Taxonomic distribution of proteins containing GASTRIN domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing GASTRIN domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Phylogeny of the cholecystokinin/gastrin family.

Johnsen AH
Front Neuroendocrinol. 1998; 19: 73-99

The neuroendocrine peptides cholecystokinin (CCK) and gastrin, originally identified in mammals, are characterized by a common amidated C-terminal tetrapeptide sequence, Trp-Met-Asp-Phe.NH2, which also constitutes the minimal structure necessary for biological activity of both. Hence, it has been proposed that CCK and gastrin have evolved from a common ancestor. Although the occurrence of CCK/gastrin-related peptides has been suggested in representatives of several invertebrate phyla, the evidence, mostly based on immunoreactivity, has not been substantiated by peptide identification. Instead, CCK/gastrin-specific antibodies might be cross-reacting with Asp-Phe-amides, like the lymnaDFamides, isolated from the freshwater snail Lymnaea stagnalis. Cionin, isolated from Ciona intestinalis, a representative of the protochordates that occupy a key position at the transition to vertebrates, so far represents the oldest genuine member of the CCK/gastrin family, dating the emergence of these peptides back to at least 500 million years ago. The CCK/gastrin family appears to be represented in the whole chordate phylum, and in addition to mammals, CCK and gastrin have recently been identified in a number of nonmammalian species representing the major vertebrate classes, including fishes, amphibians, reptiles, and birds. This now makes it possible to consider the CCK/gastrin phylogeny based on structural information. A duplication of the ancestral gene appears to have already occurred before or during the appearance of cartilaginous fish, giving rise to two peptides most likely homologous to mammalian CCK and gastrin. Indicative of a function of gastrin, the acid secretory system appears to have developed concomitantly in sharks. The segregation of CCK and gastrin early in vertebrate evolution resembles the situation in other peptide families, in accordance with a suggested widespread pattern of multiplication within vertebrate peptide and protein families around 400 million years ago. At the amphibian level, two separate peptide systems, resembling mammalian CCK and gastrin, have been characterized by identification of the mature bioactive peptides, cDNAs, gene structures, primary and secondary sites of gene expression, and their physiological actions. The overall gene structure, including exon/intron organization, is similar in all mammalian and nonmammalian CCK/gastrin genes. CCK is well conserved in all vertebrate species investigated, while the mammalian gastrins at first sight appear as a distinct group with little similarity to the nonmammalian gastrins outside the invariant C-terminal tetrapeptide and the C-terminal flanking peptide of the prohormone. However, evidence indicates that the transition from nonmammalian to mammalian gastrin may not be as dramatic as first anticipated. In conclusion, the CCK/gastrin family appears to be represented in most, if not all, chordates, to which group it may also be limited. The two major classes, CCK and gastrin, probably arose as distinct peptide systems early in vertebrate history. While CCK is well conserved in all vertebrates, a major structural change of gastrin accompanied the transition to mammals.

Active peptides in the skins of one hundred amphibian species from Australia and Papua New Guinea.

Erspamer V, Erspamer GF, Mazzanti G, Endean R
Comp Biochem Physiol C. 1984; 77: 99-108

Extracts prepared from the dried skins of approximately one hundred amphibian species from Australia and Papua New Guinea were subjected to biological screening in order to determine the nature and amounts of peptides active on smooth muscle preparations and systemic blood pressure present in these extracts. The most frequently and abundantly occurring peptides were those of the caerulein, bombesin and tachykinin peptide families represented, respectively, by caerulein; litorin, Glu(OMe)2-litorin and Glu(OEt)2-litorin; uperolein and Lys5-Thr6-physalaemin. Bradykinin-like peptides seem to have a rather diffuse distribution, in the species examined, but so far no peptide of this family has been isolated and sequenced. The only angiotensin-like peptide ever found in amphibian skin, crinia angiotensin II, has been isolated from skin extracts of a few species, belonging to the genera Crinia, Geocrinia, Ranidella and Litoria. The array of peptides occurring in amphibians from Australia and Papua New Guinea is destined to increase, because several apparently novel peptides have been identified in skin extracts by bioassay and radioimmunoassay.

Structure of a human gastrin gene.

Wiborg O, Berglund L, Boel E, Norris F, Norris K, Rehfeld JF, Marcker KA, Vuust J
Proc Natl Acad Sci U S A. 1984; 81: 1067-9

A gastrin gene was isolated from a genomic library of human DNA. The human gastrin gene is about 4100 base pairs long and contains two intervening sequences. Thus, a 3500-base-pair intervening sequence is located 5 base pairs proximal to the ATG initiator codon, while a 129-base-pair intervening sequence separates the region coding for the principal hormonal form of gastrin, the heptadecapeptide, from the region coding for the major amino-terminal portion of the gastrin precursor. The 5' flanking region of the gene contains the conserved sequences, T-A-T-A-A and G-A-C-T-C-A-T-A-T, in positions similar to those of other eukaryotic genes.