ADRB2 encodes the beta-2 adrenergic receptor, a seven-transmembrane catecholamine GPCR that acts mainly at the plasma membrane. Epinephrine and norepinephrine binding activate bifurcated G protein signaling, especially Gs/cAMP/PKA and context-dependent Gi branches, with downstream effects on MAPK signaling, smooth-muscle and cardiovascular physiology, thermogenesis, and adipocyte lipolysis. Activated receptors are regulated by arrestin- and ubiquitin-dependent endocytosis, recycling, lysosomal sorting, and Golgi-associated palmitoylation-dependent trafficking. Beyond terminating signaling, internalized beta-arrestin-bound receptors can sustain G protein signaling from endosomes, so receptor output is shaped by subcellular location as well as ligand.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0043410 positive regulation of MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of MAPK cascade is a supported ADRB2 signaling branch. Reason: ADRB2 activates ERK/MAPK through beta-arrestin/Src/EGFR-associated receptor complexes, so this is a real receptor signaling output rather than a project-level inference. Supporting Evidence: PMID:10734107 beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization PMID:10734107 beta(2)AR-dependent signaling to ERK1/2 PMID:15123695 regulate adenylyl cyclase and extracellular signal-regulated kinase activity |
| GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Adenylate cyclase-activating adrenergic receptor signaling is a core ADRB2 function. Reason: The core beta-2 adrenergic receptor activity couples catecholamine binding to Gs, cAMP/PKA, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase PMID:15123695 isoproterenol to stimulate adenylyl cyclase |
| GO:0002025 norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Systemic blood-pressure vasodilation is plausible phylogenetic physiology context, but not a core ADRB2 molecular function. Reason: This IBA row is retained as non-core physiology context from phylogenetic/curated annotation. The cached MARCH2 paper only provides background about vascular tone and is not used as experimental support for this term; the local review does not identify direct human ADRB2 vasodilation experiments among the cached sources. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to |
| GO:0004941 beta2-adrenergic receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Beta2-adrenergic receptor activity is the core ADRB2 molecular function. Reason: ADRB2 is the beta-2 adrenergic receptor; mutagenesis and UniProt evidence support catecholamine binding, Gs/Gi coupling, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0051380 norepinephrine binding | IBA GO_REF:0000033 | ACCEPT | Summary: Norepinephrine binding is supported as part of the catecholamine receptor activity. Reason: ADRB2 binds catecholamines including norepinephrine, although epinephrine has higher affinity. This ligand-binding term supports the core beta-2 adrenergic receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0004930 G protein-coupled receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic GPCR activity is correct but too broad for ADRB2. Reason: Replace the broad GPCR activity term with the more specific beta2-adrenergic receptor activity already supported for ADRB2. Proposed replacements: beta2-adrenergic receptor activity Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase |
| GO:0004935 adrenergic receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic adrenergic receptor activity is correct but less specific than beta2-adrenergic receptor activity. Reason: ADRB2 is specifically the beta-2 adrenergic receptor, so the specific child term should be used rather than a broader adrenergic receptor activity term. Proposed replacements: beta2-adrenergic receptor activity Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0004939 beta-adrenergic receptor activity | IEA GO_REF:0000117 | MODIFY | Summary: Beta-adrenergic receptor activity is correct but less specific than beta2-adrenergic receptor activity. Reason: ADRB2 should be annotated to beta2-adrenergic receptor activity rather than the broader beta-adrenergic receptor parent. Proposed replacements: beta2-adrenergic receptor activity Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0004941 beta2-adrenergic receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Beta2-adrenergic receptor activity is the core ADRB2 molecular function. Reason: ADRB2 is the beta-2 adrenergic receptor; mutagenesis and UniProt evidence support catecholamine binding, Gs/Gi coupling, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Golgi apparatus is a supported receptor itinerary location but not the primary active signaling location. Reason: Activated ADRB2 can traffic through the Golgi in a palmitoylation-dependent itinerary, but the primary core location for receptor signaling is the plasma membrane. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt Golgi apparatus PMID:27481942 traffics along a previously undescribed intracellular itinerary via the Golgi complex PMID:27481942 Cys-265 S-palmitoylation is mediated by the Golgi-resident palmitoyl transferases |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0006940 regulation of smooth muscle contraction | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Regulation of smooth muscle contraction is broad vascular physiology context and is not directly supported by the cached ADRB2 experiments. Reason: The previous MARCH2 citation was introductory background rather than experimental support. Because the cached evidence directly supports ADRB2 receptor signaling and trafficking rather than smooth-muscle contraction regulation, this broad IEA physiology row should be treated as over-annotated. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Generic GPCR signaling is too broad for ADRB2. Reason: Replace the broad GPCR signaling pathway with adrenergic receptor signaling and, where appropriate, the adenylate cyclase-activating adrenergic receptor signaling pathway. Proposed replacements: adrenergic receptor signaling pathway adenylate cyclase-activating adrenergic receptor signaling pathway Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase |
| GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Generic adenylate cyclase-activating GPCR signaling is too broad for ADRB2. Reason: Use the adrenergic receptor-specific adenylate cyclase-activating pathway term for ADRB2 rather than the generic GPCR parent. Proposed replacements: adenylate cyclase-activating adrenergic receptor signaling pathway Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Membrane is correct but too broad for ADRB2 localization. Reason: ADRB2 is a multi-pass receptor whose core location is the plasma membrane; the generic membrane term should be replaced with plasma membrane. Proposed replacements: plasma membrane Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0097746 blood vessel diameter maintenance | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Blood vessel diameter maintenance is broad vascular physiology context and is not directly supported by the cached ADRB2 experiments. Reason: The previous MARCH2 citation was introductory background rather than experimental support. The reviewed evidence supports catecholamine receptor signaling, but not a direct ADRB2-specific blood-vessel-diameter maintenance assay, so this IEA row is over-annotated. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to |
| GO:0005515 protein binding | IPI PMID:17148612 A system for quantifying dynamic protein interactions define... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:17170700 Dosage-dependent switch from G protein-coupled to G protein-... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:20353789 Beta-2 adrenergic receptor mediated ERK activation is regula... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:23291003 Adenosine A1 receptors heterodimerize with Ξ²1- and Ξ²2-adrene... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:28298427 Systematic protein-protein interaction mapping for clinicall... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:9671706 A C-terminal motif found in the beta2-adrenergic receptor, P... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0042802 identical protein binding | IPI PMID:15518545 Biochemical and biophysical characterization of serotonin 5-... | KEEP AS NON CORE | Summary: Identical protein binding reflects receptor oligomerization, but it is not ADRB2 core function. Reason: ADRB2 oligomerization/hetero-oligomerization is supported, but the core molecular function remains catecholamine receptor activity and downstream GPCR signaling. Supporting Evidence: PMID:15123695 hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors |
| GO:0042802 identical protein binding | IPI PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors in... | KEEP AS NON CORE | Summary: Identical protein binding reflects receptor oligomerization, but it is not ADRB2 core function. Reason: ADRB2 oligomerization/hetero-oligomerization is supported, but the core molecular function remains catecholamine receptor activity and downstream GPCR signaling. Supporting Evidence: PMID:15123695 hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors |
| GO:0042802 identical protein binding | IPI PMID:20590567 Physical and functional interaction between CB1 cannabinoid ... | KEEP AS NON CORE | Summary: Identical protein binding reflects receptor oligomerization, but it is not ADRB2 core function. Reason: ADRB2 oligomerization/hetero-oligomerization is supported, but the core molecular function remains catecholamine receptor activity and downstream GPCR signaling. Supporting Evidence: PMID:15123695 hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors |
| GO:0005634 nucleus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Nucleus is not supported as a primary ADRB2 location. Reason: The reviewed UniProt and publication evidence supports plasma membrane, endosomal/lysosomal trafficking, and Golgi itinerary contexts, not a nuclear ADRB2 location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Golgi apparatus |
| GO:0008179 adenylate cyclase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Adenylate cyclase binding is supported as receptor-effector complex context but is not the core MF term. Reason: ADRB2 can associate with adenylyl cyclase and channel-effector complexes, but beta2-adrenergic receptor activity is the more direct core molecular function. Supporting Evidence: PMID:12297500 beta(2)-adrenergic receptors (beta(2)-AR) form stable complexes with Kir3 channels PMID:12297500 beta(2)AR interacts directly with Kir3.1/3.4 and Kir3.1/3.2c heterotetramers as well as with adenylyl cyclase |
| GO:0010666 positive regulation of cardiac muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cardiac muscle cell apoptosis is a context-specific signaling output. Reason: Cardiomyocyte apoptotic/survival effects derive from bifurcated Gs/Gi signaling and are tissue-context outputs rather than the core receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte file:human/ADRB2/ADRB2-uniprot.txt Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of cardiac muscle cell apoptosis is a context-specific signaling output. Reason: Cardiomyocyte apoptotic/survival effects derive from bifurcated Gs/Gi signaling and are tissue-context outputs rather than the core receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte file:human/ADRB2/ADRB2-uniprot.txt Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apical plasma membrane is plausible specialized plasma-membrane context, but not the primary localization term. Reason: ADRB2 is primarily a plasma-membrane GPCR; apical plasma membrane can be retained as cell-type context but should not replace the core plasma membrane annotation. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic enzyme binding is not an informative ADRB2 molecular function. Reason: ADRB2 has specific signaling and trafficking partners, but generic enzyme binding should not be used as a functional endpoint when beta2-adrenergic receptor activity and specific pathway terms are available. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Specific interaction contexts such as receptor oligomerization |
