GHSR encodes the ghrelin receptor (growth hormone secretagogue receptor type 1a), a 366-residue class A seven-transmembrane G protein-coupled receptor of the plasma membrane. It binds the stomach hormone ghrelin, whose Ser3 octanoyl group is required for binding, as well as synthetic growth hormone secretagogues. Ligand binding activates mainly Gq/11-phospholipase C-IP3/Ca2+ signaling, with additional Gi/o, G12/13 and beta-arrestin coupling. The receptor has high ligand-independent (constitutive) activity, which LEAP2 suppresses as an inverse agonist. In the anterior pituitary and hypothalamus (arcuate GHRH and AgRP/NPY neurons) GHSR signaling stimulates pulsatile growth hormone release and appetite. Human variants that remove constitutive activity cause short stature. In other neurons GHSR can also act without ghrelin, forming heteromers with dopamine DRD1 and DRD2 receptors and redirecting their signaling. This supports hippocampal synaptic plasticity and spinal control of defecation. Peripheral effects include anti-inflammatory actions on immune cells and gut prokinetic effects. Splicing also produces a truncated five-transmembrane isoform (GHSR1b) that does not bind ghrelin and dampens GHSR1a surface expression and signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001616 growth hormone secretagogue receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Ghrelin (growth hormone secretagogue) receptor activity is the defining molecular function of GHSR1a. Reason: GHSR was cloned as the G protein-coupled target of synthetic growth hormone secretagogues (PMID:8688086); acyl-ghrelin was then purified as its specific endogenous ligand (PMID:10604470) and confirmed as a full agonist (PMID:11322507). Cryo-EM structures of the human receptor bound to octanoylated ghrelin and G protein show the ligand in the orthosteric pocket (PMID:35027551), and Ghsr-null mice lose ghrelin-evoked GH release and feeding (PMID:15070777). The IBA comes from PAINT node PTN002797666, a GHSR-specific Euteleostomi clade seeded by human, rat and pig receptors; Q92847 is in PANTHER subfamily SF7 inside that clade. The target appearing in its own WITH/FROM reflects its experimental grounding. Supporting Evidence: PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:11322507 We also confirmed that the endogenous ligand ghrelin is a full agonist of the GHS-R. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:35027551 an acylated modification, typically an octanoyl group, of the hydroxyl group of the Ser+3 residue is required for the biological action of ghrelin as the unacylated form of ghrelin does not bind or activate the ghrelin receptor at all file:human/GHSR/GHSR-uniprot.txt PTHR24243:SF7; GROWTH HORMONE SECRETAGOGUE RECEPTOR TYPE 1 |
| GO:0001616 growth hormone secretagogue receptor activity | IDA PMID:11322507 Growth hormone secretagogue receptor family members and liga... | ACCEPT | Summary: Ghrelin (growth hormone secretagogue) receptor activity is the defining molecular function of GHSR1a. Reason: GHSR was cloned as the G protein-coupled target of synthetic growth hormone secretagogues (PMID:8688086); acyl-ghrelin was then purified as its specific endogenous ligand (PMID:10604470) and confirmed as a full agonist (PMID:11322507). Cryo-EM structures of the human receptor bound to octanoylated ghrelin and G protein show the ligand in the orthosteric pocket (PMID:35027551), and Ghsr-null mice lose ghrelin-evoked GH release and feeding (PMID:15070777). The IBA comes from PAINT node PTN002797666, a GHSR-specific Euteleostomi clade seeded by human, rat and pig receptors; Q92847 is in PANTHER subfamily SF7 inside that clade. The target appearing in its own WITH/FROM reflects its experimental grounding. Supporting Evidence: PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:11322507 We also confirmed that the endogenous ligand ghrelin is a full agonist of the GHS-R. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:35027551 an acylated modification, typically an octanoyl group, of the hydroxyl group of the Ser+3 residue is required for the biological action of ghrelin as the unacylated form of ghrelin does not bind or activate the ghrelin receptor at all file:human/GHSR/GHSR-uniprot.txt PTHR24243:SF7; GROWTH HORMONE SECRETAGOGUE RECEPTOR TYPE 1 |
| GO:0001616 growth hormone secretagogue receptor activity | IDA PMID:8688086 A receptor in pituitary and hypothalamus that functions in g... | ACCEPT | Summary: Ghrelin (growth hormone secretagogue) receptor activity is the defining molecular function of GHSR1a. Reason: GHSR was cloned as the G protein-coupled target of synthetic growth hormone secretagogues (PMID:8688086); acyl-ghrelin was then purified as its specific endogenous ligand (PMID:10604470) and confirmed as a full agonist (PMID:11322507). Cryo-EM structures of the human receptor bound to octanoylated ghrelin and G protein show the ligand in the orthosteric pocket (PMID:35027551), and Ghsr-null mice lose ghrelin-evoked GH release and feeding (PMID:15070777). The IBA comes from PAINT node PTN002797666, a GHSR-specific Euteleostomi clade seeded by human, rat and pig receptors; Q92847 is in PANTHER subfamily SF7 inside that clade. The target appearing in its own WITH/FROM reflects its experimental grounding. Supporting Evidence: PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:11322507 We also confirmed that the endogenous ligand ghrelin is a full agonist of the GHS-R. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:35027551 an acylated modification, typically an octanoyl group, of the hydroxyl group of the Ser+3 residue is required for the biological action of ghrelin as the unacylated form of ghrelin does not bind or activate the ghrelin receptor at all file:human/GHSR/GHSR-uniprot.txt PTHR24243:SF7; GROWTH HORMONE SECRETAGOGUE RECEPTOR TYPE 1 |
| GO:0001616 growth hormone secretagogue receptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ghrelin (growth hormone secretagogue) receptor activity is the defining molecular function of GHSR1a. Reason: GHSR was cloned as the G protein-coupled target of synthetic growth hormone secretagogues (PMID:8688086); acyl-ghrelin was then purified as its specific endogenous ligand (PMID:10604470) and confirmed as a full agonist (PMID:11322507). Cryo-EM structures of the human receptor bound to octanoylated ghrelin and G protein show the ligand in the orthosteric pocket (PMID:35027551), and Ghsr-null mice lose ghrelin-evoked GH release and feeding (PMID:15070777). The IBA comes from PAINT node PTN002797666, a GHSR-specific Euteleostomi clade seeded by human, rat and pig receptors; Q92847 is in PANTHER subfamily SF7 inside that clade. The target appearing in its own WITH/FROM reflects its experimental grounding. Supporting Evidence: PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:11322507 We also confirmed that the endogenous ligand ghrelin is a full agonist of the GHS-R. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:35027551 an acylated modification, typically an octanoyl group, of the hydroxyl group of the Ser+3 residue is required for the biological action of ghrelin as the unacylated form of ghrelin does not bind or activate the ghrelin receptor at all file:human/GHSR/GHSR-uniprot.txt PTHR24243:SF7; GROWTH HORMONE SECRETAGOGUE RECEPTOR TYPE 1 |
