Cholecystokinin A receptor

CCKAR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1D6G, 1HZN
Identifiers
Aliases	CCKAR, CCK-A, CCK1-R, CCK1R, CCKRA, cholecystokinin A receptor
External IDs	OMIM: 118444; MGI: 99478; HomoloGene: 37337; GeneCards: CCKAR; OMA:CCKAR - orthologs
Gene location (Human) Chr. Chromosome 4 (human) Band 4p15.2 Start 26,481,396 bp End 26,490,484 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5 C1|5 29.52 cM Start 53,855,118 bp End 53,865,047 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gallbladder body of stomach fundus embryo islet of Langerhans duodenum ganglionic eminence hypothalamus sensory organ tonsil Top expressed in epithelium of stomach right lung lobe lumbar spinal ganglion right kidney proximal tubule pyloric antrum human kidney left lung left lung lobe thyroid gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity peptide binding cholecystokinin receptor activity peptide hormone binding Cellular component integral component of membrane plasma membrane integral component of plasma membrane membrane Biological process axonogenesis neuron migration phospholipase C-activating G protein-coupled receptor signaling pathway forebrain development signal transduction regulation of hormone secretion cellular response to hormone stimulus response to peptide G protein-coupled receptor signaling pathway cholecystokinin signaling pathway feeding behavior Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 886 12425 Ensembl ENSG00000163394 ENSMUSG00000029193 UniProt P32238 O08786 RefSeq (mRNA) NM_000730 NM_009827 NM_001347354 RefSeq (protein) NP_000721 NP_001334283 NP_033957 Location (UCSC) Chr 4: 26.48 – 26.49 Mb Chr 5: 53.86 – 53.87 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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
SCOP2	1d6g / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj 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.

Function

This gene encodes a G-protein coupled receptor that binds 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.

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.

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

External links

• "Cholecystokinin Receptors: CCK₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2012-10-23. Retrieved 2008-12-04.

Further reading

• Varga G, Bálint A, Burghardt B, D'Amato M (Apr 2004). "Involvement of endogenous CCK and CCK1 receptors in colonic motor function". British Journal of Pharmacology. 141 (8): 1275–84. doi:10.1038/sj.bjp.0705769. PMC 1574909. PMID 15100163.
• Wang J, Si YM, Liu ZL, Yu L (Jun 2003). "Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease". Pharmacogenetics. 13 (6): 365–9. doi:10.1097/00008571-200306000-00008. PMID 12777967.
• Miller LJ, Holicky EL, Ulrich CD, Wieben ED (Oct 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 (Feb 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. PMC 6736545. PMID 7759110.
• de Weerth A, Pisegna JR, Huppi K, Wank SA (Jul 1993). "Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor". Biochemical and Biophysical Research Communications. 194 (2): 811–8. doi:10.1006/bbrc.1993.1894. PMID 8343165.
• Ulrich CD, Ferber I, Holicky E, Hadac E, Buell G, Miller LJ (May 1993). "Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor". Biochemical and Biophysical Research Communications. 193 (1): 204–11. doi:10.1006/bbrc.1993.1610. PMID 8503909.
• Kennedy K, Gigoux V, Escrieut C, Maigret B, Martinez J, Moroder L, Fréhel D, Gully D, Vaysse N, Fourmy D (Jan 1997). "Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin". The Journal of Biological Chemistry. 272 (5): 2920–6. doi:10.1074/jbc.272.5.2920. PMID 9006937.
• Inoue H, Iannotti CA, Welling CM, Veile R, Donis-Keller H, Permutt MA (Jun 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, Maigret B, Gouilleux L, Fehrentz JA, Gully D, Moroder L, Vaysse N, Fourmy D (Jun 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". The Journal of Biological Chemistry. 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. doi:10.1159/000051459. PMID 10026437. S2CID 41117645.
• Gigoux V, Escrieut C, Fehrentz JA, Poirot S, Maigret B, Moroder L, Gully D, Martinez J, Vaysse N, Fourmy D (Jul 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". The Journal of Biological Chemistry. 274 (29): 20457–64. doi:10.1074/jbc.274.29.20457. PMID 10400673.
• Gigoux V, Maigret B, Escrieut C, Silvente-Poirot S, Bouisson M, Fehrentz JA, Moroder L, Gully D, Martinez J, Vaysse N, Fourmy AD (Nov 1999). "Arginine 197 of the cholecystokinin-A receptor binding site interacts with the sulfate of the peptide agonist cholecystokinin". Protein Science. 8 (11): 2347–54. doi:10.1110/ps.8.11.2347. PMC 2144185. PMID 10595537.
• Funakoshi A, Miyasaka K, Matsumoto H, Yamamori S, Takiguchi S, Kataoka K, Takata Y, Matsusue K, Kono A, Shimokata H (Jan 2000). "Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism". FEBS Letters. 466 (2–3): 264–6. doi:10.1016/S0014-5793(00)01080-2. PMID 10682840. S2CID 11683500.
• Tachikawa H, Harada S, Kawanishi Y, Okubo T, Shiraishi H (Apr 2000). "Novel polymorphisms of the human cholecystokinin A receptor gene: an association analysis with schizophrenia". American Journal of Medical Genetics. 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 (Apr 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, Schmitz H, Stüber E, Herzig K, Schmidt WE (Sep 2001). "Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells". Regulatory Peptides. 101 (1–3): 25–33. doi:10.1016/S0167-0115(01)00281-6. PMID 11495676. S2CID 22693627.
• Tachikawa H, Harada S, Kawanishi Y, Okubo T, Suzuki T (Sep 2001). "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. S2CID 24442175.
• Schmitz F, Göke MN, Otte JM, Schrader H, Reimann B, Kruse ML, Siegel EG, Peters J, Herzig KH, Fölsch UR, Schmidt WE (Dec 2001). "Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa". Regulatory Peptides. 102 (2–3): 101–10. doi:10.1016/S0167-0115(01)00307-X. PMID 11730982. S2CID 42131386.
• Okubo T, Harada S, Higuchi S, Matsushita S (Aug 2002). "Investigation of quantitative trait loci in the CCKAR gene with susceptibility to alcoholism". Alcoholism: Clinical and Experimental Research. 26 (8 Suppl): 2S–5S. doi:10.1111/j.1530-0277.2002.tb02693.x. PMID 12198366.
• Takata Y, Takeda S, Kawanami T, Takiguchi S, Yoshida Y, Miyasaka K, Funakoshi A (2003). "Promoter analysis of human cholecystokinin type-A receptor gene". Journal of Gastroenterology. 37 (10): 815–20. doi:10.1007/s005350200135. PMID 12424565. S2CID 35526543.

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

This article incorporates text from the public domain Pfam and InterPro: IPR015276