| GO:0061885 positive regulation of mini excitatory postsynaptic potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of mini excitatory postsynaptic potential is a neuronal downstream context. Reason: The amyloid-beta/AMPA receptor study supports a neuronal beta2AR signaling complex affecting excitatory postsynaptic currents, but this is a specialized context rather than the core ADRB2 function. Supporting Evidence: PMID:20395454 soluble Abeta binds to beta(2)AR PMID:20395454 binding is required to induce G-protein/cAMP/protein kinase A (PKA) signaling PMID:20395454 beta(2)AR and GluR1 also form a complex |
| GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Adenylate cyclase-activating adrenergic receptor signaling is a core ADRB2 function. Reason: The core beta-2 adrenergic receptor activity couples catecholamine binding to Gs, cAMP/PKA, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase PMID:15123695 isoproterenol to stimulate adenylyl cyclase |
| GO:0071881 adenylate cyclase-inhibiting adrenergic receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Adenylate cyclase-inhibiting adrenergic receptor signaling is supportable as the Gi arm of ADRB2 signaling. Reason: UniProt describes ADRB2 coupling to both Gs and Gi proteins; the Gi branch is part of bifurcated beta-2 adrenergic receptor signaling even if it is more context-dependent than the canonical Gs/cAMP arm. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase |
| GO:0098992 neuronal dense core vesicle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Neuronal dense core vesicle is not supported as a primary ADRB2 active location. Reason: The local evidence supports plasma membrane receptor activity and endosomal/Golgi trafficking. Dense-core vesicle activity is not established by the reviewed ADRB2 publications. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0106134 positive regulation of cardiac muscle cell contraction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cardiac muscle cell contraction is a downstream tissue-specific output. Reason: Cardiomyocyte contraction-rate regulation is a physiological output of beta-adrenergic signaling and is secondary to the core receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte file:human/ADRB2/ADRB2-uniprot.txt Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate |
| GO:0120162 positive regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cold-induced thermogenesis is not supported as an ADRB2-specific annotation by the cited triple-knockout study. Reason: PMID:12387862 tests beta1/beta2/beta3 adrenoceptor triple-knockout mice, so its cold-intolerance phenotype supports beta-adrenergic signaling broadly, not ADRB2 specifically. ADRB2-specific adipocyte evidence supports cAMP-stimulated lipolysis, but not direct positive regulation of cold-induced thermogenesis at the gene level. Supporting Evidence: PMID:12387862 TKO mice exhibited normophagic obesity and cold-intolerance PMID:12387862 beta-adrenergic signalling is essential for the resistance to obesity and cold PMID:23708524 ADRB2-cAMP-stimulated lipolysis in fat cells |
| GO:1904646 cellular response to amyloid-beta | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to amyloid-beta is a supported disease-context signaling response. Reason: A beta binds beta2AR and induces PKA-dependent AMPA receptor hyperactivity, but this Alzheimer-disease-related context is not ADRB2 core physiology. Supporting Evidence: PMID:20395454 soluble Abeta binds to beta(2)AR PMID:20395454 binding is required to induce G-protein/cAMP/protein kinase A (PKA) signaling PMID:20395454 beta(2)AR and GluR1 also form a complex |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | EXP PMID:20559325 Arrestin domain-containing protein 3 recruits the NEDD4 E3 l... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | EXP PMID:25220262 Insights into Ξ²2-adrenergic receptor binding from structures... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | EXP PMID:2831218 Site-directed mutagenesis and continuous expression of human... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | EXP PMID:7915137 Amino-terminal polymorphisms of the human beta 2-adrenergic ... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0071875 adrenergic receptor signaling pathway | IGI PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | ACCEPT | Summary: Adrenergic receptor signaling pathway is a core ADRB2 signaling annotation. Reason: ADRB2 transduces catecholamine binding into adrenergic receptor signaling through G protein, cAMP/PKA, beta-arrestin, and MAPK-associated branches. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase PMID:10734107 beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization PMID:10734107 beta(2)AR-dependent signaling to ERK1/2 PMID:15123695 regulate adenylyl cyclase and extracellular signal-regulated kinase activity |
| GO:1900451 positive regulation of glutamate receptor signaling pathway | IGI PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | KEEP AS NON CORE | Summary: Positive regulation of glutamate receptor signaling is a neuronal amyloid-beta context. Reason: The amyloid-beta study supports beta2AR/AMPA receptor complex signaling, but this is a specialized neuronal disease-context output rather than the central ADRB2 function. Supporting Evidence: PMID:20395454 soluble Abeta binds to beta(2)AR PMID:20395454 binding is required to induce G-protein/cAMP/protein kinase A (PKA) signaling PMID:20395454 beta(2)AR and GluR1 also form a complex |
| GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway | IGI PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | ACCEPT | Summary: Adenylate cyclase-activating adrenergic receptor signaling is a core ADRB2 function. Reason: The core beta-2 adrenergic receptor activity couples catecholamine binding to Gs, cAMP/PKA, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase PMID:15123695 isoproterenol to stimulate adenylyl cyclase |
| GO:0004941 beta2-adrenergic receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Beta2-adrenergic receptor activity is the core ADRB2 molecular function. Reason: ADRB2 is the beta-2 adrenergic receptor; mutagenesis and UniProt evidence support catecholamine binding, Gs/Gi coupling, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0004941 beta2-adrenergic receptor activity | IMP PMID:2831218 Site-directed mutagenesis and continuous expression of human... | ACCEPT | Summary: Beta2-adrenergic receptor activity is the core ADRB2 molecular function. Reason: ADRB2 is the beta-2 adrenergic receptor; mutagenesis and UniProt evidence support catecholamine binding, Gs/Gi coupling, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0005886 plasma membrane | IDA PMID:19584355 Oxygen-regulated beta(2)-adrenergic receptor hydroxylation b... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0010666 positive regulation of cardiac muscle cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of cardiac muscle cell apoptosis is a context-specific signaling output. Reason: Cardiomyocyte apoptotic/survival effects derive from bifurcated Gs/Gi signaling and are tissue-context outputs rather than the core receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte file:human/ADRB2/ADRB2-uniprot.txt Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of cardiac muscle cell apoptosis is a context-specific signaling output. Reason: Cardiomyocyte apoptotic/survival effects derive from bifurcated Gs/Gi signaling and are tissue-context outputs rather than the core receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte file:human/ADRB2/ADRB2-uniprot.txt Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate |
| GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway | IC PMID:2831218 Site-directed mutagenesis and continuous expression of human... | ACCEPT | Summary: Adenylate cyclase-activating adrenergic receptor signaling is a core ADRB2 function. Reason: The core beta-2 adrenergic receptor activity couples catecholamine binding to Gs, cAMP/PKA, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase PMID:15123695 isoproterenol to stimulate adenylyl cyclase |
| GO:0071881 adenylate cyclase-inhibiting adrenergic receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Adenylate cyclase-inhibiting adrenergic receptor signaling is supportable as the Gi arm of ADRB2 signaling. Reason: UniProt describes ADRB2 coupling to both Gs and Gi proteins; the Gi branch is part of bifurcated beta-2 adrenergic receptor signaling even if it is more context-dependent than the canonical Gs/cAMP arm. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase |
| GO:0106134 positive regulation of cardiac muscle cell contraction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of cardiac muscle cell contraction is a downstream tissue-specific output. Reason: Cardiomyocyte contraction-rate regulation is a physiological output of beta-adrenergic signaling and is secondary to the core receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte file:human/ADRB2/ADRB2-uniprot.txt Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate |
| GO:0042803 protein homodimerization activity | IPI PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | KEEP AS NON CORE | Summary: Protein homodimerization activity is supported receptor oligomerization context but not core function. Reason: ADRB2 can form receptor oligomers, but oligomerization is secondary to catecholamine receptor activity and signaling. Supporting Evidence: PMID:15123695 hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors |
| GO:0044877 protein-containing complex binding | IPI PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | KEEP AS NON CORE | Summary: Protein-containing complex binding is supported by the amyloid-beta/AMPA receptor complex context. Reason: The amyloid-beta study supports beta2AR participation in a postsynaptic signaling complex, but this generic binding term is less informative than receptor activity and pathway-specific signaling terms. Supporting Evidence: PMID:20395454 soluble Abeta binds to beta(2)AR PMID:20395454 binding is required to induce G-protein/cAMP/protein kinase A (PKA) signaling PMID:20395454 beta(2)AR and GluR1 also form a complex |
| GO:0098990 AMPA selective glutamate receptor signaling pathway | IGI PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | KEEP AS NON CORE | Summary: AMPA-selective glutamate receptor signaling is a specialized neuronal output. Reason: Beta2AR can mediate amyloid-beta-induced AMPA receptor hyperactivity, but this is a disease/neuron signaling branch rather than ADRB2 core function. Supporting Evidence: PMID:20395454 soluble Abeta binds to beta(2)AR PMID:20395454 binding is required to induce G-protein/cAMP/protein kinase A (PKA) signaling PMID:20395454 beta(2)AR and GluR1 also form a complex |
| GO:0045744 negative regulation of G protein-coupled receptor signaling pathway | IDA PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | KEEP AS NON CORE | Summary: Negative regulation of GPCR signaling is supported as receptor regulation/desensitization context. Reason: Hetero-oligomerization and beta-arrestin/endocytic regulation can dampen ADRB2 signaling, but the central function remains receptor activation of adrenergic signaling pathways. Supporting Evidence: PMID:15123695 hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes |
| GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway | IDA PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | ACCEPT | Summary: Adenylate cyclase-activating adrenergic receptor signaling is a core ADRB2 function. Reason: The core beta-2 adrenergic receptor activity couples catecholamine binding to Gs, cAMP/PKA, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase PMID:15123695 isoproterenol to stimulate adenylyl cyclase |
