GJB2 encodes connexin-26, a 226-residue membrane protein with four transmembrane helices. It assembles into connexons that dock between neighboring cells, forming channels for ionic and small-molecule exchange. These channels support electrical and metabolic communication. Pathogenic variants cause hearing loss and, in some allelic contexts, skin disorders.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005243 gap junction channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved connexin channel activity with direct human functional support. Reason: AN0/PTN008334405 lies above target AN401. The exact IBD donors and four aligned membrane regions support inheritance, corroborated by direct human channel evidence. Human self evidence is legitimate experimental grounding; no lineage-specific loss is established. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008334405 · PTN008334405 SUPPORTS TRANSFER Actual AN0/PTN008334405 placement, literal IBD donor identities and descent to P29033 were read. Direct human WT channel measurements corroborate transfer; donor count and target self-membership are not objections. |
| GO:0005243 gap junction channel activity | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Human Cx26 channels pass small dyes. Reason: Human pIRES permeability supports this activity. Supporting Evidence: PMID:12767933 hCx26-pIRES transfectants were permeable to dyes up to 622 Da |
| GO:0005243 gap junction channel activity | IDA PMID:21094651 Asymmetric configurations and N-terminal rearrangements in c... | ACCEPT | Summary: Wild-type Cx26 supports junctional currents. Reason: Paired-oocyte WT recordings support channel activity; M34A/deletion structures are distinct. |
| GO:0005243 gap junction channel activity | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse ortholog transfer agrees with direct human channel assays. Reason: Q00977 and ENSMUSP00000054343 identify the mouse ortholog with experimental channel evidence. Independent human measurements corroborate the transfer. The current donor record is verified; its original protocol was not separately read. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q00977 SUPPORTS TRANSFER The official Q00977 record maps the incoming ENSMUSP00000054343 identifier to its current versioned protein cross-reference. Its current annotation record includes direct IDA support for this role; human target assays independently corroborate the function. No new inspection of the cited mouse original is claimed. ensembl:ENSMUSP00000054343 SUPPORTS TRANSFER Official Q00977 Ensembl cross-reference identifies the current .8 protein version; the literal incoming unversioned identifier is preserved. |
| GO:0005509 calcium ion binding | IDA PMID:26753910 An electrostatic mechanism for Ca(2+)-mediated regulation of... | KEEP AS NON CORE | Summary: Structural calcium binding is real but secondary to channel function. Reason: The engineered human structure directly resolves calcium contacts. Retain this ancillary facet without inferring a new sensing process or treating the accompanying simulation as direct permeation measurement. Supporting Evidence: PMID:26753910 coordination sites reside at the interfaces between adjacent subunits |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative PEX12 interaction. Reason: PEX12 participates in peroxisomal receptor recycling. This pair does not assign GJB2 a role in that machinery or justify a specific enzyme-binding function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative GPR42 interaction. Reason: GPR42 is a short-chain-fatty-acid receptor. Receptor identity alone does not establish that GJB2 regulates its signaling or acts as a receptor-binding effector. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative FFAR2 interaction. Reason: FFAR2 has established ligand-dependent signaling, but the binding record does not demonstrate GJB2 participation in that response. A receptor-binding refinement would add an unsupported functional interpretation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative KCNK5 interaction. Reason: KCNK5 conducts potassium, but this association does not demonstrate GJB2 control of its conductance or assembly. Partner channel identity is insufficient for a useful binding-function refinement. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding does not distinguish the GJB1 partnership. Reason: GJB1 is another connexin. The positive pair is compatible with channel biology, but a generic or transporter-binding label does not distinguish an additional GJB2 molecular function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative KLRC1 interaction. Reason: The source specifies P26715-1 while the incoming row is gene-level. KLRC1 immune-receptor function does not establish a GJB2 signaling role through this association. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative TRHR interaction. Reason: TRHR responds to thyrotropin-releasing hormone. The pair supplies no target-specific evidence that GJB2 is a ligand, signaling adaptor or regulator of that receptor. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative APLNR interaction. Reason: APLNR receptor and mechanosensing functions do not establish a corresponding role for GJB2. Preserve the interaction without converting partner function into a specific binding annotation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic GJA5 binding adds no defined channel mechanism. Reason: GJA5 is a connexin, but partner class and this binary association alone do not establish functional mixed-channel composition. Generic binding remains uninformative. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic GJA8 binding adds no defined channel mechanism. Reason: GJA8 forms lens gap junctions. This pair does not establish a distinct GJB2 binding function or transfer GJA8 tissue-specific channel roles to GJB2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative interaction with the specified SLC18A1 product. Reason: P54219-3 matches the source literally. The record does not establish GJB2 regulation of monoamine transport, and isoform 1 transporter activity should not be assigned to the tested partner by default. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Positive GJB2–TBXA2R association lacks a defined functional binding role; exact historical product mapping remains unresolved. Reason: The positive HuRI association is retained, but it does not establish how GJB2 binding to TBXA2R performs a specific molecular function. TBXA2R receptor identity alone does not justify a receptor-binding refinement. Remove the generic protein-binding annotation as uninformative, without declaring the association false. The incoming Q0VAB0 identifier and source K7ER80/ORF 70162 both map to TBXA2R; their current 259-residue records differ at residue 136 (C versus R), and the full historical clone sequence has not been established. That mapping question is recorded separately and does not provide the reason for removal. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative AQP6 interaction. Reason: AQP6 channel function does not establish that GJB2 regulates its permeability. The positive pair supports association, without identifying a separate informative transporter-binding function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative EBP interaction. Reason: EBP catalyzes sterol isomerization. Association with this enzyme does not show GJB2 regulation of its catalysis or a role in cholesterol synthesis; enzyme-binding refinement is unwarranted. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative SHISAL1 interaction. Reason: The SHISAL1 protein identity is supported, but the retained record does not establish a functional binding mechanism for GJB2. Generic binding adds no useful molecular-function information. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative ARL13B interaction. Reason: The source specifies Q3SXY8-1. ARL13B ciliary and nucleotide-binding roles do not demonstrate that GJB2 regulates its activity or serves as its functional effector. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative FAM209A interaction. Reason: FAM209A has a by-similarity acrosome-biogenesis description. Neither that provisional partner role nor the pair establishes a specific GJB2 binding function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative MFSD6 interaction. Reason: MFSD6 has a documented viral-entry receptor role. The GJB2 association does not demonstrate a viral-entry function or justify deriving transporter binding from the family name. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative HSD17B13 interaction. Reason: The source specifies HSD17B13-1, whose retinol activity differs from isoform 2. No GJB2 effect on the tested partner activity is demonstrated; an enzyme-binding refinement would be uninformative. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative AMIGO1 interaction. Reason: AMIGO1 adhesion and potassium-channel-associated functions do not demonstrate a GJB2 role in either mechanism. Retain the pair as evidence without assigning those partner functions to GJB2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative TEX29 interaction. Reason: TEX29 identity is established, but the available partner record and binary association do not identify a specific molecular role for GJB2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative LHFPL5 interaction. Reason: LHFPL5 is a mechanotransduction-complex auxiliary protein by similarity. Shared auditory relevance does not establish a GJB2 coupling or adaptor mechanism from this pair. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative GPR152 interaction. Reason: GPR152 is an orphan receptor. Its receptor classification does not demonstrate GJB2-dependent signaling, ligand action or a useful receptor-binding function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative SSMEM1 interaction. Reason: SSMEM1 has a by-similarity spermiogenesis role. The pair does not establish GJB2 participation in Golgi positioning or a specific binding mechanism. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative TMEM106A interaction. Reason: The source specifies TMEM106A-1. Its signaling and proliferation effects do not define a functional GJB2 interaction; generic binding remains uninformative. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative PLEKHB2 interaction. Reason: The source specifies PLEKHB2-1. Its endosomal transport role does not establish GJB2 cargo selection or scaffold activity through this pair. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative MS4A6E interaction. Reason: MS4A6E has a tentative receptor-complex signaling description. That provisional role cannot supply the missing functional interpretation of its association with GJB2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative TLCD4 interaction. Reason: TLCD4 identity and the positive pair are preserved. The retained evidence does not demonstrate a specific GJB2 binding function, and the domain-family name supplies no mechanism. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative interaction with the specified TMEM237 product. Reason: Q96Q45-2 matches the source literally. TMEM237 ciliary-transition-zone function does not establish a ciliary or scaffolding role for GJB2 through this association. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative SLC30A2 interaction. Reason: The source specifies SLC30A2-1, a zinc transporter with product-dependent localization. No GJB2 regulation of transport is established, so channel or transporter class alone is insufficient. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative TM2D2 interaction. Reason: The source specifies TM2D2-1. The positive pair is retained, but the available evidence does not resolve an informative GJB2 binding mechanism. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative LRRC4C interaction. Reason: LRRC4C adhesion and synaptic roles do not demonstrate that GJB2 functions in that interaction system. Partner adhesion identity alone does not justify a specific molecular-function replacement. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative TIMMDC1 interaction. Reason: TIMMDC1 assembles mitochondrial complex I. This association does not demonstrate GJB2 participation in that machinery; compartment concerns are limits on physiological interpretation, not proof of an artifact. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative SAR1A interaction. Reason: The source specifies SAR1A-1. Its GTPase and COPII-coat functions do not show GJB2 regulation of nucleotide cycling or a specific binding role in vesicle formation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative ERGIC3 interaction. Reason: The source specifies ERGIC3-1. Secretory-trafficking activity of the partner does not establish a GJB2 cargo-receptor or adaptor mechanism from this binary association. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative TMX2 interaction. Reason: The source specifies TMX2-1. Its probable redox-regulatory role does not establish GJB2-dependent thiol exchange or enzyme regulation, so a specific binding refinement is unsupported. |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | TAS Reactome:R-HSA-451056 | KEEP AS NON CORE | Summary: A curated Cx26 cargo complex occupies the ER-Golgi intermediate compartment. Reason: The exact input complex 190641 contains six human P29033 subunits, entity 190614, residues 1–226, in ERGIC. Retain transit localization as non-core; cargo presence does not establish trafficking activity or the event-title mechanism. Supporting Evidence: Reactome:R-HSA-451056 |
| GO:0005886 plasma membrane | EXP PMID:16849369 Pathogenetic role of the deafness-related M34T mutation of C... | ACCEPT | Summary: Human Cx26 forms functional cell-surface junctions. Reason: Selected human WT HeLa experiments support membrane junctions. M34T targeting does not establish normal function; no native cochlear imaging is claimed. Supporting Evidence: |
| GO:0005886 plasma membrane | EXP PMID:17551008 Three-dimensional structure of a human connexin26 gap juncti... | ACCEPT | Summary: Plasma-membrane localization is correct, with structural-source limits. Reason: The source reconstituted engineered protein is not a native-cell localization assay. Independent WT cellular evidence supports the term. |
| GO:0005886 plasma membrane | EXP PMID:19340074 Structure of the connexin 26 gap junction channel at 3.5 A r... | ACCEPT | Summary: Cell-surface channel localization remains supported beyond the structural preparation. Reason: The inspected structure and supplement establish architecture; main Methods were inaccessible. Independent WT cellular evidence supports the location. |
| GO:0005886 plasma membrane | EXP PMID:19384972 Different functional consequences of two missense mutations ... | ACCEPT | Summary: Variant trafficking defects do not negate WT plasma-membrane localization. Reason: The abstract distinguishes tagged WT and variants. Host and tag position remain unverified. Independent target evidence supports the location; mutant dysfunction does not contradict WT residence. |
| GO:0005886 plasma membrane | EXP PMID:26753910 An electrostatic mechanism for Ca(2+)-mediated regulation of... | ACCEPT | Summary: The target is a plasma-membrane channel; the structural source has mixed-preparation limits. Reason: The structural preparation mixed plasma and organellar membranes and cannot isolate surface residence. Independent WT cellular evidence supports this location. |
| GO:0005886 plasma membrane | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Human Cx26 reaches cell-contact membranes. Reason: Human expression supports membrane residence. |