| GO:0004930 G protein-coupled receptor activity | IDA PMID:8688086 A receptor in pituitary and hypothalamus that functions in g... | MODIFY | Summary: GHSR is a class A G protein-coupled receptor, but the generic term is subsumed by the ghrelin receptor term. Reason: GO:0001616 growth hormone secretagogue receptor activity is an is_a descendant of GO:0004930 (OLS, 2026-10-20) and is already carried by this gene with experimental and IBA support. The generic term is true but less specific than the evidence supports. Proposed replacements: growth hormone secretagogue receptor activity Supporting Evidence: PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0004930 G protein-coupled receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: GHSR is a class A G protein-coupled receptor, but the generic term is subsumed by the ghrelin receptor term. Reason: GO:0001616 growth hormone secretagogue receptor activity is an is_a descendant of GO:0004930 (OLS, 2026-10-20) and is already carried by this gene with experimental and IBA support. The generic term is true but less specific than the evidence supports. Proposed replacements: growth hormone secretagogue receptor activity Supporting Evidence: PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: GHSR acts at the plasma membrane, where extracellular ghrelin binds and intracellular loops engage heterotrimeric G proteins. Reason: UniProt records cell membrane localization from the human structural studies (PMID:35027551, PMID:39833471). The seven-transmembrane architecture and G protein complex structures place the functional receptor at the cell surface. The IBA (PTN002797649) is a broad GPCR-clade inference consistent with this. Reactome's Gq-activating GPCR reactions place the liganded receptor at the plasma membrane. Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0005886 plasma membrane | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | ACCEPT | Summary: GHSR acts at the plasma membrane, where extracellular ghrelin binds and intracellular loops engage heterotrimeric G proteins. Reason: UniProt records cell membrane localization from the human structural studies (PMID:35027551, PMID:39833471). The seven-transmembrane architecture and G protein complex structures place the functional receptor at the cell surface. The IBA (PTN002797649) is a broad GPCR-clade inference consistent with this. Reactome's Gq-activating GPCR reactions place the liganded receptor at the plasma membrane. Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0005886 plasma membrane | IDA PMID:35027551 Molecular mechanism of agonism and inverse agonism in ghreli... | ACCEPT | Summary: GHSR acts at the plasma membrane, where extracellular ghrelin binds and intracellular loops engage heterotrimeric G proteins. Reason: UniProt records cell membrane localization from the human structural studies (PMID:35027551, PMID:39833471). The seven-transmembrane architecture and G protein complex structures place the functional receptor at the cell surface. The IBA (PTN002797649) is a broad GPCR-clade inference consistent with this. Reactome's Gq-activating GPCR reactions place the liganded receptor at the plasma membrane. Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: GHSR acts at the plasma membrane, where extracellular ghrelin binds and intracellular loops engage heterotrimeric G proteins. Reason: UniProt records cell membrane localization from the human structural studies (PMID:35027551, PMID:39833471). The seven-transmembrane architecture and G protein complex structures place the functional receptor at the cell surface. The IBA (PTN002797649) is a broad GPCR-clade inference consistent with this. Reactome's Gq-activating GPCR reactions place the liganded receptor at the plasma membrane. Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-379048 | ACCEPT | Summary: GHSR acts at the plasma membrane, where extracellular ghrelin binds and intracellular loops engage heterotrimeric G proteins. Reason: UniProt records cell membrane localization from the human structural studies (PMID:35027551, PMID:39833471). The seven-transmembrane architecture and G protein complex structures place the functional receptor at the cell surface. The IBA (PTN002797649) is a broad GPCR-clade inference consistent with this. Reactome's Gq-activating GPCR reactions place the liganded receptor at the plasma membrane. Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749448 | ACCEPT | Summary: GHSR acts at the plasma membrane, where extracellular ghrelin binds and intracellular loops engage heterotrimeric G proteins. Reason: UniProt records cell membrane localization from the human structural studies (PMID:35027551, PMID:39833471). The seven-transmembrane architecture and G protein complex structures place the functional receptor at the cell surface. The IBA (PTN002797649) is a broad GPCR-clade inference consistent with this. Reactome's Gq-activating GPCR reactions place the liganded receptor at the plasma membrane. Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749452 | ACCEPT | Summary: GHSR acts at the plasma membrane, where extracellular ghrelin binds and intracellular loops engage heterotrimeric G proteins. Reason: UniProt records cell membrane localization from the human structural studies (PMID:35027551, PMID:39833471). The seven-transmembrane architecture and G protein complex structures place the functional receptor at the cell surface. The IBA (PTN002797649) is a broad GPCR-clade inference consistent with this. Reactome's Gq-activating GPCR reactions place the liganded receptor at the plasma membrane. Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0007154 cell communication | IEA GO_REF:0000117 | TOO GENERAL | Summary: Cell communication from an ARBA rule. Reason: GO:0007154 is an ancestor of GO:0007186 G protein-coupled receptor signaling pathway, which is accepted. Supporting Evidence: PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0007186 G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: GHSR transduces ghrelin binding into heterotrimeric G protein signaling. Reason: Ghrelin-bound receptor-G protein complexes (PMID:35027551) and the cloning pharmacology (PMID:8688086) establish GPCR signaling. GHSR couples to Gq/11 and also to Gi/o and G12/13, so this broad term is not redundant with the Gq-specific GO:0007200. The IBA (PTN002797649) is a sound class A GPCR clade inference. Supporting Evidence: PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:25605885 This complex is specific of Gq and is not observed with Gi. file:human/GHSR/GHSR-deep-research-falcon.md Gi/o-dependent signaling is implicated in pancreatic suppression of glucose-stimulated insulin secretion. |
