CFTR is a membrane anion channel of the ATP-binding cassette protein family. Phosphorylation and ATP-dependent conformational cycling regulate its pore, which conducts chloride and bicarbonate down their electrochemical gradients. Its ATPase activity controls gating rather than pumping anions against a gradient. At epithelial apical membranes, CFTR supports salt, fluid and bicarbonate transport; tissue-specific consequences include airway surface hydration, pancreatic and intestinal secretion, and sweat-duct salt handling. Cytosolic terminal and regulatory regions engage trafficking adaptors, chaperones and regulatory proteins. The channel cycles through biosynthetic and endosomal compartments, and misfolded forms can be retained in the endoplasmic reticulum and eliminated through quality-control pathways. Pathogenic variants cause cystic fibrosis; the common F508del variant disrupts folding and cell-surface delivery, reducing epithelial anion secretion.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005260 intracellularly ATP-gated chloride channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP-gated chloride conduction is the conserved core activity. Reason: The PAINT assertion agrees with purified CFTR ATPase/gating measurements and human epithelial chloride transport. The historical ancestral placement was not reconstructed; target evidence independently supports the activity without criticizing donor count or target self-evidence. |
| GO:0005254 chloride channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic annotation correctly identifies chloride channel activity. Reason: Direct channel measurements support passive chloride conductance through CFTR. ATP regulates gating; this does not turn chloride movement into primary active transport. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: Specify the experimentally established nucleotide ligand. Reason: CFTR binds ATP at its nucleotide-binding domains, and purified-protein experiments measure ATP hydrolysis coupled to gating. ATP binding is more informative than the original generic nucleotide-binding keyword inference. Proposed replacements: ATP binding |
| GO:0005260 intracellularly ATP-gated chloride channel activity | IEA GO_REF:0000003 | ACCEPT | Summary: The enzyme mapping correctly identifies ATP-gated channel activity. Reason: Official EC 5.6.1.6 concerns ATP-dependent conformational control of CFTR conductance. Direct hydrolysis/gating evidence supports this channel activity while ions move passively. |
| GO:0005515 protein binding | IPI PMID:12369822 The down regulated in adenoma (dra) gene product binds to th... | MODIFY | Summary: The actual source pair supports PDZ-domain binding. Reason: The preserved GOA partner is NHERF2/E3KARP Q15599. The primary abstract describes direct in-vitro binding to its second PDZ domain, with CFTR as the affinity comparator. This refines the target association; the DRA-centered title does not make DRA the preserved CFTR partner. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:12369822 affinity being comparable to that of the known ligand CFTR file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:12471024 The PDZ-binding chloride channel ClC-3B localizes to the Gol... | KEEP AS NON CORE | Summary: Retain the source-specific PDZ-organized protein associations. Reason: Exact positive records include NHERF1, ClC-3B, PDZK1 and GOPC, using CFTR-tail pull-downs and cellular co-IP. Some contacts are within PDZ-organized complexes; a single binary PDZ-binding claim would not describe every preserved partner. No CFTR-mediated ClC-3B trafficking mechanism is inferred. Supporting Evidence: PMID:12471024 only PDZK1 was found to promote interaction between the two channels file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:14679199 Inhibitory regulation of cystic fibrosis transmembrane condu... | MODIFY | Summary: The Shank interaction is specifically PDZ-dependent. Reason: The primary reports yeast-two-hybrid and co-IP association and loss of binding after mutation of the Shank PDZ domain. The source partner is rat Shank Q9QX74; cellular functional corroboration includes mammalian expression and human T84 antisense experiments. This is domain-binding evidence, not proof of a native human binary affinity. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:14679199 this interaction was abolished by mutations in the PDZ domain of Shank2 file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:16203867 Lysophosphatidic acid inhibits cholera toxin-induced secreto... | KEEP AS NON CORE | Summary: Retain CFTR association with the LPA-receptor regulatory complex. Reason: Exact records separate CFTR/NHERF2 fragment pull-down from LPAR2-containing co-IP/crosslinking complexes. The association and receptor-dependent regulation are real source findings, but they do not confer receptor or scaffold activity on CFTR or establish all contacts as binary. |
| GO:0005515 protein binding | IPI PMID:16546175 Rescue of functional delF508-CFTR channels in cystic fibrosi... | KEEP AS NON CORE | Summary: Retain the calnexin association in the tested folding context. Reason: The authentic abstract reports loss of the F508del-CFTR/calnexin interaction after miglustat treatment, alongside mutant rescue. Retain the experimentally curated association with explicit mutant/quality-control scope; do not generalize it into a constitutive mature-channel interaction or assign CFTR chaperone activity. Supporting Evidence: PMID:16546175 prevents delF508-CFTR/calnexin interaction file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:16901789 Sequential quality-control checkpoints triage misfolded cyst... | KEEP AS NON CORE | Summary: Retain associations with the ER quality-control machinery. Reason: Exact human 293T records support CFTR association with RNF5 and DERL1 under wild-type/mutant expression conditions. CFTR is a quality-control client; these associations do not establish intrinsic ubiquitin-ligase or retrotranslocase activity. |
| GO:0005515 protein binding | IPI PMID:17110338 Hsp90 cochaperone Aha1 downregulation rescues misfolding of ... | KEEP AS NON CORE | Summary: Retain the actual source partner set rather than the title-level regulator alone. Reason: The preserved six-partner set is supported by exact co-IP records, including endogenous human epithelial assays. The paper foregrounds proteostasis remodeling, but the original partners are not interchangeable with Aha1. Complex recovery is retained without claiming purified binary binding or a shared function for every partner. |
| GO:0005515 protein binding | IPI PMID:17244609 Dynamic regulation of cystic fibrosis transmembrane conducta... | MODIFY | Summary: The measured terminal-peptide contacts are PDZ-domain binding. Reason: Exact surface-plasmon-resonance records test a GST CFTR C-terminal fragment against NHERF1 and rat Shank PDZ constructs. The direct domain-level interaction supports this refinement while fragment, tag and species limits remain explicit. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:17244609 physical and physiological competition between EBP50-CFTR and Shank2-CFTR associations file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:18555783 BAP31 interacts with Sec61 translocons and promotes retrotra... | KEEP AS NON CORE | Summary: Retain BAP31 association during mutant-channel quality control. Reason: Exact records include F508del CFTR and an N-terminal fragment in human expression systems. The association supports this non-core client-protein binding assertion, not a role for CFTR as an ER export factor. |
| GO:0005515 protein binding | IPI PMID:19465887 The ER-resident ubiquitin-specific protease 19 participates ... | KEEP AS NON CORE | Summary: Retain USP19 association with the mutant quality-control substrate. Reason: The normal cache omits relevant Results despite its full-text flag. Independently recovered original Results explicitly report Figure 5 co-IP of USP19 with GFP-F508del CFTR, separate from substrate-stabilization measurements. This supports a tagged mutant-containing complex, not a purified binary interface or universal mature wild-type association. |
| GO:0005515 protein binding | IPI PMID:19878303 Deletion of Phe508 in the first nucleotide-binding domain of... | KEEP AS NON CORE | Summary: Retain the source-scoped Hsc70 association. Reason: The authentic abstract explicitly tests murine wild-type/F508del NBD1 with Hsc70 by surface plasmon resonance; the preserved partner is bovine Hsc70. Independent human CFTR chaperone-binding evidence supports the broad conserved association. This source is not presented as a full-length human-CFTR experiment. Supporting Evidence: PMID:19878303 F508del-murine (m)NBD1 binds Hsc70 with higher affinity file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:21455491 A Pseudomonas aeruginosa toxin that hijacks the host ubiquit... | KEEP AS NON CORE | Summary: The actual preserved partner is USP10. Reason: Selected full Results and Figure 4A show CFTR co-IP with USP10 from early endosomes of human airway epithelial cells, reduced by Cif treatment. The seeded Q14694 pair is not CFTR binding to the bacterial Cif toxin. Retain complex association without calling the deubiquitinase activity CFTR intrinsic. |
| GO:0005515 protein binding | IPI PMID:21884936 Rescue of ΞF508-CFTR trafficking via a GRASP-dependent uncon... | MODIFY | Summary: GRASP55 binds the CFTR terminal PDZ-binding region. Reason: Exact fragment pull-down and HEK293 co-IP records resolve the GRASP55 PDZ domain and CFTR C terminus. The specific domain interaction is supported in the unconventional trafficking study; the channel itself is not assigned GRASP-mediated export machinery activity. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:22038833 Disruption of cytokeratin-8 interaction with F508del-CFTR co... | KEEP AS NON CORE | Summary: Retain the measured cytoskeletal associations. Reason: Exact records support keratin-8 and actin association with wild-type/F508del CFTR in HeLa assays; direct SPR concerns keratin-8 and NBD1. These mixed assays support the original grouped binding assertion without converting co-IP into a purified actin interface or CFTR cytoskeletal-scaffold activity. Supporting Evidence: PMID:22038833 CFTR was immunoprecipitated from HeLa cells file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:22121115 The testis anion transporter TAT1 (SLC26A8) physically and f... | KEEP AS NON CORE | Summary: Retain SLC26A8 association and functional coupling. Reason: The authentic abstract explicitly reports physical interaction and enhanced CFTR activity in oocyte/CHO expression assays, with mouse reproductive phenotypes. Retain the curated association while avoiding an unverified human-construct assignment based solely on the host cell. Supporting Evidence: PMID:22121115 TAT1 and CFTR physically interact file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:22768251 Proteomic identification of calumenin as a G551D-CFTR associ... | KEEP AS NON CORE | Summary: Retain calumenin association in the tested variant context. Reason: Exact records support calumenin isoform 1 association with G551D CFTR in HeLa pull-down/co-IP assays; the authentic abstract additionally reports SPR. The reported folding-support hypothesis is not established as an intrinsic CFTR or calumenin catalytic mechanism by this association alone. Supporting Evidence: PMID:22768251 calumenin was present in the protein complex linked to G551D-CFTR file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:25661196 SERCA and PMCA pumps contribute to the deregulation of Ca2+ ... | KEEP AS NON CORE | Summary: Retain the SERCA2-containing CFTR complex. Reason: Exact co-IP and proximity-ligation records in human airway-cell contexts support the preserved SERCA2 association. These are positive complex-level assays, not grounds to deny binding because calcium-pump regulation is discussed. They do not establish CFTR calcium-pump activity or a purified binary interface. |
