GHSR

Summary: Ghrelin/growth-hormone-secretagogue receptor activity is the core molecular function.

Reason: Receptor cloning, endogenous ligand identification and modern ghrelin-bound receptor structures establish this specific function. The full-length horse receptor retains the seven-transmembrane architecture and 95.1% identity, supporting transfer of ligand class and receptor mechanism; the equine expression paper verifies GHSR1a transcripts but is not a ligand-binding assay.

Summary: Ghrelin/growth-hormone-secretagogue receptor activity is the core molecular function.

Reason: Receptor cloning, endogenous ligand identification and modern ghrelin-bound receptor structures establish this specific function. The full-length horse receptor retains the seven-transmembrane architecture and 95.1% identity, supporting transfer of ligand class and receptor mechanism; the equine expression paper verifies GHSR1a transcripts but is not a ligand-binding assay.

Summary: The ghrelin receptor term captures the experimentally established specificity.

Reason: GHSR is a peptide-hormone-binding GPCR, but the specific ghrelin/growth-hormone-secretagogue receptor activity is more informative than generic receptor or peptide-binding terms.

Proposed replacements: growth hormone secretagogue receptor activity

Summary: The seven-transmembrane receptor functions at the cell surface.

Reason: Cloned GHSR has membrane receptor pharmacology, and the active receptor structures show the transmembrane signaling architecture. A preserved full-length horse receptor supports the same membrane compartment.

Summary: The seven-transmembrane receptor functions at the cell surface.

Reason: Cloned GHSR has membrane receptor pharmacology, and the active receptor structures show the transmembrane signaling architecture. A preserved full-length horse receptor supports the same membrane compartment.

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: Neuronal receptor-heteromer roles are context-specific and distinct from ghrelin ligand recognition.

Reason: The curated mammalian synthesis describes GHSR/DRD1 or GHSR/DRD2 heteromers in synaptic plasticity and defecation. Broad neuronal/coreceptor effects are retained as non-core evolutionary inferences; precise synapse subdivisions and postsynaptic organization require inspection of the donor experiment. No heteromer claim establishes oxytocin receptor activity.

Summary: Neuronal receptor-heteromer roles are context-specific and distinct from ghrelin ligand recognition.

Reason: The curated mammalian synthesis describes GHSR/DRD1 or GHSR/DRD2 heteromers in synaptic plasticity and defecation. Broad neuronal/coreceptor effects are retained as non-core evolutionary inferences; precise synapse subdivisions and postsynaptic organization require inspection of the donor experiment. No heteromer claim establishes oxytocin receptor activity.

Summary: Immune-cell membrane organization/cytoskeletal effects require the stated tissue context.

Reason: The human primary GHSR immune-cell study supplies these IDA observations. Retain the human observation as non-core; the corresponding horse annotation lacks a verified horse cellular context, and receptor conservation alone does not establish membrane-raft partitioning or actin remodeling in that tissue.

Summary: Feeding/appetite regulation is a supported physiological context of ghrelin signaling.

Reason: Ghrelin/GHSR signaling promotes appetite in mammalian pharmacological studies. This is a plausible conserved physiological effect, but the equine hormone concentration study does not directly demonstrate that receptor activity causes feeding behavior.

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: The seven-transmembrane receptor functions at the cell surface.

Reason: Cloned GHSR has membrane receptor pharmacology, and the active receptor structures show the transmembrane signaling architecture. A preserved full-length horse receptor supports the same membrane compartment.

Summary: Neuronal receptor-heteromer roles are context-specific and distinct from ghrelin ligand recognition.

Reason: The curated mammalian synthesis describes GHSR/DRD1 or GHSR/DRD2 heteromers in synaptic plasticity and defecation. Broad neuronal/coreceptor effects are retained as non-core evolutionary inferences; precise synapse subdivisions and postsynaptic organization require inspection of the donor experiment. No heteromer claim establishes oxytocin receptor activity.

Summary: The seven-transmembrane receptor functions at the cell surface.

Reason: Cloned GHSR has membrane receptor pharmacology, and the active receptor structures show the transmembrane signaling architecture. A preserved full-length horse receptor supports the same membrane compartment.

Proposed replacements: plasma membrane

Summary: The cited ligand is ghrelin, not growth-hormone-releasing hormone.

Reason: QuickGO defines GO:0016520 as binding growth-hormone-releasing hormone, whereas GO:0001616 binds ghrelin. The discovery paper explicitly distinguishes the ghrelin/GHSR pathway from hypothalamic GHRH. Human IDA rows cite ghrelin/secretagogue studies, and the horse Ensembl transfer names human Q92847 as donor. Replace the ligand-confused term with the ghrelin receptor term; no claim of a wrong experimental organism or missing assay is needed.