| GO:0007186 G protein-coupled receptor signaling pathway | IDA PMID:8688086 A receptor in pituitary and hypothalamus that functions in g... | ACCEPT | Summary: GHSR transduces ghrelin binding into heterotrimeric G protein signaling. Reason: Ghrelin-bound receptor-G protein complexes (PMID:35027551) and the cloning pharmacology (PMID:8688086) establish GPCR signaling. GHSR couples to Gq/11 and also to Gi/o and G12/13, so this broad term is not redundant with the Gq-specific GO:0007200. The IBA (PTN002797649) is a sound class A GPCR clade inference. Supporting Evidence: PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:25605885 This complex is specific of Gq and is not observed with Gi. file:human/GHSR/GHSR-deep-research-falcon.md Gi/o-dependent signaling is implicated in pancreatic suppression of glucose-stimulated insulin secretion. |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: GHSR transduces ghrelin binding into heterotrimeric G protein signaling. Reason: Ghrelin-bound receptor-G protein complexes (PMID:35027551) and the cloning pharmacology (PMID:8688086) establish GPCR signaling. GHSR couples to Gq/11 and also to Gi/o and G12/13, so this broad term is not redundant with the Gq-specific GO:0007200. The IBA (PTN002797649) is a sound class A GPCR clade inference. Supporting Evidence: PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:25605885 This complex is specific of Gq and is not observed with Gi. file:human/GHSR/GHSR-deep-research-falcon.md Gi/o-dependent signaling is implicated in pancreatic suppression of glucose-stimulated insulin secretion. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Canonical GHSR signaling goes through Gq/11, phospholipase C-beta, IP3/DAG and Ca2+. Reason: Purified ghrelin receptor forms Gq-specific preassembled and active complexes (PMID:25605885), and human Gq-coupled structures confirm the pathway. In neurons the same Gq-PLC output is produced when GHSR acts with DRD1 (PMID:26590421). The rat projection and mouse ISS rows are sound orthology transfers within PTHR24243:SF7. Supporting Evidence: PMID:25605885 This complex is specific of Gq and is not observed with Gi. PMID:26590421 Real-time single-molecule analysis on hippocampal neurons revealed dimerization between apo-GHSR1a and DRD1 that is enhanced by DRD1 agonism. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Canonical GHSR signaling goes through Gq/11, phospholipase C-beta, IP3/DAG and Ca2+. Reason: Purified ghrelin receptor forms Gq-specific preassembled and active complexes (PMID:25605885), and human Gq-coupled structures confirm the pathway. In neurons the same Gq-PLC output is produced when GHSR acts with DRD1 (PMID:26590421). The rat projection and mouse ISS rows are sound orthology transfers within PTHR24243:SF7. Supporting Evidence: PMID:25605885 This complex is specific of Gq and is not observed with Gi. PMID:26590421 Real-time single-molecule analysis on hippocampal neurons revealed dimerization between apo-GHSR1a and DRD1 that is enhanced by DRD1 agonism. |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | REMOVE | Summary: 'spermatogenesis' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:0007565 female pregnancy | IEA GO_REF:0000107 | TOO GENERAL | Summary: Female pregnancy (IEA), transferred from a rat expression-pattern annotation; entailed by the decidualization annotation kept in this review. Reason: Female pregnancy is entailed by the decidualization annotation that this review keeps for GHSR on direct evidence, so the broad term is consistent with a kept row and cannot be removed while that row stands. On its own this row adds nothing: its rat source is an expression-pattern annotation, which shows that receptor levels change in pregnancy rather than that the receptor acts in it. The term is recorded as too general. |
| GO:0007611 learning or memory | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Learning or memory: projected from rat agonist pharmacology on cognition. Reason: The rat source (PMID:19652956) shows that systemic GHSR agonists improve performance in recognition and spatial memory tests. This is a behavioral readout of drug action, and the mechanistic role is covered by regulation of synaptic plasticity. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:19652956 elicit pro-cognitive effects in recognition and spatial learning and memory tests |
| GO:0007612 learning | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Learning: a behavioral outcome downstream of GHSR's hippocampal synaptic role. Reason: The mouse source (PMID:26590421) shows GHSR inactivation impairs DRD1-dependent memory. The receptor's own contribution is the coreceptor activity and the regulation of synaptic plasticity, which are kept. Learning is an organismal behavioral phenotype of that perturbation, not a process the receptor performs. The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:26590421 In mice, GHSR1a inactivation inhibits DRD1-mediated hippocampal behavior and memory. PMID:26590421 Our findings identify a previously unrecognized mechanism essential for DRD1 initiation of hippocampal synaptic plasticity that is dependent on GHSR1a |
| GO:0007612 learning | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Learning: a behavioral outcome downstream of GHSR's hippocampal synaptic role. Reason: The mouse source (PMID:26590421) shows GHSR inactivation impairs DRD1-dependent memory. The receptor's own contribution is the coreceptor activity and the regulation of synaptic plasticity, which are kept. Learning is an organismal behavioral phenotype of that perturbation, not a process the receptor performs. The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:26590421 In mice, GHSR1a inactivation inhibits DRD1-mediated hippocampal behavior and memory. PMID:26590421 Our findings identify a previously unrecognized mechanism essential for DRD1 initiation of hippocampal synaptic plasticity that is dependent on GHSR1a |
| GO:0007613 memory | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Memory: a behavioral outcome downstream of GHSR's hippocampal synaptic role. Reason: As for learning: the knockout memory phenotype (PMID:26590421) reflects the receptor's effect on hippocampal synaptic plasticity, which is annotated separately. The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:26590421 In mice, GHSR1a inactivation inhibits DRD1-mediated hippocampal behavior and memory. PMID:26590421 Our findings identify a previously unrecognized mechanism essential for DRD1 initiation of hippocampal synaptic plasticity that is dependent on GHSR1a |
| GO:0007613 memory | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Memory: a behavioral outcome downstream of GHSR's hippocampal synaptic role. Reason: As for learning: the knockout memory phenotype (PMID:26590421) reflects the receptor's effect on hippocampal synaptic plasticity, which is annotated separately. The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:26590421 In mice, GHSR1a inactivation inhibits DRD1-mediated hippocampal behavior and memory. PMID:26590421 Our findings identify a previously unrecognized mechanism essential for DRD1 initiation of hippocampal synaptic plasticity that is dependent on GHSR1a |
| GO:0008154 actin polymerization or depolymerization | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | KEEP AS NON CORE | Summary: Actin cytoskeleton changes downstream of GHSR in human immune cells. Reason: The curated IDA is from PMID:15232612, which is abstract-only in the cache, so the actin assay could not be checked and the curator's full-text reading is accepted. The receptor does not polymerize actin itself; any role is through downstream signaling, so the term is non-core. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha |
| GO:0008343 adult feeding behavior | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR-null mice show altered adult feeding behavior. Reason: GHSR-null mice eat less on a high-fat diet (PMID:16322794). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. This is a behavioral outcome of the receptor's hypothalamic signaling. Supporting Evidence: PMID:16322794 ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons |
| GO:0008343 adult feeding behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: GHSR-null mice show altered adult feeding behavior. Reason: GHSR-null mice eat less on a high-fat diet (PMID:16322794). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. This is a behavioral outcome of the receptor's hypothalamic signaling. Supporting Evidence: PMID:16322794 ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons |
| GO:0009725 response to hormone | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | TOO GENERAL | Summary: Response to hormone: true but generic. Reason: Hormone-mediated signaling pathway (GO:0009755, accepted here) is a descendant of response to hormone (OLS ancestors, 2026-10-20). In the cited paper GHS-R mediates ghrelin's effect and is upregulated by leptin (PMID:15232612), which this generic term does not distinguish. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha PMID:15232612 leptin upregulated GHS-R expression on human T lymphocytes |
| GO:0009755 hormone-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: GHSR mediates the cellular response to the circulating peptide hormone ghrelin. Reason: Ghrelin is a stomach-derived circulating hormone and GHSR is its receptor (PMID:10604470, PMID:35027551). The IBA comes from the GHSR-specific PAINT node PTN002797666, together with the GO:0001616 IBD. Supporting Evidence: PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0009755 hormone-mediated signaling pathway | IDA PMID:8688086 A receptor in pituitary and hypothalamus that functions in g... | ACCEPT | Summary: GHSR mediates the cellular response to the circulating peptide hormone ghrelin. Reason: Ghrelin is a stomach-derived circulating hormone and GHSR is its receptor (PMID:10604470, PMID:35027551). The IBA comes from the GHSR-specific PAINT node PTN002797666, together with the GO:0001616 IBD. Supporting Evidence: PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0009986 cell surface | IDA PMID:8688086 A receptor in pituitary and hypothalamus that functions in g... | ACCEPT | Summary: Cell-surface receptor binding sites for secretagogues. Reason: The cloning paper identified GHSR as the cell-surface target of GHSs. Cell surface is consistent with the plasma membrane localization of this receptor. Supporting Evidence: PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, |
| GO:0010700 negative regulation of norepinephrine secretion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Central ghrelin receptors reduce sympathetic noradrenaline release in septic rats. Reason: The rat source (PMID:17911350) attributes the sympathoinhibition to central GHSR acting through an NPY/Y1-dependent pathway. This is a multi-synaptic circuit effect several steps downstream of the receptor. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:17911350 Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. |
| GO:0015026 coreceptor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: In neurons GHSR modulates dopamine receptor signaling as a coreceptor of DRD1 and DRD2, largely independently of ghrelin. Reason: In mouse hippocampal neurons apo-GHSR1a forms heteromers with DRD1 and switches DRD1 signaling to Gq-PLC-Ca2+ (PMID:26590421). In the spinal defecation centre, GHSR constitutive activity turns D2 receptor signaling from inhibitory to excitatory (PMID:40441153). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. This is a real ligand-independent activity of the receptor, but it depends on neuronal context, so it is kept as a secondary function. Human GO-CAMs 69c59f8a00000139 and 69c59f8a00001474 model it the same way. Supporting Evidence: PMID:26590421 Real-time single-molecule analysis on hippocampal neurons revealed dimerization between apo-GHSR1a and DRD1 that is enhanced by DRD1 agonism. PMID:40441153 this reversal is a consequence of the ghrelin receptor's constitutive activity, where neither its agonism nor dimerization with the D2 receptor is required |
| GO:0015026 coreceptor activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: In neurons GHSR modulates dopamine receptor signaling as a coreceptor of DRD1 and DRD2, largely independently of ghrelin. Reason: In mouse hippocampal neurons apo-GHSR1a forms heteromers with DRD1 and switches DRD1 signaling to Gq-PLC-Ca2+ (PMID:26590421). In the spinal defecation centre, GHSR constitutive activity turns D2 receptor signaling from inhibitory to excitatory (PMID:40441153). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. This is a real ligand-independent activity of the receptor, but it depends on neuronal context, so it is kept as a secondary function. Human GO-CAMs 69c59f8a00000139 and 69c59f8a00001474 model it the same way. Supporting Evidence: PMID:26590421 Real-time single-molecule analysis on hippocampal neurons revealed dimerization between apo-GHSR1a and DRD1 that is enhanced by DRD1 agonism. PMID:40441153 this reversal is a consequence of the ghrelin receptor's constitutive activity, where neither its agonism nor dimerization with the D2 receptor is required |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Generic membrane from InterPro 7TM signatures; the receptor is specifically a plasma membrane protein. Reason: Plasma membrane (GO:0005886), already annotated with experimental support, is the correct specific descendant. Proposed replacements: plasma membrane Supporting Evidence: file:human/GHSR/GHSR-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35027551, |
| GO:0016520 growth hormone-releasing hormone receptor activity | IDA PMID:10604470 Ghrelin is a growth-hormone-releasing acylated peptide from ... | MODIFY | Summary: Ligand mismatch: GO:0016520 is the receptor activity for growth-hormone-releasing hormone (GHRH), the ligand of GHRHR, not of GHSR. Reason: QuickGO defines GO:0016520 as 'Combining with growth hormone-releasing hormone' and GO:0001616 as 'Combining with ghrelin' (checked 2026-10-20). The cited papers show GHSR responding to synthetic secretagogues (PMID:8688086) and ghrelin (PMID:10604470), and the ghrelin paper explicitly describes this as a GH-release pathway distinct from GHRH. Ghrelin releases GH but is not GHRH, so the receptor function is right in substance and the correct term is GO:0001616. The rat Ensembl-projected row inherits the same mismatch from rat O08725 (PMID:25605885). GO-CAM 67f85f2b00000823 also uses GO:0016520 for GHSR (see suggested_questions). Proposed replacements: growth hormone secretagogue receptor activity Supporting Evidence: PMID:10604470 there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH) PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. |
| GO:0016520 growth hormone-releasing hormone receptor activity | IDA PMID:8688086 A receptor in pituitary and hypothalamus that functions in g... | MODIFY | Summary: Ligand mismatch: GO:0016520 is the receptor activity for growth-hormone-releasing hormone (GHRH), the ligand of GHRHR, not of GHSR. Reason: QuickGO defines GO:0016520 as 'Combining with growth hormone-releasing hormone' and GO:0001616 as 'Combining with ghrelin' (checked 2026-10-20). The cited papers show GHSR responding to synthetic secretagogues (PMID:8688086) and ghrelin (PMID:10604470), and the ghrelin paper explicitly describes this as a GH-release pathway distinct from GHRH. Ghrelin releases GH but is not GHRH, so the receptor function is right in substance and the correct term is GO:0001616. The rat Ensembl-projected row inherits the same mismatch from rat O08725 (PMID:25605885). GO-CAM 67f85f2b00000823 also uses GO:0016520 for GHSR (see suggested_questions). Proposed replacements: growth hormone secretagogue receptor activity Supporting Evidence: PMID:10604470 there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH) PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. |