| GO:0005515 protein binding | IPI PMID:25712891 G551D-CFTR needs more bound actin than wild-type CFTR to mai... | KEEP AS NON CORE | Summary: Retain the actin association in wild-type and mutant expression contexts. Reason: Exact records support actin recovery with CFTR in HeLa co-IP experiments. The source is appropriately retained as non-core association, without inferring that CFTR itself bundles actin or serves as a general cytoskeletal scaffold. Supporting Evidence: PMID:25712891 a higher amount of actin was bound onto G551D-CFTR than onto Wt-CFTR file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:26618866 βF508 CFTR interactome remodelling promotes rescue of cystic... | KEEP AS NON CORE | Summary: Human CFTR co-purifies with multiple proteins in wild-type, F508del and rescue/treatment contexts. Reason: The original source is retained. PMID:26618866 uses anti-CFTR CoPIT in human bronchial epithelial cell lines, with CFTR-null and bead-only controls; complexes include indirect as well as direct associations. Exact publisher Table S1 contains 24 of the 31 original GOA partner accessions. Six further partners map through official human UniProt identities to CFTR-containing edges in Tables S7-S13 under temperature-shift, SAHA/TSA or HDAC7-depletion conditions; Q9P035 maps to HACD3/PTPLAD1, for which the main Results and Extended Data Figure 2 describe reciprocal co-IP. Therefore these are not 31 untreated wild-type binary interfaces. The heterogeneous partner set supports retained non-core protein association under the campaign instruction; it does not establish one narrower shared molecular activity. The original source object has no WITH field and is not backfilled. |
| GO:0005515 protein binding | IPI PMID:27092946 Investigating CFTR and KCa3.1 Protein/Protein Interactions. | KEEP AS NON CORE | Summary: Retain CFTR association with KCa3.1. Reason: Exact records include human-protein fragments in bacterial two-hybrid assays and co-IP from CFBE cells expressing wild-type or F508del CFTR. These support source-specific association; they do not make CFTR a potassium channel or establish a universal regulatory effect of KCa3.1. |
| GO:0005515 protein binding | IPI PMID:28360110 The CFTR trafficking mutation F508del inhibits the constitut... | KEEP AS NON CORE | Summary: Retain the source-specific terminal-domain and complex associations. Reason: The exact partner set includes PDZ-protein interactions and a channel-associated partner. Fragment fluorescence-polarization and complex assays have different resolution, so retain the grouped generic assertion rather than assign every partner a single PDZ interaction mechanism. |
| GO:0005515 protein binding | IPI PMID:29924966 A Proteomic Variant Approach (ProVarA) for Personalized Medi... | KEEP AS NON CORE | Summary: Retain variant-dependent proteomic associations. Reason: All 17 original partner accessions have exact positive source records in the ProVarA panel. Variant-dependent recoveries are not treated as independent wild-type positives, and pooled or feature-free records are not used to erase mutation context. |
| GO:0006695 cholesterol biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the source-qualified upstream effect on cholesterol synthesis as non-core. Reason: The preserved GOA qualifier is acts_upstream_of_or_within, also present on the mouse IMP donor. PMID:17085523 measures increased synthesis by deuterium incorporation/GC-MS after Cftr loss. This supports the broad upstream assertion, without assigning CFTR a sterol-synthetic reaction. The qualifier field now records the relationship already present in the preserved GOA. Supporting Evidence: GO_REF:0000107 PMID:17085523 increased de novo cholesterol synthesis file:human/CFTR/CFTR-source-evidence.json |
| GO:0030301 cholesterol transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the source-qualified upstream effect on cholesterol movement as non-core. Reason: The preserved GOA and mouse donor use acts_upstream_of_or_within. PMID:17085523 reports abnormal cholesterol distribution and correction in cells expressing full-length wild-type CFTR. Retain that causal upstream scope; the molecular transport mechanism remains unresolved, and this is not evidence that CFTR translocates cholesterol through its pore. The qualifier field now records the relationship already present in the preserved GOA. |
| GO:0051649 establishment of localization in cell | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact broad localization transfer remains unresolved. Reason: The original GOA qualifier is acts_upstream_of_or_within. Its historical Ensembl mapping to this broad localization term has not been reconstructed from the current mouse records. The cholesterol findings support upstream homeostasis but do not identify which localization assertion generated this transfer. Preserve the source while leaving that specific mapping unresolved; uncertainty is not limited to inaccessible publications. The qualifier field now records the relationship already present in the preserved GOA. |
| GO:0005515 protein binding | IPI PMID:29393851 Gq activity- and Ξ²-arrestin-1 scaffolding-mediated ADGRG2/CF... | KEEP AS NON CORE | Summary: Retain the ADGRG2-associated signaling complex. Reason: Full Results show association in mouse efferent ductules and tagged HEK293 co-IP; beta-arrestin-1 is implicated in organizing the complex. This supports the original CFTR association without assigning the scaffolding activity to CFTR or treating mouse tissue as a human endogenous assay. |
| GO:0005515 protein binding | IPI PMID:23818989 Ubiquitination and degradation of CFTR by the E3 ubiquitin l... | KEEP AS NON CORE | Summary: Retain MARCH2 association through a trafficking complex. Reason: Full Figure 7 and Results show HA-MARCH2 co-IP with GFP-CFTR in HEK293 cells, with terminal deletion affecting the interaction, and cellular colocalization. This is a supported substrate-containing complex; it does not confer ubiquitin-ligase activity on CFTR or resolve a purified binary MARCH2 interface. |
| GO:0005254 chloride channel activity | IDA PMID:15010471 Dynamic control of cystic fibrosis transmembrane conductance... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: Oocyte channel measurements establish chloride permeation; the dynamic external-chloride selectivity interpretation belongs to this paper. |
| GO:0005254 chloride channel activity | IDA PMID:19019741 Mechanism of direct bicarbonate transport by the CFTR anion ... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: Inside-out patches from BHK cells expressing human CFTR directly measure anion permeation. This paper finds stable selectivity under the tested conditions. |
| GO:0005254 chloride channel activity | IMP PMID:19621064 CFTR delivery to 25% of surface epithelial cells restores no... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: Human CF airway-culture gene delivery restores chloride transport alongside epithelial fluid and sodium-transport phenotypes. |
| GO:0005254 chloride channel activity | IDA PMID:11524016 A monomer is the minimum functional unit required for channe... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: The authentic primary abstract describes human CFTR channel and ATPase measurements; independent purified-protein evidence corroborates the activity. |
| GO:0005260 intracellularly ATP-gated chloride channel activity | IMP PMID:8910473 ATPase activity of the cystic fibrosis transmembrane conduct... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: Purified, reconstituted CFTR directly hydrolyzes ATP in a gating-coupled system. |
| GO:0005254 chloride channel activity | IDA PMID:11707463 A Golgi-associated PDZ domain protein modulates cystic fibro... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: The source reports CFTR channel activity in its CAL/PDZ trafficking context; the partner-centered title does not negate the target functional assay. |
| GO:0005254 chloride channel activity | IMP PMID:24885604 CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exo... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: Full human/mouse beta-cell Results measure cAMP-dependent currents and their sensitivity to CFTR antagonists; pharmacological attribution is distinguished from a purified pore assay. |
| GO:0005254 chloride channel activity | IDA PMID:18570918 Endosomal SNARE proteins regulate CFTR activity and traffick... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: The authentic recycling study supports channel function at the apical membrane alongside localization and trafficking measurements. |
| GO:0005515 protein binding | IPI PMID:19289574 SLC26A9 is a constitutively active, CFTR-regulated anion con... | KEEP AS NON CORE | Summary: Retain SLC26A9 co-association and functional coupling. Reason: Selected full Results support co-IP and CFTR-dependent SLC26A9 conductance in expression systems. ER retention is offered as a possible explanation, not directly established. Association is not treated as a purified binary interaction or as evidence about ENaC. |
| GO:0005515 protein binding | IPI PMID:20658517 SLC26A9 stimulates CFTR expression and function in human bro... | KEEP AS NON CORE | Summary: Retain the airway-cell SLC26A9 association. Reason: The authentic abstract explicitly reports co-IP and apical functional association in bronchial epithelia. This corroborates a contextual channel complex, without assigning CFTR an intrinsic exchanger mechanism. |
| GO:0005254 chloride channel activity | IDA PMID:22178883 CFTR and TMEM16A are separate but functionally related Cl- c... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: The authentic abstract reports CFTR current and TMEM16A coupling; this supports CFTR channel activity without attributing all calcium-activated current to CFTR. |
