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HighlightsIntroduction of CCKAR
Cholecystokinin (CCK) is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. CCK binds with high affinity to CCKAR, a seven-transmembrane domain G protein-coupled receptor expressed in pancreatic acinar cells, gallbladder, smooth muscle, chief and D cells of the gastric mucosa, and the central and peripheral nervous systems. Activation of CCKAR stimulates multiple interacting signaling cascades initiated through the Gq family, G13, Gs, and arrestin. The genes of CCKAR consist of five exons interrupted by four introns. Structurally, the extracellular domain of this protein, which adopts a tertiary structure consisting of a few helical turns and a disulfide-cross linked loop, is critical for interactions with its corresponding ligands.
| Basic Information of CCKAR | |
| Protein Name | Cholecystokinin receptor type A |
| Gene Name | CCKAR |
| Aliases | Cholecystokinin-1 receptor |
| Organism | Homo sapiens (Human) |
| UniProt ID | P32238 |
| Transmembrane Times | 7 |
| Length (aa) | 428 |
| Sequence |
MDVVDSLLVNGSNITPPCELGLENETLFCLDQPRPSKEWQPAVQILLYSLIFLLSVLGNT LVITVLIRNKRMRTVTNIFLLSLAVSDLMLCLFCMPFNLIPNLLKDFIFGSAVCKTTTYF MGTSVSVSTFNLVAISLERYGAICKPLQSRVWQTKSHALKVIAATWCLSFTIMTPYPIYS NLVPFTKNNNQTANMCRFLLPNDVMQQSWHTFLLLILFLIPGIVMMVAYGLISLELYQGI KFEASQKKSAKERKPSTTSSGKYEDSDGCYLQKTRPPRKLELRQLSTGSSSRANRIRSNS SAANLMAKKRVIRMLIVIVVLFFLCWMPIFSANAWRAYDTASAERRLSGTPISFILLLSY TSSCVNPIIYCFMNKRFRLGFMATFPCCPNPGPPGARGEVGEEEEGGTTGASLSRFSYSH MSASVPPQ |
Functions of CCKAR Membrane Protein
Upon binding to this ligand, CCKAR mediates various physiological processes, including pancreatic growth and enzyme secretion, smooth muscle contraction of the gallbladder and stomach, and secretion from gastric mucosal cells in the gastrointestinal system. In the central and peripheral nervous system, this receptor regulates satiety and the release of beta-endorphin and dopamine. OLETF rats have been established as a useful experimental model for examining the biological functions of the CCKAR because of its natural lack of this receptor. Specifically, CCKAR has been shown to be overexpressed in human pancreatic ductal adenocarcinomas (PDAC) and was proposed to be a promising therapeutic approach for treating pancreatic cancer in a gene therapy setting. Besides, genetic variation in this receptor may be implicated in schizophrenia and may also modulate language lateralization due to its impact on dopaminergic pathways. In addition, studies have reported the association of CCKAR polymorphisms with gallbladder diseases.
Applications of CCKAR Membrane Protein in Literature
1. Miller L J., Desai A J. Metabolic actions of the type 1 cholecystokinin receptor: its potential as a therapeutic target. Trends in Endocrinology & Metabolism. 2016, 27(9): 609-619. PMID: 27156041
This article reviewed the potential of type 1 cholecystokinin receptor as a therapeutic target to treat obesity.
2. Kazmi H R., et al. Polymorphism and expression profile of cholecystokinin type A receptor in relation to gallstone disease susceptibility. Biochemical Genetics. 2016, 54(5): 665-675. PMID: 27287528
This article investigated the expression pattern of cholecystokinin type A receptor (CCKAR) in relation to its polymorphism (rs1800857, T/C) in gallstone disease (GSD) patients and controls. This polymorphism may be related to the susceptibility of GSD.
3. Desai A J., et al. Molecular mechanism of action of triazolobenzodiazepinone agonists of the type 1 cholecystokinin receptor. Possible cooperativity across the receptor homodimeric complex. Journal of medicinal chemistry. 2015, 58(24): 9562-9577. PMID: 26654202
This article defined the mechanism of binding and activity of two triazolobenzodiazepinone agonists of the type 1 cholecystokinin receptor: CE-326597 and PF-04756956.
4. Tinoco A B., et al. Two cholecystokinin receptor subtypes are identified in goldfish, being the CCKAR involved in the regulation of intestinal motility. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. 2015, 187: 193-201. PMID: 26051613
The distribution pattern of two cholecystokinin receptors has been identified in goldfish and the CCKAR subtype is mainly involved in the regulation of intestinal motility by the CCK-8S.
CCKAR Preparation Options
Generating stable conditions for membrane proteins after extraction from their lipid bilayer environment is essential for their structural and functional characterization as well as the subsequent applications. As a leading service provider specializing in custom membrane protein preparation, Creative Biolabs provides a number of preparation options suited for different research purposes, ranging from traditional detergents and liposomes to newly developed tools such as nanodiscs, lipoparticles, and polymers. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CCKAR antibody development services.
Strong integrated expertise in membrane protein biochemistry and the chemistry of reagents for protein isolation, working experience with various difficult-to-prepare membrane protein-related projects, up-to-date knowledge in protein technologies, enable us to become a reliable and resourceful research partner for our clients. contact us for more details about our membrane protein preparation services.
All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.
