Cftr

Summary: IBA annotation consistent with CFTR being a multi-pass apical cell membrane protein.

Reason: CFTR is annotated as a multi-pass cell membrane protein with apical membrane localization in epithelial cells.

Summary: CFTR is an ABC transporter family member but functions as an ATP-gated anion channel rather than an active transporter.

Reason: The ABC transporter activity term implies ATP-driven substrate transport, while CFTR primarily gates passive anion flow using ATP binding/hydrolysis.

Summary: Basolateral plasma membrane is a specific membrane domain mouse Cftr does not occupy, and the seed set behind this node points to a basolaterally distributed ABCC paralog rather than to CFTR.

Reason: Apical and basolateral plasma membrane are disjoint sibling domains, neither subsuming the other, so this is not a case of a broad compartment merely being imprecise. Mouse Cftr's own experimental localization in GOA is apical plasma membrane (two independent IDA rows) with no basolateral evidence, and UniProt gives the apical cell membrane. The IBD sits at PANTHER node PTN002384279 in PTHR24223 (ATP-BINDING CASSETTE SUB-FAMILY C), and the seed carrying this term is human ABCC4, an ABCC exporter that is basolateral in several epithelia; the basolateral domain is that member's property and does not follow descent onto CFTR. Marked over-annotated rather than removed because CFTR trafficking is regulated and a minor basolateral pool in particular cell types cannot be excluded from the evidence in hand.

Summary: IBA annotation consistent with ATP-gated chloride channel function.

Reason: CFTR gating depends on ATP binding/hydrolysis by its nucleotide-binding domains, producing ATP-gated chloride channel activity.

Summary: CFTR regulates epithelial ion and water transport indirectly through ion movement and fluid homeostasis.

Reason: CFTR-driven anion transport supports epithelial water transport but is not a direct water channel.

Summary: IBA annotation consistent with CFTR permeability to bicarbonate.

Reason: CFTR is permeable to HCO3- and contributes to epithelial bicarbonate handling, though chloride transport is the core function.

Summary: IBA annotation reflecting CFTR-mediated chloride movement across membranes.

Reason: CFTR mediates chloride ion transport across the cell membrane as its primary physiological role.

Summary: Cytosol reflects CFTR's large cytosol-facing regulatory and nucleotide-binding domains and is directly observed for mouse Cftr, but the compartment where CFTR does its work is the apical plasma membrane, so this is retained as non-core.

Reason: Unlike the basolateral row, this one rests on direct experimental evidence - mouse Cftr carries its own curated IDA cytosol annotation in GOA (PMID:24885604). That experimental annotation is what grounds this propagation - the IBD at PANTHER node PTN002795422 carries this term on mouse Cftr (MGI:88388) and human CFTR (P13569) themselves - so there is no propagation failure to report here. A broad or adjacent compartment over a more specific true location is not grounds for a flag; the annotation is simply uninformative about the functional compartment, so it is kept as non-core rather than marked over-annotated.

Summary: IBA annotation for apical membrane localization of CFTR in epithelial cells.

Reason: CFTR localizes to the apical cell membrane where it forms chloride channels.

Summary: General nucleotide binding annotation capturing ATP binding by CFTR nucleotide-binding domains.

Reason: ATP binding is necessary for channel gating but is not the primary molecular function compared to chloride channel activity.

Summary: CFTR functions as a chloride channel in epithelial membranes.

Reason: CFTR forms a chloride channel in the apical membrane and is activated by cAMP/PKA signaling.

Summary: Automated annotation for ATP-gated chloride channel activity.

Reason: CFTR gating depends on ATP binding/hydrolysis by its nucleotide-binding domains, enabling ATP-gated chloride conductance.

Summary: ATP binding by CFTR nucleotide-binding domains drives channel gating.

Reason: ATP binding is required for channel opening in the CFTR gating cycle.

Summary: Processed CFTR products have been detected in the nucleus in specific contexts.

