Preproghrelin peptide (IPR005441)

Short name: Preproghrelin

Overlapping homologous superfamilies


Family relationships



Growth hormone (GH) is a pituitary hormone involved in cell and overall body growth, carbohydrate-protein-lipid metabolism and osmotic homeostasis. Control of GH release was initially ascribed to 2 pathways: stimulation by hypothalamic GH-releasing hormone (GHRH) and inhibition by somatostatin. More recently, synthetic compounds, termed GH secretagogues (GHS), were shown to stimulate GH release strongly. This effect is elicited by an orphan G protein-coupled receptor (GPCR), subsequently named the GHS receptor (GHS-R). The endogenous ligand for this receptor was purified from rat and human stomach and named ghrelin [PMID: 11306336].

The purified cDNA for ghrelin encodes a 117 amino acid prepropeptide. The first 23 amino acid residues form a signal peptide that is cleaved to leave proghrelin. Residues 24-51 are cleaved to yield active ghrelin, discarding the C-terminal fragment [PMID: 10604470]. The 28-residue ghrelin peptide that is left is biologically inactive. Esterification with n-octanoic acid at Ser3 is required for biological activity. Ghrelin mRNA is expressed mainly in the stomach in a distinct endocrine cell type in the submucosal layer, known as X/A-like cells. The active peptide is secreted into the bloodstream rather than the stomach. Ghrelin responsive cells are found in abundance in a limited area of the hypothalamic arcuate nucleus (ARC), a region involved in control of food intake. As well as releasing GH indirectly via its action on the ARC region of the hypothalamus, ghrelin also appears to be able to stimulate GH release via direct action on the pituitary [PMID: 11483998].

A further variant of the ghrelin peptide exists in rat stomach, des-Gln14- ghrelin. This is produced by alternative splicing and does not require the esterification by n-octanoic acid for biological activity. However, its presence in only small quantities in the stomach suggests ghrelin is the major active form. The ghrelin active peptide and the GHS receptor share sequence similarity with motilin and the motilin receptor, respectively, suggesting an evolutionary relationship.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0016608 growth hormone-releasing hormone activity

Cellular Component

GO:0005576 extracellular region

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.