| GO:0005515 protein binding | IPI PMID:22178883 CFTR and TMEM16A are separate but functionally related Cl- c... | KEEP AS NON CORE | Summary: Retain TMEM16A association in its measured regulatory context. Reason: The authentic abstract reports co-IP and suppression of calcium-activated TMEM16A currents by CFTR. This is partner-specific complex/coupling evidence, not sodium-channel regulation or proof of an isolated binary interface. |
| GO:0005515 protein binding | IPI PMID:11707463 A Golgi-associated PDZ domain protein modulates cystic fibro... | MODIFY | Summary: The CAL interaction is specifically PDZ-domain binding. Reason: The authentic source reports interaction between the CFTR terminal motif and the CAL/GOPC PDZ domain. This supports the more precise domain-binding activity already independently demonstrated for CFTR; preserve the source IPI assertion. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:11707463 The PDZ domain of CAL binds to the C terminus of CFTR file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:15247260 Myosin VI regulates endocytosis of the cystic fibrosis trans... | KEEP AS NON CORE | Summary: Retain the human epithelial endocytic complex associations. Reason: The authentic source reports CFTR in a complex with Dab2 and myosin VI in polarized Calu-3 cells. Co-complex recovery supports the grouped binding assertion; the motor and adaptor activities belong to the partners. Supporting Evidence: PMID:15247260 formed a complex with myosin VI file:human/CFTR/CFTR-source-evidence.json |
| GO:0005260 intracellularly ATP-gated chloride channel activity | NAS PMID:11707463 A Golgi-associated PDZ domain protein modulates cystic fibro... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: The NAS statement agrees with independently measured ATP-regulated CFTR conductance; the original citation is preserved without upgrading its evidence code. |
| GO:0005254 chloride channel activity | TAS PMID:9931011 Walker mutations reveal loose relationship between catalytic... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: The original TAS channel statement is independently established by purified CFTR and human epithelial experiments; it is not treated as a new direct assay in this citation. |
| GO:0005260 intracellularly ATP-gated chloride channel activity | TAS PMID:10581360 Differential function of the two nucleotide binding domains ... | ACCEPT | Summary: Retain the experimentally supported CFTR channel function. Reason: The authentic NBD study supports differential nucleotide-domain contributions to CFTR gating, consistent with independent purified-channel evidence. |
| GO:0005515 protein binding | IPI PMID:31324722 Inhibition of calpain 1 restores plasma membrane stability t... | KEEP AS NON CORE | Summary: Retain condition- and variant-dependent interactome recovery. Reason: All 19 original partners join exact positive records from tagged CFTR proteomics in CFBE41o cells. Wild-type, rescued F508del and mutant-selective recovery are distinguished; CAPN1 is not promoted to a universal wild-type interaction. These are co-complex assays rather than purified binary affinities. |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | KEEP AS NON CORE | Summary: Human wild-type and F508del CFTR show construct-dependent MaMTH associations with the original partner set. Reason: The genuine publisher Dataset EV4 contains all 94 original GOA partner accessions with its MaMTH detection flag positive, and all 94 match the actual Dataset EV2 ORF/replicate rows: 32 wild-type-only, 44 F508del-only and 18 shared. The assay uses full-length human CFTR with C-terminal Cub-GAL4TF-P2A-tagBFP and N-terminal Nub-tagged human ORFeome preys in HEK293 reporters. These are cellular reporter associations, not purified binary affinities or proof of all endogenous tissues/isoforms. Dataset EV5 and Table EV2 independently within the same paper report mixed retest/co-IP outcomes; an HTS detection must not be described as universal orthogonal validation. Imported/predicted IID-only edges are excluded from this target support. Retain non-core association without forcing a single partner-class refinement across this diverse group. |
| GO:0140359 ABC-type transporter activity | IBA GO_REF:0000033 | REMOVE | Summary: CFTR is not a primary-active ABC transporter under this term definition. Reason: Current GO:0140359 requires transport powered directly by ATP hydrolysis. Human CFTR instead uses ATP-dependent gating while anions move down an electrochemical gradient. This target-specific functional divergence challenges the inherited activity, not the family membership or number of PAINT donors; the historical node was not reconstructed. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN009085477 UNRESOLVED The literal historical PAINT node is preserved; full IBD placement/alignment was not reconstructed. Target-specific passive CFTR conduction contradicts the primary-active-transport requirement, independently of donor count. Supporting Evidence: GO_REF:0000033 file:human/CFTR/CFTR-source-evidence.json |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma-membrane localization supports the core channel role. Reason: The PAINT location agrees with direct human epithelial localization and transport. No ancestral-node reconstruction or donor-count argument is required to recognize this independently established target location. |
| GO:0016323 basolateral plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Basolateral association is supported in a specific epithelial context. Reason: The authentic PMID:1720311 abstract reports human sweat-duct staining predominantly apically but also near the basolateral membrane using two CFTR peptide antibodies. Predominant apical function does not refute the broader IBA location. Preserve the historical source while keeping tissue and spatial-resolution limits explicit; no universal basolateral distribution is asserted. |
| GO:0006833 water transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CFTR contributes to epithelial water movement through ion transport. Reason: Human airway rescue supports fluid homeostasis coupled to CFTR-mediated salt transport. Retain the broad existing biological process without claiming that the CFTR pore itself is an aquaporin or that water conduction was directly measured through the protein. |
| GO:0015701 bicarbonate transport | IBA GO_REF:0000033 | ACCEPT | Summary: Bicarbonate movement is a core channel process. Reason: Human CFTR directly conducts bicarbonate in inside-out patch measurements. This positive target evidence supports the PAINT process without equating the inherited assertion with a freshly reconstructed ancestral node. |
| GO:1902476 chloride transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: CFTR directly performs chloride transmembrane transport. Reason: The pore carries chloride; it is not merely a substrate required by another chloride transporter. Purified and epithelial measurements support the conserved process. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytosolic CFTR species occur during quality control. Reason: The retained broad location is supported by retrotranslocation and cytosolic deglycosylated CFTR described in the Sec61 study. Cytosolic domains of an intact membrane protein alone would not establish this location. The PAINT history remains distinct from the independent trafficking evidence. |
| GO:0016324 apical plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Apical plasma membrane is a principal site of channel activity. Reason: Direct human epithelial localization and functional rescue support the PAINT location. Tissue-specific additional pools do not negate this major active compartment. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: ATP binding is intrinsic to CFTR gating. Reason: The electronic inference agrees with nucleotide-dependent gating and ATPase experiments. Binding and hydrolysis are distinct but both supported; no active-anion-pump mechanism follows. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization has a processed-product/ortholog context. Reason: Full rat primary Methods/Results show Sertoli nuclear immunofluorescence, peptide-blocking and independent-antibody controls, and an approximately 85-kDa nuclear fraction band. The authors propose a processed CFTR fragment; nuclear gene regulation is untested. Retain this unscoped source conservatively as non-core ortholog/product context, not evidence that intact human CFTR is a nuclear anion channel. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the broad cytoplasmic compartment as a non-core cellular pool. Reason: The original electronic compartment is compatible with CFTR biosynthetic, endosomal and degradation-associated intracellular pools. It does not localize the intact active pore freely in cytosol or infer activity merely from exposed cytoplasmic domains. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CFTR occupies the ER membrane during biosynthesis and quality control. Reason: This source location is consistent with folding, retention and ER-associated degradation of CFTR, including F508del. It is a trafficking/quality-control compartment distinct from the principal epithelial surface activity. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic plasma-membrane location is correct. Reason: Human localization and electrophysiology independently place functional CFTR at the cell surface. Preserve the original mapping without claiming every cellular pool is surface active. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000120 | ACCEPT | Summary: Ion transport is a correct broad description of the core channel process. Reason: CFTR directly moves chloride and bicarbonate across membranes. The broad electronic process is supported alongside its more specific source annotations. |
| GO:0006821 chloride transport | IEA GO_REF:0000120 | ACCEPT | Summary: Chloride transport is directly performed by CFTR. Reason: The channel mediates chloride flux; hydrolysis controls gating rather than providing uphill transport energy. |
| GO:0015701 bicarbonate transport | IEA GO_REF:0000117 | ACCEPT | Summary: The bicarbonate-transport inference agrees with direct target experiments. Reason: Human CFTR bicarbonate permeation is directly resolved in membrane-patch assays. The ARBA source is retained without manufacturing a separate mechanistic donor chain. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane insertion is integral to the channel function. Reason: The InterPro membrane assertion agrees with the genuine multipass UniProt record and functional membrane-reconstituted CFTR. Membrane association is not inferred solely from a partner. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Apical localization is independently established. Reason: Human epithelial localization and CF airway surface rescue support the combined electronic location, with tissue-dependent distribution acknowledged. |
