GABRG2 contributes the gamma2 subunit to heteromeric GABA-A receptors. The review separates human receptor function, ortholog localization, specific partner assertions and recombinant construct evidence. It contains 74 existing contexts and 31 manually assessed references, with no proposed NEW annotation.
The reviewed human entry is UniProt P18507. Direct sequences and independent variation reconstruction agree on the displayed long product P18507-2 (475 residues), short P18507-1 (467) and inserted-segment P18507-3 (515). The eight-residue deletion distinguishes the short form. Purification tags and engineered M3–M4 loop replacements are experimental constructs, not natural product definitions. PMID:30602789 Methods explicitly identifies the long P18507-2 backbone despite the UniProt reference-position range 1–467. Native human mass spectrometry reports short and long gamma2, without assigning a splice product to every structural map.
The core is contribution to a GABA-gated chloride channel in a heteromeric GABA-A receptor complex. Gamma2 contributes pore structure and the alpha/gamma benzodiazepine interface. The orthosteric GABA interfaces are principally beta/alpha interfaces; neither an autonomous gamma2 channel nor gamma2-specific GABA binding is asserted. Receptor composition and the chloride gradient constrain physiological interpretation.
The 74 decisions are 47 ACCEPT, 11 KEEP_AS_NON_CORE, 11 MODIFY, 1 UNDECIDED and 4 REMOVE. The original two contributes_to relations are preserved. There are no original extension atoms.
The unresolved context is the human GABARAPL1 partner attributed to PMID:9892355. Its accessible abstract establishes GABARAP association; the later mouse motif study does not independently verify that original human partner record. The source-specific NAS negative-regulation attribution from PMID:33234346 is removed because the inspected source assigns the inhibitory trafficking step to CLPTM1 and other accessory regulators, while gamma2-containing receptors are the regulated target. This does not claim that gamma2 can never influence transmission negatively in another context.
Three positive association contexts have their uninformative generic protein-binding annotations removed; this does not deny the observed interactions. Their exact assay and access scopes remain recorded. The separate unresolved partner context remains UNDECIDED. Histamine responsiveness is a receptor-composition context, not proof of gamma2 histamine binding. Axonal, vesicular and extrasynaptic pools remain distinct from the principal postsynaptic role. PMID:25172774 directly concerns gamma2 transport-vesicle delivery; it is not used to manufacture matching alpha1 or beta3 evidence.
The actual retained PTHR18945 tree, alignment, node lookup and IBD records place human P18507 at AN1793/PTN002498426. Seven incoming assertions descend from AN1671/PTN008360627; the plasma-membrane assertion descends from AN7/PTN001054635. All eight origins lie on the target lineage, and none of 14 retained negative family records lies on that lineage. The aligned target matches the 475-residue displayed sequence exactly. Legitimate target self-donation is retained; donor counts are not treated as evidence quality. The incoming plasma-membrane set of 66 donors is older than the 147-donor retained record and remains literal.
Nine refinements follow inspected is_a edges. Postsynaptic membrane within postsynaptic specialization and dendrite membrane within dendrite use part_of, not is_a. The chloride-channel-complex assertion is retained as ACCEPT. Both the original and fresh QuickGO queries return no is_a/part_of path from GABA-A receptor complex to chloride channel complex; that absence does not license replacement of a true claim. The possible ontology relationship is raised as a question. The previous semantic-composition proposal is preserved explicitly as withdrawn in the source evidence. The compact evidence file preserves each row's typed relation and official query URL. These refinements preserve positive biology and do not allege that the broad terms are false.
The Reactome975340 reaction was traced through catalyst 975314, complex 975268, set 5340318, heteropentamer 5357502 and gamma set 975308 to entity 975350. The terminal entity names human P18507 residues 40–475 at plasma membrane. This is curated model membership, not an experiment demonstrating every possible subunit combination in vivo.
The normal source union is 41 paths: 35 publications, 3 Reactome records and 3 existing family files. The 31 assessed references comprise 22 publications, 7 GO_REF method documents, one Reactome reaction and UniProt. Unused UniProt bibliography entries are not automatically described as manually read. Existing A1/B2/B3 source blobs remain immutable reuse; the owned PTHR18945 review is excluded. Original 34-path qualification is a dated bounded snapshot. A separate seven-addition check at main b89135d found four immutable-reuse additions and three missing unowned additions; no complete current repository inventory is claimed.