Reason: Nuclear localization is context-specific and not central to CFTR channel activity.

Summary: ER membrane localization reflects CFTR biogenesis and trafficking.

Reason: CFTR is synthesized and processed in the ER before trafficking to the plasma membrane.

Summary: Automated annotation capturing primary membrane localization.

Reason: CFTR functions as a membrane chloride channel.

Summary: This broad parent annotation is supported by Cftr-mediated chloride conductance but is non-core because chloride transmembrane transport captures the process more precisely.

Reason: The term is correct by the True Path Rule but less informative than chloride transmembrane transport.

Summary: Automated annotation for CFTR-mediated chloride transport.

Reason: CFTR mediates chloride ion transport across epithelial membranes.

Summary: General membrane localization annotation for a multi-pass membrane protein.

Reason: The plasma membrane/apical membrane terms are more informative; membrane is retained as a broad non-core localization.

Summary: Automated annotation capturing apical membrane localization.

Reason: CFTR forms chloride channels at the apical membrane of epithelial cells.

Summary: No evidence supports isomerase activity for CFTR.

Reason: CFTR is an ATP-gated anion channel and lacks isomerase catalytic motifs.

Summary: Cftr has intrinsic ATPase activity; ATP binding and hydrolysis at its nucleotide-binding domains drive the channel-gating cycle.

Reason: Intrinsic ATP hydrolysis is a conserved core biochemical activity coupled directly to Cftr channel gating.

Summary: Cftr traffics through early-endosomal membranes during internalization and recycling to the cell surface.

Reason: Early-endosome membrane localization reflects trafficking rather than Cftr's core site of action.

Summary: Cftr mediates monoatomic-ion transmembrane movement through its anion channel; this is broader than the chloride-specific core process.

Reason: The term is valid by the True Path Rule but less informative than chloride transmembrane transport.

Summary: Cftr is the pore-forming component of a chloride-channel complex; this keyword-derived localization is compatible but less informative than channel activity.

Reason: The complex term is compatible with Cftr biology but is secondary to its specific channel molecular function.

Summary: Cftr enters recycling-endosome membranes during surface internalization and recycling.

Reason: Recycling-endosome membrane localization reflects channel trafficking rather than its core functional site.

Summary: Cftr conducts anions across membranes; this broad parent is less informative than chloride transmembrane transport.

Reason: The term is valid by the True Path Rule but is too broad to represent Cftr's core function.

Summary: Mouse Cftr is expressed by ameloblasts, and Cftr loss causes hypomineralized enamel, supporting a non-core role in amelogenesis.

Reason: The mouse evidence supports involvement in amelogenesis, but this tissue-specific role is not Cftr's core molecular function.

Summary: CFTR is an ABC transporter family member but functions as an ATP-gated anion channel rather than an active transporter.

Reason: The ABC transporter activity term implies ATP-driven substrate transport, while CFTR primarily gates passive anion flow using ATP binding/hydrolysis.

Summary: CFTR NBD1 binds the chaperone Hsc70; this is a specific protein-protein interaction but not core channel function.

Reason: Evidence supports interaction with Hsc70; however, binding is not the primary molecular function of CFTR.

Summary: CFTR participates in protein interactions with SLC26A3/SLC26A6 and SLC9A3R1 in mouse sperm.

Reason: Protein interactions are documented but are not the core molecular function compared to channel activity.

Summary: Cytoplasmic localization reported in neurons.

Reason: Neuronal cytoplasmic localization has been reported, though CFTR is primarily a membrane channel.

Summary: Cftr is internalized into an early-endosomal recycling compartment en route back to the plasma membrane.

Reason: Endosomal localization reflects Cftr trafficking and recycling rather than its core site of action.

Summary: CFTR is a polytopic membrane protein, but its large cytosolic regulatory and nucleotide-binding regions do face the cytosol, so this is an imprecise parent rather than a wrong compartment.