| GO:0005886 plasma membrane | IDA PMID:21094651 Asymmetric configurations and N-terminal rearrangements in c... | ACCEPT | Summary: Cx26 forms plaques where HeLa cells contact. Reason: WT and mutant GFP-4C constructs formed contact plaques; localization alone does not establish conductance. Supporting Evidence: PMID:21094651 gap junctions at cell apposition areas |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic evidence supports the established surface location. Reason: The verified donor and human SL-0039 record agree with the established membrane channel. Preserve every incoming source member; the combined row is not several independent experiments. PMID:19864490 provides qualified mouse/rat Cx26 corroboration in HeLa: surface plaques and intracellular cargo accumulation do not identify ERGIC residence. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q00977 SUPPORTS TRANSFER Current mouse plasma-membrane annotations include direct IDA15692151 and EXP19864490; target WT data independently support localization. ensembl:ENSMUSP00000054343 SUPPORTS TRANSFER Official Q00977 cross-reference confirms the incoming mouse protein identity. UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER The official human target record explicitly lists Cell membrane, with experimental evidence references. Supporting Evidence: GO_REF:0000120 UniProtKB:Q00977 UniProtKB:P29033 PMID:19864490 formed immunostained plaques at cell–cell contacts |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-451056 | ACCEPT | Summary: The curated trafficking output explicitly places Cx26 at the plasma membrane. Reason: The actual output complex 112301 contains six human P29033 subunits, entity 53211, residues 1–226, at the plasma membrane. Reaction-level cytosol is not assigned to the integral membrane cargo. Supporting Evidence: Reactome:R-HSA-451056 |
| GO:0005921 gap junction | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Cx26 occupies intercellular gap junctions. Reason: Human coupling and independent plaque evidence support junction residence. |
| GO:0005921 gap junction | IEA GO_REF:0000120 | ACCEPT | Summary: Cx26 belongs at gap junctions rather than merely near an interacting protein. Reason: Human SL-0124 and experimentally grounded mouse records support junction localization. Preserve the combined provenance without treating it as replicate assays or universal heteromeric composition. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q00977 SUPPORTS TRANSFER Current mouse gap-junction annotations include direct IDA source records; no solely circular inference is alleged. ensembl:ENSMUSP00000054343 SUPPORTS TRANSFER Verified mouse product cross-reference. UniProtKB-SubCell:SL-0124 SUPPORTS TRANSFER Official target location is Cell junction, gap junction; independently consistent with WT plaque/coupling evidence. |
| GO:0005922 connexin complex | IBA GO_REF:0000033 | ACCEPT | Summary: Core structural subunit of the hexameric connexon. Reason: AN0/PTN008334405 is ancestral to the target. Experimental assemblies and target function support the six-subunit connexin complex, distinct from the docked twelve-subunit channel. MSA architecture is corroboration, not an assembly assay; self evidence is legitimate. The quoted docking observation concerns engineered M34A. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008334405 · PTN008334405 SUPPORTS TRANSFER Actual AN0/PTN008334405 complex assertion and target descent are secure. Human structural/functional evidence supports complex membership; hexameric connexons remain distinct from the dodecameric paired channel. Supporting Evidence: GO_REF:0000033 PMID:17551008 two hemichannels redocked at their extracellular surfaces into full intercellular channels |
| GO:0005922 connexin complex | IDA PMID:21094651 Asymmetric configurations and N-terminal rearrangements in c... | ACCEPT | Summary: Cx26 supplies subunits of the connexon. Reason: The hexameric connexon and paired channel are distinct assemblies. Supporting Evidence: |
| GO:0005922 connexin complex | IEA GO_REF:0000120 | ACCEPT | Summary: The combined sources correctly identify the connexon complex. Reason: Human connexin features and the verified mouse product support this complex assignment. The six-subunit hemichannel is distinct from a docked pair. Multiple source mappings are not independent experiments. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q00977 SUPPORTS TRANSFER Current mouse complex annotation includes IDA15692151; human target structure and functional evidence independently corroborate membership. ensembl:ENSMUSP00000054343 SUPPORTS TRANSFER Current official Q00977 protein cross-reference matches the incoming identifier. InterPro:IPR000500 SUPPORTS TRANSFER Connexin family entry is present on the official target record. InterPro:IPR002268 SUPPORTS TRANSFER Connexin26 entry is present on the official target record. InterPro:IPR017990 SUPPORTS TRANSFER Connexin conserved-site entry is present on the official target record. |
