Cholecystokinin A receptor

Cholecystokinin A receptor
PDB rendering based on 1d6g.
Available structures PDB 1D6G, 1HZN, 1PB2
Identifiers
Symbols	CCKAR; CCK-A; CCK1-R; CCKRA
External IDs	OMIM: 118444 MGI: 99478 HomoloGene: 37337 GeneCards: CCKAR Gene
Gene Ontology Molecular function • receptor activity • G-protein coupled receptor activity • cholecystokinin receptor activity Cellular component • cytoplasm • lysosome • endosome • endoplasmic reticulum • plasma membrane • plasma membrane • integral to plasma membrane • terminal button Biological process • temperature homeostasis • gastric acid secretion • neuron migration • reduction of food intake in response to dietary excess • activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger • elevation of cytosolic calcium ion concentration • axonogenesis • response to nutrient • digestion • feeding behavior • response to radiation • response to heat • insulin secretion • pancreatic juice secretion • forebrain development • pancreas development • organ regeneration • actin cytoskeleton reorganization • response to lipopolysaccharide • cellular response to hormone stimulus • response to starvation • regulation of potassium ion transport • regulation of hormone secretion • response to steroid hormone stimulus • response to glucocorticoid stimulus • positive regulation of calcium ion transport via voltage-gated calcium channel activity • positive regulation of somatostatin secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	886	12425
Ensembl	ENSG00000163394	ENSMUSG00000029193
UniProt	P32238	Q3TPL0
RefSeq (mRNA)	NM_000730	NM_009827.2
RefSeq (protein)	NP_000721	NP_033957.1
Location (UCSC)	Chr 4: 26.48 – 26.49 Mb	Chr 5: 54.09 – 54.1 Mb
PubMed search	[1]	[2]

Cholecystokinin A receptor, N-terminal domain
molecular complex of cholecystokinin-8 and n-terminus of the cholecystokinin a receptor by nmr spectroscopy
Identifiers
Symbol	CholecysA-Rec_N
Pfam	PF09193
InterPro	IPR015276
SCOP	1d6g
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

The Cholecystokinin A receptor is a human protein, also known as CCKAR or CCK₁, with CCK₁ now being the IUPHAR-recommended name.

This gene encodes a G-protein coupled receptor that binds non-sulfated members of the cholecystokinin (CCK) family of peptide hormones. This receptor is a major physiologic mediator of pancreatic enzyme secretion and smooth muscle contraction of the gallbladder and stomach. In the central and peripheral nervous system this receptor regulates satiety and the release of beta-endorphin and dopamine.^[1]

The extracellular, N-terminal, domain of this protein adopts a tertiary structure consisting of a few helical turns and a disulfide-cross linked loop. It is required for interaction of the cholecystokinin A receptor with its corresponding hormonal ligand.^[2]

Selective Ligands

Agonists

• Cholecystokinin
• CCK-4
• SR-146,131
• A-71623 - modified tetrapeptide, potent and selective CCK_A agonist, IC₅₀ 3.7nM, 1200x selectivity over CCK_B, CAS# 130408-77-4

Antagonists

• Proglumide
• Lorglumide
• Devazepide
• Dexloxiglumide
• Asperlicin
• SR-27897
• IQM-95333
• JNJ-17156516

See also

• Cholecystokinin receptor
• Cholecystokinin antagonist

References

1. ^ "Entrez Gene: CCKAR cholecystokinin A receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=886. 
2. ^ Pellegrini M, Mierke DF (November 1999). "Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy". Biochemistry 38 (45): 14775–83. doi:10.1021/bi991272l. PMID 10555959. 

External links

• "Cholecystokinin Receptors: CCK₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2247. 