| GO:0005515 protein binding | IPI PMID:23166351 MARCH2 promotes endocytosis and lysosomal sorting of carvedi... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005886 plasma membrane | IDA PMID:23166351 MARCH2 promotes endocytosis and lysosomal sorting of carvedi... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005794 Golgi apparatus | IDA PMID:27481942 S-Palmitoylation of a Novel Site in the Ξ²2-Adrenergic Recept... | KEEP AS NON CORE | Summary: Golgi apparatus is a supported receptor itinerary location but not the primary active signaling location. Reason: Activated ADRB2 can traffic through the Golgi in a palmitoylation-dependent itinerary, but the primary core location for receptor signaling is the plasma membrane. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt Golgi apparatus PMID:27481942 traffics along a previously undescribed intracellular itinerary via the Golgi complex PMID:27481942 Cys-265 S-palmitoylation is mediated by the Golgi-resident palmitoyl transferases |
| GO:0005886 plasma membrane | IDA PMID:27481942 S-Palmitoylation of a Novel Site in the Ξ²2-Adrenergic Recept... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868658 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane is a supported receptor trafficking location. Reason: Activated ADRB2 is internalized through clathrin-coated pits/vesicles during receptor down-regulation and sorting, but this is receptor lifecycle context rather than the core active signaling location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868659 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane is a supported receptor trafficking location. Reason: Activated ADRB2 is internalized through clathrin-coated pits/vesicles during receptor down-regulation and sorting, but this is receptor lifecycle context rather than the core active signaling location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868660 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane is a supported receptor trafficking location. Reason: Activated ADRB2 is internalized through clathrin-coated pits/vesicles during receptor down-regulation and sorting, but this is receptor lifecycle context rather than the core active signaling location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868661 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane is a supported receptor trafficking location. Reason: Activated ADRB2 is internalized through clathrin-coated pits/vesicles during receptor down-regulation and sorting, but this is receptor lifecycle context rather than the core active signaling location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8869438 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane is a supported receptor trafficking location. Reason: Activated ADRB2 is internalized through clathrin-coated pits/vesicles during receptor down-regulation and sorting, but this is receptor lifecycle context rather than the core active signaling location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871193 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane is a supported receptor trafficking location. Reason: Activated ADRB2 is internalized through clathrin-coated pits/vesicles during receptor down-regulation and sorting, but this is receptor lifecycle context rather than the core active signaling location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871194 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane is a supported receptor trafficking location. Reason: Activated ADRB2 is internalized through clathrin-coated pits/vesicles during receptor down-regulation and sorting, but this is receptor lifecycle context rather than the core active signaling location. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:12387862 Beta(1)/beta(2)/beta(3)-adrenoceptor knockout mice are obese... | MARK AS OVER ANNOTATED | Summary: Cold-induced thermogenesis is not supported as an ADRB2-specific annotation by the cited triple-knockout study. Reason: PMID:12387862 tests beta1/beta2/beta3 adrenoceptor triple-knockout mice, so its cold-intolerance phenotype supports beta-adrenergic signaling broadly, not ADRB2 specifically. ADRB2-specific adipocyte evidence supports cAMP-stimulated lipolysis, but not direct positive regulation of cold-induced thermogenesis at the gene level. Supporting Evidence: PMID:12387862 TKO mice exhibited normophagic obesity and cold-intolerance PMID:12387862 beta-adrenergic signalling is essential for the resistance to obesity and cold PMID:23708524 ADRB2-cAMP-stimulated lipolysis in fat cells |
| GO:0001540 amyloid-beta binding | IDA PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | KEEP AS NON CORE | Summary: Amyloid-beta binding is direct but disease-context and not a core ADRB2 function. Reason: Soluble amyloid beta binding to beta2AR is experimentally supported, but it is a specialized Alzheimer-disease-related interaction rather than ADRB2 canonical catecholamine receptor function. Supporting Evidence: PMID:20395454 soluble Abeta binds to beta(2)AR PMID:20395454 binding is required to induce G-protein/cAMP/protein kinase A (PKA) signaling PMID:20395454 beta(2)AR and GluR1 also form a complex |
