Gastrin/cholecystokinin type B receptor

NameGastrin/cholecystokinin type B receptor
Synonyms
  • CCK-B receptor
  • CCK2-R
  • CCKRB
  • Cholecystokinin-2 receptor
Gene NameCCKBR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002303|Gastrin/cholecystokinin type B receptor
MELLKLNRSVQGTGPGPGASLCRPGAPLLNSSSVGNLSCEPPRIRGAGTRELELAIRITL
YAVIFLMSVGGNMLIIVVLGLSRRLRTVTNAFLLSLAVSDLLLAVACMPFTLLPNLMGTF
IFGTVICKAVSYLMGVSVSVSTLSLVAIALERYSAICRPLQARVWQTRSHAARVIVATWL
LSGLLMVPYPVYTVVQPVGPRVLQCVHRWPSARVRQTWSVLLLLLLFFIPGVVMAVAYGL
ISRELYLGLRFDGDSDSDSQSRVRNQGGLPGAVHQNGRCRPETGAVGEDSDGCYVQLPRS
RPALELTALTAPGPGSGSRPTQAKLLAKKRVVRMLLVIVVLFFLCWLPVYSANTWRAFDG
PGAHRALSGAPISFIHLLSYASACVNPLVYCFMHRRFRQACLETCARCCPRPPRARPRAL
PDEDPPTPSIASLSRLSYTTISTLGPG
Number of residues447
Molecular Weight48418.51
Theoretical pI10.24
GO Classification
Functions
  • gastrin receptor activity
  • type B gastrin/cholecystokinin receptor binding
  • phosphatidylinositol phospholipase C activity
  • 1-phosphatidylinositol-3-kinase regulator activity
  • cholecystokinin receptor activity
Processes
  • regulation of phosphatidylinositol 3-kinase activity
  • gland development
  • sensory perception
  • cell proliferation
  • digestion
  • positive regulation of cytosolic calcium ion concentration
  • cell surface receptor signaling pathway
  • positive regulation of cell proliferation
  • phospholipase C-activating G-protein coupled receptor signaling pathway
  • gastric acid secretion
  • cholecystokinin signaling pathway
  • feeding behavior
  • digestive tract development
Components
  • cytosol
  • integral component of plasma membrane
  • plasma membrane
General FunctionType b gastrin/cholecystokinin receptor binding
Specific FunctionReceptor for gastrin and cholecystokinin. The CKK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.Isoform 2 is constitutively activated and may regulate cancer cell proliferation via a gastrin-independent mechanism.
Pfam Domain Function
Transmembrane Regions58-79 88-109 132-150 171-189 220-242 334-355 374-394
GenBank Protein ID306489
UniProtKB IDP32239
UniProtKB Entry NameGASR_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0019073|Gastrin/cholecystokinin type B receptor (CCKBR)
ATGGAGCTGCTAAAGCTGAACCGGAGCGTGCAGGGAACCGGACCCGGGCCGGGGGCTTCC
CTGTGCCGCCCGGGGGCGCCTCTCCTCAACAGCAGCAGTGTGGGCAACCTCAGCTGCGAG
CCCCCTCGCATTCGCGGAGCCGGGACACGAGAATTGGAGCTGGCCATTAGAATCACTCTT
TACGCAGTGATCTTCCTGATGAGCGTTGGAGGAAATATGCTCATCATCGTGGTCCTGGGA
CTGAGCCGCCGCCTGAGGACTGTCACCAATGCCTTCCTCCTCTCACTGGCAGTCAGCGAC
CTCCTGCTGGCTGTGGCTTGCATGCCCTTCACCCTCCTGCCCAATCTCATGGGCACATTC
ATCTTTGGCACCGTCATCTGCAAGGCGGTTTCCTACCTCATGGGGGTGTCTGTGAGTGTG
TCCACGCTAAGCCTCGTGGCCATCGCACTGGAGCGGTACAGCGCCATCTGCCGACCACTG
CAGGCACGAGTGTGGCAGACGCGCTCCCACGCGGCTCGCGTGATTGTAGCCACGTGGCTG
CTGTCCGGACTACTCATGGTGCCCTACCCCGTGTACACTGTCGTGCAACCAGTGGGGCCT
CGTGTGCTGCAGTGCGTGCATCGCTGGCCCAGTGCGCGGGTCCGCCAGACCTGGTCCGTA
CTGCTGCTTCTGCTCTTGTTCTTCATCCCGGGTGTGGTTATGGCCGTGGCCTACGGGCTT
ATCTCTCGCGAGCTCTACTTAGGGCTTCGCTTTGACGGCGACAGTGACAGCGACAGCCAA
AGCAGGGTCCGAAACCAAGGCGGGCTGCCAGGGGCTGTTCACCAGAACGGGCGTTGCCGG
CCTGAGACTGGCGCGGTTGGCGAAGACAGCGATGGCTGCTACGTGCAACTTCCACGTTCC
CGGCCTGCCCTGGAGCTGACGGCGCTGACGGCTCCTGGGCCGGGATCCGGCTCCCGGCCC