Reason: Aligned with the IBA row for the same term. Mouse Cftr carries its own curated IDA cytosol annotation (PMID:24885604), and cytosol is not mutually exclusive with CFTR's apical membrane location the way nucleus is with cytoplasm. Per the IBA review project's localization rule an adjacent or subsuming compartment is not grounds for flagging, so this is retained as non-core - uninformative about the functional compartment, which is the apical membrane, but not an error.

Summary: Cftr is a multi-pass cell-surface membrane protein in epithelial cells.

Reason: Cell-surface localization is valid but less specific than apical plasma membrane.

Summary: CFTR is permeable to bicarbonate and contributes to epithelial HCO3- conductance, supporting a bicarbonate transmembrane permeation role although chloride conduction is the core function.

Reason: CFTR conducts bicarbonate as an anion-selective channel, but this is secondary to its chloride channel function.

Summary: Cftr conducts bicarbonate and contributes to epithelial bicarbonate transport, secondary to its core chloride-channel role.

Reason: Bicarbonate transport is supported but secondary to Cftr's principal chloride-transport role.

Summary: This ortholog-transferred annotation reflects experimentally demonstrated human CFTR inhibition of TMEM16A/ANO1 chloride-channel currents; the regulatory activity is plausible but non-core in mouse.

Reason: Human experimental evidence supports the transferred activity, but regulation of another chloride channel is secondary to Cftr's own channel function.

Summary: CFTR participates in multiprotein interaction hubs; enzyme-binding term is generic.

Reason: CFTR interacts with multiple regulatory partners, but enzyme-specific binding is not well defined.

Summary: NHERF1 PDZ domains bind the CFTR C-terminus.

Reason: PDZ-mediated interactions modulate CFTR trafficking and gating.

Summary: CFTR assembles into membrane protein complexes with multiple partners.

Reason: CFTR-containing complexes coordinate epithelial ion transport.

Summary: Endoplasmic-reticulum stress can trigger GORASP2-dependent unconventional trafficking of core-glycosylated Cftr to the cell surface, supporting a context-specific stress response.

Reason: The stress response is experimentally grounded but context-specific and not a core Cftr function.

Summary: Cftr-mediated epithelial anion movement drives transepithelial water transport indirectly through osmotic coupling.

Reason: Water transport is a physiological consequence of Cftr ion conductance rather than a direct molecular function.

Summary: CFTR monomers can be cross-linked within a dimeric channel complex.

Reason: Evidence supports CFTR dimeric complexes, but the term is generic.

Summary: Cftr-dependent epithelial ion and water transport contributes to organismal fluid homeostasis as a downstream, non-core role.

Reason: Organismal water homeostasis is a downstream consequence of epithelial anion transport, not Cftr's core molecular function.

Summary: CFTR engages chaperone machinery during folding.

Reason: Cytosolic chaperones monitor CFTR during biogenesis.

Summary: Cftr is internalized from the cell surface into a recycling-endosome compartment and recycled back to the plasma membrane.

Reason: Recycling-endosome localization reflects channel trafficking rather than its core functional site.

Summary: 14-3-3 proteins bind phosphorylated CFTR.

Reason: 14-3-3 binding modulates CFTR trafficking and activity.

Summary: CFTR insertion into the ER uses the translocon.

Reason: Co-translational insertion involves the ER translocon machinery.

Summary: Cftr directly mediates chloride movement across epithelial membranes, a core physiological process.

Reason: Chloride transmembrane transport is a direct, conserved core process mediated by Cftr.

Summary: Forskolin elevates cAMP and modulates CFTR activity.

Reason: Forskolin-dependent cAMP signaling affects CFTR activation.

Summary: Evidence for multimeric or cross-linked CFTR complexes does not justify retaining the generic identical-protein-binding term as a specific core function.

Reason: The generic binding term obscures the relevant channel complex and adds no informative molecular function.

Summary: Cftr forms a chloride-selective ion channel at the plasma membrane.

Reason: This is a direct, conserved core molecular function of Cftr.

