GCGR is the class B1 G protein-coupled receptor for the pancreatic hormone glucagon. A seven-transmembrane protein of the plasma membrane, it captures glucagon with its extracellular N-terminal domain and transmembrane core, then couples mainly to Gs to activate adenylyl cyclase and raise cAMP, with additional Ca2+ mobilization. In liver this drives glycogenolysis and gluconeogenesis, making GCGR a central regulator of blood glucose and of the metabolic response to fasting; glucagon also controls hepatic amino-acid catabolism through it. Ligand binding promotes phosphorylation of the C-terminal tail and rapid receptor endocytosis. Biallelic loss-of-function variants cause Mahvash disease, with hyperglucagonemia, pancreatic alpha-cell hyperplasia, neuroendocrine tumors and hyperaminoacidemia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic transmembrane signaling receptor activity from InterPro. Reason: Correct but too general; the gene carries the specific glucagon receptor activity. Proposed replacements: glucagon receptor activity Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
| GO:0004930 G protein-coupled receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic GPCR activity from InterPro. Reason: Correct but too general; glucagon receptor activity is the supported descendant already annotated. Proposed replacements: glucagon receptor activity Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
| GO:0004967 glucagon receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: GCGR binds glucagon and signals through Gs to raise cAMP. Reason: Core molecular function, supported by cloning, mutagenesis, structural and patient-variant studies. Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding PMID:8144028 binds [125I]glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate |
| GO:0004967 glucagon receptor activity | IDA PMID:28514451 Structure of the full-length glucagon class B G-protein-coup... | ACCEPT | Summary: Full-length GCGR structure with glucagon-induced cAMP assays. Reason: Structure-function study measuring glucagon-induced cAMP for WT and mutant receptor. Supporting Evidence: PMID:28514451 we measured glucagon-induced cAMP accumulation for both WT GCGR and its mutants V130C/L210C, V130C and L210C |
| GO:0004967 glucagon receptor activity | IDA PMID:9287038 Role of the glucagon receptor COOH-terminal domain in glucag... | ACCEPT | Summary: Truncated receptors retain ligand binding and cAMP signaling. Reason: Direct evidence of glucagon-stimulated signaling by human GCGR in CHO cells. Supporting Evidence: PMID:9287038 the COOH-terminal 62 amino acids, which comprise the majority of the tail, are not required for ligand binding, cAMP accumulation, or Ca2+ mobilization |
| GO:0004967 glucagon receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: GCGR binds glucagon and signals through Gs to raise cAMP. Reason: Core molecular function, supported by cloning, mutagenesis, structural and patient-variant studies. Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding PMID:8144028 binds [125I]glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate |
| GO:0004967 glucagon receptor activity | TAS PMID:8144028 The human glucagon receptor encoding gene: structure, cDNA s... | ACCEPT | Summary: GCGR binds glucagon and signals through Gs to raise cAMP. Reason: Core molecular function, supported by cloning, mutagenesis, structural and patient-variant studies. Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding PMID:8144028 binds [125I]glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate |
| GO:0004967 glucagon receptor activity | TAS Reactome:R-HSA-163625 | ACCEPT | Summary: Reactome glucagon binding reaction. Reason: Consistent with core receptor activity. Supporting Evidence: Reactome:R-HSA-163625 The activity of this receptor is mediated by coupling to Gs and q |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-825631 | MODIFY | Summary: Reactome describes glucagon-bound GCGR catalysing GDP-GTP exchange on Gs. Reason: Receptor-catalysed nucleotide exchange on a heterotrimeric G protein is what G protein-coupled receptor activity describes; GO captures it with the receptor term rather than the generic GEF term, so the specific glucagon receptor activity is the better annotation. Proposed replacements: glucagon receptor activity Supporting Evidence: Reactome:R-HSA-825631 releases a molecule of bound GDP, binds a molecule of GTP, and dissociates to yield a G(s)alpha:GTP complex and a G-beta:G-gamma dimer |
| GO:0005515 protein binding | IPI PMID:32371397 Cryo-electron microscopy structure of the glucagon receptor ... | MODIFY | Summary: Cryo-EM GCGR-Gs complex bound to glucagon/dual agonist. Reason: The interaction with the glucagon peptide is ligand binding; the informative term is glucagon family peptide binding rather than bare protein binding. Proposed replacements: glucagon family peptide binding Supporting Evidence: PMID:32371397 GCGR-Gs complex bound to GCG. |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | REMOVE | Summary: Generic protein binding from interaction screens. Reason: Bare protein binding is uninformative under the protein-binding policy; removal does not dispute the reported interaction. Supporting Evidence: PMID:39083597 Receptor activity-modifying proteins (RAMPs) form complexes with G protein-coupled receptors (GPCRs) |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | REMOVE | Summary: Generic protein binding from interaction screens. Reason: Bare protein binding is uninformative under the protein-binding policy; removal does not dispute the reported interaction. Supporting Evidence: PMID:39083597 Receptor activity-modifying proteins (RAMPs) form complexes with G protein-coupled receptors (GPCRs) |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | REMOVE | Summary: Generic protein binding from interaction screens. Reason: Bare protein binding is uninformative under the protein-binding policy; removal does not dispute the reported interaction. Supporting Evidence: PMID:39083597 Receptor activity-modifying proteins (RAMPs) form complexes with G protein-coupled receptors (GPCRs) |