Reference notes below distinguish a native cache from an external original and selected reading from full-paper or image inspection. Full-text availability alone does not mean the entire article, supplements, figures or raw data were read. Initial failed BioC/browser responses are retained as failures. In particular, PMID:15620359's original full text was subsequently found in immutable main and its gamma2 dendritic-surface Results and rat-culture Methods were read.
GO_REF:0000002 — MEDIUM; VERIFIED. Official InterPro-to-GO method description read in the retained method packet. Curated family/domain/site mappings follow signature matches; literal incoming InterPro identifiers remain intact. Human receptor evidence, rather than the method document, adjudicates biological specificity.
GO_REF:0000024 — MEDIUM; VERIFIED. Official curator-mediated orthology-transfer method read. Literal mouse P22723 and rat P18508 sources are preserved and traced to current experimental records where relevant. Retrieving a donor GOA record is not equivalent to reading its original paper; source-specific access limits remain explicit.
GO_REF:0000033 — MEDIUM; VERIFIED. Official PAINT phylogenetic inference description read alongside the actual retained PTHR18945 tree, alignment and IBD records. All eight origins are ancestral to the exact human target with no retained target-path loss. The older incoming plasma-membrane donor subset is preserved separately. Donor count and legitimate target self-donation are not defects.
GO_REF:0000044 — MEDIUM; VERIFIED. Official UniProt subcellular-vocabulary mapping method read. SL identifiers project curated location statements and do not constitute independent microscopy. The gamma2 vesicle statement is traced to the rat UniProt evidence block and its authentic PMID:25172774 abstract, with detailed assay limits retained.
GO_REF:0000107 — MEDIUM; VERIFIED. Official Ensembl Compara transfer method read, including orthology and experimentally supported source requirements. The original mouse accession and Ensembl identifiers are preserved. Current mouse GOA is used to identify donor contexts, not to fabricate a primary-paper reading or natural-product match.
GO_REF:0000108 — MEDIUM; VERIFIED. Official inter-ontology logical-inference method read. The membrane-potential process is derived from GO1904315, not another independent experiment. Receptor currents corroborate the logical link, with gradient-dependent effects kept explicit.
GO_REF:0000120 — MEDIUM; VERIFIED. Official combined electronic-annotation method read. Multiple supplied orthology, InterPro or subcellular sources remain literal. Their combination is not counted as independent biological replication.
PMID:15620359(https://pubmed.ncbi.nlm.nih.gov/15620359/) — HIGH; VERIFIED. Authentic PubMed identity and the immutable main full-text cache were read. Selected Results and Methods (cache lines 90–123 and 167–199) explicitly report gamma2/alpha2 receptor clustering on dendrites, MAP2 colabeling and live-cell antibody evidence of surface localization; Methods describe E18 rat hippocampal cultures and gamma2-specific antibodies. This establishes a gamma2 dendritic-surface context in the coculture model, not gamma2 as the neurexin/neuroligin synaptogenic executor or proof of every native human compartment. Original images and supplements were not inspected. Earlier BioC error and browser challenge responses remain historical access failures; they do not describe the subsequently located main cache.
PMID:18281286(https://pubmed.ncbi.nlm.nih.gov/18281286/) — HIGH; VERIFIED. Authentic native PubMed abstract read alongside exact mouse P22723 donor IDA and UniProt records. Histamine directly gates beta2/beta3 homomers, whereas it potentiates alpha1/beta2(/gamma2) GABA responses in a gamma2-controlled manner. This supports the contextual cellular response, not gamma2 histamine binding. The abstract does not independently establish original clone species, natural product suffixes or full assay methods.
PMID:23909897(https://pubmed.ncbi.nlm.nih.gov/23909897/) — HIGH; VERIFIED. Authentic selected original co-culture Results and Methods read in the retained alpha1 receptor study. Alpha1/beta2/gamma2-expressing cells form stable functional inhibitory contacts; gamma2 alone is not sufficient. This supports receptor participation in a reduced contact model, not a gamma2-only adhesion mechanism or universal in-vivo assembly role. The HEK host does not independently establish each clone species.
