UniProt-P43220 — Glucagon-like Peptide 1 Receptor (GLP1R)

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

Entry

UniProt accession: P43220 (entry name GLP1R_HUMAN)
Alt accessions: Q2M229, Q99669
Protein name: Glucagon-like peptide 1 receptor (GLP-1 receptor, GLP-1-R, GLP-1R)
Gene: GLP1R
Organism: Homo sapiens (Human)
Sequence length: 463 amino acids
Molecular weight: 53,026 Da
Receptor class: G-protein-coupled receptor, class B (secretin-family / peptide hormone receptor)

Function Summary

GLP1R is the receptor for glucagon-like peptide 1 (GLP-1, released from intestinal L-cells after nutrient ingestion). Ligand binding triggers Gs-protein coupling, adenylyl cyclase activation, and intracellular cAMP accumulation. Key downstream effects include:

Pancreatic β-cell: glucose-dependent insulin secretion potentiation
Pancreatic α-cell: glucagon-secretion suppression (glucose-dependent)
Stomach/GI: delayed gastric emptying
CNS (hypothalamus / hindbrain / area postrema): appetite reduction, satiety signaling, nausea (therapeutic + side-effect)
Cardiovascular / renal: emerging pleiotropic effects via endothelial, inflammatory, and direct cardiomyocyte signaling

Forms homodimers and heterodimers with GIPR (P48546). Allosteric modulators characterized: NNC0640, PF-06372222, MK-0893.

Relevance to Module 5 Peptides

Semaglutide: Primary target; 94% sequence homology to native GLP-1 at the receptor-binding peptide
Liraglutide: Primary target
Tirzepatide: GLP-1R arm of dual GIP/GLP-1 agonism
Retatrutide: GLP-1R arm of triple GIP/GLP-1/glucagon agonism
CagriSema: GLP-1R component via semaglutide
Orforglipron: Small-molecule non-peptide GLP-1R agonist

Cross-References to Vault Research Notes

PMID-33320179 – Semaglutide Mechanism and Pharmacology — GLP-1R pharmacology review
PMID-33567185 – Once-Weekly Semaglutide in Adults with Overweight or Obesity — STEP 1 (GLP-1R activation at 2.4 mg weekly)
PMID-37952131 – SELECT Cardiovascular Outcomes Trial — GLP-1R-mediated CV benefit
PMID-40162642 – SOUL Oral Semaglutide CV Outcomes — oral GLP-1R CV benefit
UniProt-P48546 – GIPR GIP Receptor — heterodimer partner; tirzepatide/retatrutide co-target
UniProt-P47871 – GCGR Glucagon Receptor — retatrutide co-target

Orchestrator Notes

Primary mechanism reference for Semaglutide/Tirzepatide/Retatrutide profile Mechanism sections.
Verified 2026-04-19 via UniProt REST flat-file API (https://rest.uniprot.org/uniprotkb/P43220.txt).