| GO:0005886 plasma membrane | EXP PMID:19657311 Homozygous P86S mutation of the human glucagon receptor is a... | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | EXP PMID:23863937 Structure of the human glucagon class B G-protein-coupled re... | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | EXP PMID:27111510 Extra-helical binding site of a glucagon receptor antagonist... | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | EXP PMID:30294546 The first pediatric case of glucagon receptor defect due to ... | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | EXP PMID:32677665 Characterization of a naturally occurring mutation V368M in ... | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane inherited from the GPCR family node. Reason: Inherited location matches direct evidence. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. |
| GO:0005886 plasma membrane | IDA PMID:9287038 Role of the glucagon receptor COOH-terminal domain in glucag... | ACCEPT | Summary: Immunofluorescence of cell-surface receptor in CHO cells. Reason: Direct surface-expression assay. Supporting Evidence: PMID:9287038 a region of the COOH-terminal tail that is required for proper cell surface expression |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | IMP PMID:28514451 Structure of the full-length glucagon class B G-protein-coup... | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS PMID:8144028 The human glucagon receptor encoding gene: structure, cDNA s... | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-163625 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-379044 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-379048 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-744886 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-744887 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749448 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749452 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-825631 | ACCEPT | Summary: GCGR is a seven-transmembrane receptor at the plasma membrane. Reason: Supported by topology, cell-surface expression of wild-type and variant receptors and ligand-induced internalization; PM is the site of glucagon reception. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. file:human/GCGR/GCGR-uniprot.txt Is rapidly internalized after ligand-binding. |
| GO:0006091 generation of precursor metabolites and energy | TAS PMID:7773293 A missense mutation in the glucagon receptor gene is associa... | MARK AS OVER ANNOTATED | Summary: Generation of precursor metabolites and energy, from a diabetes association study. Reason: GCGR signaling regulates hepatic glucose output, but the receptor does not participate in energy-generating metabolism itself; the cited paper reports a genetic association and reduced binding affinity of a variant. Glucose homeostasis captures the relevant physiology. Supporting Evidence: PMID:7773293 this mutation results in a receptor which binds glucagon with a three-fold lower affinity compared to the wild type receptor |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Generic cell-surface receptor signaling. Reason: Correct but too general; the specific pathway is adenylate cyclase-activating GPCR signaling. Proposed replacements: adenylate cyclase-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Generic GPCR signaling. Reason: Correct but too general; the gene carries the specific Gs/adenylate cyclase-activating pathway. Proposed replacements: adenylate cyclase-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
| GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | MODIFY | Summary: Adenylate cyclase-modulating GPCR signaling. Reason: Correct but less specific than supported; GCGR couples to Gs and stimulates cAMP production, so the activating child term applies. Proposed replacements: adenylate cyclase-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding PMID:8144028 binds [125I]glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate |
| GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway | IMP PMID:9287038 Role of the glucagon receptor COOH-terminal domain in glucag... | MODIFY | Summary: Adenylate cyclase-modulating GPCR signaling. Reason: Correct but less specific than supported; GCGR couples to Gs and stimulates cAMP production, so the activating child term applies. Proposed replacements: adenylate cyclase-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding PMID:8144028 binds [125I]glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate |
| GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway | TAS PMID:8144028 The human glucagon receptor encoding gene: structure, cDNA s... | MODIFY | Summary: Adenylate cyclase-modulating GPCR signaling. Reason: Correct but less specific than supported; GCGR couples to Gs and stimulates cAMP production, so the activating child term applies. Proposed replacements: adenylate cyclase-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding PMID:8144028 binds [125I]glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate |
| GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Glucagon-stimulated Gs-adenylyl cyclase signaling. Reason: Core signaling pathway of GCGR. Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
| GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway | IDA PMID:28514451 Structure of the full-length glucagon class B G-protein-coup... | ACCEPT | Summary: Glucagon-stimulated Gs-adenylyl cyclase signaling. Reason: Core signaling pathway of GCGR. Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
| GO:0007584 response to nutrient | TAS PMID:7773293 A missense mutation in the glucagon receptor gene is associa... | MARK AS OVER ANNOTATED | Summary: Response to nutrient from a diabetes association study. Reason: The cited paper is a genetic association with NIDDM; it does not show GCGR participating in a response to a nutrient. The relevant physiology is response to glucagon and glucose homeostasis. Supporting Evidence: PMID:7773293 We report the association of a single heterozygous Gly to Ser missense mutation in the glucagon receptor gene with late-onset NIDDM. |
| GO:0008217 regulation of blood pressure | TAS PMID:8563746 Glucagon receptor gene mutation in essential hypertension. | MARK AS OVER ANNOTATED | Summary: Regulation of blood pressure from a hypertension association letter. Reason: A single genetic association letter (no abstract, cached title only) does not establish that GCGR acts in blood-pressure regulation; this is peripheral at best. |
| GO:0009267 cellular response to starvation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cellular response to starvation transferred from mouse Gcgr. Reason: Glucagon signaling mediates fasting responses; true but systemic/physiological rather than the receptor's core function. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Plays an important role in mediating the responses to fasting. |
| GO:0010628 positive regulation of gene expression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of gene expression transferred from mouse Gcgr. Reason: Glucagon-cAMP signaling induces gluconeogenic gene expression; downstream and generic. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Generic membrane. Reason: Correct but too general; GCGR is a plasma membrane receptor, a location already annotated. Proposed replacements: plasma membrane Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. |
| GO:0016020 membrane | TAS PMID:8144028 The human glucagon receptor encoding gene: structure, cDNA s... | MODIFY | Summary: Generic membrane. Reason: Correct but too general; GCGR is a plasma membrane receptor, a location already annotated. Proposed replacements: plasma membrane Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Multi-pass membrane protein PMID:30294546 Phe320del GCGR are both expressed on the cell surface. |
| GO:0042593 glucose homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: Glucose homeostasis. Reason: GCGR is the receptor through which glucagon raises hepatic glucose output; loss-of-function variants and knock-in mice lower fasting glucose. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis PMID:32677665 These GcgrV369M+/+ mice displayed lower fasting blood glucose levels with improved glucose tolerance compared with wild-type controls. |
| GO:0042593 glucose homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: Glucose homeostasis. Reason: GCGR is the receptor through which glucagon raises hepatic glucose output; loss-of-function variants and knock-in mice lower fasting glucose. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis PMID:32677665 These GcgrV369M+/+ mice displayed lower fasting blood glucose levels with improved glucose tolerance compared with wild-type controls. |
| GO:0042594 response to starvation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to starvation from mouse Gcgr. Reason: GCGR mediates hepatic responses to fasting; physiological outcome of glucagon signaling. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Plays an important role in mediating the responses to fasting. |
| GO:0042594 response to starvation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Response to starvation from mouse Gcgr. Reason: GCGR mediates hepatic responses to fasting; physiological outcome of glucagon signaling. Supporting Evidence: file:human/GCGR/GCGR-uniprot.txt Plays an important role in mediating the responses to fasting. |
| GO:0071377 cellular response to glucagon stimulus | IDA PMID:9287038 Role of the glucagon receptor COOH-terminal domain in glucag... | ACCEPT | Summary: Glucagon-stimulated cAMP, Ca2+ and endocytosis responses of GCGR-expressing CHO cells. Reason: Direct experimental evidence. Supporting Evidence: PMID:9287038 phosphorylation of the COOH-terminal tail is crucial for glucagon-stimulated receptor endocytosis |
| GO:0071377 cellular response to glucagon stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: Cellular response to glucagon stimulus. Reason: GCGR is the receptor initiating the cellular response to glucagon. Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
| GO:0071377 cellular response to glucagon stimulus | TAS Reactome:R-HSA-163359 | ACCEPT | Summary: Cellular response to glucagon stimulus. Reason: GCGR is the receptor initiating the cellular response to glucagon. Supporting Evidence: PMID:19657311 GCGR is a G protein-coupled receptor that activates the stimulatory Ξ± G protein (Gs) and increases cAMP production upon glucagon binding |
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Download this section (compressed HTML)Q: How much of GCGR's control of hepatic amino-acid catabolism depends on Gs-cAMP versus Gq/Ca2+ signaling, and do RAMP complexes bias this?
Q: Where does GCGR signal after ligand-induced endocytosis, and does endosomal signaling contribute to sustained gluconeogenic gene expression?
Experiment: Compare surface-retained versus internalization-defective (tail phosphorylation mutant) GCGR in primary human hepatocytes for cAMP kinetics and gluconeogenic gene induction.
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