| GO:0004941 beta2-adrenergic receptor activity | NAS PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | ACCEPT | Summary: Beta2-adrenergic receptor activity is the core ADRB2 molecular function. Reason: ADRB2 is the beta-2 adrenergic receptor; mutagenesis and UniProt evidence support catecholamine binding, Gs/Gi coupling, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0016020 membrane | NAS PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | MODIFY | Summary: Membrane is correct but too broad for ADRB2 localization. Reason: ADRB2 is a multi-pass receptor whose core location is the plasma membrane; the generic membrane term should be replaced with plasma membrane. Proposed replacements: plasma membrane Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:1904646 cellular response to amyloid-beta | IGI PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | KEEP AS NON CORE | Summary: Cellular response to amyloid-beta is a supported disease-context signaling response. Reason: A beta binds beta2AR and induces PKA-dependent AMPA receptor hyperactivity, but this Alzheimer-disease-related context is not ADRB2 core physiology. Supporting Evidence: PMID:20395454 soluble Abeta binds to beta(2)AR PMID:20395454 binding is required to induce G-protein/cAMP/protein kinase A (PKA) signaling PMID:20395454 beta(2)AR and GluR1 also form a complex |
| GO:1990911 response to psychosocial stress | TAS PMID:20395454 Binding of amyloid beta peptide to beta2 adrenergic receptor... | MARK AS OVER ANNOTATED | Summary: Response to psychosocial stress is too high-level for a direct ADRB2 gene annotation from the reviewed evidence. Reason: The supporting ADRB2 evidence is receptor signaling and amyloid-beta neuronal signaling; a broad organismal psychosocial-stress response annotation is not a precise gene-product function. Supporting Evidence: PMID:20395454 non-neurotransmitter Abeta has a binding capacity to beta(2)AR |
| GO:0004941 beta2-adrenergic receptor activity | IDA PMID:19710023 Structure of an arrestin2-clathrin complex reveals a novel c... | ACCEPT | Summary: Beta2-adrenergic receptor activity is the core ADRB2 molecular function. Reason: ADRB2 is the beta-2 adrenergic receptor; mutagenesis and UniProt evidence support catecholamine binding, Gs/Gi coupling, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0005886 plasma membrane | IDA PMID:19710023 Structure of an arrestin2-clathrin complex reveals a novel c... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0071875 adrenergic receptor signaling pathway | IDA PMID:19710023 Structure of an arrestin2-clathrin complex reveals a novel c... | ACCEPT | Summary: Adrenergic receptor signaling pathway is a core ADRB2 signaling annotation. Reason: ADRB2 transduces catecholamine binding into adrenergic receptor signaling through G protein, cAMP/PKA, beta-arrestin, and MAPK-associated branches. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase PMID:10734107 beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization PMID:10734107 beta(2)AR-dependent signaling to ERK1/2 PMID:15123695 regulate adenylyl cyclase and extracellular signal-regulated kinase activity |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5696968 | KEEP AS NON CORE | Summary: Endosome membrane is a supported post-endocytic receptor trafficking location. Reason: Internalized ADRB2 is sorted between recycling and lysosomal routes from endosomes, but this is secondary to the plasma-membrane receptor signaling role. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes PMID:19424180 sort internalized receptors to the lysosomes for degradation |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8851797 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8852167 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866269 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866283 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982641 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:1901098 positive regulation of autophagosome maturation | IDA PMID:23708524 Ξ²-adrenergic receptor-stimulated lipolysis requires the RAB7... | KEEP AS NON CORE | Summary: Positive regulation of autophagosome maturation is supported in ADRB2-stimulated adipocyte lipolysis but is non-core. Reason: ADRB2 stimulation increases autophagy-targeted lipid droplets, but the direct lipophagy machinery in the paper is RAB7; therefore this is retained as an upstream adipocyte signaling output rather than a core ADRB2 function. Supporting Evidence: PMID:23708524 ADRB2-stimulated lipolysis was reduced after inhibition of early or late autophagy PMID:23708524 ADRB2 stimulation has caused a marked increase in the autophagy-targeted LDs for lysosomal degradation PMID:23708524 during ADRB2 stimulation, a subset of LDs are packaged into autophagosomes and delivered to the lysosomes for degradation PMID:23708524 RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells file:human/ADRB2/ADRB2-notes.md do not add direct `lipophagy` for ADRB2 |
| GO:1904504 positive regulation of lipophagy | IDA PMID:23708524 Ξ²-adrenergic receptor-stimulated lipolysis requires the RAB7... | KEEP AS NON CORE | Summary: Positive regulation of lipophagy is supported as upstream ADRB2 adipocyte signaling, but should not be upgraded to direct lipophagy. Reason: The PN projection to direct lipophagy is not accepted for ADRB2. PMID:23708524 supports ADRB2 stimulation as an upstream signal that increases lipophagy/autophagy-targeted lipid droplets, while RAB7 is the direct lipid-droplet recruitment and autolysosomal degradation factor. Supporting Evidence: PMID:23708524 ADRB2-stimulated lipolysis was reduced after inhibition of early or late autophagy PMID:23708524 ADRB2 stimulation has caused a marked increase in the autophagy-targeted LDs for lysosomal degradation PMID:23708524 during ADRB2 stimulation, a subset of LDs are packaged into autophagosomes and delivered to the lysosomes for degradation PMID:23708524 RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells file:human/ADRB2/ADRB2-notes.md do not add direct `lipophagy` for ADRB2 |
| GO:0005515 protein binding | IPI PMID:24405750 CNIH4 interacts with newly synthesized GPCR and controls the... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0043235 signaling receptor complex | IDA PMID:23382219 Structural basis for endosomal trafficking of diverse transm... | ACCEPT | Summary: Signaling receptor complex is a supported core context for ADRB2 signaling. Reason: ADRB2 functions in receptor-effector and receptor-scaffold complexes that support beta-adrenergic signaling, including beta2/beta3 receptor signaling units and postsynaptic complexes. Supporting Evidence: PMID:15123695 hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors PMID:12297500 beta(2)-adrenergic receptors (beta(2)-AR) form stable complexes with Kir3 channels |