PMID:25172774(https://pubmed.ncbi.nlm.nih.gov/25172774/) — HIGH; VERIFIED. Authentic native abstract and exact rat P18508 UniProt evidence block read. Gamma2 specifically co-precipitates and co-localizes with KIF21B; knockdown reduces gamma2-containing receptor clusters and the authors support transport-vesicle delivery into dendrites. The target is gamma2, unlike unresolved alpha1/beta3-specific extensions of this source. Full Methods and detailed vesicle-population imaging remain inaccessible; gamma2 is receptor cargo, not the kinesin transport executor.
PMID:2538761(https://pubmed.ncbi.nlm.nih.gov/2538761/) — HIGH; VERIFIED. Authentic cached abstract read: gamma2 coexpression with alpha1/beta1 yields functional GABA-A receptors and benzodiazepine pharmacology. Detailed original constructs and species were not resolved from the accessible abstract. Human structures and current measurements independently support the molecular claims; native postsynaptic localization is supported by separate original evidence.
PMID:25489750(https://pubmed.ncbi.nlm.nih.gov/25489750/) — HIGH; VERIFIED. Selected original JoVE sections and captions read in the retained primary packet. The protocol discusses alpha1/beta3/gamma2 contact assays and reuses some 2013 alpha1/beta2/gamma2 material. Figure 1B repeats beta2 in its caption despite the beta3 context. This source inconsistency is retained; reused panels are not independent replication, and no original image or raw-data reanalysis is claimed.
PMID:27733149(https://pubmed.ncbi.nlm.nih.gov/27733149/) — HIGH; VERIFIED. Authentic PubMed record and original PMC5062898 BioC selected abstract/Results/Methods/Figure2 caption read. Reciprocal NOVA1/gamma2 co-IP in human Huh7 and SMMC-7721 cells, with IgG and buffer controls, supports association. It is not purified binary binding or proof that gamma2 executes NOVA1 RNA-processing functions. Xenograft and cancer-phenotype work remains distinct from the interaction assay.
PMID:27864268(https://pubmed.ncbi.nlm.nih.gov/27864268/) — HIGH; VERIFIED. PubMed identity and indexed original PMC Methods plus selected Results were read. Human alpha1/beta2/gamma2L HEK293T assays compare wild type with six variants. HA is inserted after mature residue 4 for surface imaging; biotinylation and gamma2 immunoblots independently assess surface abundance. Whole-cell GABA currents support receptor function. Mutant ER retention does not establish an ER core function for wild-type gamma2. Structural calculations are models, not experimental structures. Some original prose has internally inconsistent variant names and percent-reduction wording; do not use those sentences for quantitative or variant-specific conclusions without checking the figures/supplement. No complete clone sequence or current suffix is inferred solely from gamma2L wording.
PMID:28978485(https://pubmed.ncbi.nlm.nih.gov/28978485/) — HIGH; VERIFIED. Selected original full-cache Results and Figure 1 caption read. Mouse turboGFP-LHFPL4 co-immunoprecipitates SEP-tagged gamma2 in COS-7 cells; the separate human LHFPL4 experiment tests alpha1. The inspected main text does not independently resolve gamma2 clone species or all supplemental construct details. Neuronal localization and receptor retention experiments are distinct from purified binary-binding evidence.
PMID:29950725(https://pubmed.ncbi.nlm.nih.gov/29950725/) — HIGH; VERIFIED. Authentic native original selected Results/Methods read. Human alpha1/beta2/gamma2 expression and patched structural constructs establish receptor function and benzodiazepine-interface contribution. Gamma2 carries an N-terminal twin-strep tag and an engineered M3–M4 loop replacement; this is not a natural short product. GABA sites are beta/alpha interfaces; flumazenil occupies the alpha/gamma interface. Mature-residue numbering and cDNA/transduction ratios differ from physiological stoichiometry. No current natural gamma2 suffix is assigned from the engineered construct alone.
