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1  structure 82  species 0  interactions 88  sequences 1  architecture

Family: CholecysA-Rec_N (PF09193)

Summary: Cholecystokinin A receptor, N-terminal

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Cholecystokinin A receptor". More...

Cholecystokinin A receptor Edit Wikipedia article

CCKAR
Protein CCKAR PDB 1d6g.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CCKAR, CCK-A, CCK1-R, CCK1R, CCKRA, cholecystokinin A receptor
External IDs MGI: 99478 HomoloGene: 37337 GeneCards: CCKAR
Gene location (Human)
Chromosome 4 (human)
Chr. Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for CCKAR
Genomic location for CCKAR
Band 4p15.2 Start 26,481,400 bp[1]
End 26,490,462 bp[1]
RNA expression pattern
PBB GE CCKAR 211173 at fs.png

PBB GE CCKAR 211174 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
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: 53.7 – 53.71 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Cholecystokinin A receptor, N-terminal domain
PDB 1d6g EBI.jpg
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
SUPERFAMILY 1d6g

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.[5]

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.[6]

Selective Ligands

Agonists

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

Antagonists

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163394 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029193 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ "Entrez Gene: CCKAR cholecystokinin A receptor". 
  6. ^ Pellegrini M, Mierke DF (Nov 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

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 1574909Freely accessible. 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. 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. 
  • 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 2144185Freely accessible. 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. 
  • 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. 
  • 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. 
  • 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. 
  • 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:10.1097/01.ALC.0000026826.96191.FB. 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. 

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Cholecystokinin A receptor, N-terminal Provide feedback

Members of this family are found in the extracellular region of the cholecystokinin A receptor, where they adopt a tertiary structure consisting of a few helical turns and a disulphide-crosslinked loop. They are required for interaction of the cholecystokinin A receptor with it's corresponding hormonal ligand [1].

Literature references

  1. Pellegrini M, Mierke DF; , Biochemistry. 1999;38:14775-14783.: Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy. PUBMED:10555959 EPMC:10555959


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR015276

This entry represents the extracellular N-terminal domain of the cholecystokinin A receptor. This domain adopts a tertiary structure consisting of a few helical turns and a disulphide-cross linked loop. It is required for interaction of the cholecystokinin A receptor with its corresponding hormonal ligand [PUBMED:10555959].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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  Seed
(4)
Full
(88)
Representative proteomes UniProt
(106)
NCBI
(254)
Meta
(0)
RP15
(7)
RP35
(21)
RP55
(68)
RP75
(88)
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  Seed
(4)
Full
(88)
Representative proteomes UniProt
(106)
NCBI
(254)
Meta
(0)
RP15
(7)
RP35
(21)
RP55
(68)
RP75
(88)
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  Seed
(4)
Full
(88)
Representative proteomes UniProt
(106)
NCBI
(254)
Meta
(0)
RP15
(7)
RP35
(21)
RP55
(68)
RP75
(88)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: pdb_1d6g
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Sammut SJ
Number in seed: 4
Number in full: 88
Average length of the domain: 48.30 aa
Average identity of full alignment: 66 %
Average coverage of the sequence by the domain: 11.36 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 21.9 28.1
Noise cut-off 20.7 20.7
Model length: 50
Family (HMM) version: 10
Download: download the raw HMM for this family

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CholecysA-Rec_N domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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