CLDN14 encodes claudin-14, a four-pass membrane protein that forms structural strands of epithelial tight junctions. Its self-association and interactions with other claudins restrict paracellular permeability, supporting the inner-ear barrier and regulated renal calcium handling. In model junctions, claudin-14 can form a barrier on its own and replace claudin-16 within claudin-19-containing strands. Its cytoplasmic C-terminal motif binds PDZ domains. Human loss-of-function variants cause recessive nonsyndromic deafness, while renal expression is responsive to calcium-sensing pathways.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005198 structural molecule activity | IEA GO_REF:0000002 | ACCEPT | Summary: CLDN14 supplies structural components of tight-junction strands. Reason: Claudin-domain mapping agrees with CLDN14 self-assembly, junctional strand formation and reduced paracellular permeability. The newer heterologous-cell work resolves polymerization and replacement of CLDN16 in CLDN19-containing meshworks; it does not establish an autonomous ion-conducting pore. Its construct species is unspecified in the inspected supplement, while the older mechanistic study explicitly uses mouse CLDN14. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR006187 SUPPORTS TRANSFER The claudin-domain structural assignment is independently corroborated by target-family strand and barrier experiments. Supporting Evidence: GO_REF:0000002 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the screen-supported association with MAL. Reason: Three exact positive human CLDN14–MAL records comprise validated, array and prey-pooling two-hybrid assays. The source uses pairwise retesting and sequence verification, but these records do not establish a native junctional mechanism or assign MAL activity to CLDN14. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the screen-supported association with CTXN3. Reason: Three exact positive human CLDN14–CTXN3 records comprise validated, array and prey-pooling two-hybrid assays. The source uses pairwise retesting and sequence verification, but these records do not establish a native junctional mechanism or assign CTXN3 activity to CLDN14. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the screen-supported association with PLLP. Reason: Three exact positive human CLDN14–PLLP records comprise validated, array and prey-pooling two-hybrid assays. The source uses pairwise retesting and sequence verification, but these records do not establish a native junctional mechanism or assign PLLP activity to CLDN14. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with MPDZ fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with MPDZ PDZ-domain fragments spanning residues 688–793, 1858–1949, 1624–1716. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with DLG4 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with DLG4 PDZ-domain fragments spanning residues 306–403, 62–152, 155–249. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with TJP1 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with TJP1 PDZ-domain fragments spanning residues 415–516, 184–264. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with DLG1 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with DLG1 PDZ-domain fragments spanning residues 221–314, 457–571. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with IL16 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with IL16 PDZ-domain fragments spanning residues 1203–1332, 210–306, 1106–1201. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with SCRIB fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with SCRIB PDZ-domain fragments spanning residues 858–949, 998–1093, 718–814. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with DLG2 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with DLG2 PDZ-domain fragments spanning residues 418–513, 189–283. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with PDZK1 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with PDZK1 PDZ-domain fragments spanning residues 2–107, 238–329, 375–459. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with FRMPD2 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with FRMPD2 PDZ-domain fragments spanning residues 1073–1166, 770–861, 944–1038. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with MAGI2 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with MAGI2 PDZ-domain fragments spanning residues 772–866, 1141–1229, 915–1017, 410–522, 600–682. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with NHERF4 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with NHERF4 PDZ-domain fragments spanning residues 464–550, 220–308. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with LNX2 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with LNX2 PDZ-domain fragments spanning residues 334–427, 459–560. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with PATJ fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with PATJ PDZ-domain fragments spanning residues 238–335, 113–229, 1673–1763, 1058–1167, 547–651, 359–469. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with LNX1 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with LNX1 PDZ-domain fragments spanning residues 500–596, 261–371. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with DLG3 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with DLG3 PDZ-domain fragments spanning residues 222–314, 124–219, 381–476. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with MAGI1 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with MAGI1 PDZ-domain fragments spanning residues 1–106, 456–580. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with APBA2 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with APBA2 PDZ-domain fragments spanning residues 655–735, 565–653. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with GRIP2 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with GRIP2 PDZ-domain fragments spanning residues 934–1023, 446–548, 648–740, 544–642, 238–339. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with WHRN fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with WHRN PDZ-domain fragments spanning residues 813–904, 263–379, 136–226. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Specify PDZ-domain binding demonstrated with GRIP1 fragments. Reason: Positive holdup records pair the human CLDN14 C-terminal peptide (residues 230–239) with GRIP1 PDZ-domain fragments spanning residues 563–659, 242–344, 996–1086, 464–567, 145–239. The interaction supports PDZ-domain binding at the tested peptide/domain scope; it does not establish full-length native complex formation or an activity unique to a particular CLDN14 transcript. Proposed replacements: PDZ domain binding |
| GO:0005783 endoplasmic reticulum | HDA PMID:16780588 Cell array-based intracellular localization screening reveal... | KEEP AS NON CORE | Summary: Retain the observed ER pool in the overexpression screen. Reason: The exact human CLDN14 Table 1 entry (NM_012130/AAG60052) reports ER and plasma membrane localization in HEK293T cells. Figure 4 shows overlap with the ER marker PDI. This is positive localization of tagged overexpressed protein, without a demonstrated ER-specific biological function. |
| GO:0005886 plasma membrane | HDA PMID:16780588 Cell array-based intracellular localization screening reveal... | ACCEPT | Summary: Human CLDN14 is detected at the plasma membrane. Reason: The same exact target row in the original localization supplement reports a plasma membrane pool alongside ER staining. Membrane residence is consistent with CLDN14 junctional assembly, while the human ORF and overexpression context are retained. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited plasma membrane compartment. Reason: The curated PAINT assertion has experimental claudin-family grounding, and the human CLDN14 localization screen independently corroborates the compartment. Structural strand formation supplies a membrane activity; the screen alone is not described as a native human functional assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000243505 SUPPORTS TRANSFER Current descendant experimental plasma membrane records and target localization support the curated transfer. The historical tree, alignment and IBD placement were not reconstructed. Supporting Evidence: GO_REF:0000033 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the combined-method plasma membrane assignment. Reason: The mapped Q9Z0S3 protein is mouse Cldn14, with experimental localization evidence, and the human target screen directly reports plasma membrane staining. The ortholog, Ensembl product and subcellular vocabulary identifiers remain distinct source components. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0S3 SUPPORTS TRANSFER Authenticated mouse Cldn14 localization and independent human target staining corroborate the mapped compartment. Supporting Evidence: GO_REF:0000120 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0005923 bicellular tight junction | IBA GO_REF:0000033 | ACCEPT | Summary: CLDN14 acts as a structural protein in bicellular tight junctions. Reason: The curated family-level location is consistent with endogenous mammalian cochlear junctional staining, mouse renal junctional localization and target strand formation in heterologous cells. The is_active_in assertion is preserved with structural participation as its biological basis. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000243505 SUPPORTS TRANSFER Verified experimental descendant tight-junction records support the curated ancestral assignment, with independent CLDN14 junctional evidence. Historical node reconstruction was not performed. Supporting Evidence: GO_REF:0000033 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0005923 bicellular tight junction | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the combined ortholog/domain tight-junction location. Reason: Mouse Cldn14 has experimental junctional localization, and CLDN14 forms membrane strands in heterologous cells. These observations support the combined Cldn14, claudin-domain and subcellular-location mapping without conflating transcript identifiers with separately tested protein products. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0S3 SUPPORTS TRANSFER Mouse Cldn14 identity and experimental localization are authenticated; the claudin and subcellular-location mappings are biologically concordant. Supporting Evidence: GO_REF:0000120 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0005923 bicellular tight junction | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the claudin-family inference of tight-junction localization. Reason: O88552 is mouse Cldn2, with direct experimental tight-junction annotations. Its paralog identity does not by itself invalidate the curated ISS transfer; independent CLDN14 junctional staining and strand formation corroborate the target compartment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:O88552 SUPPORTS TRANSFER The donor is explicitly mouse Cldn2 rather than the Cldn14 ortholog. Its experimental junctional grounding and independent target evidence support this conserved compartment. Supporting Evidence: GO_REF:0000024 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Specify the junctional membrane structure occupied by CLDN14. Reason: The broad membrane-domain association is correct, but bicellular tight junction describes the directly supported structural compartment more precisely. The refinement retains the original InterPro source and does not erase the experimentally observed ER pool. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR004031 SUPPORTS TRANSFER The broad membrane association is valid; target junctional localization supplies the more informative compartment. Proposed replacements: bicellular tight junction Supporting Evidence: GO_REF:0000002 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0016338 calcium-independent cell-cell adhesion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the supported family inference of calcium-independent adhesion. Reason: Mouse Cldn2 has a genuine IDA annotation from the claudin-transfectant adhesion study, whose authentic abstract reports calcium-independent adhesion. CLDN14 strand assembly supports a related structural role, but an equivalent target-specific calcium-dependence assay was not established here. Calcium regulation of CLDN14 expression in kidney is a different question and does not contradict calcium-independent adhesion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88552 SUPPORTS TRANSFER The donor annotation is experimentally grounded. Retention respects the curated family transfer while keeping donor assay scope and untested target calcium dependence explicit. Supporting Evidence: GO_REF:0000024 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0042802 identical protein binding | ISS GO_REF:0000024 | ACCEPT | Summary: Self-association contributes to CLDN14 strand formation. Reason: The Cldn2 donor has direct homopolymer and paired-strand evidence. Independent mouse CLDN14 two-hybrid self-association and newer CLDN14 polymerization corroborate the target role. These results support identical-protein binding without specifying a dimer-only stoichiometry or universal compatibility with all other claudins. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:O88552 SUPPORTS TRANSFER Direct donor self-association and independent target-family self-assembly support retention of the curated inference. Supporting Evidence: GO_REF:0000024 file:human/CLDN14/CLDN14-source-evidence.json |
| GO:0065003 protein-containing complex assembly | TAS PMID:7644498 The WW domain of Yes-associated protein binds a proline-rich... | MODIFY | Summary: Refine the assembly role while correcting the supporting citation. Reason: The complete original five-page PMID:7644498 paper assays YAP WW-domain recognition of WBP proline-rich ligands; it does not test CLDN14 or tight-junction assembly. Independent CLDN14 strand and copolymer experiments support bicellular tight junction assembly: the protein itself contributes the sealing structure, rather than merely being required for an outcome. The 2025 transgene species is unspecified in the inspected construct description, and the older target constructs are mouse. Preserve the original TAS/reference fields and attach these independent sources for the replacement. Proposed replacements: bicellular tight junction assembly Supporting Evidence: file:human/CLDN14/CLDN14-source-evidence.json |
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Download this section (compressed HTML)Q: Which claudins directly pair with CLDN14 across the native human cochlear junction, and how does that composition differ from the renal barrier?
Q: Which CLDN14 C-terminal PDZ interactions operate in intact polarized epithelia, and how do they affect junctional residence or strand architecture?
Q: How do the older CLDN14–CLDN16 association assays and the newer CLDN14–CLDN19 strand-replacement model relate across expression levels, cis/trans geometry and epithelial context?
Q: What was the intended source for the original protein-containing-complex assembly TAS assertion attributed to PMID:7644498?
Experiment: Introduce sequence-verified human CLDN14 into an isogenic claudin-deficient epithelial background, measure strand architecture and ion permeability together, and compare matched CLDN14/16/19 combinations and self-association mutants.
Experiment: Test the CLDN14 terminal motif and selected PDZ partners in polarized human epithelial cells with endogenous expression controls, separating trafficking effects from direct strand assembly.
Experiment: Resolve native cochlear junction partners with spatially restricted interaction measurements and species-matched rescue; distinguish cis oligomerization from trans pairing across neighboring cells.
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