Summary: ATP binding and hydrolysis at the Cftr nucleotide-binding domains gate its chloride channel, directly supporting this specific molecular function.

Reason: ATP-dependent gating is the most specific representation of Cftr's core channel activity.

Summary: Orthology transfer reports a context-specific nuclear Cftr pool; this localization is peripheral to its plasma-membrane channel function.

Reason: The transferred nuclear localization is context-specific and not part of Cftr's core membrane-channel role.

Summary: Cytoplasmic localization reported in neurons.

Reason: Neuronal cytoplasmic localization has been reported, though CFTR is primarily a membrane channel.

Summary: Cftr is internalized into an early-endosomal recycling compartment en route back to the plasma membrane.

Reason: Endosomal localization reflects Cftr trafficking and recycling rather than its core site of action.

Summary: Cftr is internalized into an early-endosomal recycling compartment en route back to the plasma membrane.

Reason: Endosomal localization reflects Cftr trafficking and recycling rather than its core site of action.

Summary: Endoplasmic-reticulum membrane localization reflects cotranslational insertion, folding, and quality control during Cftr biogenesis.

Reason: ER membrane residence is a biogenesis and quality-control intermediate, not Cftr's principal functional localization.

Summary: CFTR is a polytopic membrane protein, but its large cytosolic regulatory and nucleotide-binding regions do face the cytosol, so this is an imprecise parent rather than a wrong compartment.

Reason: Aligned with the IBA and IEA rows for the same term. The ortholog transfer is not the problem - mouse Cftr has its own curated IDA cytosol annotation (PMID:24885604), so the term is imprecise rather than wrong. Retained as non-core because the functionally informative location is the apical plasma membrane.

Summary: Cftr is a multi-pass plasma-membrane channel, especially at apical epithelial membranes.

Reason: The plasma membrane is a core functional localization where Cftr conducts anions.

Summary: Apical membrane localization suggests possible microvillar association.

Reason: Evidence supports apical membrane localization; microvillus-specific localization is not well defined.

Summary: Cftr directly mediates chloride transport across epithelial membranes.

Reason: Chloride transport is a direct, core physiological role of Cftr.

Summary: Cftr affects water transport indirectly by driving epithelial ion gradients; it is not itself a water channel.

Reason: Water movement is an indirect consequence of Cftr-mediated anion transport, so it is valid but non-core.

Summary: No direct evidence for xenobiotic response; CFTR is primarily an epithelial ion channel.

Reason: CFTR's established role is in epithelial ion and water transport.

Summary: Cftr is a multi-pass cell-surface membrane protein in epithelial cells.

Reason: Cell-surface localization is valid but less specific than apical plasma membrane.

Summary: Cftr is permeable to bicarbonate and supports bicarbonate conductance as a secondary anion-channel function.

Reason: Bicarbonate conductance is supported but secondary to Cftr's principal chloride-channel function.

Summary: Cftr conducts bicarbonate and contributes to epithelial bicarbonate transport, secondary to its core chloride-channel role.

Reason: Bicarbonate transport is supported but secondary to Cftr's principal chloride-transport role.

Summary: Cftr conducts bicarbonate and contributes to epithelial bicarbonate transport, secondary to its core chloride-channel role.

Reason: Bicarbonate transport is supported but secondary to Cftr's principal chloride-transport role.

Summary: Cftr is an integral multi-pass membrane protein; this broad term is less informative than plasma-membrane and apical-plasma-membrane terms.

Reason: The broad membrane term is valid but does not identify Cftr's core apical plasma-membrane localization.

Summary: Basolateral localization is not supported by primary CFTR localization evidence.

Reason: CFTR is primarily documented at the apical membrane in epithelial cells; basolateral localization appears over-annotated.

Summary: Cftr localizes to the apical plasma membrane of polarized epithelia, its principal functional site.

Reason: The apical plasma membrane is a core localization for epithelial Cftr channel activity.

Summary: Cftr localizes to the apical plasma membrane of polarized epithelia, its principal functional site.