| GO:0016853 isomerase activity | IEA GO_REF:0000043 | MODIFY | Summary: Use the specific ATP-hydrolysis activity within the valid EC classification. Reason: GO:0016853 explicitly includes EC class 5 enzymes, and EC 5.6.1.6 classifies CFTR ATP-dependent conformational control. Thus the old broad isomerase mapping is not fabricated or biologically impossible. ATP hydrolysis is the experimentally measured, more informative molecular activity; passive ion flow remains distinct from pumping. Proposed replacements: ATP hydrolysis activity Supporting Evidence: GO_REF:0000043 file:human/CFTR/CFTR-source-evidence.json |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: CFTR directly hydrolyzes ATP. Reason: Purified reconstituted CFTR measurements establish the catalytic activity. Its purpose here is conformational gating, not chemical transformation of chloride or primary active anion transport. |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Early-endosome membrane is a recycling compartment for CFTR. Reason: The original location mapping agrees with the USP10 and Cif trafficking studies. CFTR is the membrane cargo regulated in these experiments, not the deubiquitinase. |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000120 | ACCEPT | Summary: Ion movement across a membrane is the core transport process. Reason: Chloride and bicarbonate permeation through the CFTR pore supports this broad electronic term; the direction follows electrochemical conditions. |
| GO:0034707 chloride channel complex | IEA GO_REF:0000043 | ACCEPT | Summary: CFTR is a functional component of chloride-channel assemblies. Reason: The keyword-derived complex term is concordant with membrane CFTR and documented regulatory complexes. It does not require an unverified fixed oligomeric stoichiometry or make all recovered partners obligatory pore subunits. |
| GO:0055038 recycling endosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Recycling-endosome membrane is a supported trafficking location. Reason: The endosomal SNARE and USP10 studies support CFTR cycling through recycling compartments. The original location does not assign recycling-machinery activity to the cargo. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: The broad transmembrane-transport process is correct. Reason: The membrane pore directly performs anion translocation. This broad process is compatible with passive channel conductance and does not inherit an ATP-driven pump mechanism from the ABC fold. |
| GO:0098660 obsolete inorganic ion transmembrane transport | IEA GO_REF:0000117 | MODIFY | Summary: Retain the ion-transport meaning with the current supported process term. Reason: The official current response marks the original ID obsolete, but the original machine term is preserved. Independently measured monatomic-ion movement supports GO:0034220; this is a semantic update, not evidence that CFTR lacks the old process. Proposed replacements: monoatomic ion transmembrane transport |
| GO:0140359 ABC-type transporter activity | IEA GO_REF:0000002 | REMOVE | Summary: The ABC-family domain mapping overextends to primary active transport. Reason: IPR011527 supports ABC-family architecture; the current GO activity additionally requires ATP-powered primary active transport. CFTR-specific passive conduction with ATP-dependent gating fails that mechanistic requirement. Retain the original domain/source fields while rejecting this activity inference. Supporting Evidence: GO_REF:0000002 file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | UNDECIDED | Summary: The source reports CFTR-centered proximity labeling, which does not by itself resolve the original protein-binding assertion. Reason: PMID:36012204 uses N-terminal APEX2/TurboID-CFTR in transfected human HEK293 cells, including wild-type, G551D and W1282X/truncated constructs. The central exact IntAct join recovers 148 positive records for 66 of the 70 original GOA partners, but every matched record is explicitly MI:1314 proximity-dependent biotin identification with MI:2364 proximity. The full primary Discussion states that the method also labels noninteracting nearby proteins. This is an assay-resolution uncertainty, not absence of target data or proof that these proteins cannot bind. The four unmatched accessions are O60869, O75127, P07099 and P60709; an empty query result is not negative evidence. Preserve all original assertions and source fields, keep the positive proximity findings, and leave the source-specific binding claim unresolved. Independent binding evidence from other publications remains separately valid and is not silently substituted for this paper. Supporting Evidence: PMID:36012204 both direct binding partners and proximal non-interacting proteins file:human/CFTR/CFTR-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r... | KEEP AS NON CORE | Summary: Retain engineered fragment-level positive interactions. Reason: Exact positive records concern a CFTR peptide with an engineered CASK kinase-domain construct and a separate CFTR peptide/PTBP1 RRM experiment with mutation features. These support contextual binding capability, not intact wild-type CFTR association with both partners in native cells; no partner enzymatic or RNA-binding activity is transferred. |
| GO:0005515 protein binding | IPI PMID:9671706 A C-terminal motif found in the beta2-adrenergic receptor, P... | MODIFY | Summary: The CFTR C-terminal sequence directly engages an NHERF PDZ domain. Reason: Full Results and Figure 4 show terminal-fusion overlays and in-vitro translated full-length CFTR binding to NHERF; N-terminal and truncated-terminal controls distinguish the site. This directly supports PDZ-domain binding rather than generic binding alone. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:9671706 NHERF also binds to the tail of the cystic fibrosis transmembrane conductance regulator file:human/CFTR/CFTR-source-evidence.json |
| GO:0055085 transmembrane transport | TAS Reactome:R-HSA-382556 | ACCEPT | Summary: Retain transmembrane transport with the CFTR channel mechanism. Reason: The Reactome parent pathway broadly describes ABC transporters. Its generic active-transport prose is not evidence that CFTR pumps anions; independent CFTR pore measurements establish the sound broad transport annotation. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the orthology-based cytosolic quality-control pool. Reason: The source is a mouse transfer, not an independent human localization assay. Human CFTR retrotranslocation and deglycosylated cytosolic species support the broad location; exposed domains alone are not the rationale. |
| GO:0015106 bicarbonate transmembrane transporter activity | IEA GO_REF:0000107 | MODIFY | Summary: Specify bicarbonate movement by a channel. Reason: The preserved mouse-derived transporter annotation has a correct transported ion. Direct human CFTR patch assays establish a conductive pore rather than a bicarbonate pump or exchanger, supporting the more precise activity. Proposed replacements: bicarbonate channel activity |
| GO:0015108 chloride transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: Chloride transmembrane transport activity is correct. Reason: The mouse-derived broad activity agrees with direct human channel assays. The original source remains untouched; passive channel conduction supplies the molecular mechanism. |
| GO:0048240 sperm capacitation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the reproductive context of CFTR-dependent sperm capacitation. Reason: The source transfer is grounded in mouse CFTR-dependent chloride/pH/electrical responses during capacitation. The accessed primary material reports pharmacological perturbations and transporter cooperation, not a human purified assay or an additional autonomous sperm-development mechanism. |
| GO:0051454 intracellular pH elevation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the sperm-context intracellular alkalinization role. Reason: The mouse source links CFTR-dependent anion handling to capacitation-associated pH change. Keep the physiological process as a contextual consequence of channel participation; this does not establish direct proton transport through CFTR or universal pH regulation in every compartment. Supporting Evidence: GO_REF:0000107 file:human/CFTR/CFTR-source-evidence.json |
| GO:0060081 membrane hyperpolarization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain context-dependent membrane hyperpolarization. Reason: Selected mouse primary Discussion reports reduced capacitation-associated hyperpolarization after CFTR inhibition alongside chloride-pathway interactions. The channel can contribute to an electrical response without becoming the sole voltage-determining transporter. |
| GO:0070175 positive regulation of enamel mineralization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse-supported enamel mineralization role. Reason: Full mouse knockout Methods/Results measure hypomineralized incisors and altered chloride, sodium and potassium profiles, with fluoride context. This supports the transferred enamel process while CFTR remains an anion channel, not a calcium transporter or mineral-deposition enzyme. |
| GO:0071320 cellular response to cAMP | IEA GO_REF:0000107 | ACCEPT | Summary: cAMP-dependent channel regulation is a core cellular response. Reason: PKA-dependent CFTR phosphorylation and gating connect elevated cAMP to anion conductance. This is a channel response to signaling, not intrinsic adenylate-cyclase or kinase activity. Supporting Evidence: GO_REF:0000107 file:human/CFTR/CFTR-source-evidence.json |
| GO:0097186 amelogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the developmental enamel context. Reason: The source mouse knockout and elemental/ultrastructural readouts support CFTR participation in enamel physiology. Preserve the IEA/ISS provenance and avoid upgrading the mouse result to a direct human ameloblast assay. |
| GO:1902476 chloride transmembrane transport | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the conserved chloride-transport process. Reason: The orthology-based assertion is independently supported by human CFTR electrophysiology and epithelial transport. The donor fields are preserved rather than replaced with a new evidence code. Supporting Evidence: GO_REF:0000107 file:human/CFTR/CFTR-source-evidence.json |
| GO:1902476 chloride transmembrane transport | IDA PMID:22006324 Anoctamin 6 is an essential component of the outwardly recti... | ACCEPT | Summary: The target chloride-transport assertion remains supported. Reason: The ANO6-focused authentic abstract also reports CFTR-related transport measurements. Do not reject a target assay merely because another channel is foregrounded; independent CFTR electrophysiology confirms the same process. |