| GO:0016520 growth hormone-releasing hormone receptor activity | IEA GO_REF:0000107 | MODIFY | Summary: Ligand mismatch: GO:0016520 is the receptor activity for growth-hormone-releasing hormone (GHRH), the ligand of GHRHR, not of GHSR. Reason: QuickGO defines GO:0016520 as 'Combining with growth hormone-releasing hormone' and GO:0001616 as 'Combining with ghrelin' (checked 2026-10-20). The cited papers show GHSR responding to synthetic secretagogues (PMID:8688086) and ghrelin (PMID:10604470), and the ghrelin paper explicitly describes this as a GH-release pathway distinct from GHRH. Ghrelin releases GH but is not GHRH, so the receptor function is right in substance and the correct term is GO:0001616. The rat Ensembl-projected row inherits the same mismatch from rat O08725 (PMID:25605885). GO-CAM 67f85f2b00000823 also uses GO:0016520 for GHSR (see suggested_questions). Proposed replacements: growth hormone secretagogue receptor activity Supporting Evidence: PMID:10604470 there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH) PMID:10604470 We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. PMID:8688086 A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. |
| GO:0017046 peptide hormone binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR binds the peptide hormone ghrelin directly in its orthosteric pocket. Reason: Direct binding of octanoylated ghrelin is shown structurally (PMID:35027551). GO has no ghrelin-binding child of GO:0017046, so the term is as precise as a binding term can be. It is non-core because ligand binding is already part of GO:0001616 receptor activity. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin PMID:35027551 an acylated modification, typically an octanoyl group, of the hydroxyl group of the Ser+3 residue is required for the biological action of ghrelin as the unacylated form of ghrelin does not bind or activate the ghrelin receptor at all |
| GO:0023052 signaling | IEA GO_REF:0000117 | TOO GENERAL | Summary: Signaling from an ARBA rule. Reason: GO:0023052 is an ancestor of GO:0007186 G protein-coupled receptor signaling pathway, which is accepted. Supporting Evidence: PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0030252 growth hormone secretion | TAS PMID:16511605 Loss of constitutive activity of the growth hormone secretag... | MODIFY | Summary: GHSR stimulates GH secretion from somatotrophs but does not carry out secretion. Reason: The receptor's role is to drive GH release through pituitary and hypothalamic signaling (PMID:8688086, PMID:15070777). The secretory machinery belongs to the somatotroph. The relationship is captured by positive regulation of growth hormone secretion (GO:0060124). The cited paper (PMID:16511605) links loss of constitutive activity to short stature. Proposed replacements: positive regulation of growth hormone secretion Supporting Evidence: PMID:8688086 this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release PMID:15070777 acute treatment of Ghsr-null mice with ghrelin stimulated neither GH release nor food intake, showing that the GHSR is a biologically relevant ghrelin receptor. PMID:16511605 We report the identification of a GHSR missense mutation that segregates with short stature within 2 unrelated families. |
| GO:0032099 negative regulation of appetite | IEA GO_REF:0000107 | REMOVE | Summary: Negative regulation of appetite, projected from a paradoxical rat antagonist study; it contradicts the receptor's established orexigenic role. Reason: The rat source (PMID:21778696) reports that an antagonist unexpectedly increased food intake, and the authors themselves say the result is inconsistent with a simple hormone-receptor model. Loss of GHSR abolishes ghrelin-induced feeding in mice (PMID:15070777, PMID:16322794), and clinical GHSR agonists increase appetite. Projecting 'negative regulation of appetite' to human contradicts this consistent evidence; the human row keeps positive regulation of appetite. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:21778696 unexpectedly stimulated FI and BW gain in both rats and dogs, a profile associated with decreased ghrelin plasma level PMID:21778696 The observed dissociation between effects on GH secretion and effects on FI/BW is inconsistent with a simple hormone-receptor model PMID:16322794 ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons |
| GO:0032100 positive regulation of appetite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR mediates ghrelin's orexigenic action. Reason: Ghrelin fails to stimulate food intake in Ghsr-null mice (PMID:15070777, PMID:16322794), and attenuating arcuate GHS-R in rats reduces feeding (PMID:12045256). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Appetite is a key physiological output, but it is a circuit-level consequence of the receptor's activity in AgRP/NPY neurons, not the molecular function itself. Supporting Evidence: PMID:16322794 ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons PMID:15070777 acute treatment of Ghsr-null mice with ghrelin stimulated neither GH release nor food intake, showing that the GHSR is a biologically relevant ghrelin receptor. PMID:12045256 These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. |
| GO:0032100 positive regulation of appetite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: GHSR mediates ghrelin's orexigenic action. Reason: Ghrelin fails to stimulate food intake in Ghsr-null mice (PMID:15070777, PMID:16322794), and attenuating arcuate GHS-R in rats reduces feeding (PMID:12045256). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Appetite is a key physiological output, but it is a circuit-level consequence of the receptor's activity in AgRP/NPY neurons, not the molecular function itself. Supporting Evidence: PMID:16322794 ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons PMID:15070777 acute treatment of Ghsr-null mice with ghrelin stimulated neither GH release nor food intake, showing that the GHSR is a biologically relevant ghrelin receptor. PMID:12045256 These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. |
| GO:0032354 response to follicle-stimulating hormone | IEA GO_REF:0000107 | REMOVE | Summary: 'response to follicle-stimulating hormone' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | REMOVE | Summary: 'response to estradiol' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:0032691 negative regulation of interleukin-1 beta production | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | KEEP AS NON CORE | Summary: GHSR-dependent inhibition of IL-1beta production in human immune cells. Reason: Supported by human monocyte/T cell experiments (PMID:15232612); peripheral and context-dependent. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha |
| GO:0032715 negative regulation of interleukin-6 production | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | KEEP AS NON CORE | Summary: GHSR-dependent inhibition of IL-6 production in human immune cells. Reason: Supported by human monocyte/T cell experiments (PMID:15232612); peripheral and context-dependent. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha |
| GO:0032720 negative regulation of tumor necrosis factor production | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | KEEP AS NON CORE | Summary: GHSR mediates ghrelin's inhibition of TNF-alpha production in immune cells. Reason: In human monocytes and T cells ghrelin acts via GHS-R to inhibit IL-1beta, IL-6 and TNF-alpha expression (PMID:15232612). The rat row (PMID:17911350) reports the same direction in sepsis. This is a peripheral, context-dependent immunomodulatory output. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha PMID:17911350 Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. |
