synapse / mitochondrial outer membrane / presynaptic membrane
General 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). 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)
Specific Function
cannabinoid receptor activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
117-142 155-175 188-212 233-255 274-299 345-365 378-399
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010146|Cannabinoid receptor 1 (CNR1)
ATGAAGTCGATCCTAGATGGCCTTGCAGATACCACCTTCCGCACCATCACCACTGACCTC
CTGTACGTGGGCTCAAATGACATTCAGTACGAAGACATCAAAGGTGACATGGCATCCAAA
TTAGGGTACTTCCCACAGAAATTCCCTTTAACTTCCTTTAGGGGAAGTCCCTTCCAAGAG
AAGATGACTGCGGGAGACAACCCCCAGCTAGTCCCAGCAGACCAGGTGAACATTACAGAA
TTTTACAACAAGTCTCTCTCGTCCTTCAAGGAGAATGAGGAGAACATCCAGTGTGGGGAG
AACTTCATGGACATAGAGTGTTTCATGGTCCTGAACCCCAGCCAGCAGCTGGCCATTGCA
GTCCTGTCCCTCACGCTGGGCACCTTCACGGTCCTGGAGAACCTCCTGGTGCTGTGCGTC
ATCCTCCACTCCCGCAGCCTCCGCTGCAGGCCTTCCTACCACTTCATCGGCAGCCTGGCG
GTGGCAGACCTCCTGGGGAGTGTCATTTTTGTCTACAGCTTCATTGACTTCCACGTGTTC
CACCGCAAAGATAGCCGCAACGTGTTTCTGTTCAAACTGGGTGGGGTCACGGCCTCCTTC
ACTGCCTCCGTGGGCAGCCTGTTCCTCACAGCCATCGACAGGTACATATCCATTCACAGG
CCCCTGGCCTATAAGAGGATTGTCACCAGGCCCAAGGCCGTGGTGGCGTTTTGCCTGATG
TGGACCATAGCCATTGTGATCGCCGTGCTGCCTCTCCTGGGCTGGAACTGCGAGAAACTG
CAATCTGTTTGCTCAGACATTTTCCCACACATTGATGAAACCTACCTGATGTTCTGGATC
GGGGTCACCAGCGTACTGCTTCTGTTCATCGTGTATGCGTACATGTATATTCTCTGGAAG
GCTCACAGCCACGCCGTCCGCATGATTCAGCGTGGCACCCAGAAGAGCATCATCATCCAC
ACGTCTGAGGATGGGAAGGTACAGGTGACCCGGCCAGACCAAGCCCGCATGGACATTAGG
TTAGCCAAGACCCTGGTCCTGATCCTGGTGGTGTTGATCATCTGCTGGGGCCCTCTGCTT
GCAATCATGGTGTATGATGTCTTTGGGAAGATGAACAAGCTCATTAAGACGGTGTTTGCA
TTCTGCAGTATGCTCTGCCTGCTGAACTCCACCGTGAACCCCATCATCTATGCTCTGAGG
AGTAAGGACCTGCGACACGCTTTCCGGAGCATGTTTCCCTCTTGTGAAGGCACTGCGCAG
CCTCTGGATAACAGCATGGGGGACTCGGACTGCCTGCACAAACACGCAAACAATGCAGCC
AGTGTTCACAGGGCCGCAGAAAGCTGCATCAAGAGCACGGTCAAGATTGCCAAGGTAACC
ATGTCTGTGTCCACAGACACGTCTGCCGAGGCTCTGTGA
Chromosome Location
6
Locus
6q15
External Identifiers
ResourceLink
UniProtKB IDP21554
UniProtKB Entry NameCNR1_HUMAN
GenBank Protein ID29915
GenBank Gene IDX54937
GeneCard IDCNR1
GenAtlas IDCNR1
HGNC IDHGNC:2159
PDB ID(s)1LVQ, 1LVR, 2B0Y, 2KOE, 2MZ2, 2MZ3, 2MZA, 5TGZ, 5U09, 5XR8, 5XRA, 6KPG, 6KQI, 6N4B, 7FEE, 7V3Z, 7WV9, 8GAG, 8GHV, 8IKG, 8IKH, 8K8J, 8WRZ, 8WU1
KEGG IDhsa:1268
IUPHAR/Guide To Pharmacology ID56
NCBI Gene ID1268
General References
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  4. Ryberg E, Vu HK, Larsson N, Groblewski T, Hjorth S, Elebring T, Sjogren S, Greasley PJ: Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett. 2005 Jan 3;579(1):259-64. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Dronabinolapproved, illicityestargetagonistDetails
Nabiloneapproved, investigationalyestargetpartial agonistDetails
V24343investigationalunknowntargetDetails
OtenabantinvestigationalyestargetantagonistDetails
SLV319investigationalunknowntargetDetails
DrinabantinvestigationalunknowntargetDetails
Rimonabantapproved, investigationalyestargetantagonistDetails
Ricinoleic acidexperimentalunknowntargetDetails
Cannabidiolapproved, investigationalyestargetantagonistmodulatorDetails
PropacetamolexperimentalyestargetantagonistDetails
NabiximolsinvestigationalyestargetDetails
Medical Cannabisexperimental, investigationalyestargetnegative modulatorDetails
TetrahydrocannabivarininvestigationalyestargetantagonistDetails
Cannabinolexperimental, investigationalyestargetagonistDetails
Oleic monoethanolamideinvestigationalyestargetinhibitorDetails
ParaoxonexperimentalyestargetinhibitorDetails
TaranabantinvestigationalyestargetantagonistDetails
SurinabantinvestigationalyestargetmodulatorDetails
Orlistatapproved, investigationalyestargetinhibitorDetails
WIN 55212-2experimentalyestargetinhibitorDetails