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Protein

Cannabinoid receptor 1

Gene

CNR1

Organism
Pan troglodytes (Chimpanzee)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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 Ca2+ 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).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Names & Taxonomyi

Protein namesi
Recommended name:
Cannabinoid receptor 1
Short name:
CB-R
Short name:
CB1
Gene namesi
Name:CNR1
OrganismiPan troglodytes (Chimpanzee)
Taxonomic identifieri9598 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
Proteomesi
  • UP000002277 Componenti: Chromosome 6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 116ExtracellularBy similarityAdd BLAST116
Transmembranei117 – 142Helical; Name=1By similarityAdd BLAST26
Topological domaini143 – 154CytoplasmicBy similarityAdd BLAST12
Transmembranei155 – 175Helical; Name=2By similarityAdd BLAST21
Topological domaini176 – 187ExtracellularBy similarityAdd BLAST12
Transmembranei188 – 212Helical; Name=3By similarityAdd BLAST25
Topological domaini213 – 232CytoplasmicBy similarityAdd BLAST20
Transmembranei233 – 255Helical; Name=4By similarityAdd BLAST23
Topological domaini256 – 273ExtracellularBy similarityAdd BLAST18
Transmembranei274 – 299Helical; Name=5By similarityAdd BLAST26
Topological domaini300 – 344CytoplasmicBy similarityAdd BLAST45
Transmembranei345 – 365Helical; Name=6By similarityAdd BLAST21
Topological domaini366 – 377ExtracellularBy similarityAdd BLAST12
Transmembranei378 – 399Helical; Name=7By similarityAdd BLAST22
Topological domaini400 – 472CytoplasmicBy similarityAdd BLAST73

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane, Mitochondrion, Mitochondrion outer membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693171 – 472Cannabinoid receptor 1Add BLAST472

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi77N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi83N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi415S-palmitoyl cysteineBy similarity1
Modified residuei425PhosphoserineBy similarity1
Modified residuei429PhosphoserineBy similarity1

Post-translational modificationi

Palmitoylation at Cys-415 is important for recruitment at both plasma membrane and lipid rafts and association with G protein alpha subunits.By similarity

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ5IS73.

Expressioni

Gene expression databases

BgeeiENSPTRG00000018411.

Interactioni

Subunit structurei

Interacts (via C-terminus) with CNRIP1; this interaction attenuates constitutive, but not agonist-dependent, inhibition of voltage-gated Ca2+ 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).By similarity

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000055363.

Structurei

3D structure databases

ProteinModelPortaliQ5IS73.
SMRiQ5IS73.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 23Required for mitochondrial localizationBy similarityAdd BLAST22

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118804.
HOGENOMiHOG000049272.
HOVERGENiHBG051045.
InParanoidiQ5IS73.
KOiK04277.
OMAiTRMDIRL.
OrthoDBiEOG091G05O3.
TreeFamiTF330052.

Family and domain databases

CDDicd15340. 7tmA_CB1. 1 hit.
InterProiView protein in InterPro
IPR000810. Canbinoid_rcpt_1.
IPR002230. Cnbnoid_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
PANTHERiPTHR22750:SF47. PTHR22750:SF47. 1 hit.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PIRSFiPIRSF037995. Cnoid_rcpt_1. 1 hit.
PRINTSiPR00522. CANABINOID1R.
PR00362. CANNABINOIDR.
PR00237. GPCRRHODOPSN.
SMARTiView protein in SMART
SM01381. 7TM_GPCR_Srsx. 1 hit.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q5IS73-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSILDGLAD TTFRTITTDL LYVGSNDIQY EDIKGDMASK LGYFPQKFPL
60 70 80 90 100
TSFRGSPFQE KMTAGDNPQL VPADQVNITE FYNKSLSSFK ENEENIQCGE
110 120 130 140 150
NFMDIECFMV LNPSQQLAIA VLSLTLGTFT VLENLLVLCV ILHSRSLRCR
160 170 180 190 200
PSYHFIGSLA VADLLGSVIF VYSFIDFHVF HRKDSRNVFL FKLGGVTASF
210 220 230 240 250
TASVGSLFLT AIDRYISIHR PLAYKRIVTR PKAVVAFCLM WTIAIVIAVL
260 270 280 290 300
PLLGWNCEKL QSVCSDIFPH IDETYLMFWI GVTSVLLLFI VYAYMYILWK
310 320 330 340 350
AHSHAVRMIQ RGTQKSIIIH TSEDGKVQVT RPDQARMDIR LAKTLVLILV
360 370 380 390 400
VLIICWGPLL AIMVYDVFGK MNKLIKTVFA FCSMLCLLNS TVNPIIYALR
410 420 430 440 450
SKDLRHAFRS MFPSCEGTAQ PLDNSMGDSD CLHKHANNAA SVHRAAESCI
460 470
KSTVKIAKVT MSVSTDTSAE AL
Length:472
Mass (Da):52,858
Last modified:February 15, 2005 - v1
Checksum:i1D2E49061D12ABF2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY665255 mRNA. Translation: AAV74293.1.
RefSeqiNP_001013035.1. NM_001013017.1.
XP_009449804.1. XM_009451529.2.
XP_009449805.1. XM_009451530.2.
XP_009449806.1. XM_009451531.2.
UniGeneiPtr.6364.

Genome annotation databases

EnsembliENSPTRT00000063819; ENSPTRP00000055363; ENSPTRG00000018411.
GeneIDi472066.
KEGGiptr:472066.

Similar proteinsi

Entry informationi

Entry nameiCNR1_PANTR
AccessioniPrimary (citable) accession number: Q5IS73
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: February 15, 2005
Last modified: October 25, 2017
This is version 95 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families