| GO:0032720 negative regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR mediates ghrelin's inhibition of TNF-alpha production in immune cells. Reason: In human monocytes and T cells ghrelin acts via GHS-R to inhibit IL-1beta, IL-6 and TNF-alpha expression (PMID:15232612). The rat row (PMID:17911350) reports the same direction in sepsis. This is a peripheral, context-dependent immunomodulatory output. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha PMID:17911350 Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. |
| GO:0036321 ghrelin secretion | IEA GO_REF:0000107 | REMOVE | Summary: Ghrelin secretion is carried out by gastric X/A-like endocrine cells, not by the receptor. Reason: The rat source (PMID:21778696) found lower plasma ghrelin after antagonist treatment, an indirect pharmacological correlate. GHSR does not secrete ghrelin. A feedback effect would at most be regulation of ghrelin secretion, and that is not established for the human receptor. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:21778696 unexpectedly stimulated FI and BW gain in both rats and dogs, a profile associated with decreased ghrelin plasma level PMID:21778696 The observed dissociation between effects on GH secretion and effects on FI/BW is inconsistent with a simple hormone-receptor model |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000117 | MODIFY | Summary: Generic signaling receptor activity from an ARBA rule; GHSR is specifically a ghrelin receptor. Reason: GO:0001616 is a descendant of GO:0038023 and is directly supported for this receptor. The ARBA-derived generic term adds nothing. Proposed replacements: growth hormone secretagogue receptor activity Supporting Evidence: PMID:35027551 active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:16511605 Loss of constitutive activity of the growth hormone secretag... | KEEP AS NON CORE | Summary: Human GHSR loss-of-constitutive-activity variant causes familial short stature. Reason: A missense variant that selectively impairs constitutive activity segregates with short stature (PMID:16511605). This shows the receptor's basal tone contributes to growth through the GH axis. It is an organism-level outcome downstream of GH regulation, so it is non-core. Supporting Evidence: PMID:16511605 We report the identification of a GHSR missense mutation that segregates with short stature within 2 unrelated families. PMID:16511605 selectively impairs the constitutive activity of the GHSR, while preserving its ability to respond to ghrelin |
| GO:0043005 neuron projection | IDA PMID:12890514 Growth hormone secretagogue receptors in rat and human gastr... | KEEP AS NON CORE | Summary: GHSR immunoreactivity in enteric neuronal cell bodies and fibres. Reason: Human and rat gut preparations showed GHS-R immunoreactivity in neuronal cell bodies and fibres (PMID:12890514). This neuronal location is consistent with the receptor's neural actions on gut motility, but it is tissue-specific. Supporting Evidence: PMID:12890514 expressed GHS-R-Ir within neuronal cell bodies and fibres |
| GO:0043134 regulation of hindgut contraction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Spinal GHSR activation triggers colorectal propulsive contractions. Reason: Activating ghrelin receptors in the lumbosacral defecation centre empties the colorectum in rats (PMID:16873401); the mouse mechanism is GHSR-dependent reversal of D2 signaling (PMID:40441153). This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:16873401 activation of ghrelin receptors in the lumbo-sacral spinal cord triggers co-ordinated propulsive contractions that empty the colo-rectum PMID:40441153 This reversal is required for the physiological control of defecation |
| GO:0045121 membrane raft | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | KEEP AS NON CORE | Summary: GHSR association with lipid rafts in human immune cells. Reason: The curated IDA comes from human T cells and monocytes (PMID:15232612); only the abstract is cached, so the raft assay itself could not be checked here and the curator's reading of the full text is accepted. Raft partitioning is a sub-domain of the plasma membrane localization, not a separate core site. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha |
| GO:0045923 positive regulation of fatty acid metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of fatty acid metabolic process, projected from rat antisense knockdown with less adipose tissue. Reason: The source (PMID:12045256) reports lower body weight and adiposity after arcuate GHS-R knockdown. This is a systemic energy-balance phenotype mediated by feeding and GH. It does not show that the receptor directly controls fatty acid metabolism. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:12045256 These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. |
| GO:0045927 positive regulation of growth | IEA GO_REF:0000107 | MODIFY | Summary: Positive regulation of growth: generic version of the organismal-growth role. Reason: The specific supported descendant is positive regulation of multicellular organism growth (GO:0040018), already annotated from the human short-stature genetics (PMID:16511605). This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Proposed replacements: positive regulation of multicellular organism growth Supporting Evidence: PMID:12045256 These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. PMID:16511605 We report the identification of a GHSR missense mutation that segregates with short stature within 2 unrelated families. |
| GO:0046697 decidualization | IDA PMID:17494105 Facilitation of decidualization by locally produced ghrelin ... | KEEP AS NON CORE | Summary: Ghrelin promotes decidualization of human endometrial stromal cells, where GHS-R is expressed. Reason: Human endometrium expresses GHS-R cyclically, and ghrelin enhances decidualization markers in stromal cells (PMID:17494105). Only the abstract is cached and receptor dependence was not shown by knockdown, so this is kept as a tissue-specific, non-core role. Supporting Evidence: PMID:17494105 Ghrelin administered in combination with sex steroids to HESC, resulted in an increase in PRL and IGFBP-1 production |
| GO:0048167 regulation of synaptic plasticity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR regulates hippocampal synaptic plasticity, both as a DRD1 coreceptor and as a ghrelin receptor. Reason: In mouse, GHSR1a is needed for DRD1-initiated hippocampal synaptic plasticity (PMID:26590421). In rat, ghrelin acting on GHS-R1a increases synaptic AMPA receptor delivery and LTP (PMID:24367106). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:26590421 Our findings identify a previously unrecognized mechanism essential for DRD1 initiation of hippocampal synaptic plasticity that is dependent on GHSR1a PMID:24367106 We propose that GHS-R1a activation in the hippocampus enhances excitatory synaptic transmission and synaptic plasticity by regulating AMPAR trafficking. |
| GO:0048167 regulation of synaptic plasticity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: GHSR regulates hippocampal synaptic plasticity, both as a DRD1 coreceptor and as a ghrelin receptor. Reason: In mouse, GHSR1a is needed for DRD1-initiated hippocampal synaptic plasticity (PMID:26590421). In rat, ghrelin acting on GHS-R1a increases synaptic AMPA receptor delivery and LTP (PMID:24367106). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:26590421 Our findings identify a previously unrecognized mechanism essential for DRD1 initiation of hippocampal synaptic plasticity that is dependent on GHSR1a PMID:24367106 We propose that GHS-R1a activation in the hippocampus enhances excitatory synaptic transmission and synaptic plasticity by regulating AMPAR trafficking. |
