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Cannabinoid receptor 1 (CB-R) (CB1)

 CNR1_TAEGU              Reviewed;         473 AA.
P56971;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-DEC-2000, sequence version 1.
23-MAY-2018, entry version 104.
RecName: Full=Cannabinoid receptor 1;
Short=CB-R;
Short=CB1;
Name=CNR1;
Taeniopygia guttata (Zebra finch) (Poephila guttata).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
Coelurosauria; Aves; Neognathae; Passeriformes; Passeroidea;
Estrildidae; Estrildinae; Taeniopygia.
NCBI_TaxID=59729;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
Soderstrom K., Johnson F.;
"Behavioral, pharmacologic and molecular characterization of a Zebra
finch CB1 cannabinoid receptor.";
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: G-protein coupled receptor for cannabinoids, including
endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also
called anandamide or AEA) and 2-arachidonoylglycerol (2-AG).
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 (By similarity). 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 (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. In the liver, activation by
cannabinoids 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. 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. In
response to cannabinoid anandamide, elicits a proinflammatory
response in macrophages, which involves NLRP3 inflammasome
activation and IL1B and IL18 secretion (By similarity).
{ECO:0000250|UniProtKB:O02777, ECO:0000250|UniProtKB:P21554,
ECO:0000250|UniProtKB:P47746}.
-!- SUBUNIT: Interacts (via C-terminus) with CNRIP1; this interaction
attenuates constitutive, but not agonist-dependent, inhibition of
voltage-gated Ca(2+) channels in neurons (By similarity).
Associates with G protein alpha subunits, including G(i) alpha-
1/GNAI1, G(i) alpha-3/GNAI3 and G(o) alpha/GNAO1; palmitoylation
is important for interaction with GNAI3 and GNAO1 (By similarity).
{ECO:0000250|UniProtKB:P21554}.
-!- SUBCELLULAR LOCATION: Cell membrane
{ECO:0000250|UniProtKB:P47746}; Multi-pass membrane protein
{ECO:0000250|UniProtKB:P21554}. Mitochondrion outer membrane
{ECO:0000250|UniProtKB:P47746}. Cell projection, axon
{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}.
-!- PTM: Palmitoylation at Cys-417 is important for recruitment at
both plasma membrane and lipid rafts and association with G
protein alpha subunits. {ECO:0000250|UniProtKB:P21554}.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
{ECO:0000255|PROSITE-ProRule:PRU00521}.
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EMBL; AF255388; AAF78049.1; -; mRNA.
RefSeq; NP_001041727.1; NM_001048262.1.
UniGene; Tgu.6743; -.
ProteinModelPortal; P56971; -.
SMR; P56971; -.
STRING; 59729.ENSTGUP00000012797; -.
BindingDB; P56971; -.
PRIDE; P56971; -.
Ensembl; ENSTGUT00000012943; ENSTGUP00000012797; ENSTGUG00000012436.
GeneID; 751607; -.
KEGG; tgu:751607; -.
CTD; 1268; -.
eggNOG; KOG3656; Eukaryota.
eggNOG; ENOG410XRW9; LUCA.
GeneTree; ENSGT00760000118804; -.
HOGENOM; HOG000049272; -.
HOVERGEN; HBG051045; -.
InParanoid; P56971; -.
KO; K04277; -.
OMA; TRMDIRL; -.
OrthoDB; EOG091G05O3; -.
TreeFam; TF330052; -.
Reactome; R-TGU-373076; Class A/1 (Rhodopsin-like receptors).
Reactome; R-TGU-418594; G alpha (i) signalling events.
Proteomes; UP000007754; Chromosome 3.
GO; GO:0005623; C:cell; IDA:AgBase.
GO; GO:0044297; C:cell body; IDA:AgBase.
GO; GO:0030175; C:filopodium; IDA:AgBase.
GO; GO:0030426; C:growth cone; IEA:Ensembl.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0016020; C:membrane; IDA:AgBase.
GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
GO; GO:0005886; C:plasma membrane; IDA:AgBase.
GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl.
GO; GO:0004949; F:cannabinoid receptor activity; IMP:AgBase.
GO; GO:1904483; F:synthetic cannabinoid binding; IDA:AgBase.
GO; GO:0007188; P:adenylate cyclase-modulating G-protein coupled receptor signaling pathway; IEA:Ensembl.
GO; GO:0007413; P:axonal fasciculation; IEA:Ensembl.
GO; GO:0016049; P:cell growth; IMP:AgBase.
GO; GO:0060997; P:dendritic spine morphogenesis; IMP:AgBase.
GO; GO:0046847; P:filopodium assembly; IMP:AgBase.
GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; IMP:AgBase.
GO; GO:1903295; P:negative regulation of glutamate secretion, neurotransmission; IMP:AgBase.