| GO:0071889 14-3-3 protein binding | EXP PMID:26888287 Characterization and small-molecule stabilization of the mul... | KEEP AS NON CORE | Summary: Retain phosphorylation-dependent 14-3-3 association. Reason: Full primary peptide-binding, structural and mutational results establish CFTR regulatory-region engagement by 14-3-3. Assays use phosphorylated fragments and engineered crystallographic linkers as specified; beta binding is distinguished from zeta/gamma structures. The activity is an ancillary trafficking/regulatory contact, not CFTR adaptor catalysis. Supporting Evidence: |
| GO:0071889 14-3-3 protein binding | IMP PMID:26888287 Characterization and small-molecule stabilization of the mul... | KEEP AS NON CORE | Summary: Retain phosphorylation-dependent 14-3-3 association. Reason: Full primary peptide-binding, structural and mutational results establish CFTR regulatory-region engagement by 14-3-3. Assays use phosphorylated fragments and engineered crystallographic linkers as specified; beta binding is distinguished from zeta/gamma structures. The activity is an ancillary trafficking/regulatory contact, not CFTR adaptor catalysis. Supporting Evidence: PMID:26888287 The key binding site of CFTR (pS768) occupies one groove |
| GO:0071889 14-3-3 protein binding | IPI PMID:26888287 Characterization and small-molecule stabilization of the mul... | KEEP AS NON CORE | Summary: Retain phosphorylation-dependent 14-3-3 association. Reason: Full primary peptide-binding, structural and mutational results establish CFTR regulatory-region engagement by 14-3-3. Assays use phosphorylated fragments and engineered crystallographic linkers as specified; beta binding is distinguished from zeta/gamma structures. The activity is an ancillary trafficking/regulatory contact, not CFTR adaptor catalysis. Supporting Evidence: |
| GO:0016324 apical plasma membrane | IDA PMID:32487539 TMEM16A deficiency: a potentially fatal neonatal disease res... | ACCEPT | Summary: The apical location is correct in the human epithelial context. Reason: Retain the experimental source location, independently corroborated by human CFTR localization and surface-rescue studies. The source is not discarded because its broader physiological topic differs from channel biophysics. |
| GO:0070175 positive regulation of enamel mineralization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse-supported enamel mineralization role. Reason: Full mouse knockout Methods/Results measure hypomineralized incisors and altered chloride, sodium and potassium profiles, with fluoride context. This supports the transferred enamel process while CFTR remains an anion channel, not a calcium transporter or mineral-deposition enzyme. |
| GO:0097186 amelogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the developmental enamel context. Reason: The source mouse knockout and elemental/ultrastructural readouts support CFTR participation in enamel physiology. Preserve the IEA/ISS provenance and avoid upgrading the mouse result to a direct human ameloblast assay. |
| GO:1902476 chloride transmembrane transport | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the conserved chloride-transport process. Reason: The orthology-based assertion is independently supported by human CFTR electrophysiology and epithelial transport. The donor fields are preserved rather than replaced with a new evidence code. Supporting Evidence: GO_REF:0000024 file:human/CFTR/CFTR-source-evidence.json |
| GO:0017081 chloride channel regulator activity | TAS Reactome:R-HSA-383190 | KEEP AS NON CORE | Summary: Retain contextual regulation of another chloride conductance. Reason: The original Reactome summary mainly describes CFTR bicarbonate/channel activity and does not itself resolve ORCC or ClC regulation. Independent SLC26A9 co-IP and functional coupling support a bounded regulatory role. Its proposed ER-retention explanation remains hypothetical; no general regulation of every chloride channel is asserted. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:11524016 A monomer is the minimum functional unit required for channe... | ACCEPT | Summary: Retain directly assayed ATP hydrolysis. Reason: The authentic human CFTR primary study measures ATPase activity alongside channel behavior. This is enzyme activity in the gating cycle, not ATP-driven solute pumping. Supporting Evidence: PMID:11524016 purified, reconstituted CFTR monomers are sufficient to mediate regulated chloride conduction and ATPase activity |
| GO:0016887 ATP hydrolysis activity | IDA PMID:8910473 ATPase activity of the cystic fibrosis transmembrane conduct... | ACCEPT | Summary: Purified reconstituted CFTR directly hydrolyzes ATP. Reason: The original experiment measures ATP turnover by purified CFTR and relates it to gating. Preserve the IDA assertion and distinguish hydrolysis from passive anion permeation. Supporting Evidence: PMID:8910473 ATP hydrolysis by purified, reconstituted CFTR |
| GO:0015108 chloride transmembrane transporter activity | TAS Reactome:R-HSA-5678822 | ACCEPT | Summary: The normal chloride-transport activity remains correct despite disease-event context. Reason: The source event describes defective CFTR failure to transport chloride, so it is variant/pathway provenance rather than a positive wild-type assay. Independent human CFTR measurements establish the retained activity; do not attribute normal transport to the defective variant. |
| GO:0015108 chloride transmembrane transporter activity | TAS Reactome:R-HSA-5678863 | ACCEPT | Summary: The Reactome chloride-conduction event matches the core activity. Reason: The curated event models wild-type CFTR chloride movement. Independent electrophysiology supports its channel mechanism without interpreting CFTR as a primary-active transporter. |
| GO:0043225 obsolete ATPase-coupled inorganic anion transmembrane transporter activity | TAS Reactome:R-HSA-1454916 | MODIFY | Summary: Replace the pump-like activity with the experimentally supported ATP-gated channel. Reason: The original Reactome parent describes broad MRP organic-anion transport and does not demonstrate a CFTR ATPase-driven anion pump. CFTR hydrolysis controls gating while anions flow passively. The official obsolete source ID is preserved; the replacement corrects the functional mechanism rather than simply reacting to obsolescence. Proposed replacements: intracellularly ATP-gated chloride channel activity Supporting Evidence: Reactome:R-HSA-1454916 file:human/CFTR/CFTR-source-evidence.json |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868658 | KEEP AS NON CORE | Summary: Retain the endocytic-vesicle membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in HSPA8-mediated uncoating. This is its own curated event/complex provenance, not a separate localization experiment for each row. The location is compatible with endocytosis; the enzyme or mechanical work named by the event is not assigned to CFTR. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868659 | KEEP AS NON CORE | Summary: Retain the endocytic-vesicle membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in auxilin recruitment. This is its own curated event/complex provenance, not a separate localization experiment for each row. The location is compatible with endocytosis; the enzyme or mechanical work named by the event is not assigned to CFTR. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868660 | KEEP AS NON CORE | Summary: Retain the endocytic-vesicle membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in ATP-dependent HSPA8 association. This is its own curated event/complex provenance, not a separate localization experiment for each row. The location is compatible with endocytosis; the enzyme or mechanical work named by the event is not assigned to CFTR. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868661 | KEEP AS NON CORE | Summary: Retain the endocytic-vesicle membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in dynamin-dependent vesicle scission. This is its own curated event/complex provenance, not a separate localization experiment for each row. The location is compatible with endocytosis; the enzyme or mechanical work named by the event is not assigned to CFTR. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8869438 | KEEP AS NON CORE | Summary: Retain the endocytic-vesicle membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in clathrin-coat dissociation. This is its own curated event/complex provenance, not a separate localization experiment for each row. The location is compatible with endocytosis; the enzyme or mechanical work named by the event is not assigned to CFTR. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871193 | KEEP AS NON CORE | Summary: Retain the endocytic-vesicle membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in AAK1/AP2-associated uncoating. This is its own curated event/complex provenance, not a separate localization experiment for each row. The location is compatible with endocytosis; the enzyme or mechanical work named by the event is not assigned to CFTR. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871194 | KEEP AS NON CORE | Summary: Retain the endocytic-vesicle membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in RAB5/GAPVD1-associated uncoating. This is its own curated event/complex provenance, not a separate localization experiment for each row. The location is compatible with endocytosis; the enzyme or mechanical work named by the event is not assigned to CFTR. |
| GO:0005886 plasma membrane | IDA PMID:28067262 Sec16A is critical for both conventional and unconventional ... | ACCEPT | Summary: CFTR reaches the plasma membrane in the tested trafficking context. Reason: The authentic source reports stress-linked surface trafficking; independent human CFTR surface function supports the same location. Preserve the original IDA without equating unconventional export with an intrinsic CFTR transport-machinery activity. |
| GO:0034976 response to endoplasmic reticulum stress | IDA PMID:28067262 Sec16A is critical for both conventional and unconventional ... | KEEP AS NON CORE | Summary: Retain the documented stress-responsive channel-trafficking context. Reason: The source examines CFTR redistribution under ER-stress/unconventional secretion conditions. Retain this existing response annotation with cargo context; it does not establish CFTR as an ER stress sensor, transcription factor or export catalyst. |
| GO:0005886 plasma membrane | IDA PMID:21884936 Rescue of ΞF508-CFTR trafficking via a GRASP-dependent uncon... | ACCEPT | Summary: The trafficking study supports surface localization of CFTR. Reason: GRASP-dependent export places CFTR at the plasma membrane, where channel activity is independently established. The source is retained without attributing GRASP adaptor activity to the cargo. Supporting Evidence: |