| GO:0050728 negative regulation of inflammatory response | IDA PMID:15232612 Ghrelin inhibits leptin- and activation-induced proinflammat... | KEEP AS NON CORE | Summary: GHSR-mediated anti-inflammatory signaling in human immune cells. Reason: Ghrelin acting through GHS-R suppresses proinflammatory cytokine expression (PMID:15232612). Kept as a peripheral, non-core output. Supporting Evidence: PMID:15232612 ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha |
| GO:0051969 regulation of transmission of nerve impulse | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ghrelin excites gastric-distension-responsive septal neurons. Reason: The rat source (PMID:23525979) records ghrelin-evoked neuronal firing and gastric motility changes after injection into the lateral septum. The nerve-impulse framing over-interprets a circuit-level pharmacological effect. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:23525979 Gastric motility was significantly enhanced by the administration of ghrelin in the lateral septum in a dose-dependent manner. |
| GO:0060123 regulation of growth hormone secretion | IEA GO_REF:0000107 | MODIFY | Summary: GHSR signaling stimulates GH secretion. Reason: The rat source (PMID:12045256) and mouse knockouts (PMID:15070777) show the effect is stimulatory. Positive regulation of growth hormone secretion (GO:0060124) is the specific descendant. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Proposed replacements: positive regulation of growth hormone secretion Supporting Evidence: PMID:12045256 These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. PMID:15070777 acute treatment of Ghsr-null mice with ghrelin stimulated neither GH release nor food intake, showing that the GHSR is a biologically relevant ghrelin receptor. |
| GO:0060259 regulation of feeding behavior | IEA GO_REF:0000107 | MODIFY | Summary: Regulation of feeding behavior: the direction is stimulatory. Reason: Positive regulation of eating behavior (GO:1904000), a descendant already annotated here, states the supported direction. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Proposed replacements: positive regulation of eating behavior Supporting Evidence: PMID:12045256 These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. PMID:16322794 ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons |
| GO:0060416 response to growth hormone | IEA GO_REF:0000107 | REMOVE | Summary: 'response to growth hormone' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:0071222 cellular response to lipopolysaccharide | IEA GO_REF:0000107 | REMOVE | Summary: 'cellular response to lipopolysaccharide' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:0071548 response to dexamethasone | IEA GO_REF:0000107 | REMOVE | Summary: 'response to dexamethasone' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:0090327 negative regulation of locomotion involved in locomotory behavior | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Locomotor activity change in rats with reduced GHS-R expression. Reason: Transgenic rats with antisense knockdown of GHS-R showed higher dark-period locomotor activity (PMID:19931319). This is an organismal behavioral phenotype of an energy-balance perturbation, not a process the receptor carries out. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:19931319 dark-period locomotor activity |
| GO:0097060 synaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synaptic localization of GHSR in hippocampal excitatory neurons (rat SynGO data). Reason: Rat SynGO annotations (PMID:24367106) place GHS-R1a near hippocampal excitatory synapses. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. The location is credible in neurons but secondary to the plasma membrane. Supporting Evidence: PMID:24367106 GHS-R1a is localized in the vicinity of hippocampal excitatory synapses |
| GO:0097067 cellular response to thyroid hormone stimulus | IEA GO_REF:0000107 | REMOVE | Summary: 'cellular response to thyroid hormone stimulus' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:0098685 Schaffer collateral - CA1 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR acting at hippocampal Schaffer collateral-CA1 synapses (rat SynGO data). Reason: Rat CA1 electrophysiology attributes ghrelin-induced potentiation to postsynaptic GHS-R1a (PMID:26153524). This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:26153524 the potentiation of synaptic transmission by GHS-R1a at hippocampal CA1 excitatory synapses probably results from postsynaptic mechanisms |
| GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHS-R1a activation promotes synaptic AMPA receptor delivery. Reason: Rat hippocampal data (PMID:24367106) show GHS-R1a activation increases AMPAR delivery to synapses. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:24367106 We propose that GHS-R1a activation in the hippocampus enhances excitatory synaptic transmission and synaptic plasticity by regulating AMPAR trafficking. |
| GO:0098794 postsynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Postsynapse, inferred from the postsynaptic modulation process annotation. Reason: This GO_REF:0000108 row is inferred from GO:0099170, which rests on rat CA1 data (PMID:26153524) pointing to a postsynaptic site of action. It is non-core, as for the other synaptic locations. Supporting Evidence: PMID:26153524 the potentiation of synaptic transmission by GHS-R1a at hippocampal CA1 excitatory synapses probably results from postsynaptic mechanisms |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glutamatergic synapse localization of GHSR in hippocampus (rat SynGO data). Reason: Rat SynGO curation from hippocampal studies (PMID:24367106, PMID:26153524, PMID:22516464). This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:24367106 GHS-R1a is localized in the vicinity of hippocampal excitatory synapses PMID:26153524 the potentiation of synaptic transmission by GHS-R1a at hippocampal CA1 excitatory synapses probably results from postsynaptic mechanisms |
| GO:0099170 postsynaptic modulation of chemical synaptic transmission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Postsynaptic modulation of excitatory transmission by GHS-R1a at CA1 synapses. Reason: Rat CA1 data (PMID:26153524) attribute ghrelin-induced potentiation to postsynaptic GHS-R1a. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:26153524 the potentiation of synaptic transmission by GHS-R1a at hippocampal CA1 excitatory synapses probably results from postsynaptic mechanisms |
| GO:0099175 regulation of postsynapse organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of postsynapse organization: dendritic spine remodelling. Reason: In cultured rat hippocampal slices ghrelin increased F-actin-rich spines, and this was blocked by a GHSR antagonist (PMID:22516464). This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:22516464 Our results suggest ghrelin may have a stimulating effect on the generation or remodeling of dendritic spines |