ACCCAGGCCAAGCTGCTGGCTAAGAAGCGCGTGGTGCGAATGTTGCTGGTGATCGTTGTG
CTTTTTTTTCTGTGTTGGTTGCCAGTTTATAGTGCCAACACGTGGCGCGCCTTTGATGGC
CCGGGTGCACACCGAGCACTCTCGGGTGCTCCTATCTCCTTCATTCACTTGCTGAGCTAC
GCCTCGGCCTGTGTCAACCCCCTGGTCTACTGCTTCATGCACCGTCGCTTTCGCCAGGCC
TGCCTGGAAACTTGCGCTCGCTGCTGCCCCCGGCCTCCACGAGCTCGCCCCAGGGCTCTT
CCCGATGAGGACCCTCCCACTCCCTCCATTGCTTCGCTGTCCAGGCTTAGCTACACCACC
ATCAGCACACTGGGCCCTGGCTGA
GenBank Gene IDL08112
GeneCard IDNot Available
GenAtlas IDCCKBR
HGNC IDHGNC:1571
Chromosome Location11
Locus11p15.4
References
  1. Pisegna JR, de Weerth A, Huppi K, Wank SA: Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization. Biochem Biophys Res Commun. 1992 Nov 30;189(1):296-303. 1280419
  2. Lee YM, Beinborn M, McBride EW, Lu M, Kolakowski LF Jr, Kopin AS: The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. J Biol Chem. 1993 Apr 15;268(11):8164-9. 7681836
  3. Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, Nakata H, Chiba T, Chihara K: Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin. J Biol Chem. 1993 Aug 25;268(24):18300-5. 8349705
  4. Song I, Brown DR, Wiltshire RN, Gantz I, Trent JM, Yamada T: The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9085-9. 8415658
  5. Herget T, Sethi T, Wu SV, Walsh JH, Rozengurt E: Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors. Ann N Y Acad Sci. 1994 Mar 23;713:283-97. 8185170
  6. Ito M, Iwata N, Taniguchi T, Murayama T, Chihara K, Matsui T: Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene. Cell Growth Differ. 1994 Oct;5(10):1127-35. 7848914
  7. Miyake A: A truncated isoform of human CCK-B/gastrin receptor generated by alternative usage of a novel exon. Biochem Biophys Res Commun. 1995 Mar 8;208(1):230-7. 7887934
  8. Hellmich MR, Rui XL, Hellmich HL, Fleming RY, Evers BM, Townsend CM Jr: Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth. J Biol Chem. 2000 Oct 13;275(41):32122-8. 10913157
  9. Schmitz F, Schrader H, Otte J, Schmitz H, Stuber E, Herzig K, Schmidt WE: Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells. Regul Pept. 2001 Sep 15;101(1-3):25-33. 11495676
  10. Smith JP, Verderame MF, McLaughlin P, Martenis M, Ballard E, Zagon IS: Characterization of the CCK-C (cancer) receptor in human pancreatic cancer. Int J Mol Med. 2002 Dec;10(6):689-94. 12429993
  11. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  12. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  13. O'Briant KC, Ali SY, Weier HU, Bepler G: An 84-kilobase physical map and repeat polymorphisms of the gastrin/cholecystokinin brain receptor region at the junction of chromosome segments 11p15.4 and 15.5. Chromosome Res. 1998 Aug;6(5):415-8. 9872672
  14. Sethi T, Herget T, Wu SV, Walsh JH, Rozengurt E: CCKA and CCKB receptors are expressed in small cell lung cancer lines and mediate Ca2+ mobilization and clonal growth. Cancer Res. 1993 Nov 1;53(21):5208-13. 8221657
  15. Zimonjic DB, Popescu NC, Matsui T, Ito M, Chihara K: Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5-->p15.4 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;65(3):184-5. 8222757
  16. Giragossian C, Mierke DF: Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin-2 receptor. Biochemistry. 2002 Apr 9;41(14):4560-6. 11926817