| GO:0034976 response to endoplasmic reticulum stress | IDA PMID:21884936 Rescue of ΞF508-CFTR trafficking via a GRASP-dependent uncon... | KEEP AS NON CORE | Summary: Retain the ER-stress-linked trafficking response. Reason: The source reports GRASP-associated unconventional export under ER-to-Golgi blockade/stress conditions. CFTR is a responding channel/cargo, not established as the upstream UPR sensor; no new general stress-pathway assertion is added. Supporting Evidence: |
| GO:0106138 Sec61 translocon complex binding | IDA PMID:9792704 The mechanism underlying cystic fibrosis transmembrane condu... | KEEP AS NON CORE | Summary: Retain association with the Sec61 translocon complex. Reason: The authentic source reports membrane CFTR in a complex with Sec61 during retrotranslocation/quality control. This is a specific client-complex association, not evidence that CFTR itself constitutes a protein-translocation pore. Supporting Evidence: |
| GO:0051087 protein-folding chaperone binding | IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu... | KEEP AS NON CORE | Summary: Retain directly supported chaperone binding. Reason: Selected full source describes human CFTR NBD1 peptide recognition by purified Hsc70 and BAG-2 in a folding-quality-control context. CFTR is the client; the chaperone activity belongs to the binding proteins. Supporting Evidence: |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the rat-supported nuclear processed-product context. Reason: Full rat primary Methods/Results show Sertoli nuclear immunofluorescence, peptide-blocking and independent-antibody controls, and an approximately 85-kDa nuclear fraction band. The authors propose a processed CFTR fragment; nuclear gene regulation is untested. Retain this unscoped source conservatively as non-core ortholog/product context, not evidence that intact human CFTR is a nuclear anion channel. |
| GO:0005886 plasma membrane | IDA PMID:28130590 Expression of epithelial sodium channel (ENaC) and CFTR in t... | ACCEPT | Summary: Retain CFTR localization in human epithelial membranes. Reason: The authentic primary abstract explicitly reports human epidermal/eccrine CFTR localization. This supports the preserved plasma/apical location without requiring every tissue to have identical polarity. Supporting Evidence: |
| GO:0016324 apical plasma membrane | IDA PMID:28130590 Expression of epithelial sodium channel (ENaC) and CFTR in t... | ACCEPT | Summary: Retain CFTR localization in human epithelial membranes. Reason: The authentic primary abstract explicitly reports human epidermal/eccrine CFTR localization. This supports the preserved plasma/apical location without requiring every tissue to have identical polarity. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:15010471 Dynamic control of cystic fibrosis transmembrane conductance... | ACCEPT | Summary: The functional expression assay supports plasma-membrane CFTR. Reason: Oocyte electrophysiology establishes functional membrane expression. This does not resolve an endogenous human tissue distribution, which is independently supported by human localization studies. |
| GO:0015106 bicarbonate transmembrane transporter activity | IDA PMID:15010471 Dynamic control of cystic fibrosis transmembrane conductance... | MODIFY | Summary: Specify a bicarbonate-conducting channel. Reason: The source measures CFTR chloride/bicarbonate permeation in oocytes and proposes dynamic selectivity. Independent human-CFTR BHK patches establish direct bicarbonate conduction while reporting invariant selectivity under their tested conditions. Preserve both source claims with their conditions; do not attribute the dynamic-selectivity claim to the latter paper. Proposed replacements: bicarbonate channel activity |
| GO:0015106 bicarbonate transmembrane transporter activity | IDA PMID:19019741 Mechanism of direct bicarbonate transport by the CFTR anion ... | MODIFY | Summary: The human-protein patch assay supports bicarbonate channel activity. Reason: Inside-out patches from BHK cells expressing human CFTR directly measure bicarbonate permeation. This is channel-mediated transport, not an exchanger or ATP-driven bicarbonate pump; the tested selectivity is reported as stable. Proposed replacements: bicarbonate channel activity Supporting Evidence: PMID:19019741 share a common transport pathway in CFTR file:human/CFTR/CFTR-source-evidence.json |
| GO:0015701 bicarbonate transport | IDA PMID:15010471 Dynamic control of cystic fibrosis transmembrane conductance... | ACCEPT | Summary: Retain bicarbonate transport in the source expression assay. Reason: The oocyte study directly measures CFTR-dependent bicarbonate permeation. Its dynamic external-chloride selectivity interpretation remains source-specific rather than a universal pore property. Supporting Evidence: |
| GO:0015701 bicarbonate transport | IDA PMID:19019741 Mechanism of direct bicarbonate transport by the CFTR anion ... | ACCEPT | Summary: Retain directly measured bicarbonate transport. Reason: Human CFTR inside-out patch assays establish bicarbonate flow through the anion pore, with condition-specific relative permeability and conductance. Supporting Evidence: |
| GO:0016324 apical plasma membrane | IMP PMID:19621064 CFTR delivery to 25% of surface epithelial cells restores no... | ACCEPT | Summary: Apical epithelial CFTR is functionally restored by gene delivery. Reason: The full human airway-culture study places CFTR at the luminal surface and measures rescue of chloride/fluid transport. This is direct epithelial context, not a purified channel stoichiometry assay. Supporting Evidence: |
| GO:0035377 transepithelial water transport | IMP PMID:19621064 CFTR delivery to 25% of surface epithelial cells restores no... | KEEP AS NON CORE | Summary: Retain CFTR-dependent transepithelial fluid movement. Reason: Human airway-culture rescue measures fluid/airway-surface consequences of restored CFTR. Ion transport supplies the osmotic contribution; the experiment does not establish direct water passage through the CFTR protein. Supporting Evidence: |
| GO:0050891 multicellular organismal-level water homeostasis | IMP PMID:19621064 CFTR delivery to 25% of surface epithelial cells restores no... | KEEP AS NON CORE | Summary: Retain the broad epithelial contribution to water homeostasis. Reason: The human airway rescue provides a physiological context for CFTR-dependent hydration, while the experiment is an epithelial culture rather than a whole-body water-balance assay. Preserve the existing broad IMP with that scope and avoid adding another process solely from mucus clearance. Supporting Evidence: |
| GO:1902476 chloride transmembrane transport | IDA PMID:19019741 Mechanism of direct bicarbonate transport by the CFTR anion ... | ACCEPT | Summary: Human CFTR directly transports chloride across a membrane. Reason: Inside-out patch currents support anion movement through the pore. ATP dependence of gating is distinguished from the electrochemical driving force for chloride flux. Supporting Evidence: |
| GO:1902476 chloride transmembrane transport | IMP PMID:19621064 CFTR delivery to 25% of surface epithelial cells restores no... | ACCEPT | Summary: Human epithelial rescue supports chloride transport. Reason: The source measures CFTR-dependent chloride secretion after gene delivery. Associated sodium and fluid responses are distinct endpoints and are not all assigned to a single direct CFTR inhibitory interface. Supporting Evidence: |
| GO:1904322 cellular response to forskolin | IDA PMID:15010471 Dynamic control of cystic fibrosis transmembrane conductance... | KEEP AS NON CORE | Summary: Retain the pharmacological forskolin-response context. Reason: Forskolin raises cAMP in the source assay and activates phosphorylation-dependent CFTR transport. This is a useful experimental response annotation but not a separate defining molecular activity of the channel. Supporting Evidence: |
| GO:1904322 cellular response to forskolin | IDA PMID:19621064 CFTR delivery to 25% of surface epithelial cells restores no... | KEEP AS NON CORE | Summary: Retain the pharmacological forskolin-response context. Reason: Forskolin raises cAMP in the source assay and activates phosphorylation-dependent CFTR transport. This is a useful experimental response annotation but not a separate defining molecular activity of the channel. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:11524016 A monomer is the minimum functional unit required for channe... | ACCEPT | Summary: Functional human CFTR occupies the plasma membrane. Reason: The source combines CFTR functional analysis with its membrane expression; the location is independently consistent with epithelial and patch measurements. |
| GO:0016020 membrane | IDA PMID:8910473 ATPase activity of the cystic fibrosis transmembrane conduct... | ACCEPT | Summary: The reconstituted channel is membrane associated. Reason: Purified CFTR is reconstituted for functional/ATPase measurements, directly supporting membrane association. This does not identify a native tissue compartment by itself. Supporting Evidence: |
| GO:1902476 chloride transmembrane transport | IDA PMID:11524016 A monomer is the minimum functional unit required for channe... | ACCEPT | Summary: Retain the source-supported chloride flux. Reason: The human-CFTR channel/ATPase study supports chloride movement, corroborated independently by direct patch assays. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:11707463 A Golgi-associated PDZ domain protein modulates cystic fibro... | KEEP AS NON CORE | Summary: Retain the ER membrane pool in CFTR trafficking. Reason: The CAL-centered primary supports intracellular trafficking/retention context for the channel. ER localization is also independently consistent with CFTR biogenesis and quality control; it is not presented as the dominant mature epithelial location. |
| GO:0005886 plasma membrane | IMP PMID:11707463 A Golgi-associated PDZ domain protein modulates cystic fibro... | ACCEPT | Summary: Retain plasma-membrane localization in the trafficking perturbation. Reason: The source measures changes in CFTR surface function/trafficking after perturbing its CAL interaction. The native channel surface location remains core despite regulated intracellular retention. Supporting Evidence: |