Reason: The apical plasma membrane is a core localization for epithelial Cftr channel activity.

Summary: Cftr has intrinsic ATPase activity; ATP binding and hydrolysis at its nucleotide-binding domains drive the channel-gating cycle.

Reason: Intrinsic ATP hydrolysis is a conserved core biochemical activity coupled directly to Cftr channel gating.

Summary: This ortholog-transferred annotation reflects experimentally demonstrated human CFTR inhibition of TMEM16A/ANO1 chloride-channel currents; the regulatory activity is plausible but non-core in mouse.

Reason: Human experimental evidence supports the transferred activity, but regulation of another chloride channel is secondary to Cftr's own channel function.

Summary: CFTR participates in multiprotein interaction hubs; enzyme-binding term is generic.

Reason: CFTR interacts with multiple regulatory partners, but enzyme-specific binding is not well defined.

Summary: NHERF1 PDZ domains bind the CFTR C-terminus.

Reason: PDZ-mediated interactions modulate CFTR trafficking and gating.

Summary: CFTR mediates transepithelial chloride secretion across epithelial monolayers.

Reason: CFTR supports transepithelial chloride transport in epithelial tissues.

Summary: CFTR supports airway epithelial ion transport; developmental role is not established.

Reason: Evidence supports respiratory epithelial function rather than lung development per se.

Summary: Neuronal expression reported; dendritic localization not established.

Reason: CFTR is expressed in neurons, but dendrite-specific localization is not documented.

Summary: CFTR assembles into membrane protein complexes with multiple partners.

Reason: CFTR-containing complexes coordinate epithelial ion transport.

Summary: CFTR is expressed in immune cells; mast cell-specific activation is not established.

Reason: Evidence for immune cell expression does not directly support mast cell activation.

Summary: Endoplasmic-reticulum stress can trigger GORASP2-dependent unconventional trafficking of core-glycosylated Cftr to the cell surface, supporting a context-specific stress response.

Reason: The stress response is experimentally grounded but context-specific and not a core Cftr function.

Summary: Cftr-mediated epithelial anion movement drives transepithelial water transport indirectly through osmotic coupling.

Reason: Water transport is a physiological consequence of Cftr ion conductance rather than a direct molecular function.

Summary: CFTR regulates ENaC-mediated sodium transport in epithelia.

Reason: CFTR modulates sodium transport indirectly via ENaC.

Summary: No direct evidence for vasodilation; CFTR primarily regulates epithelial ion and water transport.

Reason: CFTR's established role is epithelial ion and water transport.

Summary: Neuronal expression reported; cell body localization not established.

Reason: CFTR is expressed in neurons, but cell body-specific localization is not documented.

Summary: Cftr-dependent epithelial ion and water transport contributes to organismal fluid homeostasis as a downstream, non-core role.

Reason: Organismal water homeostasis is a downstream consequence of epithelial anion transport, not Cftr's core molecular function.

Summary: CFTR engages chaperone machinery during folding.

Reason: Cytosolic chaperones monitor CFTR during biogenesis.

Summary: Cftr is internalized from the cell surface into a recycling-endosome compartment and recycled back to the plasma membrane.

Reason: Recycling-endosome localization reflects channel trafficking rather than its core functional site.

Summary: Cftr-null mice form hypomineralized enamel, supporting a non-core role in enamel mineralization.

Reason: The mouse phenotype supports this developmental role, but it is tissue-specific and downstream of Cftr ion transport.

Summary: 14-3-3 proteins bind phosphorylated CFTR.

Reason: 14-3-3 binding modulates CFTR trafficking and activity.

Summary: CFTR insertion into the ER uses the translocon.

Reason: Co-translational insertion involves the ER translocon machinery.

Summary: Cftr directly mediates chloride movement across epithelial membranes, a core physiological process.

Reason: Chloride transmembrane transport is a direct, conserved core process mediated by Cftr.

