GJB3

Summary: Inherited channel activity is corroborated.

Reason: The actual PTHR11984 tree places the exact 270-residue human O75712 sequence below AN0/PTN008334405, where the inspected IBD assigns this activity. The literal donor set matches and no target-path loss assertion was found. Donor count is not used as a measure of evidential strength, and no different connexin’s selectivity is transferred.

Summary: Human connexin-31 forms intercellular channels.

Reason: The authentic PMID:9704026 abstract establishes human cloning and expression, but its full functional evidence remains inaccessible. See the human assay synopsis. Retain the NAS citation and evidence code; lack of access does not establish that the older paper lacked assays.

Summary: Generic binding adds no useful GJB3 function; the pair and source concern are retained.

Reason: The HuRI pair is positive, but neither it nor the partner trafficking account establishes a useful GJB3 molecular function beyond generic association. Even assuming the intended partner correspondence, no target-specific regulatory or adaptor mechanism is demonstrated. Removal concerns informativeness, not a false interaction. Incoming A5PKU2 and source Q8IXB3/ORF72045 remain literal; their four sequence differences and unresolved complete historical clone identity are recorded separately as a suspected source concern.

Summary: The LAT interaction does not define a GJB3 signaling function.

Reason: HuRI retains a positive GJB3 interaction with the short LAT product O43561-2. LAT independently recruits signaling proteins downstream of immune receptors, but the inspected pair evidence does not establish GJB3 as a functional participant in that recruitment. Remove the uninformative protein-binding term without denying the interaction or converting LAT’s adaptor role into a GJB3 activity.

Summary: MFSD11 association lacks a supported functional refinement.

Reason: The original positive HuRI pair identifies MFSD11 O43934-1. Its official record places it in the UNC93 family and expressly cautions against inferring the major facilitator superfamily from its name. Neither this classification nor the interaction establishes transport regulation by GJB3. Remove generic protein binding as uninformative while retaining the measured association.

Summary: COMT association alone does not establish enzyme regulation by GJB3.

Reason: HuRI identifies the membrane-bound COMT product P21964-1. COMT’s catechol methyltransferase activity is independently established, but the pair does not demonstrate a GJB3-specific effect on that chemistry, recruitment or a defined interface function. Remove the generic term as uninformative rather than replacing it solely from the partner’s enzyme class; the positive interaction is retained.

Summary: The IGFBP5 pair does not identify a growth-factor-related GJB3 activity.

Reason: HuRI reports a positive GJB3–IGFBP5 pair. IGFBP5 independently controls IGF availability and has secreted and intracellular contexts, but this screen does not assign GJB3 an IGF-binding, receptor-bridging or growth-regulatory role. Remove the uninformative generic term while preserving the pair, without a blanket localization-based artifact claim.

Summary: TMEM97 interaction does not establish a GJB3 receptor-binding mechanism.

Reason: The positive HuRI partner Q5BJF2 is TMEM97, the sigma-2 receptor, with independently described sterol and membrane-trafficking roles. Those partner functions do not establish a corresponding functional role for GJB3 in the inspected interaction evidence. Remove generic protein binding as uninformative; neither receptor-class binding nor sterol isomerase activity is inferred.

Summary: TMUB2 association has no informative GJB3 functional assignment.

Reason: HuRI reports GJB3 with the TMUB2 product Q71RG4-2, whereas the incoming context is gene-level Q71RG4. The exact source product is retained without claiming isoform specificity. Its transmembrane and ubiquitin-like domains do not by themselves identify a GJB3 ubiquitin-related mechanism. Remove the generic binding term as uninformative while preserving the positive pair.

Summary: The LHFPL5 pair does not establish GJB3 participation in mechanotransduction.

Reason: HuRI supports the GJB3–LHFPL5 interaction. LHFPL5 is independently described as an auxiliary component of the hair-cell mechanotransducer channel, principally by orthology in the inspected official account. This screen does not demonstrate GJB3 coupling to that channel or performing LHFPL5’s role. Remove the uninformative generic term, preserving the positive association without inferring an auditory mechanism from shared context.

Summary: BTN2A2 interaction does not define an immune-regulatory GJB3 function.

Reason: The source identifies a positive pair with BTN2A2 Q8WVV5-1. BTN2A2’s independently inferred effects on activated T cells do not establish GJB3-mediated immune signaling or a functional receptor interface. Remove generic protein binding as uninformative while retaining the pair and the source product designation.

Summary: GIMAP5 association is insufficient for a GJB3 GTPase-related refinement.

Reason: The positive HuRI pair names GIMAP5 Q96F15-1. Its GTPase-family classification and independently described vesicular and lymphocyte-survival functions do not demonstrate a functional GJB3 interaction mechanism. Remove the uninformative generic term; no GTPase regulation or mitochondrial localization is transferred to GJB3.

Summary: RPRM association does not assign a cell-cycle activity to GJB3.

Reason: HuRI reports a positive pair with RPRM. Its official functional account describes a possible role in cell-cycle arrest by similarity; that separate evidence does not establish GJB3 regulation of the cell cycle or a specific molecular interface. Remove generic protein binding as uninformative and retain the measured pair.