| GO:0007154 cell communication | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad cell communication adds little beyond the retained specific roles. Reason: Both retained cell-cell signaling and electrical communication have verified is_a paths to this broad parent. The family mappings are credible; the generic term adds no useful specificity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR000500 SUPPORTS TRANSFER Official target record contains the Connexin entry; the broad process is compatible but already represented by specific retained children. InterPro:IPR002268 SUPPORTS TRANSFER Official target record contains the Connexin26 entry; no family-identity discrepancy is alleged. InterPro:IPR017990 SUPPORTS TRANSFER Official target record contains the Connexin conserved-site entry; this does not add specificity beyond the retained processes. Supporting Evidence: GO_REF:0000002 UniProtKB:P29033 |
| GO:0007267 cell-cell signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Connexin-mediated transfer of information between adjacent cells. Reason: The exact AN0/PTN008334405 signaling assertion is ancestral to the target. Channel-mediated communication fits the definition. Conserved architecture and direct target evidence provide no indication of loss; a ligand-receptor mechanism is not implied. The controlled calcium-wave experiment documents information transfer between cells; this specificity is absent from the broader cell-communication parent. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008334405 · PTN008334405 SUPPORTS TRANSFER The actual AN0/PTN008334405 signaling assertion and donor group are retained. Direct target channel and intercellular signaling observations support the inherited role. Supporting Evidence: GO_REF:0000033 file:human/GJB2/GJB2-deep-research-manual.md consistently followed by the intercellular spreading of a calcium wave |
| GO:0007267 cell-cell signaling | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based cell-cell signaling is appropriate for Cx26. Reason: Verified mouse orthology and experimental grounding agree with the human channel role. Retain this inference without adding a specific receptor pathway or neuronal context. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q00977 SUPPORTS TRANSFER The official Q00977 record maps the incoming ENSMUSP00000054343 identifier to its current versioned protein cross-reference. Its current annotation record includes direct IDA support for this role; human target assays independently corroborate the function. No new inspection of the cited mouse original is claimed. ensembl:ENSMUSP00000054343 SUPPORTS TRANSFER The official mouse accession crosswalk resolves this literal protein identifier; no different paralog or isoform is substituted. |
| GO:0007267 cell-cell signaling | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse-supported signaling role is corroborated in human Cx26. Reason: The mouse donor has direct experimental signaling support. The target channel itself conveys information between cells; no receptor cascade is inferred. Original mouse protocols were not independently inspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q00977 SUPPORTS TRANSFER Current mouse signaling annotation includes IDA15692151. Target channel and calcium-communication evidence supports the transferred role without relying solely on inferred mouse rows. |
| GO:0010644 cell communication by electrical coupling | IEA GO_REF:0000108 | ACCEPT | Summary: Electrical-coupling process follows the explicitly linked channel activity. Reason: The actual source activity has a part_of edge to this process. This typed inter-aspect inference accords with electrical coupling; it is not an MF-to-BP is_a claim or a tissue-specific assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:1903763 SUPPORTS TRANSFER Actual current ontology: gap junction channel activity involved in electrical coupling part_of GO0010644. The target has this activity with experimental source support. |
| GO:0016264 gap junction assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Cx26 supplies the subunits that assemble intercellular junctions. Reason: The AN394/PTN000240686 IBD contains human and mouse Cx26 evidence. GJB2 supplies structural subunits for assembly, rather than merely being transported cargo. No target-specific loss is established; full protocols for the older source remain unavailable. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000240686 · PTN000240686 SUPPORTS TRANSFER Actual AN394/PTN000240686 IBD uses mouse MGI:MGI:95720 and human P29033 descendants. Human plaque/assembly and functional evidence supports transfer; self evidence is not circular. |
| GO:0016264 gap junction assembly | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Cx26 subunits assemble into intercellular junctions. Reason: The protein supplies junction structure, not the cargo-delivery machinery. Supporting Evidence: PMID:21094651 all constructs formed gap junctions at cell apposition areas |
| GO:0042802 identical protein binding | IPI PMID:17551008 Three-dimensional structure of a human connexin26 gap juncti... | KEEP AS NON CORE | Summary: Direct Cx26 self contacts support oligomeric assembly. Reason: The engineered M34A preparation supports self-association in a higher-order channel. This useful assembly context is ancillary to channel activity; a homodimerization replacement would impose the wrong stoichiometry. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:19340074 Structure of the connexin 26 gap junction channel at 3.5 A r... | KEEP AS NON CORE | Summary: Resolved interfaces support Cx26 self association. Reason: The abstract and inspected supplementary interfaces support protomer contacts. Main Methods remain unavailable. Retain ancillary self-association without reclassifying a connexon as a dimer. Supporting Evidence: |
