GKN3P Human

Gastrokines are a family of proteins secreted by the mucus cells of the stomach. They play a crucial role in maintaining the integrity of the gastric mucosa and have been implicated in various gastric diseases, including gastric cancer. The gastrokine family includes several members, with Gastrokine 1 (GKN1) and Gastrokine 2 (GKN2) being the most well-studied. Recently, a third member, Gastrokine 3 (GKN3), has been identified and characterized.

Gastrokine 3 (GKN3) was identified through studies of molecular structure, evolutionary conservation, and tissue expression. It encodes a secreted protein of approximately 19 kilodaltons that is co-expressed with trefoil factor 2 (TFF2) in the distal stomach . GKN3 is distinct from its counterparts, GKN1 and GKN2, in terms of its molecular structure and functional properties.

In humans, GKN3 has undergone significant evolutionary changes. A widespread homozygosity for a premature stop codon polymorphism, W59X, has likely rendered GKN3 non-functional in many individuals . Population genetic analysis has revealed that an ancestral GKN3 read-through allele predominates in Africans, indicating the rapid expansion of the W59X allele among non-Africans during recent evolution .

GKN3 is strongly up-regulated in conditions of gastric atrophy, a pre-cancerous state often associated with Helicobacter pylori infection . It marks a non-proliferative, GS-II positive lineage with features of spasmolytic polypeptide-expressing metaplasia (SPEM). Overexpression of GKN3 has been shown to inhibit proliferation in gastric epithelial cell lines, independently of incubation with recombinant human TFF2 or apoptosis .

The loss of GKN3 expression has been linked to gastric cancer, suggesting a potential role in tumor suppression . The spread of the human GKN3 stop allele W59X might have been selected for among non-Africans due to its effects on pre-neoplastic outcomes in the stomach . Understanding the functional role of GKN3 in gastric pathology could provide new insights into the mechanisms underlying gastric diseases and potential therapeutic targets.