GNB2 encodes GΞ²2, whose canonical product has a seven-bladed WD40 beta-propeller architecture. With a GΞ³ partner it forms the mature GΞ²Ξ³ signaling unit, which associates with inactive GDP-bound GΞ± in resting heterotrimers. Receptor activation promotes nucleotide exchange on GΞ± and allows GΞ²Ξ³ to regulate downstream effectors. GΞ²2/Ξ³2 regulates cardiac GIRK potassium channels. CCT and PDCL assist GΞ² folding and assembly in the cytosol. A GNB2 variant causes familial cardiac conduction dysfunction. Recurrent de novo variants also cause syndromic developmental delay and intellectual disability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003924 GTPase activity | TAS PMID:2902634 Chromosomal localization of genes encoding guanine nucleotid... | REMOVE | Reason: GTP hydrolysis is not a beta-subunit catalytic function. The original paper maps G-protein genes and distinguishes nucleotide-bound alpha from beta/gamma subunits; the independently inspected Rhes paper explicitly places intrinsic GTPase activity on alpha. Remove this TAS catalytic assertion while retaining GNB2 signaling and complex membership. |
| GO:0005515 protein binding | IPI PMID:16498633 Ataxin 10 induces neuritogenesis via interaction with G-prot... | REMOVE | Reason: The abstract directly reports Gbeta2 binding to ATXN10 by two-hybrid screening, with coimmunoprecipitation and colocalization. Remove the uninformative generic binding annotation, without disputing that interaction or converting the overexpression phenotype into a core developmental function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu... | REMOVE | Reason: Retain the curated HTT association: the original study used tagged HTT fragments and tissue or cell lysates, followed by tandem purification and mass spectrometry. This does not identify a specific GNB2 molecular function or establish a purified binary interaction. Remove the uninformative generic term. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26900580 Pathogenic mechanism of recurrent mutations of SCN8A in epil... | REMOVE | Reason: The original study coimmunoprecipitated Gbeta2, coexpressed with Ggamma3, with an HA-tagged SCN8A C-terminal fragment in HEK cells. Retain that positive association as evidence, but remove generic protein binding; it does not independently establish a full-length channel regulatory mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28219978 A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus ... | MODIFY | Reason: Native Gbeta2 co-immunoprecipitates with Ggamma2 and Galphai2 in the tested heterotrimer; refine generic binding to the two identified subunit classes. Proposed replacements: G-protein alpha-subunit binding G-protein gamma-subunit binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Reason: The human GNB2βTARDBP association is supported by the retained BioPlex record and original affinity-purification methods. Preserve the tagged HEK293T assay context; generic binding does not identify a GNB2 functional role. Remove this uninformative term. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29924966 A Proteomic Variant Approach (ProVarA) for Personalized Medi... | REMOVE | Reason: Preserve the CFTR-associated GNB2 evidence across the recorded variant conditions. Original Methods describe CFBE41o- expression followed by lysate immunoprecipitation and mass spectrometry; the curated in-vitro preparation field is not the expression host. Remove generic binding as uninformative, without assigning CFTR variants to GNB2 or inferring direct channel regulation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31324722 Inhibition of calpain 1 restores plasma membrane stability t... | REMOVE | Reason: Retain the curated CFTR association and its CFBE41o- cross-linking context. Indexed primary Figure 1 and cell-culture Methods support surface-complex capture, but the complete original and target supplement were not recovered. Removal addresses the uninformative generic function; it does not reject the interaction or claim a GNB2-specific calpain mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Reason: Uninformative term; interaction retained. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | REMOVE | Reason: Preserve the positive F508del-CFTR MaMTH-HTS result in tagged HEK293 cells. Original supplementary rows identify GNB2 in both technical replicates, while conventional interaction retests were unconfirmed and CFBE trafficking assays showed no significant effect. Remove the uninformative generic term without denying the screening result or inferring a physiological CFTR-regulatory function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | REMOVE | Reason: The retained CFTRβGNB2 records describe proximity labeling in HEK293 cells with specified CFTR variants. Original Methods confirm biotin-labeling and mass-spectrometry workflows. Preserve this positive proximity evidence; it does not establish purified binary binding or a specific GNB2 channel-regulatory function. Remove the uninformative generic term. Supporting Evidence: |
| GO:0030159 signaling receptor complex adaptor activity | IBA GO_REF:0000033 | ACCEPT | Reason: The exact 340-residue human sequence descends from the asserted AN0 node. In the fission-yeast donor experiment, Git5 strengthened Gpa2βGit3 interaction in a heterologous yeast two-hybrid assay with a control third protein. This supports receptor-complex assembly rather than assigning nucleotide exchange chemistry to beta. The later IBD adds donors; the incoming donor list remains literal. This ancestral inference is compatible with the human beta-subunit role. |
| GO:0044877 protein-containing complex binding | IDA PMID:23209302 KIF14 negatively regulates Rap1a-Radil signaling during brea... | KEEP AS NON CORE | Reason: Figure 3B explicitly includes GNB2 in FLAG-mRadil and FLAG-mRadil-deltaPDZ complexes from human MDA-MB-231 cells. Retain this complex association as contextual evidence. Affinity purification with a mouse Radil bait does not establish a direct GNB2-KIF14 contact or a GNB2-specific migration mechanism. Supporting Evidence: |