| GO:0005515 protein binding | IPI PMID:20733053 SNX27 mediates PDZ-directed sorting from endosomes to the pl... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-379044 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-744886 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-744887 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982645 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9609310 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9611751 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9611851 | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0005515 protein binding | IPI PMID:19584355 Oxygen-regulated beta(2)-adrenergic receptor hydroxylation b... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005515 protein binding | IPI PMID:19424180 The deubiquitinases USP33 and USP20 coordinate beta2 adrener... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005886 plasma membrane | IDA PMID:12297500 G protein-coupled receptors form stable complexes with inwar... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0015459 potassium channel regulator activity | IDA PMID:12297500 G protein-coupled receptors form stable complexes with inwar... | KEEP AS NON CORE | Summary: Potassium channel regulator activity is supported receptor-effector context but not core ADRB2 function. Reason: ADRB2 can form stable complexes with Kir3 potassium channels and adenylyl cyclase, but this specialized effector-complex role is secondary to beta2-adrenergic receptor activity. Supporting Evidence: PMID:12297500 beta(2)-adrenergic receptors (beta(2)-AR) form stable complexes with Kir3 channels PMID:12297500 beta(2)AR interacts directly with Kir3.1/3.4 and Kir3.1/3.2c heterotetramers as well as with adenylyl cyclase |
| GO:0005886 plasma membrane | IDA PMID:9235896 A novel interaction between adrenergic receptors and the alp... | ACCEPT | Summary: Plasma membrane is the primary active location for ADRB2 catecholamine receptor signaling. Reason: ADRB2 is a multi-pass cell-surface GPCR; plasma membrane localization is central to catecholamine binding, G protein coupling, and downstream signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt SUBCELLULAR LOCATION: Cell membrane file:human/ADRB2/ADRB2-uniprot.txt Multi-pass membrane protein PMID:2831218 expression of the human beta 2-adrenergic receptor in mouse L cells |
| GO:0004941 beta2-adrenergic receptor activity | IDA PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | ACCEPT | Summary: Beta2-adrenergic receptor activity is the core ADRB2 molecular function. Reason: ADRB2 is the beta-2 adrenergic receptor; mutagenesis and UniProt evidence support catecholamine binding, Gs/Gi coupling, and adenylate cyclase signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0005515 protein binding | IPI PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0006898 receptor-mediated endocytosis | IDA PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | KEEP AS NON CORE | Summary: Receptor-mediated endocytosis is supported receptor lifecycle regulation. Reason: Agonist-induced beta2AR internalization and down-regulation are well supported, but this is post-activation receptor trafficking rather than the primary receptor signaling function. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes |
| GO:0043235 signaling receptor complex | IDA PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | ACCEPT | Summary: Signaling receptor complex is a supported core context for ADRB2 signaling. Reason: ADRB2 functions in receptor-effector and receptor-scaffold complexes that support beta-adrenergic signaling, including beta2/beta3 receptor signaling units and postsynaptic complexes. Supporting Evidence: PMID:15123695 hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit PMID:19763081 Ligand-regulated oligomerization of beta(2)-adrenoceptors PMID:12297500 beta(2)-adrenergic receptors (beta(2)-AR) form stable complexes with Kir3 channels |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | ACCEPT | Summary: Positive regulation of MAPK cascade is a supported ADRB2 signaling branch. Reason: ADRB2 activates ERK/MAPK through beta-arrestin/Src/EGFR-associated receptor complexes, so this is a real receptor signaling output rather than a project-level inference. Supporting Evidence: PMID:10734107 beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization PMID:10734107 beta(2)AR-dependent signaling to ERK1/2 PMID:15123695 regulate adenylyl cyclase and extracellular signal-regulated kinase activity |
| GO:0051380 norepinephrine binding | IDA PMID:15123695 Hetero-oligomerization between beta2- and beta3-adrenergic r... | ACCEPT | Summary: Norepinephrine binding is supported as part of the catecholamine receptor activity. Reason: ADRB2 binds catecholamines including norepinephrine, although epinephrine has higher affinity. This ligand-binding term supports the core beta-2 adrenergic receptor activity. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt ADRB2 binds epinephrine (Epi) with an file:human/ADRB2/ADRB2-uniprot.txt approximately 30-fold greater affinity than norepinephrine (NE) PMID:2831218 affinity for isoproterenol, epinephrine, and norepinephrine |
| GO:0005515 protein binding | IPI PMID:9560162 The beta2-adrenergic receptor interacts with the Na+/H+-exch... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative ADRB2 molecular-function annotation. Reason: The interaction records identify many receptor partners, but GO protein binding does not describe ADRB2 function. More informative terms are beta2-adrenergic receptor activity, catecholamine binding/signaling, receptor-complex context, and specific trafficking or signaling outputs. Supporting Evidence: file:human/ADRB2/ADRB2-notes.md Generic `protein binding` rows are not informative ADRB2 molecular functions |