PMID:30602789(https://pubmed.ncbi.nlm.nih.gov/30602789/) — HIGH; VERIFIED. Authentic native original receptor-purification and electrophysiology Methods explicitly identify full-length human gamma2L as UniProt P18507-2 with a C-terminal (GGS)3GK-1D4 tag. Thus the natural backbone is explicitly identified independently of a conflicting 1–467 range in UniProt reference-position metadata. Nanodisc structural reconstruction and separate cellular current/binding assays must remain distinct; unresolved intracellular density is not an absent natural sequence. GABA-binding interfaces are beta/alpha, while gamma2 contributes receptor architecture and pore.
PMID:33234346(https://pubmed.ncbi.nlm.nih.gov/33234346/) — HIGH; MISCITED. Complete authentic PMC7855156 main text and relevant captions read. The review attributes reduced receptor forward trafficking and GABAergic transmission to CLPTM1 and discusses other accessory regulators, including SHISA7; gamma2-containing receptors are their targets. The negative-regulation NAS attribution is MISCITED for gamma2 as executor, while the paper remains useful receptor biology. No universal absence assertion or fabricated replacement identifier is made.
PMID:33436612(https://pubmed.ncbi.nlm.nih.gov/33436612/) — MEDIUM; VERIFIED. Authentic PMC7803741 selected original abstract, Results, Methods and binding captions read. Methods explicitly use mouse gamma2 P22723-2 and mouse GABARAP/GABARAPL1, with human beta2 in receptor experiments. Motif mapping and a GABARAPL1-peptide structure corroborate association biology but do not verify the human Q9H0R8 context of the original PMID:9892355 record. The reported failure of an older short peptide to bind under this assay is not a universal refutation of receptor association.
PMID:34417930(https://pubmed.ncbi.nlm.nih.gov/34417930/) — MEDIUM; VERIFIED. Authentic native abstract and selected full-cache structural/distribution sections read. This is a review, not a new primary experiment. It correctly describes gamma2-containing GABA-A receptor complexes and distinct GABA versus benzodiazepine interfaces, with composition-dependent synaptic and extrasynaptic contexts. Broad disease and pharmacology discussion is not converted into additional process annotations.
PMID:35355020(https://pubmed.ncbi.nlm.nih.gov/35355020/) — HIGH; VERIFIED. Original selected Results and Methods retained in the shared primary packet were read, including human gamma2L construction and alpha4/beta3/gamma2 plus beta3/gamma2 structures. Gamma2L is full length with a C-terminal purification tag. Most new detailed GABA/histamine current experiments concern delta-containing cell preparations; these are not reassigned to gamma2. Recombinant stoichiometric diversity is not direct proof of the abundance or localization of every assembly in native tissue.
PMID:37892178(https://pubmed.ncbi.nlm.nih.gov/37892178/) — HIGH; VERIFIED. Authentic native abstract read. It explicitly describes human alpha5/beta3/gamma2L and alpha1/beta2/gamma2L receptors in HEK expression assays, supporting functional complex membership. Rat behavioral experiments are a separate scope. Full original Methods, figures and exact construct sequences were not independently inspected.
PMID:39843743(https://pubmed.ncbi.nlm.nih.gov/39843743/) — HIGH; VERIFIED. Selected genuine native human-brain Results and Methods read: lines91/93/103/105/107/109/111/123/129/131/133/141/195/201/203/213/219/229/235. Main receptor maps explicitly identify gamma2, including the predominant beta2/alpha1/beta2/alpha1/gamma2 assembly. Five maps have mixed identities at other positions; gamma-x is the separate auxiliary-complex map. Mass spectrometry reports short gamma2 in Dataset1 and short plus long forms in Dataset2, not splice assignment of every map. Original images, maps, spectra and supplements were not independently inspected.
PMID:9014148(https://pubmed.ncbi.nlm.nih.gov/9014148/) — HIGH; VERIFIED. Authentic original PubMed abstract read. The experiments explicitly use rat alpha4/beta3/gamma2 subunits in HEK293 cells and sequential immunoaffinity procedures resolving more than one receptor population. This is positive receptor-complex evidence with an ortholog/recombinant scope, not a wholly human preparation or proof of one universal stoichiometry. Independent human receptor structures support the target complex claim.