| GO:0051020 GTPase binding | IPI PMID:19255495 The cationic region of Rhes mediates its interactions with s... | KEEP AS NON CORE | Reason: Full-length human Gbeta2 interacted with Rhes in controlled reciprocal yeast two-hybrid assays. Rhes is a small GTPase, making the binding term appropriate. Retain this specific partner interaction outside the core summary; the subsequent Gbeta1 domain mapping was not a Gbeta2 experiment. Supporting Evidence: |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | TOO GENERAL | Reason: The family-based signaling assignment is consistent with GNB2 biology, but the existing GPCR signaling annotations capture its established role more precisely. GO:0007186 is an is_a descendant of this term. Supporting Evidence: GO_REF:0000002 GO_REF:0000033 |
| GO:0007186 G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Reason: The target inherits the AN0 assertion. Native bovine beta1βgamma1 participates in a light-activated receptor complex with engineered alpha, supporting a beta-subunit contribution to GPCR signaling. This is phylogenetic support, not a direct human beta2 experiment; the incoming donor version remains unchanged. |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:7649993 Mitogen-activated protein kinase activation requires two sig... | ACCEPT | Reason: Retain the established GPCR signaling role, corroborated by UniProt. The cited abstract describes receptor-dependent HEK293 signaling; target-specific construct details were unavailable. |
| GO:1901379 regulation of potassium ion transmembrane transport | IMP PMID:28219978 A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus ... | ACCEPT | Reason: The study compares wild-type and Arg52Leu Gbeta2 with Ggamma2 in HEK293T cells and Xenopus oocytes, showing altered cardiac GIRK activation. This supports regulation of potassium transport by the signaling complex, without making GNB2 a channel pore or generalizing the mutant gain of function to normal physiology. Supporting Evidence: |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Reason: The exact target lies below the cytoplasmic-activity assertion, with all listed donors resolved on the family tree. Its own inclusion is legitimate descendant evidence, not circularity. Retain the actual is_active_in relation: narrower location-only observations do not independently specify where this molecular activity occurs. No target-specific loss or contradictory compartment requirement was established. |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The stated donor P62880 is mouse Gnb2. Current SynGO records provide experimental synapse evidence, and the cited study detects Gbeta2 in stimulated mouse-brain synaptosome SNARE complexes. Retain the orthology-based localization as a neuronal context, without representing it as a direct human assay. |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | KEEP AS NON CORE | Reason: Retain the curated extracellular detection associated with human colostrum proteomics. This is a sampling context rather than evidence for an extracellular signaling function of GNB2. The target peptide inventory was not independently reread; the source extension is preserved. Supporting Evidence: |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | KEEP AS NON CORE | Reason: Retain contextual lysosomal-membrane localization. Original human-placenta Table 1 lists beta-2 (IPI00003348) with 16 peptides, 63.4% coverage and significant enrichment. This supports preparation-specific association; it does not establish integral topology or a lysosome-specific catalytic function. Peptide uniqueness and the historical IPI sequence were not independently reconstructed. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814119 | KEEP AS NON CORE | Reason: Retain cytosolic localization of the unfolded beta-subunit client during CCT capture as non-core; the chaperonin performs the folding. Supporting Evidence: Reactome:R-HSA-6814119 file:human/GNB2/GNB2-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814120 | KEEP AS NON CORE | Reason: CCT-mediated folding contains unfolded and partially folded beta-subunit clients in the cytosol. Retain this maturation location as non-core, without assigning ATP hydrolysis or chaperone activity to the client. Supporting Evidence: Reactome:R-HSA-6814120 file:human/GNB2/GNB2-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814121 | KEEP AS NON CORE | Reason: PDCL binds the partially folded beta-subunit client on CCT. Its explicit cytosolic location is retained as non-core maturation context. Supporting Evidence: Reactome:R-HSA-6814121 file:human/GNB2/GNB2-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814124 | KEEP AS NON CORE | Reason: ATP binds the CCT chaperonin around its unfolded beta-subunit client. Retain the client's cytosolic location as non-core; ATP binding is not assigned to the beta subunit. Supporting Evidence: Reactome:R-HSA-6814124 file:human/GNB2/GNB2-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814418 | KEEP AS NON CORE | Reason: PDCL-assisted beta-gamma assembly retains a cytosol-labeled beta-subunit member within its plasma-membrane product. Keep this preparatory client location as non-core. Supporting Evidence: Reactome:R-HSA-6814418 file:human/GNB2/GNB2-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-825631 | KEEP AS NON CORE | Reason: The event places the cytosol-labeled GNB2 member within plasma-membrane heterotrimer and beta-gamma complexes. Retain the member location as non-core; this hierarchy does not establish cytosol as a core site of signaling activity. Supporting Evidence: Reactome:R-HSA-825631 