| GO:0120058 positive regulation of small intestinal transit | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ghrelin receptor agonists accelerate intestinal transit. Reason: Ghrelin and GHRP-6 accelerated gastric emptying and transit in rats (PMID:15890336). This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:15890336 Ghrelin and GHRP-6 but not motilin accelerated gastric emptying and transit in rats. |
| GO:1902065 response to L-glutamate | IEA GO_REF:0000107 | REMOVE | Summary: 'response to L-glutamate' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:1903672 positive regulation of sprouting angiogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ghrelin-GHSR pharmacology promotes pathological retinal neovascularization in rats. Reason: The source (PMID:21642627) is a rat oxygen-induced retinopathy model using ghrelin analogs and antagonists. It shows phase-dependent, even opposing, vascular effects, which do not amount to a general role for the receptor in sprouting angiogenesis. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:21642627 during the neovascular phase, ghrelin promotes pathologic angiogenesis through the activation of GHSR-1a |
| GO:1904000 positive regulation of eating behavior | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of eating behavior by ghrelin-GHSR signaling. Reason: In the rat source, an antagonist reduced ghrelin-driven food intake (PMID:26512025); this agrees with the mouse knockout data. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:26512025 Ghrelin effect on food intake was confirmed by treating MENX rats with a GHS-R1a antagonist. PMID:16322794 ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons |
| GO:1904349 positive regulation of small intestine smooth muscle contraction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of small intestine smooth muscle contraction. Reason: The rat data show neurally mediated prokinetic effects (PMID:15890336), and human and rat gut smooth muscle cells lack GHS-R immunoreactivity (PMID:12890514). Framing the role as regulation of smooth muscle contraction places it on the wrong cell type and overstates a neural effect. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:12890514 Smooth muscle cells and epithelia were devoid of GHS-R-Ir PMID:15890336 Ghrelin and GHRP-6 but not motilin accelerated gastric emptying and transit in rats. |
| GO:1905333 regulation of gastric motility | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ghrelin receptor activation stimulates gastric motility. Reason: GHSR agonists are gastroprokinetic in rats (PMID:15890336, PMID:23525979), and agonists accelerate gastric emptying in humans. The effect is mediated by neurons, since gut smooth muscle lacks the receptor (PMID:12890514). This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:15890336 Ghrelin and GHRP-6 but not motilin accelerated gastric emptying and transit in rats. PMID:23525979 Gastric motility was significantly enhanced by the administration of ghrelin in the lateral septum in a dose-dependent manner. PMID:12890514 Smooth muscle cells and epithelia were devoid of GHS-R-Ir |
| GO:1905564 positive regulation of vascular endothelial cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Endothelial proliferation in the rat retinopathy model. Reason: Same rat oxygen-induced retinopathy pharmacology (PMID:21642627) as the angiogenesis row; it is pathology-specific. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:21642627 during the neovascular phase, ghrelin promotes pathologic angiogenesis through the activation of GHSR-1a |
| GO:1990314 cellular response to insulin-like growth factor stimulus | IEA GO_REF:0000107 | REMOVE | Summary: 'cellular response to insulin-like growth factor stimulus' is projected from a rat expression-pattern (IEP) annotation, not from evidence of receptor function. Reason: The rat source annotation (checked in QuickGO, 2026-10-20) is IEP: it records that rat Ghsr transcript or protein levels change under this condition. An expression change does not show that the receptor carries out the response, and an expression pattern is not a function that can be transferred by orthology. Nothing in the human literature reviewed here supports the claim independently. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. |
| GO:2000110 negative regulation of macrophage apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR mediates ghrelin's anti-apoptotic effect in alveolar macrophages. Reason: In rat alveolar macrophages, siRNA against GHSR-1a abolished ghrelin's protection from LPS-induced apoptosis (PMID:25337654). This cell-autonomous result transfers reasonably within SF7, but it is peripheral and context-dependent. This Ensembl Compara row (GO_REF:0000107) projects an annotation from rat Ghsr O08725, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7) and below the GHSR PAINT node PTN002797666, so the orthology is sound; the question is whether the rat claim itself holds and transfers. Supporting Evidence: PMID:25337654 These effects of ghrelin were mediated by GHSR-1a because a GHSR-1a-targeting small interfering RNA abolished the antiapoptotic action of ghrelin. |
| GO:2000292 regulation of defecation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GHSR constitutive activity in spinal defecation centre neurons controls defecation. Reason: In mouse spinal neurons, GHSR constitutive activity reverses dopamine D2 signaling, and this reversal is required for physiological control of defecation (PMID:40441153). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:40441153 this reversal is a consequence of the ghrelin receptor's constitutive activity, where neither its agonism nor dimerization with the D2 receptor is required PMID:40441153 This reversal is required for the physiological control of defecation |
| GO:2000292 regulation of defecation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: GHSR constitutive activity in spinal defecation centre neurons controls defecation. Reason: In mouse spinal neurons, GHSR constitutive activity reverses dopamine D2 signaling, and this reversal is required for physiological control of defecation (PMID:40441153). The donor is mouse Ghsr Q99P50, a one-to-one ortholog in the same PANTHER subfamily (PTHR24243:SF7), so the receptor and its coupling properties are conserved. Supporting Evidence: PMID:40441153 this reversal is a consequence of the ghrelin receptor's constitutive activity, where neither its agonism nor dimerization with the D2 receptor is required PMID:40441153 This reversal is required for the physiological control of defecation |
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Download this section (compressed HTML)Q: GO-CAM 67f85f2b00000823 (Ghrelin-GHSR pair leading to G-alphaQ activation) gives GHSR the activity GO:0016520 growth hormone-releasing hormone receptor activity, and gives ghrelin GO:0016608 growth hormone-releasing hormone activity. By their definitions those terms describe the GHRH-GHRHR pair. Should the model use GO:0001616 growth hormone secretagogue receptor activity for GHSR, and should the human and rat GO:0016520 IDA rows be moved to GO:0001616?
Q: How much of GHSR's physiological signaling in human tissues comes from constitutive activity rather than ghrelin, and does the GHSR1b isoform regulate this in vivo?
Experiment: In human iPSC-derived hypothalamic or spinal neurons, compare GHSR knockout, a constitutive-activity-dead variant (A204E) and LEAP2 treatment. Readouts would be DRD1/DRD2-evoked Gq signaling and ghrelin responses, to separate ligand-dependent from constitutive functions in human cells.
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