PMID:9014159(https://pubmed.ncbi.nlm.nih.gov/9014159/) — HIGH; VERIFIED. Authentic original PubMed abstract read alongside literal rat P18508 donor IDA. The abstract explicitly reports gamma2 at junctional membrane specializations, proximal/distal dendritic synapses and axo-axonic synapses on axon initial segments, with gamma2-specific immunolabeling. The exact donor species comes from the curated donor record; uninspected full Methods and images are not claimed read.
PMID:9464994(https://pubmed.ncbi.nlm.nih.gov/9464994/) — HIGH; VERIFIED. Authentic original native abstract read. Adult rat granule-cell immunogold experiments explicitly include gamma2 at GABAergic Golgi-cell synapses and at lower concentration in extrasynaptic membranes; selected glutamatergic mossy-fiber synapses also label. Golgi-cell synapses are not the Golgi organelle. The combined beta2/3 antibody limitation is not transferred to the separately described gamma2 label. Images and quantitative reanalysis were not performed.
PMID:9682826(https://pubmed.ncbi.nlm.nih.gov/9682826/) — MEDIUM; VERIFIED. Authentic PubMed abstract read and exact mouse P22723 donor source traced. The study compares alpha2/alpha5 targeting in mouse neurons and describes gamma2 distribution, but the accessible abstract does not resolve the specific axonal panel. The source is not rejected from its title or incomplete access; independent gamma2 axon-initial-segment evidence is kept distinct.
PMID:9892355(https://pubmed.ncbi.nlm.nih.gov/9892355/) — HIGH; VERIFIED. Authentic original PubMed abstract read; the original Nature full-text attempt was inaccessible. The abstract positively reports gamma2 interaction with GABARAP and synaptic colocalization. It does not resolve the distinct human Q9H0R8/GABARAPL1 partner context, which remains UNDECIDED. The citation identity is verified; no wrong-identifier or wrong-paralog assertion is inferred from incomplete access.
Reactome:R-HSA-975340 — HIGH; VERIFIED. Official reaction/catalyst/participant objects were inspected. The chain 975340→975314→975268→5340318→5357502→975308→975350 resolves human P18507 residues 40–475 at plasma membrane. This establishes target membership in the curated channel reaction, not every possible subunit combination in vivo. The model and direct human receptor evidence are separate evidence types.
UniProtKB:P18507 — HIGH; VERIFIED. Official reviewed human identity, alternative products, features and reference metadata were inspected. Three direct FASTAs and independent sequence-variation reconstruction agree at 475/467/515 residues. The displayed product is P18507-2; suffix order is not inferred from names. The 1–467 reference-position metadata does not override PMID:30602789 Methods explicitly identifying the long P18507-2 backbone. Curated comments and orthology-transferred locations are source statements, not substitute primary experiments.
The source evidence preserves all 74 literal raw contexts and the separate actual native mapping, product sequences, phylogenetic summary and exact quotation offsets/hashes. Genuine seeded target fetch produced 74 contexts and all 16 exporter columns matching the retained forecast. All 41 normal sources remain exact: eight immutable main objects, 20 published sibling-source reuses and 13 missing-only acquisitions. Two native titles differ from the private proposal only in GABA(A) punctuation. Cache availability remains separate from the manual reading scopes above.
Four core quotations now anchor the receptor identity, M2 pore lining, beta/alpha GABA interfaces and alpha/gamma flumazenil interface. The original 12-word quote remains unchanged. Total quoted words per source are 24 for PMID:30602789 and 21 for PMID:29950725; the quotes are not repeated in the notes or offset ledger. These are selected exact primary-source anchors, not claims of independent figure or map analysis. The redundant plasma-membrane parent was removed from the core location list; source annotations and the separately supported surface pools remain unchanged.
The first journal entry's statement that positive generic-binding retention followed project policy is corrected by the appended follow-up, while the earlier journal and CREATE record remain intact. Three generic-binding removals concern annotation informativeness, not refutation of the interactions. The source-specific negative-regulation removal remains separately grounded in the cited paper's executor distinction. Scoped-check outcomes and genuine EDIT history are recorded in the notes. No provider research file or existing source cache is rewritten.