CNR1_PANTR
ID CNR1_PANTR Reviewed; 472 AA.
AC Q5IS73;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Cannabinoid receptor 1;
DE Short=CB-R;
DE Short=CB1;
GN Name=CNR1;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15620360; DOI=10.1016/j.cell.2004.11.040;
RA Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L.,
RA Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.;
RT "Accelerated evolution of nervous system genes in the origin of Homo
RT sapiens.";
RL Cell 119:1027-1040(2004).
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). Mediates
CC many cannabinoid-induced effects, acting, among others, on food intake,
CC memory loss, gastrointestinal motility, catalepsy, ambulatory activity,
CC anxiety, chronic pain. Signaling typically involves reduction in cyclic
CC AMP (By similarity). In the hypothalamus, may have a dual effect on
CC mitochondrial respiration depending upon the agonist dose and possibly
CC upon the cell type. Increases respiration at low doses, while decreases
CC respiration at high doses. At high doses, CNR1 signal transduction
CC involves G-protein alpha-i protein activation and subsequent inhibition
CC of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP
CC concentration, inhibition of protein kinase A (PKA)-dependent
CC phosphorylation of specific subunits of the mitochondrial electron
CC transport system, including NDUFS2. In the hypothalamus, inhibits
CC leptin-induced reactive oxygen species (ROS) formation and mediates
CC cannabinoid-induced increase in SREBF1 and FASN gene expression. In
CC 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. In
CC the hippocampus, regulates cellular respiration and energy production
CC in response to cannabinoids. Involved in cannabinoid-dependent
CC depolarization-induced suppression of inhibition (DSI), a process in
CC which depolarization of CA1 postsynaptic pyramidal neurons mobilizes
CC eCBs, which retrogradely activate presynaptic CB1 receptors,
CC transiently decreasing GABAergic inhibitory neurotransmission. Also
CC reduces excitatory synaptic transmission (By similarity). In superior
CC cervical ganglions and cerebral vascular smooth muscle cells, inhibits
CC voltage-gated Ca(2+) channels in a constitutive, as well as agonist-
CC dependent manner (By similarity). Induces leptin production in
CC adipocytes and reduces LRP2-mediated leptin clearance in the kidney,
CC hence participating in hyperleptinemia. In adipose tissue, CNR1
CC signaling leads to increased expression of SREBF1, ACACA and FASN
CC genes. In the liver, activation by cannabinoids leads to increased de
CC novo lipogenesis and reduced fatty acid catabolism, associated with
CC increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN
CC genes. May also affect de novo cholesterol synthesis and HDL-
CC cholesteryl ether uptake. Peripherally modulates energy metabolism. In
CC high 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. In
CC response to cannabinoid anandamide, elicits a pro-inflammatory response
CC in macrophages, which involves NLRP3 inflammasome activation and IL1B
CC and IL18 secretion (By similarity). {ECO:0000250|UniProtKB:O02777,
CC ECO:0000250|UniProtKB:P21554, ECO:0000250|UniProtKB:P47746}.
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; this interaction
CC attenuates constitutive, but not agonist-dependent, inhibition of
CC voltage-gated Ca(2+) channels in neurons (By similarity). Associates
CC with G protein alpha subunits, including G(i) alpha-1/GNAI1, G(i)
CC alpha-3/GNAI3 and G(o)-alpha/GNAO1; palmitoylation is important for
CC interaction with GNAI3 and GNAO1 (By similarity).
CC {ECO:0000250|UniProtKB:P21554}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P47746};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P21554}.
CC Mitochondrion outer membrane {ECO:0000250|UniProtKB:P47746}. Cell
CC projection, axon {ECO:0000250|UniProtKB:P20272}. Presynapse
CC {ECO:0000250|UniProtKB:P20272}. Note=Unexpectedly, in the mitochondria,
CC the C-terminus is located in the mitochondrial intermembrane space, a
CC compartment topologically considered as extracellular. In canonical
CC seven-transmembrane G-protein coupled receptors, the C-terminus is
CC cytosolic (By similarity). Found on presynaptic axon terminals in some
CC GABAergic neurons in the somatosensory cortex (By similarity).
CC {ECO:0000250|UniProtKB:P20272, ECO:0000250|UniProtKB:P47746}.
CC -!- PTM: Palmitoylation at Cys-415 is important for recruitment at both
CC plasma membrane and lipid rafts and association with G protein alpha
CC subunits. {ECO:0000250|UniProtKB:P21554}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AY665255; AAV74293.1; -; mRNA.
DR RefSeq; NP_001013035.1; NM_001013017.1.
DR RefSeq; XP_009449804.1; XM_009451529.2.
DR RefSeq; XP_009449805.1; XM_009451530.2.
DR RefSeq; XP_009449806.1; XM_009451531.2.
DR AlphaFoldDB; Q5IS73; -.
DR SMR; Q5IS73; -.
DR STRING; 9598.ENSPTRP00000055363; -.
DR PaxDb; Q5IS73; -.
DR GeneID; 472066; -.
DR KEGG; ptr:472066; -.
DR CTD; 1268; -.
DR eggNOG; KOG3656; Eukaryota.
DR HOGENOM; CLU_009579_7_0_1; -.
DR InParanoid; Q5IS73; -.
DR OrthoDB; 822074at2759; -.
DR TreeFam; TF330052; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0004949; F:cannabinoid receptor activity; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
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:0038171; P:cannabinoid signaling pathway; IBA:GO_Central.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Cell membrane; Cell projection; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Synapse;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..472
FT /note="Cannabinoid receptor 1"
FT /id="PRO_0000069317"
FT TOPO_DOM 1..116
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 117..142
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 143..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 155..175
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 176..187
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 188..212
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 213..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 233..255
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 256..273
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 274..299
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 300..344
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 345..365
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 366..377
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TRANSMEM 378..399
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT TOPO_DOM 400..472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT REGION 2..23
FT /note="Required for mitochondrial localization"
FT /evidence="ECO:0000250|UniProtKB:P47746"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47746"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47746"
FT LIPID 415
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21554"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 472 AA; 52858 MW; 1D2E49061D12ABF2 CRC64;
MKSILDGLAD TTFRTITTDL LYVGSNDIQY EDIKGDMASK LGYFPQKFPL TSFRGSPFQE
KMTAGDNPQL VPADQVNITE FYNKSLSSFK ENEENIQCGE NFMDIECFMV LNPSQQLAIA
VLSLTLGTFT VLENLLVLCV ILHSRSLRCR PSYHFIGSLA VADLLGSVIF VYSFIDFHVF
HRKDSRNVFL FKLGGVTASF TASVGSLFLT AIDRYISIHR PLAYKRIVTR PKAVVAFCLM
WTIAIVIAVL PLLGWNCEKL QSVCSDIFPH IDETYLMFWI GVTSVLLLFI VYAYMYILWK
AHSHAVRMIQ RGTQKSIIIH TSEDGKVQVT RPDQARMDIR LAKTLVLILV VLIICWGPLL
AIMVYDVFGK MNKLIKTVFA FCSMLCLLNS TVNPIIYALR SKDLRHAFRS MFPSCEGTAQ
PLDNSMGDSD CLHKHANNAA SVHRAAESCI KSTVKIAKVT MSVSTDTSAE AL