GO; GO:1900454; P:positive regulation of long term synaptic depression; IMP:AgBase.
GO; GO:0031915; P:positive regulation of synaptic plasticity; IMP:AgBase.
GO; GO:0031623; P:receptor internalization; IMP:AgBase.
GO; GO:0099553; P:trans-synaptic signaling by endocannabinoid, modulating synaptic transmission; IEA:Ensembl.
CDD; cd15340; 7tmA_CB1; 1.
InterPro; IPR000810; Canbinoid_rcpt_1.
InterPro; IPR002230; Cnbnoid_rcpt.
InterPro; IPR000276; GPCR_Rhodpsn.
InterPro; IPR017452; GPCR_Rhodpsn_7TM.
PANTHER; PTHR22750:SF47; PTHR22750:SF47; 1.
Pfam; PF00001; 7tm_1; 1.
PIRSF; PIRSF037995; Cnoid_rcpt_1; 1.
PRINTS; PR00522; CANABINOID1R.
PRINTS; PR00362; CANNABINOIDR.
PRINTS; PR00237; GPCRRHODOPSN.
SMART; SM01381; 7TM_GPCR_Srsx; 1.
PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
2: Evidence at transcript level;
Cell membrane; Cell projection; Complete proteome;
G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
Mitochondrion; Mitochondrion outer membrane; Palmitate; Receptor;
Reference proteome; Transducer; Transmembrane; Transmembrane helix.
CHAIN 1 473 Cannabinoid receptor 1.
/FTId=PRO_0000069319.
TOPO_DOM 1 118 Extracellular.
{ECO:0000250|UniProtKB:P21554}.
TRANSMEM 119 144 Helical; Name=1.
{ECO:0000250|UniProtKB:P21554}.
TOPO_DOM 145 156 Cytoplasmic.
{ECO:0000250|UniProtKB:P21554}.
TRANSMEM 157 177 Helical; Name=2.
{ECO:0000250|UniProtKB:P21554}.
TOPO_DOM 178 189 Extracellular.
{ECO:0000250|UniProtKB:P21554}.
TRANSMEM 190 214 Helical; Name=3.
{ECO:0000250|UniProtKB:P21554}.
TOPO_DOM 215 234 Cytoplasmic.
{ECO:0000250|UniProtKB:P21554}.
TRANSMEM 235 257 Helical; Name=4.
{ECO:0000250|UniProtKB:P21554}.
TOPO_DOM 258 275 Extracellular.
{ECO:0000250|UniProtKB:P21554}.
TRANSMEM 276 301 Helical; Name=5.
{ECO:0000250|UniProtKB:P21554}.
TOPO_DOM 302 346 Cytoplasmic.
{ECO:0000250|UniProtKB:P21554}.
TRANSMEM 347 367 Helical; Name=6.
{ECO:0000250|UniProtKB:P21554}.
TOPO_DOM 368 379 Extracellular.
{ECO:0000250|UniProtKB:P21554}.
TRANSMEM 380 401 Helical; Name=7.
{ECO:0000250|UniProtKB:P21554}.
TOPO_DOM 402 473 Cytoplasmic.
{ECO:0000250|UniProtKB:P21554}.
REGION 2 23 Required for mitochondrial localization.
{ECO:0000250|UniProtKB:P47746}.
LIPID 417 417 S-palmitoyl cysteine.
{ECO:0000250|UniProtKB:P21554}.
CARBOHYD 79 79 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 85 85 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
SEQUENCE 473 AA; 53094 MW; 96ECC6D1BD25461E CRC64;
MKSILDGLAD TTFRTITTDL LYVGSNDIQY EDMKGDMASK LGYYPQKFPL SSFRGDPFQE
KMTGGDDSLL SIIPSEQVNI TEFYNKSLST FKDNEENIQC GENFMDMECF MILNPSQQLA
IAVLSLTLGT FTVLENLLVL CVILHSRSLR CRPSYHFIGS LAVADLLGSV IFVYSFVDFH
VFHRKDSPNV FLFKLGGVTA SFTASVGSLF LTAIDRYISI HRPLAYKRIV TRPKAVVAFC
VMWTIAIVIA VLPLLGWNCK KLNSVCSDIF PLIDETYLMF WIGVTSILLL FIVYAYMYIL
WKAHSHAVRM LQRGTQKSII IQSTEDGKVQ ITRPDQTRMD IRLAKTLVLI LVVLIICWGP
LLAIMVYDVF GKMNKLIKTI FAFCSMLCLL NSTVNPIIYA LRSKDLRHAF RSMFPTCEGT
AQPLDNSMES DCQHKHANNA GNVHRAAESC IKSTVKIAKV TMSVSTDTTA EAL


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