| GO:0048839 inner ear development | IBA GO_REF:0000033 | UNDECIDED | Summary: Developmental-process scope remains unresolved despite valid ancestry. Reason: The target descends from AN394/PTN000240686. Rat P21994/AN407 has independent IEP evidence, so neither the single donor nor target descent is a circularity defect. Developmental expression and hearing phenotypes do not resolve the precise participation claim; original Methods and Results remain unavailable. Keep the process-specific uncertainty. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000240686 · PTN000240686 UNRESOLVED Node placement and exact rat donor are verified. Current RGD evidence is IEP:PMID10570462, not another transfer alone; only its authentic abstract was recovered. The uncertainty concerns developmental participation and original-source scope, not descent, donor count or circularity. |
| GO:0055085 transmembrane transport | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Cx26 pores conduct solutes across coupled-cell membranes. Reason: The membrane-spanning pore directly performs core transport. GO:0005243 describes connexons traversing each membrane; GO:0055085 does not require undocked hemichannels. GO:1990349 lacks an is_a path to GO:0055085, so no descendant replacement applies. |
| GO:1903763 gap junction channel activity involved in cell communication by electrical coupling | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Cx26 channels electrically couple neighboring cells. Reason: Conductance supports electrical coupling. GO:1903763 asserts GO:0005243 part_of GO:0010644; neither component alone expresses that linkage. |
| GO:1990349 gap junction-mediated intercellular transport | IBA GO_REF:0000033 | ACCEPT | Summary: Directly mediates exchange between neighboring cytoplasms. Reason: The AN365/PTN002633521 assertion includes Cx26/Cx30 descendants and is ancestral to P29033. GJB2 forms the pore performing intercellular transport. Direct target evidence and membrane architecture support transfer; target self evidence is legitimate. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002633521 · PTN002633521 SUPPORTS TRANSFER AN365/PTN002633521 and all three named descendant sources were replayed. Positive human WT transport independently supports the inherited function; no target-specific loss is established. |
| GO:1990349 gap junction-mediated intercellular transport | IDA PMID:12767933 Permeability and gating properties of human connexins 26 and... | ACCEPT | Summary: Cx26 transfers molecules between adjacent cells. Reason: Human dye permeability supports intercellular transport; full original protocols remain unavailable. |
| GO:1990349 gap junction-mediated intercellular transport | IDA PMID:21094651 Asymmetric configurations and N-terminal rearrangements in c... | ACCEPT | Summary: Wild-type Cx26 transfers dyes between cells. Reason: WT functional evidence supports transport; the source dye-label inconsistency remains unresolved. Independent WT-Cx26-EGFP HeLa recordings in PMID:17660464 corroborate coupling; V84M plaques lacked dye transfer. |
| GO:1990349 gap junction-mediated intercellular transport | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse transport inference matches a directly established human pore role. Reason: The verified mouse product has independent experimental transport grounding, corroborated by target channel function. Reciprocal inferred rows do not erase that grounding or make the chain circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q00977 SUPPORTS TRANSFER The official Q00977 record maps the incoming ENSMUSP00000054343 identifier to its current versioned protein cross-reference. Its current annotation record includes direct IDA support for this role; human target assays independently corroborate the function. No new inspection of the cited mouse original is claimed. ensembl:ENSMUSP00000054343 SUPPORTS TRANSFER Verified current mouse product cross-reference; no target/source identity mismatch. |
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Download this section (compressed HTML)Q: Which complete historical HuRI clone sequence corresponds to the incoming TBXA2R accession Q0VAB0, given the K7ER80 source product and C136/R136 difference?
Q: Does the original rat developmental-expression source establish participation in inner-ear development beyond spatial and temporal expression, and how should that evidence constrain the inherited human annotation?
Q: Can the reported nuclear role of connexin-26 be reproduced with resolved sample and genome-alignment provenance, and separated from indirect effects of altered intercellular coupling?
Q: Under endogenous conditions, which Cx26-dependent signals use docked junctions versus undocked connexons, and how can extracellular ATP-mediated effects be separated experimentally?
Experiment: Test endogenous nuclear localization and any transcriptional effect with validated compartment controls and separation-of-function channel variants; distinguish chromatin association from purified sequence-specific DNA contact.
Type: Localization, controlled functional separation and direct binding
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