Reviewed, UniProtKB/Swiss-Prot P01350 (GAST_HUMAN)

Names and origin

Protein names

Recommended name:
    Gastrin
Cleaved into the following 6 chains:
    1- Recommended name:
            Gastrin-71
        Alternative name(s):
            Gastrin component I
    2- Recommended name:
            Gastrin-52
                Short name=G52
    3- Recommended name:
            Big gastrin
        Alternative name(s):
            Gastrin-34
              Short name=G34
            Gastrin component II
    4- Recommended name:
            Gastrin
        Alternative name(s):
            Gastrin-17
              Short name=G17
            Gastrin component III
    5- Recommended name:
            Gastrin-14
                Short name=G14
    6- Recommended name:
            Gastrin-6
                Short name=G6

Gene names

Name:	GAST
Synonyms:	GAS

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	101 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.
Subcellular location	Secreted.
Post-translational modification	Two different processing pathways probably exist in antral G-cells. In the dominant pathway progastrin is cleaved at three sites resulting in two major bioactive gastrins, gastrin-34 and gastrin-17. In the putative alternative pathway, progastrin may be processed only at the most C-terminal dibasic site resulting in the synthesis of gastrin-71. Ref.12 Ref.13 Ref.14 Sulfation enhances proteolytic processing, and blocks peptide degradation. Levels of sulfation differ between proteolytically-cleaved gastrins. Thus, gastrin-6 is almost 73% sulfated, whereas the larger gastrins are less than 50% sulfated. Sulfation levels are also tissue-specific. Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the gastrin/cholecystokinin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues Phosphoprotein Pyrrolidone carboxylic acid Sulfation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	signal transduction Non-traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	hormone activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Ref.8
	Peptide	22 – 92	71	Gastrin-71		PRO_0000010633
	Peptide	41 – 92	52	Gastrin-52		PRO_0000010634
	Peptide	59 – 92	34	Big gastrin		PRO_0000010635
	Peptide	76 – 92	17	Gastrin		PRO_0000010636
	Peptide	79 – 92	14	Gastrin-14		PRO_0000010637
	Peptide	87 – 92	6	Gastrin-6		PRO_0000010638
	Propeptide	96 – 101	6	Removed in mature form		PRO_0000010639
Sites
	Site	40 – 41	2	Cleavage
	Site	58 – 59	2	Cleavage
	Site	75 – 76	2	Cleavage
	Site	95 – 96	2	Cleavage
Amino acid modifications
	Modified residue	59	1	Pyrrolidone carboxylic acid; in form big gastrin Ref.9
	Modified residue	76	1	Pyrrolidone carboxylic acid; in form gastrin
	Modified residue	87	1	Sulfotyrosine; partial
	Modified residue	92	1	Phenylalanine amide
	Modified residue	96	1	Phosphoserine By similarity
Natural variations
	Natural variant	3	1	R → P: dbSNP rs34309618.		VAR_049127
Experimental info
	Mutagenesis	86	1	A → D: Small increase in ratio of gastrin-17 versus gastrin-34 production. No change in ratio of gastrin-17 versus gastrin-34 production; when associated with F-87. Ref.13
	Mutagenesis	87	1	Y → F: Small decrease in ratio of gastrin-17 versus gastrin-34 production. No change in ratio of gastrin-17 versus gastrin-34 production; when associated with D-86. Ref.13