| GO:1902476 chloride transmembrane transport | IDA PMID:11707463 A Golgi-associated PDZ domain protein modulates cystic fibro... | ACCEPT | Summary: Retain chloride transport in the CAL-regulated context. Reason: Changes in trafficking alter channel availability, but CFTR itself carries chloride. The source partner mechanism does not transfer an adaptor function to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866542 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in VCP-associated retrotranslocation. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866546 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in RNF5/RNF185 ubiquitination. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866551 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in ERAD-complex binding. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866553 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in proteasomal disposal. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866851 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in biosynthetic export. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866854 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in F508del retrotranslocation. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866856 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in mutant ubiquitination. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866857 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in mutant ERAD-complex association. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9641109 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in misfolded-protein polyubiquitination. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9641111 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in misfolded-client recognition. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9641127 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in polyubiquitinated-client handling. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9646348 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in HDAC6/dynein association. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9646679 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in aggresome organization. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9646685 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in aggresome release. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9700266 | KEEP AS NON CORE | Summary: Retain the source-modeled ER membrane/quality-control pool. Reason: The selected Reactome record supplies CFTR-containing complex/cargo provenance in corrector-associated F508del trafficking. Its broad pathway summary is not a new independent ER-localization experiment, and later transport/aggresome steps do not mean the client is ER-confined throughout. CFTR ER retention and biosynthesis are independently supported; the named quality-control machinery activities are not assigned to CFTR. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866854 | KEEP AS NON CORE | Summary: Retain a cytosolic retrotranslocation/degradation context. Reason: The selected Reactome event models F508del CFTR after ER extraction or during proteasomal disposal. This supports a contextual cytosolic species, consistent with the Sec61 study, rather than interpreting cytoplasmic domains of the intact membrane channel as free-cytosol localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866858 | KEEP AS NON CORE | Summary: Retain a cytosolic retrotranslocation/degradation context. Reason: The selected Reactome event models F508del CFTR after ER extraction or during proteasomal disposal. This supports a contextual cytosolic species, consistent with the Sec61 study, rather than interpreting cytoplasmic domains of the intact membrane channel as free-cytosol localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866277 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in AP2-dependent cargo capture. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in BAR-domain membrane curvature. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in CLASP recruitment. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in PIK3C2A recruitment. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in phosphoinositide phosphorylation. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in actin-machinery recruitment. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in dynamin recruitment. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in synaptojanin lipid hydrolysis. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in endophilin/synaptojanin assembly. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Retain the core plasma-membrane location. Reason: The selected Reactome record places CFTR-containing membrane cargo in vesicle scission. This is source-modeled location provenance rather than evidence that CFTR performs the event machinery work. The same plasma-membrane location is independently supported by human channel function and localization. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-6782106 | KEEP AS NON CORE | Summary: Retain endosome-membrane localization during recycling. Reason: The Reactome event describes USP10-mediated deubiquitination of CFTR in endosomes. CFTR is the membrane client; this does not assign its partner peptidase activity to the channel. |
| GO:0005829 cytosol | IDA PMID:24885604 CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exo... | KEEP AS NON CORE | Summary: Retain the source-reported intracellular imaging pool with resolution limits. Reason: Full human/mouse beta-cell Methods and Figure 1 quantify CFTR immunofluorescence in plasma-membrane versus cytosolic image regions. This supports the original broad intracellular location but does not biochemically distinguish soluble intact CFTR from internal membranes or fragments. Independent retrotranslocation evidence establishes cytosolic species; do not infer localization merely from domain topology. |
| GO:0005886 plasma membrane | IDA PMID:24885604 CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exo... | ACCEPT | Summary: Human beta-cell imaging supports plasma-membrane CFTR. Reason: Full Methods and Results quantify membrane enrichment and colocalization with syntaxin 1A. The localization is direct cellular evidence; proposed effects on granule priming remain mechanistically distinct. Supporting Evidence: PMID:24885604 CFTR was co-localized with syntaxin 1A in the plasma membrane of human beta-cells |
| GO:1902476 chloride transmembrane transport | IMP PMID:24885604 CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exo... | ACCEPT | Summary: Retain the beta-cell chloride-current contribution. Reason: Full Results measure human/mouse cAMP-dependent current components and antagonist responses. This pharmacological cellular assay is distinguished from the separate purified/heterologous pore measurements that independently establish CFTR chloride transport. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5678822 | ACCEPT | Summary: Retain the plasma-membrane channel location. Reason: The selected Reactome event concerns defective-channel chloride transport. The variant/drug context is retained; it is not a claim that untreated disease variants have normal activity. Independent human channel localization supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5678992 | ACCEPT | Summary: Retain the plasma-membrane channel location. Reason: The selected Reactome event concerns ivacaftor-rescued G551D conductance. The variant/drug context is retained; it is not a claim that untreated disease variants have normal activity. Independent human channel localization supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5679000 | ACCEPT | Summary: Retain the plasma-membrane channel location. Reason: The selected Reactome event concerns ivacaftor binding to mutant CFTR. The variant/drug context is retained; it is not a claim that untreated disease variants have normal activity. Independent human channel localization supports the compartment. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-5627275 | KEEP AS NON CORE | Summary: Retain lysosomal-membrane targeting of CFTR cargo. Reason: The Reactome event models GOPC-dependent sorting of CFTR toward lysosomes. This is a degradation/trafficking location, not an independently established lysosomal channel function. |
| GO:0005737 cytoplasm | IDA PMID:18570918 Endosomal SNARE proteins regulate CFTR activity and traffick... | KEEP AS NON CORE | Summary: Retain the broader intracellular trafficking pool. Reason: The authentic endosomal SNARE source supports intracellular CFTR alongside the apical and recycling-endosome pools. Preserve its imaging-based cytoplasmic location without equating every signal with soluble protein. Supporting Evidence: |
| GO:0016324 apical plasma membrane | IDA PMID:18570918 Endosomal SNARE proteins regulate CFTR activity and traffick... | ACCEPT | Summary: Retain apical CFTR in the recycling study. Reason: The source examines apical expression/function and its recycling regulation, consistent with the defining epithelial surface activity. Supporting Evidence: |
| GO:0055037 recycling endosome | IDA PMID:18570918 Endosomal SNARE proteins regulate CFTR activity and traffick... | KEEP AS NON CORE | Summary: Retain CFTR in recycling endosomes. Reason: The authentic endosomal SNARE study supports the channel as recycling cargo. Endosome occupancy does not make CFTR the membrane-recycling motor or adaptor. Supporting Evidence: PMID:18570918 we found a colocalization of CFTR and endosomal SNARE proteins in Rab11-positive recycling endosomes |
| GO:0030660 Golgi-associated vesicle membrane | TAS Reactome:R-HSA-5627071 | KEEP AS NON CORE | Summary: Retain the Golgi-associated vesicle membrane pool. Reason: The selected Reactome record describes GOPC/RHOQ-dependent CFTR sorting or diversion toward lysosomes. This is specific trafficking-complex provenance, not a separate channel activity in every transport vesicle. |
| GO:0030660 Golgi-associated vesicle membrane | TAS Reactome:R-HSA-5627072 | KEEP AS NON CORE | Summary: Retain the Golgi-associated vesicle membrane pool. Reason: The selected Reactome record describes GOPC/RHOQ-dependent CFTR sorting or diversion toward lysosomes. This is specific trafficking-complex provenance, not a separate channel activity in every transport vesicle. |
| GO:0030660 Golgi-associated vesicle membrane | TAS Reactome:R-HSA-5627275 | KEEP AS NON CORE | Summary: Retain the Golgi-associated vesicle membrane pool. Reason: The selected Reactome record describes GOPC/RHOQ-dependent CFTR sorting or diversion toward lysosomes. This is specific trafficking-complex provenance, not a separate channel activity in every transport vesicle. |
| GO:0009986 cell surface | IDA PMID:20658517 SLC26A9 stimulates CFTR expression and function in human bro... | ACCEPT | Summary: Retain epithelial surface/apical CFTR localization. Reason: The SLC26A9 source reports an apical functional association in bronchial epithelial cells. CFTR surface localization is independently supported by human airway rescue; no binary-binding inference is needed for this location. |
| GO:0016324 apical plasma membrane | IDA PMID:20658517 SLC26A9 stimulates CFTR expression and function in human bro... | ACCEPT | Summary: Retain epithelial surface/apical CFTR localization. Reason: The SLC26A9 source reports an apical functional association in bronchial epithelial cells. CFTR surface localization is independently supported by human airway rescue; no binary-binding inference is needed for this location. |
