Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot P32239 (GASR_HUMAN)

Last modified November 25, 2008. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Gastrin/cholecystokinin type B receptor
      Short name=CCK-B receptor
      Short name=CCK-BR
Alternative name(s):
    Cholecystokinin-2 receptor
      Short name=CCK2-R
Gene names
Name: CCKBR
Synonyms: CCKRB
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length447 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Receptor 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 may regulate cancer cell proliferation via a gastrin-independent mechanism.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Isoform 1 is expressed in brain, pancreas, stomach, the colon cancer cell line LoVo and the T-lymphoblastoma Jurkat, but not in heart, placenta, liver, lung, skeletal muscle, kidney or the stomach cancer cell line AGS. Expressed at high levels in the small cell lung cancer cell line H510, at lower levels in H345, H69 and GLC28, not expressed in GLC19. Within the stomach, expressed at high levels in the mucosa of the gastric fundus and at low levels in the antrum and duodenum. Isoform 2 is present in pancreatic cancer cells and colorectal cancer cells, but not in normal pancreas or colonic mucosa. Isoform 3 is expressed in brain, pancreas, stomach, the stomach cancer cell line AGS and the colon cancer cell line LoVo.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P32239-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P32239-2)

Also known as: CCK-C; CCK-BRi4sv;

The sequence of this isoform differs from the canonical sequence as follows:
     271-271: G → GGAGPREQNLGEAELWRATGPAGVGGTEMKVRVRRKLEMELSWERRSGGDWAGDWGDSPFSLTAHPLCSG
Isoform 3 (identifier: P32239-3)

Also known as: DeltaCCK-B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 447447Gastrin/cholecystokinin type B receptor
PRO_0000069474

Regions

Topological domain1 – 5757Extracellular Potential
Transmembrane58 – 79221 Potential
Topological domain80 – 878Cytoplasmic Potential
Transmembrane88 – 109222 Potential
Topological domain110 – 13122Extracellular Potential
Transmembrane132 – 150193 Potential
Topological domain151 – 17020Cytoplasmic Potential
Transmembrane171 – 189194 Potential
Topological domain190 – 21930Extracellular Potential
Transmembrane220 – 242235 Potential
Topological domain243 – 33391Cytoplasmic Potential
Transmembrane334 – 355226 Potential
Topological domain356 – 37318Extracellular Potential
Transmembrane374 – 394217 Potential
Topological domain395 – 44753Cytoplasmic Potential

Amino acid modifications

Lipidation4081S-palmitoyl cysteine By similarity
Glycosylation71N-linked (GlcNAc...) Potential
Glycosylation301N-linked (GlcNAc...) Potential
Glycosylation361N-linked (GlcNAc...) Potential
Disulfide bond127 ↔ 205 By similarity

Natural variations

Alternative sequence1 – 6666Missing in isoform 3.
VSP_033444
Alternative sequence2711G → GGAGPREQNLGEAELWRATG PAGVGGTEMKVRVRRKLEME LSWERRSGGDWAGDWGDSPF SLTAHPLCSG in isoform 2.
VSP_033445
Natural variant371L → F: dbSNP rs1805000.
VAR_014684
Natural variant1251V → I: dbSNP rs1805002.
VAR_014685
Natural variant2151R → H: dbSNP rs1805004.
VAR_014686
Natural variant3191R → Q: dbSNP rs1805001.
VAR_014687

Experimental info

Sequence conflict641I → T in AAF67174. Ref.8
Sequence conflict931L → F in AAC27510. Ref.16
Sequence conflict961L → M in AAC27510. Ref.16
Sequence conflict1161L → I in AAC27510. Ref.16
Sequence conflict1711A → P in AAA91831. Ref.11
Sequence conflict2271F → S in BAF84753. Ref.12
Sequence conflict2491L → V in AAA91831. Ref.11
Sequence conflict2881E → K in AAB30766. Ref.5

Secondary structure

....... 447
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: BAEEFAD4C1F85915

FASTA44748,419
        10         20         30         40         50         60 
MELLKLNRSV QGTGPGPGAS LCRPGAPLLN SSSVGNLSCE PPRIRGAGTR ELELAIRITL 

        70         80         90        100        110        120 
YAVIFLMSVG GNMLIIVVLG LSRRLRTVTN AFLLSLAVSD LLLAVACMPF TLLPNLMGTF 

       130        140        150        160        170        180 
IFGTVICKAV SYLMGVSVSV STLSLVAIAL ERYSAICRPL QARVWQTRSH AARVIVATWL 

       190        200        210        220        230        240 
LSGLLMVPYP VYTVVQPVGP RVLQCVHRWP SARVRQTWSV LLLLLLFFIP GVVMAVAYGL 

       250        260        270        280        290        300 
ISRELYLGLR FDGDSDSDSQ SRVRNQGGLP GAVHQNGRCR PETGAVGEDS DGCYVQLPRS 

       310        320        330        340        350        360 
RPALELTALT APGPGSGSRP TQAKLLAKKR VVRMLLVIVV LFFLCWLPVY SANTWRAFDG 

       370        380        390        400        410        420 
PGAHRALSGA PISFIHLLSY ASACVNPLVY CFMHRRFRQA CLETCARCCP RPPRARPRAL 

       430        440 
PDEDPPTPSI ASLSRLSYTT ISTLGPG 

« Hide

Isoform 2 (CCK-C) (CCK-BRi4sv) [UniParc].