| GO:0005764 lysosome | TAS PMID:9507004 Role of clathrin-mediated endocytosis in agonist-induced dow... | KEEP AS NON CORE | Summary: Lysosome is a supported destination for down-regulated ADRB2. Reason: Activated/internalized ADRB2 can be routed to lysosomes for degradation, but lysosome localization is receptor turnover context and not the core active signaling site. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes PMID:19424180 sort internalized receptors to the lysosomes for degradation PMID:20733053 recycling of the beta(2)-adrenoreceptor (beta(2)AR) from early endosomes PMID:23166351 Lysosomal degradation of ubiquitinated beta(2)-adrenergic receptors |
| GO:0005768 endosome | TAS PMID:10734107 The beta(2)-adrenergic receptor mediates extracellular signa... | KEEP AS NON CORE | Summary: Endosome is a supported post-endocytic ADRB2 trafficking compartment. Reason: Internalized ADRB2 traffics through endosomes for recycling or lysosomal degradation, but this is secondary to plasma-membrane signaling. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes PMID:19424180 sort internalized receptors to the lysosomes for degradation PMID:20733053 recycling of the beta(2)-adrenoreceptor (beta(2)AR) from early endosomes |
| GO:0007166 cell surface receptor signaling pathway | TAS PMID:1371121 Ligand-regulated internalization and recycling of human beta... | MODIFY | Summary: Generic cell-surface receptor signaling is too broad for ADRB2. Reason: Replace this broad parent with adrenergic receptor signaling pathway and the adenylate cyclase-activating adrenergic receptor signaling pathway where the evidence specifies cAMP/Gs signaling. Proposed replacements: adrenergic receptor signaling pathway adenylate cyclase-activating adrenergic receptor signaling pathway Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase |
| GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway | TAS PMID:2823249 Structure of the gene for human beta 2-adrenergic receptor: ... | MODIFY | Summary: Generic adenylate cyclase-modulating GPCR signaling is too broad for ADRB2. Reason: ADRB2 should be represented by adrenergic receptor signaling and its activating/inhibiting adenylate cyclase adrenergic receptor branches rather than a generic GPCR signaling term. Proposed replacements: adenylate cyclase-activating adrenergic receptor signaling pathway adenylate cyclase-inhibiting adrenergic receptor signaling pathway Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt G protein-coupled receptor for catecholamines that couples to file:human/ADRB2/ADRB2-uniprot.txt both G(s) and G(i) proteins, activating bifurcated signaling pathways PMID:2831218 associated with high affinity ligand binding, Gs coupling, and adenylate cyclase |
| GO:0008333 endosome to lysosome transport | TAS PMID:9507004 Role of clathrin-mediated endocytosis in agonist-induced dow... | KEEP AS NON CORE | Summary: Endosome to lysosome transport is a supported ADRB2 down-regulation route. Reason: ADRB2 can be sorted from endosomes to lysosomes for degradation during receptor down-regulation, but this is a non-core receptor lifecycle process. Supporting Evidence: file:human/ADRB2/ADRB2-uniprot.txt internalized into endosomes prior to their degradation in lysosomes PMID:9507004 agonist-induced internalization and down-regulation of the beta2AR PMID:9507004 trafficking of the beta2AR via the clathrin-coated pit endosomal pathway to lysosomes PMID:19424180 sort internalized receptors to the lysosomes for degradation PMID:20733053 recycling of the beta(2)-adrenoreceptor (beta(2)AR) from early endosomes PMID:23166351 Lysosomal degradation of ubiquitinated beta(2)-adrenergic receptors |
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Download this section (compressed HTML)Q: Should PN projection for ADRB2 remain at GO:1904504 positive regulation of lipophagy rather than direct GO:0061724 lipophagy?
Suggested experts: GO autophagy editors, Proteostasis Network curators
Q: Which ADRB2 trafficking locations should remain gene-level GO annotations versus pathway-context annotations from receptor lifecycle studies?
Suggested experts: GO signaling editors, GPCR trafficking experts
Q: Should endosomal/sustained beta2AR signaling (G protein activation from endosomes, beta-arrestin megaplexes) be captured as a distinct active location or signaling context for ADRB2, or treated as an emerging mechanism not yet at gene-annotation maturity?
Suggested experts: GO signaling editors, GPCR trafficking experts
Q: Does ADRB2 biased agonism (e.g., beta-arrestin/NF-kB-selective outputs in immune cells) warrant separate biological-process annotations distinct from canonical Gs/cAMP/PKA signaling?
Suggested experts: GPCR pharmacology experts, GO signaling editors
Experiment: Compare ADRB2 knockout/rescue and RAB7 knockout/rescue adipocytes during beta-adrenergic stimulation using lipid-droplet autophagosome recruitment and lysosomal flux reporters.
Hypothesis: ADRB2 acts upstream to stimulate lipophagy, whereas RAB7 is required for direct lipid-droplet autolysosomal delivery.
Experiment: Measure endogenous ADRB2 routing to recycling versus lysosomal compartments after agonists and biased ligands while perturbing ARRDC3, NEDD4, MARCH2, USP20/USP33, and SNX27.
Hypothesis: Distinct trafficking adaptors determine whether activated ADRB2 is recycled/resensitized or degraded after internalization.
Experiment: Use compartment-targeted cAMP/PKA biosensors with agonists and GRK/beta-arrestin perturbations to test whether internalized ADRB2 sustains G protein signaling from endosomes versus only at the plasma membrane.
Hypothesis: A fraction of agonist-activated ADRB2 continues to generate cAMP from endosomes in a beta-arrestin-dependent megaplex-like state, contributing a spatially distinct signaling output.
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