Summary: Forskolin elevates cAMP and modulates CFTR activity.

Reason: Forskolin-dependent cAMP signaling affects CFTR activation.

Summary: CFTR products are detected in Sertoli cells; barrier role is not established.

Reason: Sertoli cell context is noted, but barrier establishment evidence is limited.

Summary: No direct evidence for vascular smooth muscle apoptosis regulation.

Reason: CFTR's established role is epithelial ion and water transport.

Summary: CFTR supports pancreatic duct ion transport; beta-cell development role is not established.

Reason: Evidence supports pancreatic duct function rather than beta-cell development.

Summary: Cftr loss is associated with hypomineralized enamel, supporting a role in enamel mineralization during amelogenesis.

Reason: Evidence links Cftr to enamel mineralization but this is not the core function of CFTR.

Summary: Cftr is expressed in ameloblasts during enamel formation.

Reason: Supports a role in amelogenesis but is not core CFTR function.

Summary: Cftr is a chloride channel expressed in ameloblasts.

Reason: CFTR mediates chloride movement across membranes.

Summary: Cftr has intrinsic ATPase activity; ATP binding and hydrolysis at its nucleotide-binding domains drive the channel-gating cycle.

Reason: Intrinsic ATP hydrolysis is a conserved core biochemical activity coupled directly to Cftr channel gating.

Summary: CFTR surface expression can be rescued via unconventional secretion.

Reason: CFTR is a plasma membrane protein with regulated surface trafficking.

Summary: Endoplasmic-reticulum stress can trigger GORASP2-dependent unconventional trafficking of core-glycosylated Cftr to the cell surface, supporting a context-specific stress response.

Reason: The stress response is experimentally grounded but context-specific and not a core Cftr function.

Summary: Orthology transfer reports a context-specific nuclear Cftr pool; this localization is peripheral to its plasma-membrane channel function.

Reason: The transferred nuclear localization is context-specific and not part of Cftr's core membrane-channel role.

Summary: CFTR forms PKA-activated chloride channels at the apical membrane.

Reason: Direct electrophysiological evidence supports CFTR chloride channel activity.

Summary: Cftr is permeable to bicarbonate and supports bicarbonate conductance as a secondary anion-channel function.

Reason: Bicarbonate conductance is supported but secondary to Cftr's principal chloride-channel function.

Summary: Cftr conducts bicarbonate and contributes to epithelial bicarbonate transport, secondary to its core chloride-channel role.

Reason: Bicarbonate transport is supported but secondary to Cftr's principal chloride-transport role.

Summary: Cftr-mediated epithelial anion movement drives transepithelial water transport indirectly through osmotic coupling.

Reason: Water transport is a physiological consequence of Cftr ion conductance rather than a direct molecular function.

Summary: Cftr-dependent epithelial ion and water transport contributes to organismal fluid homeostasis as a downstream, non-core role.

Reason: Organismal water homeostasis is a downstream consequence of epithelial anion transport, not Cftr's core molecular function.

Summary: Apical CFTR chloride channels mediate chloride transport across the membrane.

Reason: CFTR channel activity provides chloride transmembrane transport.

Summary: Forskolin elevates cAMP and modulates CFTR activity.

Reason: Forskolin-dependent cAMP signaling affects CFTR activation.

Summary: ATP binding and hydrolysis at the Cftr nucleotide-binding domains gate its chloride channel, directly supporting this specific molecular function.

Reason: ATP-dependent gating is the most specific representation of Cftr's core channel activity.

Summary: Endoplasmic-reticulum membrane localization reflects cotranslational insertion, folding, and quality control during Cftr biogenesis.

Reason: ER membrane residence is a biogenesis and quality-control intermediate, not Cftr's principal functional localization.

Summary: Cftr is an integral multi-pass membrane protein; this broad term is less informative than plasma-membrane and apical-plasma-membrane terms.

Reason: The broad membrane term is valid but does not identify Cftr's core apical plasma-membrane localization.

