GPR39
Description
The GPR39 (G protein-coupled receptor 39) is a protein-coding gene located on chromosome 2.
G-protein coupled receptor 39 is a protein that in humans is encoded by the GPR39 gene.
GPR39 is a zinc-sensing receptor that detects changes in extracellular zinc levels, relays zinc signals, and participates in regulating various physiological processes, including glucose homeostasis, gastrointestinal motility, hormone secretion, and cell death. Activation by zinc in keratinocytes increases intracellular calcium levels and activates the ERK/MAPK and PI3K/AKT signaling pathways, leading to epithelial repair. GPR39 plays a critical role in normal wound healing by inducing the production of cytokines like IL6 through the PKC/MAPK/CEBPB pathway. It also regulates adipose tissue metabolism, especially lipolysis, by influencing the activity of lipases such as hormone-sensitive lipase and adipose triglyceride lipase. GPR39 inhibits cell death and protects against oxidative, endoplasmic reticulum, and mitochondrial stress by stimulating the secretion of the protective PEDF and potentially other protective transcripts through a GNA13/RHOA/SRE-dependent mechanism. GPR39 forms dynamic heteroreceptor complexes with HTR1A and GALR1 depending on cell type or specific physiological states, leading to signaling diversity. The HTR1A-GPR39 complex shows increased signaling through the serum response element (SRE) and NF-kappa-B pathways, while GALR1 acts as an antagonist, blocking the SRE pathway.
GPR39 is also known as ZnR.
Associated Diseases
- hyperinsulinism due to INSR deficiency
- exercise-induced hyperinsulinism
- hyperinsulinism due to glucokinase deficiency
- hyperinsulinemic hypoglycemia, familial, 2
- multicystic dysplastic kidney
- nephronophthisis
- infundibulopelvic stenosis-multicystic kidney syndrome
- polycystic liver disease 4 with or without kidney cysts
- polycystic liver disease 3 with or without kidney cysts
- hyperinsulinemic hypoglycemia, familial, 1