| GO:0015106 bicarbonate transmembrane transporter activity | ISS GO_REF:0000024 | MODIFY | Summary: Specify the bicarbonate-channel mechanism of the conserved activity. Reason: The ISS source retains its ortholog provenance. Independent human-CFTR inside-out patches establish direct bicarbonate conduction, allowing a molecular specificity refinement without changing the original evidence code or inventing a human donor assay. Proposed replacements: bicarbonate channel activity |
| GO:0015108 chloride transmembrane transporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: Retain conserved chloride-transporter activity. Reason: Direct human chloride-channel measurements independently support the broad ISS activity. Its passive pore mechanism is stated without altering the original ortholog-source assertion. |
| GO:0048240 sperm capacitation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the reproductive context of CFTR-dependent sperm capacitation. Reason: The source transfer is grounded in mouse CFTR-dependent chloride/pH/electrical responses during capacitation. The accessed primary material reports pharmacological perturbations and transporter cooperation, not a human purified assay or an additional autonomous sperm-development mechanism. |
| GO:0051454 intracellular pH elevation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the sperm-context intracellular alkalinization role. Reason: The mouse source links CFTR-dependent anion handling to capacitation-associated pH change. Keep the physiological process as a contextual consequence of channel participation; this does not establish direct proton transport through CFTR or universal pH regulation in every compartment. Supporting Evidence: GO_REF:0000024 file:human/CFTR/CFTR-source-evidence.json |
| GO:0060081 membrane hyperpolarization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain context-dependent membrane hyperpolarization. Reason: Selected mouse primary Discussion reports reduced capacitation-associated hyperpolarization after CFTR inhibition alongside chloride-pathway interactions. The channel can contribute to an electrical response without becoming the sole voltage-determining transporter. |
| GO:0071320 cellular response to cAMP | ISS GO_REF:0000024 | ACCEPT | Summary: cAMP-dependent channel regulation is a core cellular response. Reason: PKA-dependent CFTR phosphorylation and gating connect elevated cAMP to anion conductance. This is a channel response to signaling, not intrinsic adenylate-cyclase or kinase activity. Supporting Evidence: GO_REF:0000024 file:human/CFTR/CFTR-source-evidence.json |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1454916 | ACCEPT | Summary: Retain the established plasma-membrane location. Reason: The selected Reactome record supplies curated CFTR membership in the broad ABC/MRP pathway. Generic pathway mechanisms are not transferred to CFTR; the location itself agrees with direct human epithelial function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-383190 | ACCEPT | Summary: Retain the established plasma-membrane location. Reason: The selected Reactome record supplies curated CFTR membership in the bicarbonate-transport event. Generic pathway mechanisms are not transferred to CFTR; the location itself agrees with direct human epithelial function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5627071 | ACCEPT | Summary: Retain the established plasma-membrane location. Reason: The selected Reactome record supplies curated CFTR membership in GOPC/RHOQ-associated surface delivery. Generic pathway mechanisms are not transferred to CFTR; the location itself agrees with direct human epithelial function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5678863 | ACCEPT | Summary: Retain the established plasma-membrane location. Reason: The selected Reactome record supplies curated CFTR membership in wild-type chloride transport. Generic pathway mechanisms are not transferred to CFTR; the location itself agrees with direct human epithelial function and localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866851 | ACCEPT | Summary: Retain the established plasma-membrane location. Reason: The selected Reactome record supplies curated CFTR membership in biosynthetic surface delivery. Generic pathway mechanisms are not transferred to CFTR; the location itself agrees with direct human epithelial function and localization. |
| GO:0005886 plasma membrane | IDA PMID:22178883 CFTR and TMEM16A are separate but functionally related Cl- c... | ACCEPT | Summary: Retain surface localization in the TMEM16A coupling context. Reason: The authentic primary abstract reports membrane-associated CFTR/TMEM16A functional coupling and co-IP. Independent CFTR surface experiments support the retained location without equating the two channel mechanisms. Supporting Evidence: PMID:22178883 CFTR and TMEM16A were both membrane localized and could be coimmunoprecipitated |
| GO:0019869 chloride channel inhibitor activity | IDA PMID:22178883 CFTR and TMEM16A are separate but functionally related Cl- c... | KEEP AS NON CORE | Summary: Retain contextual inhibition of a chloride conductance. Reason: The source reports suppression of TMEM16A calcium-activated chloride currents by CFTR in the tested system. This is a specific regulatory observation, distinct from CFTR pore conduction, and does not establish a general ENaC or chloride-channel inhibitory mechanism. Supporting Evidence: PMID:22178883 TMEM16A-currents were attenuated by additional expression of CFTR |
| GO:0032991 protein-containing complex | IDA PMID:17462998 Myosin Vb is required for trafficking of the cystic fibrosis... | KEEP AS NON CORE | Summary: Retain participation in a trafficking protein complex. Reason: The authentic source describes CFTR with myosin Vb/Rab11a-associated machinery in polarized human airway cells. The broad complex term is supported without assigning the motor or small-GTPase activity to CFTR. Supporting Evidence: PMID:17462998 Endogenous CFTR formed a complex with endogenous myosin Vb and Rab11a |
| GO:0016324 apical plasma membrane | IDA PMID:12801959 Distribution of aquaporin water channels AQP1 and AQP5 in th... | ACCEPT | Summary: Retain apical localization in human pancreatic ducts. Reason: The authentic source explicitly describes CFTR localization in human pancreatic epithelial context. This supports the core compartment without treating every tissue-specific trafficking observation as a separate molecular function. Supporting Evidence: PMID:12801959 Both AQP1 and AQP5 were colocalised with cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of intercalated duct cells |
| GO:0005769 early endosome | IDA PMID:19398555 The deubiquitinating enzyme USP10 regulates the post-endocyt... | KEEP AS NON CORE | Summary: Retain early-endosome localization during USP10 regulation. Reason: The authentic primary describes CFTR recycling and deubiquitination in early endosomes. CFTR is the membrane substrate/cargo, not an intrinsic deubiquitinase. Supporting Evidence: |
| GO:0019899 enzyme binding | IPI PMID:19398555 The deubiquitinating enzyme USP10 regulates the post-endocyt... | KEEP AS NON CORE | Summary: Retain the substrate association with USP10. Reason: The source supports CFTR association with the deubiquitinating enzyme in the recycling pathway, corroborated by direct endosomal co-IP in PMID:21455491. Enzyme binding does not mean CFTR performs the partner enzyme reaction. |
| GO:0005515 protein binding | IPI PMID:9792704 The mechanism underlying cystic fibrosis transmembrane condu... | MODIFY | Summary: Specify the directly implicated Sec61 translocon complex. Reason: The authentic primary describes CFTR association with Sec61 during retrotranslocation, and the same source already supports a specific Sec61-complex-binding annotation. A source-preserving specificity refinement is appropriate; it does not assign translocon activity to the CFTR client. Proposed replacements: Sec61 translocon complex binding Supporting Evidence: PMID:9792704 CFTR associates with the Sec61 trimeric complex file:human/CFTR/CFTR-source-evidence.json |
| GO:0016324 apical plasma membrane | IDA PMID:15247260 Myosin VI regulates endocytosis of the cystic fibrosis trans... | ACCEPT | Summary: Retain apical CFTR in the human endocytosis study. Reason: The authentic source reports CFTR in polarized human Calu-3 cells with Dab2/myosin VI-associated endocytosis. Its surface location is core even though the machinery interactions are ancillary. Supporting Evidence: |
| GO:0030165 PDZ domain binding | IDA PMID:11707463 A Golgi-associated PDZ domain protein modulates cystic fibro... | KEEP AS NON CORE | Summary: Retain direct terminal PDZ-domain binding. Reason: The CAL/GOPC study directly supports CFTR terminal-domain engagement. This is an ancillary anchoring/trafficking interaction, consistent with independent NHERF experiments, rather than a separate defining activity-centered core. Supporting Evidence: PMID:11707463 The PDZ domain of CAL binds to the C terminus of CFTR |
| GO:0005524 ATP binding | TAS PMID:2475911 Identification of the cystic fibrosis gene: cloning and char... | ACCEPT | Summary: Retain ATP binding with independent biochemical support. Reason: The original human CFTR cDNA study supplies sequence-based nucleotide-domain context, not a newly inspected purified ATP-binding assay. Direct ATP-dependent gating and hydrolysis independently support the correct TAS molecular activity. |
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Download this section (compressed HTML)Q: Which defined CFTR molecular species underlies the rat Sertoli nuclear signal, and is an equivalent processed product present in human Sertoli nuclei?
Q: Do CFTR-dependent cholesterol changes reflect direct molecular participation in lipid handling or secondary homeostatic responses to altered anion transport and trafficking?
Q: Which proximity-labeled or variant-specific interactome partners form reproducible physical contacts with sequence-defined CFTR in the corresponding physiological compartment?
Q: What performed CFTR molecular step accounts for sodium-transport normalization in rescued human airway epithelia, and how does it depend on extracellular fluid conditions and ENaC processing?
Experiment: Map nuclear CFTR species with independent epitopes, peptide-resolved mass spectrometry, fraction-purity controls and matched rat/human Sertoli systems before assigning a nuclear biochemical role.
Experiment: Separate anion-conduction, gating, localization and cholesterol phenotypes using matched-expression variants, acute rescue and compartment-resolved lipid-flux measurements.
Experiment: Validate selected screen/proximity partners with reciprocal endogenous co-IP, compartment-compatible constructs and orthogonal binary or reconstituted assays where direct contact is claimed.
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Download this section (compressed HTML)π View Pathway Visualization Interactive pathway diagram with detailed annotations