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CNR1 Membrane Protein Introduction

Introduction of CNR1

CNR1, encoded by CNR1 gene, belongs to a member of G protein-coupled cannabinoid receptors with seven transmembrane domains, an extracellular N-terminal and an intracellular C-terminal. It is one of two cannabinoid receptors which is an important part of endocannabinoid system, involving in a variety of physiological processes including appetite, pain-sensation, mood, and memory.

Basic Information of CNR1
Protein Name Cannabinoid receptor 1
Gene Name CNR1
Aliases CB1, CNR, CB-R, CB1A, CB1R, CANN6, CB1K5
Organism Homo sapiens (Human)
UniProt ID P21554
Transmembrane Times 7
Length (aa) 472
Sequence MKSILDGLADTTFRTITTDLLYVGSNDIQYEDIKGDMASKLGYFPQKFPLTSFRGSPFQE
KMTAGDNPQLVPADQVNITEFYNKSLSSFKENEENIQCGENFMDIECFMVLNPSQQLAIA
VLSLTLGTFTVLENLLVLCVILHSRSLRCRPSYHFIGSLAVADLLGSVIFVYSFIDFHVF
HRKDSRNVFLFKLGGVTASFTASVGSLFLTAIDRYISIHRPLAYKRIVTRPKAVVAFCLM
WTIAIVIAVLPLLGWNCEKLQSVCSDIFPHIDETYLMFWIGVTSVLLLFIVYAYMYILWK
AHSHAVRMIQRGTQKSIIIHTSEDGKVQVTRPDQARMDIRLAKTLVLILVVLIICWGPLL
AIMVYDVFGKMNKLIKTVFAFCSMLCLLNSTVNPIIYALRSKDLRHAFRSMFPSCEGTAQ
PLDNSMGDSDCLHKHANNAASVHRAAESCIKSTVKIAKVTMSVSTDTSAEAL

Function of CNR1 Membrane Protein

The CNR1 may exert a pre-synaptic heteroreceptor involved in regulating neurotransmitter release when it is activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Activated CNR1 by binding to endogenous cannabinoids can decrease adenylate cyclase activity, leading to a decrease of intracellular second messenger cAMP concentration. And cAMP is coupled to a variety of ion channels, including the positively influenced inwardly rectifying potassium channels and calcium channels. Activated CNR1 also increases mitogen-activated protein kinase (MAP kinase) concentration which regulates cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. It has been shown that CNR1 is involved in controlling a variety of cannabinoid-induced effects, including food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Besides, GNR1 is involved in the maintenance of homeostasis in health and disease. Several studies have implicated that the CNR1 is up-regulated in human hepatocellular carcinoma tumor samples and other human prostate cancer cells. In addition, a selective CB1 agonist is a very important tool to be used to isolate the effects of the receptor from the CB2 receptor, lose weight and abandon smoking.

Main signaling pathways activated by cannabinoid receptors. Fig.1 Main signaling pathways activated by cannabinoid receptors. (Fernandezlopez, 2013)

Application of CNR1 Membrane Protein in Literature

  1. Gonzã l I., et al. Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets. Diabetologia. 2018, 61(6): 1470-1483. PubMed ID: 29497784

    This article reports that CNR1 functions as a negative regulator of beta cell function and a mediator of islet inflammation under conditions of metabolic stress. Moreover, CNR1 on beta cell could act as a therapeutic target for insulin resistance.

  2. Smith D R., et al. Rare genetic variants in the endocannabinoid system genes CNR1 and DAGLA are associated with neurological phenotypes in humans. Plos One. 2017, 12(11): e0187926. PubMed ID: 29145497

    This article reveals that some rare heterozygous variants in CNR1 are significantly associated with pain sensitivity (especially migraine), sleep and memory disorders-alone or along with anxiety-compared to a set of controls without such CNR1 variants.

  3. Jourdan T., et al. Decreasing CB1 receptor signaling in Kupffer cells improves insulin sensitivity in obese mice. Molecular Metabolism. 2017, 6(11): 1517-1528. PubMed ID: 29107297

    Jourdan's study finds that the decreasing expression of Cnr1 can improve glucose tolerance and insulin sensitivity in diet-induced obese mice, but not influence hepatic lipid content or body weight.

  4. Han H., et al. Cannabinoid receptor 1 contributes to sprouted innervation in endometrial ectopic growth through mitogen-activated protein kinase activation. Brain Research. 2017, 1663: 132-140. PubMed ID: 28322749

    This article shows that the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) and JNK inhibitors can decrease CB1 agonist-induced neurite elongation. And the inhibitions of CB1R and its downstream ERK and JNK signaling pathways may inhibit sprouted nerve fibers which have been involved in endometrial ectopic growth. This finding may provide a new therapeutic target for patients with endometriosis.

  5. Gouvêa E S., et al. The role of the CNR1 gene in schizophrenia: a systematic review including unpublished data. Revista Brasileira De Psiquiatria. 2017, 39(2): 160-171. PubMed ID: 28099629

    This article reviews the role of CNR1 in schizophrenia by analyzing date from comparing 182 patients with schizophrenia and 244 healthy controls. But no consistent evidence is made. Hence further studies are required to design to investigate the potential role of CNR1 in schizophrenia.

CNR1 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CNR1 antibody development services.


As a forward-looking research institute as well as a leading custom service provider in the field of membrane protein, Creative Biolabs has won good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.

Reference

  1. Fernandezlopez D., et al. (2013). Cannabinoids: Well-Suited candidates for the treatment of perinatal brain injury. Brain Sciences. 3(3), 1043-59.

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