Summary: Cftr directly mediates chloride movement across epithelial membranes, a core physiological process.

Reason: Chloride transmembrane transport is a direct, conserved core process mediated by Cftr.

Summary: PMID focuses on apical localization of ITPK1 in a CF model; CFTR apical localization is supported by other sources.

Reason: CFTR is documented at the apical plasma membrane in epithelial cells, although this PMID does not directly test CFTR localization.

Summary: CFTR functions as a cAMP-regulated chloride channel in mouse cells.

Reason: CFTR is a chloride channel whose activity is regulated by cAMP signaling.

Summary: Direct experimental cytosol annotation. CFTR's R domain and nucleotide-binding domains face the cytosol, so this is an imprecise parent term rather than a wrong compartment.

Reason: Aligned with the IBA, IEA and ISO rows for the same term, and downgraded from MARK_AS_OVER_ANNOTATED - this is the direct experimental observation that grounds them, so flagging it while accepting the propagated copies was inconsistent. A curator recorded cytosol from PMID:24885604, and cytosol is not a compartment that excludes CFTR's apical membrane location the way nucleus excludes cytoplasm. It is kept as non-core because the apical plasma membrane is the informative location, not because the observation is doubted.

Summary: CFTR is a cAMP-regulated chloride channel localized to the cell membrane.

Reason: CFTR is a membrane chloride channel required for epithelial ion transport.

Summary: CFTR contributes to epithelial chloride transport.

Reason: CFTR-mediated chloride conductance underlies epithelial ion transport.

Summary: Irbit translocates to CFTR at the plasma membrane, indicating protein interaction.

Reason: Protein interactions are reported but are not the core molecular function.

Summary: IRBIT activates luminal CFTR, indicating functional interaction.

Reason: Interaction/regulation is documented but is not core channel activity.

Summary: Study context involves Cl-/HCO3- exchangers and CFTR in sperm capacitation.

Reason: CFTR is primarily a chloride channel; bicarbonate transport is context dependent.

Summary: CFTR contributes to chloride increases during sperm capacitation.

Reason: Evidence supports CFTR involvement in chloride handling in sperm.

Summary: CFTR/SLC26A3 interaction is important for mouse sperm capacitation.

Reason: Demonstrates involvement in capacitation but not core CFTR function.

Summary: HCO3- and Cl- are essential for capacitation, consistent with pH-related changes during this process.

Reason: Evidence is indirect and context-specific.

Summary: Membrane potential hyperpolarizes during sperm capacitation.

Reason: Observed in the capacitation context; not core CFTR function.

Summary: cAMP stimulation affects CFTR-dependent chloride handling in sperm.

Reason: Response to cAMP is context-specific in sperm capacitation.

Summary: Cftr forms a chloride-selective ion channel at the plasma membrane.

Reason: This is a direct, conserved core molecular function of Cftr.

Summary: Cftr is a multi-pass plasma-membrane channel, especially at apical epithelial membranes.

Reason: The plasma membrane is a core functional localization where Cftr conducts anions.

Summary: This ortholog-transferred annotation reflects experimentally demonstrated human CFTR inhibition of TMEM16A/ANO1 chloride-channel currents; the regulatory activity is plausible but non-core in mouse.

Reason: Human experimental evidence supports the transferred activity, but regulation of another chloride channel is secondary to Cftr's own channel function.

Summary: IRBIT stimulates luminal CFTR to support epithelial anion transport.

Reason: Supports CFTR-mediated chloride transport in epithelial secretion.

Summary: Cftr is internalized into an early-endosomal recycling compartment en route back to the plasma membrane.

Reason: Endosomal localization reflects Cftr trafficking and recycling rather than its core site of action.

Summary: cftr(-/-) mice show increased de novo cholesterol synthesis.

Reason: Altered cholesterol biosynthesis is a downstream effect in CF models.

Summary: CF models show impaired intracellular cholesterol movement.

Reason: Cholesterol transport alterations are secondary to CFTR defects.