Checksum: 9B27DDCAE3A67CC7
Show »

51655,869
Isoform 3 (DeltaCCK-B) [UniParc].

Checksum: 2DF92F7D8A27773B
Show »

38141,504

References

« Hide 'large scale' references
[1]"Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization."
Pisegna J.R., de Weerth A., Huppi K., Wank S.A.
Biochem. Biophys. Res. Commun. 189:296-303(1992) [PubMed: 1280419] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization."
Lee Y.-M., Beinborn M., McBride E.W., Lu M., Kolakowski L.F. Jr., Kopin A.S.
J. Biol. Chem. 268:8164-8169(1993) [PubMed: 7681836] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin."
Ito M., Matsui T., Taniguchi T., Tsukamoto T., Murayama T., Arima N., Nakata H., Chiba T., Chihara K.
J. Biol. Chem. 268:18300-18305(1993) [PubMed: 8349705] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
Tissue: Brain.
[4]"The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs."
Song I., Brown D.R., Wiltshire R.N., Gantz I., Trent J.M., Yamada T.
Proc. Natl. Acad. Sci. U.S.A. 90:9085-9089(1993) [PubMed: 8415658] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[5]"Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors."
Herget T., Sethi T., Wu S.V., Walsh J.H., Rozengurt E.
Ann. N. Y. Acad. Sci. 713:283-297(1994) [PubMed: 8185170] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
Tissue: Fetal brain.
[6]"Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene."
Ito M., Iwata N., Taniguchi T., Murayama T., Chihara K., Matsui T.
Cell Growth Differ. 5:1127-1135(1994) [PubMed: 7848914] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
Tissue: Lung fibroblast.
[7]"A truncated isoform of human CCK-B/gastrin receptor generated by alternative usage of a novel exon."
Miyake A.
Biochem. Biophys. Res. Commun. 208:230-237(1995) [PubMed: 7887934] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
Tissue: Stomach.
[8]"Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth."
Hellmich M.R., Rui X.-L., Hellmich H.L., Fleming R.Y.D., Evers B.M., Townsend C.M. Jr.
J. Biol. Chem. 275:32122-32128(2000) [PubMed: 10913157] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY.
Tissue: Colon cancer.
[9]"Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells."
Schmitz F., Schrader H., Otte J.-M., Schmitz H., Stueber E., Herzig K.-H., Schmidt W.E.
Regul. Pept. 101:25-33(2001) [PubMed: 11495676] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ALTERNATIVE SPLICING.
Tissue: Peripheral blood.
[10]"Characterization of the CCK-C (cancer) receptor in human pancreatic cancer."
Smith J.P., Verderame M.F., McLaughlin P., Martenis M., Ballard E., Zagon I.S.
Int. J. Mol. Med. 10:689-694(2002) [PubMed: 12429993] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Tissue: Pancreatic cancer.
[11]"Cloning and expression of the human temporal cortex cholecystokinin B receptor."
Tate S.N., Gray J., Denyer J., Stolz M., Foord S., Lee M.G.
Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Temporal cortex.
[12]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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 T.-O., 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.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Stomach.
[13]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[14]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[15]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[16]"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."
O'Briant K.C., Ali S.Y., Weier H.-U.G., Bepler G.
Chromosome Res. 6:415-418(1998) [PubMed: 9872672] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 52-447.
[17]"CCKA and CCKB receptors are expressed in small cell lung cancer lines and mediate Ca2+ mobilization and clonal growth."
Sethi T., Herget T., Wu S.V., Walsh J.H., Rozengurt E.
Cancer Res. 53:5208-5213(1993) [PubMed: 8221657] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 244-333 (ISOFORMS 1/3), FUNCTION.
Tissue: Fetal brain.
[18]"Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5-->p15.4 by fluorescence in situ hybridization."
Zimonjic D.B., Popescu N.C., Matsui T., Ito M., Chihara K.
Cytogenet. Cell Genet. 65:184-185(1994) [PubMed: 8222757] [Abstract]
Cited for: CHROMOSOMAL LOCATION.
[19]"Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin-2 receptor."
Giragossian C., Mierke D.F.
Biochemistry 41:4560-4566(2002) [PubMed: 11926817] [Abstract]
Cited for: STRUCTURE BY NMR OF 352-379.
+Additional computationally mapped references.