Reviewed, UniProtKB/Swiss-Prot P32239 (GASR_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	447 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure
Gene Ontology (GO)
Biological process	activation of phospholipase C activity Ref.2 Traceable author statement. Source: ProtInc digestion Ref.2 Traceable author statement. Source: ProtInc elevation of cytosolic calcium ion concentration Ref.2 Traceable author statement. Source: ProtInc feeding behavior Ref.2 Traceable author statement. Source: ProtInc positive regulation of cell proliferation Ref.3 Traceable author statement. Source: ProtInc sensory perception Ref.2 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc
Molecular function	1-phosphatidylinositol-3-kinase regulator activity Traceable author statement. Source: ProtInc gastrin receptor activity Inferred from electronic annotation. Source: InterPro phosphoinositide phospholipase C activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-1753137,EBI-375543
FYN	P06241	1	EBI-1753137,EBI-515315
GRB2	P62993	1	EBI-1753137,EBI-401755
NCK1	P16333	1	EBI-1753137,EBI-389883

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 447

447

Gastrin/cholecystokinin type B receptor

PRO_0000069474

Regions

Topological domain

1 – 57

57

Extracellular Potential

Transmembrane

58 – 79

22

1 Potential

Topological domain

80 – 87

8

Cytoplasmic Potential

Transmembrane

88 – 109

22

2 Potential

Topological domain

110 – 131

22

Extracellular Potential

Transmembrane

132 – 150

19

3 Potential

Topological domain

151 – 170

20

Cytoplasmic Potential

Transmembrane

171 – 189

19

4 Potential

Topological domain

190 – 219

30

Extracellular Potential

Transmembrane

220 – 242

23

5 Potential

Topological domain

243 – 333

91

Cytoplasmic Potential

Transmembrane

334 – 355

22

6 Potential

Topological domain

356 – 373

18

Extracellular Potential

Transmembrane

374 – 394

21

7 Potential

Topological domain

395 – 447

53

Cytoplasmic Potential

Amino acid modifications

Lipidation

408

1

S-palmitoyl cysteine By similarity

Glycosylation

7

1

N-linked (GlcNAc...) Potential

Glycosylation

30

1

N-linked (GlcNAc...) Potential

Glycosylation

36

1

N-linked (GlcNAc...) Potential

Disulfide bond

127 ↔ 205

By similarity

Natural variations

Alternative sequence

1 – 66

66

Missing in isoform 3.

VSP_033444

Alternative sequence

271

1

G → GGAGPREQNLGEAELWRATG PAGVGGTEMKVRVRRKLEME LSWERRSGGDWAGDWGDSPF SLTAHPLCSG in isoform 2.

VSP_033445

Natural variant

37

1

L → F: dbSNP rs1805000.

VAR_014684

Natural variant

125

1

V → I: dbSNP rs1805002.

VAR_014685

Natural variant

215

1

R → H: dbSNP rs1805004.

VAR_014686

Natural variant

319

1

R → Q: dbSNP rs1805001.

VAR_014687

Experimental info

Sequence conflict

64

1

I → T in AAF67174. Ref.8

Sequence conflict

93

1

L → F in AAC27510. Ref.16

Sequence conflict

96

1

L → M in AAC27510. Ref.16

Sequence conflict

116

1

L → I in AAC27510. Ref.16

Sequence conflict

171

1

A → P in AAA91831. Ref.11

Sequence conflict

227

1

F → S in BAF84753. Ref.12

Sequence conflict

249

1

L → V in AAA91831. Ref.11

Sequence conflict

288

1

E → K in AAB30766. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

447

Helix Strand Turn

Details...

Helix

353 – 358

6

Helix

363 – 368

6

Helix

372 – 378

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: BAEEFAD4C1F85915	FASTA	447	48,419
	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
	Isoform 2 (CCK-C) (CCK-BRi4sv) [UniParc]. Checksum: 9B27DDCAE3A67CC7		516	55,869
	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 GGAGPREQNL GEAELWRATG PAGVGGTEMK 310 320 330 340 350 360 VRVRRKLEME LSWERRSGGD WAGDWGDSPF SLTAHPLCSG AVHQNGRCRP ETGAVGEDSD 370 380 390 400 410 420 GCYVQLPRSR PALELTALTA PGPGSGSRPT QAKLLAKKRV VRMLLVIVVL FFLCWLPVYS 430 440 450 460 470 480 ANTWRAFDGP GAHRALSGAP ISFIHLLSYA SACVNPLVYC FMHRRFRQAC LETCARCCPR 490 500 510 PPRARPRALP DEDPPTPSIA SLSRLSYTTI STLGPG
	Isoform 3 (DeltaCCK-B) [UniParc]. Checksum: 2DF92F7D8A27773B		381	41,504
	10 20 30 40 50 60 MSVGGNMLII VVLGLSRRLR TVTNAFLLSL AVSDLLLAVA CMPFTLLPNL MGTFIFGTVI 70 80 90 100 110 120 CKAVSYLMGV SVSVSTLSLV AIALERYSAI CRPLQARVWQ TRSHAARVIV ATWLLSGLLM 130 140 150 160 170 180 VPYPVYTVVQ PVGPRVLQCV HRWPSARVRQ TWSVLLLLLL FFIPGVVMAV AYGLISRELY 190 200 210 220 230 240 LGLRFDGDSD SDSQSRVRNQ GGLPGAVHQN GRCRPETGAV GEDSDGCYVQ LPRSRPALEL 250 260 270 280 290 300 TALTAPGPGS GSRPTQAKLL AKKRVVRMLL VIVVLFFLCW LPVYSANTWR AFDGPGAHRA 310 320 330 340 350 360 LSGAPISFIH LLSYASACVN PLVYCFMHRR FRQACLETCA RCCPRPPRAR PRALPDEDPP 370 380 TPSIASLSRL SYTTISTLGP G

References

	« Hide 'large scale' referencesShow '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. , 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.