UniProt-Q92847 — Growth Hormone Secretagogue Receptor (GHSR / Ghrelin Receptor)

[DRAFT — authored 2026-04-19. UniProt entry web-verified via REST flat-file 2026-04-19.]

Entry

UniProt accession: Q92847 (entry name GHSR_HUMAN)
Alt accessions: Q14D12, Q6ISR8, Q92848, Q96RJ7
Protein name: Growth hormone secretagogue receptor type 1 (GHS-R; GH-releasing peptide receptor; ghrelin receptor)
Gene: GHSR
Organism: Homo sapiens (Human)
Sequence length: 366 amino acids
Molecular weight: 41,329 Da
Receptor class: G-protein-coupled receptor (class A)
Subtype: GHS-R1a is the functional full-length isoform; GHS-R1b is a truncated non-signaling variant

Function Summary

GHSR binds ghrelin (the orexigenic peptide hormone produced by gastric oxyntic cells) and synthetic GH secretagogues (GHRPs and non-peptide mimetics). Activation drives:

Pituitary somatotrophs: stimulates pulsatile growth-hormone (GH) secretion via Gq/IP3/Ca²⁺ signaling → increased intracellular calcium → GH vesicle release
Hypothalamus: stimulates appetite and food intake via NPY/AgRP pathways in the arcuate nucleus
Pituitary and hypothalamus: dominant tissue expression per UniProt

Interacts with the heterotrimeric G-protein complex (GNB1 / GNG2 subunits, among others). Constitutively active (~50% of maximal activity in absence of ligand) — a pharmacologically distinctive feature that affects inverse-agonist design.

Relevance to Module 5 Peptides

GH secretagogues acting on GHSR:

Ipamorelin: selective GHS-R1a agonist, pentapeptide; minimal cortisol/prolactin cross-activation (advantage over older GHRPs)
Hexarelin: GHS-R1a agonist, hexapeptide
GHRP-2 / GHRP-6: older GHS-R1a agonists with higher prolactin/cortisol cross-activation
MK-677 (ibutamoren): orally-bioavailable non-peptide GHS-R1a agonist
Native ghrelin: endogenous ligand

NOT GHSR agonists (for contrast): Tesamorelin, Sermorelin, CJC-1295 NO DAC — these act on the GHRH receptor, not GHSR. The synergistic GH pulse from CJC + Ipamorelin stacking reflects complementary pathways: GHRHR (Gs/cAMP) + GHSR (Gq/IP3/Ca²⁺) → amplified somatotroph output.

Cross-References to Vault Research Notes

UniProt-P01241 – GH1 Human Growth Hormone — downstream GH hormone
Peptide profiles using GHSR mechanism: Ipamorelin (primary), Hexarelin, GHRP-2, GHRP-6, MK-677

Orchestrator Notes

Primary mechanism reference for Ipamorelin profile; secondary reference for CJC-1295/Ipamorelin stack discussion (complementary pathway contrast).
Verified 2026-04-19 via UniProt REST flat-file API (https://rest.uniprot.org/uniprotkb/Q92847.txt).