Proposed replacements: growth hormone secretagogue receptor activity

Summary: Ghrelin activates G-protein-dependent receptor signaling.

Reason: GHSR ligand recognition activates heterotrimeric G proteins and downstream second messengers. The specific receptor-signaling process is core; generic signaling/communication or hormone-response terms are compatible but less informative. Shared GPCR coupling does not imply oxytocin specificity.

Summary: Feeding/appetite regulation is a supported physiological context of ghrelin signaling.

Reason: Ghrelin/GHSR signaling promotes appetite in mammalian pharmacological studies. This is a plausible conserved physiological effect, but the equine hormone concentration study does not directly demonstrate that receptor activity causes feeding behavior.

Summary: GHSR-dependent cytokine inhibition is supported in human immune cells.

Reason: Human monocyte/T-cell experiments demonstrate suppression of IL-1beta, IL-6 and TNF-alpha expression through GHSR. This is a tissue-specific signaling consequence, not the defining receptor function; conservation makes horse transfer plausible but direct horse immune-cell assays are absent.

Summary: GHSR-dependent cytokine inhibition is supported in human immune cells.

Reason: Human monocyte/T-cell experiments demonstrate suppression of IL-1beta, IL-6 and TNF-alpha expression through GHSR. This is a tissue-specific signaling consequence, not the defining receptor function; conservation makes horse transfer plausible but direct horse immune-cell assays are absent.

Summary: GHSR-dependent cytokine inhibition is supported in human immune cells.

Reason: Human monocyte/T-cell experiments demonstrate suppression of IL-1beta, IL-6 and TNF-alpha expression through GHSR. This is a tissue-specific signaling consequence, not the defining receptor function; conservation makes horse transfer plausible but direct horse immune-cell assays are absent.

Summary: The ghrelin receptor term captures the experimentally established specificity.

Reason: GHSR is a peptide-hormone-binding GPCR, but the specific ghrelin/growth-hormone-secretagogue receptor activity is more informative than generic receptor or peptide-binding terms.

Proposed replacements: growth hormone secretagogue receptor activity

Summary: GHSR signaling regulates growth-hormone release and contributes to growth.

Reason: Secretagogue receptor pharmacology and human loss-of-constitutive-activity variants support this endocrine role. The horse pituitary GHSR1a transcript and conserved receptor support the general mechanism, but do not establish the magnitude of growth effects in horse.

Summary: Neuronal receptor-heteromer roles are context-specific and distinct from ghrelin ligand recognition.

Reason: The curated mammalian synthesis describes GHSR/DRD1 or GHSR/DRD2 heteromers in synaptic plasticity and defecation. Broad neuronal/coreceptor effects are retained as non-core evolutionary inferences; precise synapse subdivisions and postsynaptic organization require inspection of the donor experiment. No heteromer claim establishes oxytocin receptor activity.

Summary: Immune-cell membrane organization/cytoskeletal effects require the stated tissue context.

Reason: The human primary GHSR immune-cell study supplies these IDA observations. Retain the human observation as non-core; the corresponding horse annotation lacks a verified horse cellular context, and receptor conservation alone does not establish membrane-raft partitioning or actin remodeling in that tissue.

Summary: The decidualization evidence is from human endometrial stromal cells.

Reason: The primary study adds ghrelin to human stromal-cell decidualization cultures and detects receptor expression. This supports a human reproductive context; placentation and decidual responses differ among mammals, so this precise process is not transferred confidently to horse without relevant uterine evidence.

Summary: Neuronal receptor-heteromer roles are context-specific and distinct from ghrelin ligand recognition.

Reason: The curated mammalian synthesis describes GHSR/DRD1 or GHSR/DRD2 heteromers in synaptic plasticity and defecation. Broad neuronal/coreceptor effects are retained as non-core evolutionary inferences; precise synapse subdivisions and postsynaptic organization require inspection of the donor experiment. No heteromer claim establishes oxytocin receptor activity.

Summary: GHSR-dependent cytokine inhibition is supported in human immune cells.

Reason: Human monocyte/T-cell experiments demonstrate suppression of IL-1beta, IL-6 and TNF-alpha expression through GHSR. This is a tissue-specific signaling consequence, not the defining receptor function; conservation makes horse transfer plausible but direct horse immune-cell assays are absent.

Summary: Neuronal receptor-heteromer roles are context-specific and distinct from ghrelin ligand recognition.

Reason: The curated mammalian synthesis describes GHSR/DRD1 or GHSR/DRD2 heteromers in synaptic plasticity and defecation. Broad neuronal/coreceptor effects are retained as non-core evolutionary inferences; precise synapse subdivisions and postsynaptic organization require inspection of the donor experiment. No heteromer claim establishes oxytocin receptor activity.