CNR1 Protein
Introduction <table class="infobox infobox-protein"> <tr> <th class="infobox-header" colspan="2">CNR1 Protein</th> </tr> <tr> <td class="label">Protein Name </td> <td>Cannabinoid Receptor 1 (CB1)</td> </tr> <tr> <td class="label">Gene </td> <td>CNR1</td> </tr> <tr> <td class="label">UniProt ID </td> <td>P21554</td> </tr> <tr> <td class="label">PDB ID </td> <td>5TGZ, 6N4B</td> </tr> <tr> <td class="label">Molecular Weight </td> <td>53 kDa (un-glycosylated)</td> </tr> <tr> <td class="label">Subcellular Localization </td> <td>Plasma membrane, intracellular vesicles</td> </tr> <tr> <td class="label">Protein Family </td> <td>Class A G protein-coupled receptors (GPCR)</td> </tr> <tr> <td class="label">Drug</td> <td>Type</td> </tr> <tr> <td class="label">Dronabinol</td> <td>Full agonist</td> </tr> <tr> <td class="label">Nabilone</td> <td>Synthetic agonist</td> </tr> <tr> <td class="label">Drug</td> <td>Type</td> </tr> <tr> <td class="label">Rimonabant</td> <td>CB1 antagonist</td> </tr> <tr> <td class="label">Associated Diseases</td> <td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a></td> </tr> <tr>
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CNR1 Protein
Introduction <table class="infobox infobox-protein"> <tr> <th class="infobox-header" colspan="2">CNR1 Protein</th> </tr> <tr> <td class="label">Protein Name </td> <td>Cannabinoid Receptor 1 (CB1)</td> </tr> <tr> <td class="label">Gene </td> <td>CNR1</td> </tr> <tr> <td class="label">UniProt ID </td> <td>P21554</td> </tr> <tr> <td class="label">PDB ID </td> <td>5TGZ, 6N4B</td> </tr> <tr> <td class="label">Molecular Weight </td> <td>53 kDa (un-glycosylated)</td> </tr> <tr> <td class="label">Subcellular Localization </td> <td>Plasma membrane, intracellular vesicles</td> </tr> <tr> <td class="label">Protein Family </td> <td>Class A G protein-coupled receptors (GPCR)</td> </tr> <tr> <td class="label">Drug</td> <td>Type</td> </tr> <tr> <td class="label">Dronabinol</td> <td>Full agonist</td> </tr> <tr> <td class="label">Nabilone</td> <td>Synthetic agonist</td> </tr> <tr> <td class="label">Drug</td> <td>Type</td> </tr> <tr> <td class="label">Rimonabant</td> <td>CB1 antagonist</td> </tr> <tr> <td class="label">Associated Diseases</td> <td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a></td> </tr> <tr> <td class="label">KG Connections</td> <td><a href="/atlas" style="color:#4fc3f7">99 edges</a></td> </tr> </table>
Cnr1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Structure The CB1 cannabinoid receptor is a typical Class A GPCR with:
N-terminal extracellular domain : Contains glycosylation sites and ligand-binding region
Seven transmembrane helices : Form the classic GPCR bundle
Intracellular loops : Couple to G proteins (Gi/o)
C-terminal intracellular tail : Contains palmitoylation site and trafficking motifs
Ligand Binding
Binding pocket located within the transmembrane bundle
Binds endogenous cannabinoids (anandamide, 2-AG)
Binds plant-derived cannabinoids (THC)
Allosteric binding sites identified
Normal Function
Signaling Pathways
Gi/o protein coupling : Inhibits adenylyl cyclase, reduces cAMP
Ion channel modulation : Activates inwardly rectifying K+ channels
ERK/MAPK pathway : Regulates gene expression
β-arrestin signaling : Mediates some downstream effects
Physiological Roles
Modulates neurotransmitter release (glutamate, GABA, dopamine)
Regulates appetite and energy metabolism
Involved in memory and learning processes
Controls pain perception and emotional responses
Regulates immune function
Role in Disease
Addiction
Cannabis use disorder : Genetic variants affect addiction risk
Reward processing : Altered endocannabinoid signaling in addiction
Therapeutic target : CB1 antagonists (historical: rimonabant)
Neurological Disorders
Schizophrenia : Altered CB1 signaling contributes to psychosis
Alzheimer's Disease : Neuroprotective potential of CB1 modulation
Parkinson's Disease : CB1 changes in basal ganglia
Movement Disorders
Huntington's Disease : Progressive CB1 receptor loss
Multiple System Atrophy : Dysregulated endocannabinoid signaling
Therapeutic Targeting
Agonists
Antagonists
Drug Development
Peripherally-restricted CB1 antagonists
Allosteric modulators
FAAH inhibitors (increase anandamide)
Key Publications
Mackie K. (2006). Cannabinoid receptors . Annu Rev Pharmacol Toxicol. PMID: 16402910 (https://pubmed.ncbi.nlm.nih.gov/16402910/)
Di Marzo V. (2008). Endocannabinoid signaling . Nat Rev Neurosci. PMID: 18426499 (https://pubmed.ncbi.nlm.nih.gov/18426499/)
See Also
[CNR1 Gene](/proteins/cnr1-protein)
[Endocannabinoid System](/mechanisms/endocannabinoid-system)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Cannabis Use Disorder](/diseases/cannabis-use-disorder)
External Links
[UniProt: CNR1](https://www.uniprot.org/uniprot/P21554)
[PDB: 5TGZ](https://www.rcsb.org/structure/5TGZ)
[IUPHAR: CB1](https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=56)
Background The study of Cnr1 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
Mackie K, (2006) (2006)
Di Marzo V, (2008) (2008)
Piazza PV, et al, (2020) (2020)
Fernández-Ruiz J, et al, (2000) (2000)
García-González D, et al, (2019) (2019)
Chiarlone A, et al, (2014) (2014)
Hurd YL, (2017) (2017)
Katona I, et al, (2015) (2015)
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