Summary: SERP1 association does not establish a GJB3 chaperone function.

Reason: The positive HuRI pair involves SERP1, an ER membrane protein associated with protein translocation and protection of unfolded substrates. The inspected evidence does not show GJB3 carrying out that work or a defined functional binding mechanism. Remove the generic term as uninformative, preserving the interaction without transferring the partner’s protein-processing role.

Summary: PCYOX1 copurification does not establish a GJB3 enzyme-binding mechanism.

Reason: The authentic BioPlex 3.0 293T network contains GJB3–PCYOX1 at line 34725, supporting the reported association. The experiment used affinity purification and mass spectrometry of tagged baits, which does not by itself establish a direct interface or a GJB3 effect on PCYOX1 catalysis. PCYOX1’s independently verified oxidase class alone does not make an informative GJB3 refinement. Remove generic protein binding as uninformative while preserving the positive copurification.

Summary: A bounded intracellular pool is supported alongside junctional localization.

Reason: The mouse source P28231 has an actual MGI IDA cytoplasm assertion citing PMID:7889986. Its authentic abstract describes mouse Cx31 antibody characterization and expression, but the precise cytoplasmic images in the full article remain uninspected. Independent human HPA data report vesicular staining in HaCaT cells with HPA074472; the HPA dictionary explains this pattern as cytoplasmic vesicle-like staining without assigning a specific organelle. Retain the broad intracellular location as non-core, while the functional junctional channel remains the principal location. This does not assert soluble cytosol, infer an organelle from puncta, or treat the plasma membrane itself as cytoplasm.

Summary: Connexin-31 acts at the plasma membrane.

Reason: UniProt maps the product to the plasma membrane, and independent HPA data place it at human cell junctions. This is the functional location of the accepted channel core. Additional intracellular pools are retained separately and do not contradict membrane localization.

Summary: Gap junction provides the appropriate specificity.

Reason: The literal mouse P28231/Ensembl provenance is preserved; its IDA source PMID:7889986 remains incompletely accessible. See the human assay synopsis. GO:0005921 is the verified, more informative descendant of cell-cell junction; the specificity is not inferred from junctional staining alone. GJB3 already carries GO:0005921 in the incoming annotations.

Proposed replacements: gap junction

Summary: Gap-junction localization is supported.

Reason: The combined electronic assertion retains mouse P28231/Ensembl and UniProt SL-0124 provenance. Current mouse GOA includes an IDA from PMID:14595769, whose abstract places Cx31 in cochlear type 2 fibrocytes. The separate Cx26/Cx30 heteromeric-complex result is not transferred to Cx31. The accepted human channel core supplies independent corroboration.

Summary: Connexin-31 forms functional gap junctions.

Reason: The original NAS citation remains unchanged. PMID:9704026 concerns human cloning and keratinocyte expression, with full localization evidence inaccessible; HEK here means E6/E7-transfected keratinocytes, not HEK293. See the human assay synopsis.

Summary: The ancestral complex assignment is supported.

Reason: The inspected AN0/PTN008334405 IBD lies on the exact human GJB3 lineage, with a matching donor set and no target-path loss annotation. The official human subunit account independently agrees with this assembly role. Preserve the inference as such without claiming newly measured human stoichiometry.

Summary: Connexin-31 is a connexon subunit.

Reason: InterPro identifies the connexin family, and the official human SUBUNIT account describes its hexameric assembly by similarity. The term represents that conserved subunit role. No new human stoichiometric measurement or particular mixed-connexon composition is asserted.

Summary: Cell-cell signaling is the informative process.

Reason: The InterPro-derived annotation is biologically sound but broad. GO:0007267 is a verified descendant of GO:0007154 whose definition includes gap-junction communication. It therefore specifies the established channel role without assigning a developmental or tissue signaling pathway. GJB3 already carries GO:0007267 in the incoming annotations.

Proposed replacements: cell-cell signaling

Summary: Connexin-31 mediates cell-cell signaling.

Reason: The inspected AN0/PTN008334405 IBD is ancestral to the exact human leaf, with the incoming donor set preserved. The channel itself supplies the intercellular transfer path. This is participation, rather than a downstream phenotype-based necessity inference; no particular signaling cascade is assigned.

Summary: Gap junction specifies the functional location.

Reason: HPA reports supported junctional staining in A-431 and HaCaT cells, with additional HaCaT vesicles. See the human assay synopsis. GO:0005921 is a verified descendant of GO:0030054; this refinement does not claim HPA imaging alone resolved channel ultrastructure or exclude the vesicular pool. GJB3 already carries GO:0005921 in the incoming annotations.

Proposed replacements: gap junction

Summary: The pore supports transmembrane transport.

Reason: This electronic process inference follows from the established gap junction channel activity: the pore supplies a route through the adjoining membranes. The broad transport term is appropriate. It neither identifies an ATP-driven pump nor assigns a specific physiological cargo or freely exposed hemichannel activity.