GCGR notes

Deep research

• just deep-research-falcon human GCGR --fallback perplexity-lite failed (providers unavailable,
  2026-10-21). Notes below are from cached publications, Reactome and UniProt P47871.

Function

• Class B1 GPCR for glucagon; couples mainly to Gs/adenylyl cyclase, also Ca2+ mobilization.
  "GCGR is a G protein-coupled receptor that activates the stimulatory α G protein (Gs) and increases cAMP
  production upon glucagon binding" PMID:19657311.
• Cloned human receptor "binds [125I]glucagon and transduces a signal leading to increases in the concentration
  of intracellular cyclic adenosine 3',5'-monophosphate" PMID:8144028.
• Structures: 7TM domain PMID:23863937, full-length PMID:28514451, antagonist MK-0893 extra-helical site
  PMID:27111510, cryo-EM Gs complex with dual agonist PMID:32371397.
• C-terminal tail phosphorylation needed for glucagon-induced endocytosis; tail region needed for surface
  expression PMID:9287038.
• Loss-of-function variants (P86S, V368M, biallelic defects) cause Mahvash disease: hyperglucagonemia,
  alpha-cell hyperplasia, hyperaminoacidemia [PMID:19657311, PMID:30294546, PMID:32677665].
• Gly40Ser association with NIDDM PMID:7773293 and essential hypertension PMID:8563746 are genetic
  association reports, not process participation.
• RAMP1/2/3 complexes from multiplexed screen PMID:39083597.

Localization

• Plasma membrane, extracellular N-terminal domain (aa 26-136) binds glucagon; rapidly internalized after
  ligand binding [UniProt; PMID:9287038]. Mutant and WT GCGR "both expressed on the cell surface"
  PMID:30294546. Conclusion: PM, ECD exposed; ligand-induced endocytosis.