file:human/GNB2/GNB2-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850527 | KEEP AS NON CORE | Reason: PDCL releases the folded beta-subunit client from CCT into a cytosolic PDCL-bound intermediate. Retain this maturation location as non-core. Supporting Evidence: Reactome:R-HSA-8850527 file:human/GNB2/GNB2-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850560 | KEEP AS NON CORE | Reason: The mature heterotrimer output retains a cytosol-labeled GNB2 member inside a plasma-membrane complex. Keep the member location as non-core; maturation completion does not establish core activity in the cytosol. Supporting Evidence: Reactome:R-HSA-8850560 file:human/GNB2/GNB2-evidence.json |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Reason: UniProt cell-membrane localization agrees with independent human-cell imaging. Retain this location without treating GNB2 as an integral membrane protein. Supporting Evidence: UniProt:P62879 |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Reason: The current Human Protein Atlas record for ENSG00000172354 explicitly reports supported plasma-membrane localization by immunofluorescence. This independently corroborates the existing HPA annotation; no additional compartment is proposed from secondary antibody-specific observations. Supporting Evidence: GO_REF:0000052 file:human/GNB2/GNB2-evidence.json |
| GO:0005886 plasma membrane | IDA PMID:28219978 A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus ... | ACCEPT | Reason: Original Results report membrane localization of native and mutant beta2/gamma2 in HEK293T cells; the supplementary image itself remains uninspected. The retained UniProt record also assigns cell-membrane localization. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Reason: The original study analyzes isolated HFF1 fibroblast focal adhesions by proteomics against a human sequence database. Retain the curated GNB2 localization in that context, preserving the fibroblast extension; no independent inspection of its target-specific peptide row or adhesion mechanism is claimed. Supporting Evidence: |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | TOO GENERAL | Reason: The membrane proteomic observation is compatible with GNB2 localization. Existing plasma-membrane annotations provide a more specific is_a descendant with independent imaging support. Retain the source context without claiming that this survey alone resolves a particular membrane compartment. Supporting Evidence: |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | KEEP AS NON CORE | Reason: Retain the vesicle localization from human airway epithelial secretion proteomics, with its original cell-type extension. Detection in a vesicle preparation does not establish that GNB2 builds vesicles or mediates their antiviral effects; target-specific peptide evidence is deferred to the curator. Supporting Evidence: |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: Retain UniProt's experimentally sourced perinuclear-cytoplasm assignment as contextual localization. Its duplication of the companion experimental record does not invalidate that evidence. Supporting Evidence: UniProt:P62879 |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:16498633 Ataxin 10 induces neuritogenesis via interaction with G-prot... | KEEP AS NON CORE | Reason: Retain the curator's perinuclear location, corroborated by UniProt. The abstract reports mammalian-cell colocalization with ATXN10 but does not specify this compartment; the original imaging panel was unavailable. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Reason: Retain the curated extracellular-exosome detection in human parotid saliva, preserving the anatomical extension. This proteomic context does not establish a core exosome function for GNB2; the original target-specific inventory assignment is deferred to the curator. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Reason: Retain the unextended exosome detection associated with the B-cell proteomic study as a contextual observation. It does not demonstrate a GNB2 role in exosome biogenesis. The target-specific supplementary peptide inventory was unavailable for independent inspection. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | UNDECIDED | Reason: The exosome term is plausible, but this distinct source record adds part_of(CL:0000639), currently a pituitary basophil-cell term. The accessible publication explicitly describes B-cell-derived exosomes. Preserve the original extension and seek clarification of its provenance rather than silently merging or correcting the record. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Reason: Retain the curated exosome detection in expressed prostatic secretions collected in urine. This is a proteomic sampling context, not evidence that GNB2 drives exosome production or prostate disease. The specific GNB2 peptide inventory was not independently replayed. Supporting Evidence: |
| GO:0005834 heterotrimeric G-protein complex | IBA GO_REF:0000033 | ACCEPT | Reason: The exact human beta2 leaf inherits complex membership at AN0. Native bovine beta1βgamma1 was assembled with engineered alpha for receptor-complex structural and biochemical experiments. These donor data support heterotrimer membership without making beta the GTPase or asserting a particular human isoform assay. |
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Download this section (compressed HTML)Q: What is the provenance of the pituitary-cell extension on the exosome record?
Q: Does the shorter annotated product retain receptor-complex assembly and signaling?
Q: Which assay establishes direct GΞ²2/Ξ³2βGIRK binding beyond current regulation?
Experiment: Reconstitute receptor, alpha, beta2 and gamma partners to test adaptor assembly under controlled stoichiometry.
Type: Biochemical reconstitution
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