Sequences

	Sequence		Length	Mass (Da)
	P01350-1 [UniParc]. Last modified October 23, 1986. Version 1. Checksum: A03C847FCFE7216C	FASTA	101	11,394
	10 20 30 40 50 60 MQRLCVYVLI FALALAAFSE ASWKPRSQQP DAPLGTGANR DLELPWLEQQ GPASHHRRQL 70 80 90 100 GPQGPPHLVA DPSKKQGPWL EEEEEAYGWM DFGRRSAEDE N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression of human gastrin gene in normal and gastrinoma tissues." Kariya Y., Kato K., Hayashizaki Y., Himeno S., Tarui S., Matsubara K. Gene 50:345-352(1986) [PubMed: 3034736] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence." Ito R., Sato K., Helmer T., Jay G., Agarwal K.L. Proc. Natl. Acad. Sci. U.S.A. 81:4662-4666(1984) [PubMed: 6087340] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Molecular cloning of the human gastrin gene." Kato K., Hayashizaki Y., Takahashi Y., Himeno S., Matsubara K. Nucleic Acids Res. 11:8197-8203(1983) [PubMed: 6324077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication." Boel E., Vuust J., Norris F., Norris K., Wind A., Rehfeld J.F., Marcker K.A. Proc. Natl. Acad. Sci. U.S.A. 80:2866-2869(1983) [PubMed: 6574456] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Structure of a human gastrin gene." Wiborg O., Berglund L., Boel E., Norris F., Norris K., Rehfeld J.F., Marcker K.A., Vuust J. Proc. Natl. Acad. Sci. U.S.A. 81:1067-1069(1984) [PubMed: 6322186] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Molecular cloning of human gastrin precursor cDNA." Kato K., Himeno S., Takahashi Y., Wakabayashi T., Tarui S., Matsubara K. Gene 26:53-57(1983) [PubMed: 6689486] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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].
[8]	"Identification of gastrin component I as gastrin-71. The largest possible bioactive progastrin product." Rehfeld J.F., Johnsen A.H. Eur. J. Biochem. 223:765-773(1994) [PubMed: 8055952] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-101, CHARACTERIZATION OF GASTRIN 71. Tissue: Gastric mucosa.
[9]	"Structures of human gastrins I and II." Bentley P.H., Kenner G.W., Sheppard R.C. Nature 209:583-585(1966) [PubMed: 5921183] [Abstract] Cited for: PROTEIN SEQUENCE OF 76-92.
[10]	"Purification and structural determination of urinary NH2-terminal big gastrin fragments." Higashimoto Y., Himeno S., Shinomura Y., Nagao K., Tamura T., Tarui S. Biochem. Biophys. Res. Commun. 160:1364-1370(1989) [PubMed: 2730647] [Abstract] Cited for: PROTEIN SEQUENCE OF 59-68.
[11]	"Aminoacid constitution of two gastrins isolated from Zollinger-Ellison tumour tissue." Gregory R.A., Tracy H.J., Agarwal K.L., Grossman M.I. Gut 10:603-608(1969) [PubMed: 5822140] [Abstract] Cited for: PROTEIN SEQUENCE OF 76-92.
[12]	"Post-poly(Glu) cleavage and degradation modified by O-sulfated tyrosine: a novel post-translational processing mechanism." Rehfeld J.F., Hansen C.P., Johnsen A.H. EMBO J. 14:389-396(1995) [PubMed: 7530658] [Abstract] Cited for: PROTEOLYTIC PROCESSING, MASS SPECTROMETRY, SULFATION AT TYR-87.
[13]	"Tyrosine O-sulfation promotes proteolytic processing of progastrin." Bundgaard J.R., Vuust J., Rehfeld J.F. EMBO J. 14:3073-3079(1995) [PubMed: 7621822] [Abstract] Cited for: SULFATION, MUTAGENESIS OF ALA-86 AND TYR-87, PROTEOLYTIC PROCESSING.
[14]	"Metabolism and acid secretory effect of sulfated and nonsulfated gastrin-6 in humans." Palnaes Hansen C., Stadil F., Rehfeld J.F. Am. J. Physiol. 279:G903-G909(2000) [PubMed: 11052986] [Abstract] Cited for: PROTEOLYTIC PROCESSING, SULFATION AT TYR-87.
+	Additional computationally mapped references.

Web resources

Wikipedia

Gastrin entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	X00183 Genomic DNA. Translation: CAA25005.1. X00183 Genomic DNA. Translation: CAA25006.1. X00183 Genomic DNA. Translation: CAA25007.1. V00511 mRNA. Translation: CAA23769.1. M15958 Genomic DNA. Translation: AAA52520.1. K01254 Genomic DNA. Translation: AAB59533.1. BC069724 mRNA. Translation: AAH69724.1. BC069762 mRNA. Translation: AAH69762.1.
IPI	IPI00001624.
PIR	GMHUB. A93997.
RefSeq	NP_000796.1.
UniGene	Hs.2681
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:403N.
PTM databases
PhosphoSite	P01350.
Genome annotation databases
Ensembl	ENSG00000184502. Homo sapiens. [Contig view]
GeneID	2520.
KEGG	hsa:2520.
UCSC	uc002hxl.1. human.
Organism-specific databases
GeneCards	GC17P037124.
H-InvDB	HIX0039214.
HGNC	HGNC:4164. GAST.
HPA	CAB000038.
MIM	137250. gene.
PharmGKB	PA28577.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P01350.
HOVERGEN	P01350.
OMA	P01350. TFSEASW.
Gene expression databases
ArrayExpress	P01350.
Bgee	P01350.
CleanEx	HS_GAST.
GermOnline	ENSG00000184502. Homo sapiens.
Family and domain databases
InterPro	IPR001651. Gastrin. IPR013152. Gastrin/cholecystokinin_CS. [Graphical view]
Pfam	PF00918. Gastrin. 1 hit. [Graphical view]
SMART	SM00029. GASTRIN. 1 hit. [Graphical view]
PROSITE	PS00259. GASTRIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	9923.
PMAP-CutDB	P01350.
SOURCE	Search...

Entry information

Entry name

GAST_HUMAN

Accession

Primary (citable) accession number: P01350
Secondary accession number(s): P78463, P78464

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	October 23, 1986
Last modified:	July 7, 2009
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)