Further reading

• Varga G, Bálint A, Burghardt B, D'Amato M (2004). "Involvement of endogenous CCK and CCK1 receptors in colonic motor function.". Br. J. Pharmacol. 141 (8): 1275–84. doi:10.1038/sj.bjp.0705769. PMC 1574909. PMID 15100163. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1574909. 
• Miller LJ, Holicky EL, Ulrich CD, Wieben ED (1995). "Abnormal processing of the human cholecystokinin receptor gene in association with gallstones and obesity.". Gastroenterology 109 (4): 1375–80. doi:10.1016/0016-5085(95)90601-0. PMID 7557108. 
• Huppi K, Siwarski D, Pisegna JR, Wank S (1995). "Chromosomal localization of the gastric and brain receptors for cholecystokinin (CCKAR and CCKBR) in human and mouse.". Genomics 25 (3): 727–9. doi:10.1016/0888-7543(95)80018-H. PMID 7759110. 
• de Weerth A, Pisegna JR, Huppi K, Wank SA (1993). "Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor.". Biochem. Biophys. Res. Commun. 194 (2): 811–8. doi:10.1006/bbrc.1993.1894. PMID 8343165. 
• Ulrich CD, Ferber I, Holicky E, et al. (1993). "Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor.". Biochem. Biophys. Res. Commun. 193 (1): 204–11. doi:10.1006/bbrc.1993.1610. PMID 8503909. 
• Kennedy K, Gigoux V, Escrieut C, et al. (1997). "Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin.". J. Biol. Chem. 272 (5): 2920–6. doi:10.1074/jbc.272.5.2920. PMID 9006937. 
• Inoue H, Iannotti CA, Welling CM, et al. (1997). "Human cholecystokinin type A receptor gene: cytogenetic localization, physical mapping, and identification of two missense variants in patients with obesity and non-insulin-dependent diabetes mellitus (NIDDM).". Genomics 42 (2): 331–5. doi:10.1006/geno.1997.4749. PMID 9192855. 
• Gigoux V, Escrieut C, Silvente-Poirot S, et al. (1998). "Met-195 of the cholecystokinin-A receptor interacts with the sulfated tyrosine of cholecystokinin and is crucial for receptor transition to high affinity state.". J. Biol. Chem. 273 (23): 14380–6. doi:10.1074/jbc.273.23.14380. PMID 9603948. 
• Funakoshi A, Fukamizu Y, Miyasaka K (2000). "Mechanism of cholecystokinin-A- receptor antagonist on human pancreatic exocrine secretion. Localization of CCK-A receptor in the human duodenum.". Digestion 60 Suppl 1: 75–80. PMID 10026437. 
• Gigoux V, Escrieut C, Fehrentz JA, et al. (1999). "Arginine 336 and asparagine 333 of the human cholecystokinin-A receptor binding site interact with the penultimate aspartic acid and the C-terminal amide of cholecystokinin.". J. Biol. Chem. 274 (29): 20457–64. doi:10.1074/jbc.274.29.20457. PMID 10400673. 
• Gigoux V, Maigret B, Escrieut C, et al. (2000). "Arginine 197 of the cholecystokinin-A receptor binding site interacts with the sulfate of the peptide agonist cholecystokinin.". Protein Sci. 8 (11): 2347–54. doi:10.1110/ps.8.11.2347. PMC 2144185. PMID 10595537. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2144185. 
• Funakoshi A, Miyasaka K, Matsumoto H, et al. (2000). "Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism.". FEBS Lett. 466 (2–3): 264–6. doi:10.1016/S0014-5793(00)01080-2. PMID 10682840. 
• Tachikawa H, Harada S, Kawanishi Y, et al. (2000). "Novel polymorphisms of the human cholecystokinin A receptor gene: an association analysis with schizophrenia". Am. J. Med. Genet. 96 (2): 141–5. doi:10.1002/(SICI)1096-8628(20000403)96:2<141::AID-AJMG3>3.0.CO;2-R. PMID 10893485. 
• Giragossian C, Mierke DF (2001). "Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin A receptor". Biochemistry 40 (13): 3804–9. doi:10.1021/bi002659n. PMID 11300760. 
• Schmitz F, Schrader H, Otte J, et al. (2002). "Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells". Regul. Pept. 101 (1–3): 25–33. doi:10.1016/S0167-0115(01)00281-6. PMID 11495676. 
• Tachikawa H, Harada S, Kawanishi Y, et al. (2002). "Linked polymorphisms (-333G>T and -286A>G) in the promoter region of the CCK-A receptor gene may be associated with schizophrenia". Psychiatry research 103 (2–3): 147–55. doi:10.1016/S0165-1781(01)00276-1. PMID 11549403. 
• Schmitz F, Göke MN, Otte JM, et al. (2002). "Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa". Regul. Pept. 102 (2–3): 101–10. doi:10.1016/S0167-0115(01)00307-X. PMID 11730982. 
• Okubo T, Harada S, Higuchi S, Matsushita S (2003). "Investigation of quantitative trait loci in the CCKAR gene with susceptibility to alcoholism". Alcohol. Clin. Exp. Res. 26 (8 Suppl): 2S–5S. doi:10.1097/01.ALC.0000026826.96191.FB. PMID 12198366. 
• Takata Y, Takeda S, Kawanami T, et al. (2003). "Promoter analysis of human cholecystokinin type-A receptor gene". J. Gastroenterol. 37 (10): 815–20. doi:10.1007/s005350200135. PMID 12424565. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article includes text from the public domain Pfam and InterPro IPR015276