CLDN18 (claudin-18) is a tetraspan tight-junction protein of the claudin family: four transmembrane helices, two extracellular loops and cytoplasmic N- and C-termini, the latter ending in a PDZ-binding motif that engages ZO proteins. Two mutually exclusive first exons give tissue-restricted isoforms: CLDN18.1 (A1) in lung alveolar epithelium and CLDN18.2 (A2) in gastric mucosa; they differ in the first transmembrane segment and the first extracellular loop, the region recognized by the CLDN18.2-specific therapeutic antibody zolbetuximab, and CLDN18.2 is aberrantly expressed in gastric, pancreatic and other adenocarcinomas. As a structural component of tight-junction strands, claudin-18 seals the paracellular space: it is required for the alveolar epithelial barrier and alveolar fluid homeostasis and for the gastric barrier against acid. Its cytoplasmic tail also binds ZO-1/ZO-2 and phosphorylated YAP1, which links the junction to control of epithelial progenitor proliferation and organ size. Almost all human annotations are inferred from the well-studied mouse orthologue.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005198 structural molecule activity | IEA GO_REF:0000002 | ACCEPT | Summary: Claudin-18 is a structural component of tight-junction strands. Reason: Claudins polymerize into the intramembrane strands that form the paracellular seal; a structural rather than catalytic or transport role is the correct molecular function for the family. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Required for lung alveolarization and file:human/CLDN18/CLDN18-uniprot.txt Note=Localizes to tight junctions in epithelial cells. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary two-hybrid interactions with PMP22 and EHHADH from the HuRI interactome. Reason: Generic protein binding from a systematic screen with no follow-up; EHHADH is a peroxisomal enzyme that a tight-junction membrane protein does not meet physiologically. Removal does not assert that the assay results are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary two-hybrid interactions with PMP22 and EHHADH from the HuRI interactome. Reason: Generic protein binding from a systematic screen with no follow-up; EHHADH is a peroxisomal enzyme that a tight-junction membrane protein does not meet physiologically. Removal does not assert that the assay results are false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The C-terminal PDZ-binding motif of claudin-18 binds many PDZ domains in affinity-mapped fragmentomics. Reason: Generic protein binding is uninformative; every partner in this screen is a PDZ-domain protein engaged through the claudin C-terminal PDZ-binding motif, so PDZ domain binding is the informative and well-supported term. It is also the interaction class through which claudin-18 recruits ZO-1 and ZO-2. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Claudin-18 is a multi-pass plasma membrane protein. Reason: The four-transmembrane topology places it in the plasma membrane, where it concentrates at tight junctions between epithelial cells; conserved across the claudin family. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Cell membrane file:human/CLDN18/CLDN18-uniprot.txt TRANSMEM 7..27 |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Claudin-18 is a multi-pass plasma membrane protein. Reason: The four-transmembrane topology places it in the plasma membrane, where it concentrates at tight junctions between epithelial cells; conserved across the claudin family. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Cell membrane file:human/CLDN18/CLDN18-uniprot.txt TRANSMEM 7..27 |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Claudin-18 is a multi-pass plasma membrane protein. Reason: The four-transmembrane topology places it in the plasma membrane, where it concentrates at tight junctions between epithelial cells; conserved across the claudin family. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Cell membrane file:human/CLDN18/CLDN18-uniprot.txt TRANSMEM 7..27 |
| GO:0005911 cell-cell junction | IEA GO_REF:0000107 | MODIFY | Summary: Claudin-18 localizes to cell-cell junctions. Reason: Correct but less specific than supported; the junction in question is the bicellular tight junction, which the gene already carries by IBA, IEA and ISS. Proposed replacements: bicellular tight junction Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Cell junction, tight junction |
| GO:0005911 cell-cell junction | ISS GO_REF:0000024 | MODIFY | Summary: Claudin-18 localizes to cell-cell junctions. Reason: Correct but less specific than supported; the junction in question is the bicellular tight junction, which the gene already carries by IBA, IEA and ISS. Proposed replacements: bicellular tight junction Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Cell junction, tight junction |
| GO:0005923 bicellular tight junction | IBA GO_REF:0000033 | ACCEPT | Summary: Claudin-18 is a component of epithelial tight junctions. Reason: Its two extracellular loops interact in trans across the paracellular space to form the seal; this is the defining location of a claudin and is supported by the phylogenetic assignment and the mouse orthologue. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Note=Localizes to tight junctions in epithelial cells. file:human/CLDN18/CLDN18-uniprot.txt Cell junction, tight junction |
| GO:0005923 bicellular tight junction | IEA GO_REF:0000120 | ACCEPT | Summary: Claudin-18 is a component of epithelial tight junctions. Reason: Its two extracellular loops interact in trans across the paracellular space to form the seal; this is the defining location of a claudin and is supported by the phylogenetic assignment and the mouse orthologue. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Note=Localizes to tight junctions in epithelial cells. file:human/CLDN18/CLDN18-uniprot.txt Cell junction, tight junction |
| GO:0005923 bicellular tight junction | ISS GO_REF:0000024 | ACCEPT | Summary: Claudin-18 is a component of epithelial tight junctions. Reason: Its two extracellular loops interact in trans across the paracellular space to form the seal; this is the defining location of a claudin and is supported by the phylogenetic assignment and the mouse orthologue. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Note=Localizes to tight junctions in epithelial cells. file:human/CLDN18/CLDN18-uniprot.txt Cell junction, tight junction |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: PMP-22/claudin family mapping to membrane. Reason: Membrane is true but uninformative; claudin-18 is a multi-pass plasma membrane protein concentrated at tight junctions. Proposed replacements: plasma membrane bicellular tight junction Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Cell membrane |
| GO:0016328 lateral plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The gastric isoform A2 is also found along the lateral cell membrane. Reason: Consistent with the UniProt isoform-specific location; peripheral to the tight-junction pool that carries the barrier function. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt SUBCELLULAR LOCATION: [Isoform A2]: Cell junction, tight junction file:human/CLDN18/CLDN18-uniprot.txt Lateral cell membrane |
| GO:0016328 lateral plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The gastric isoform A2 is also found along the lateral cell membrane. Reason: Consistent with the UniProt isoform-specific location; peripheral to the tight-junction pool that carries the barrier function. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt SUBCELLULAR LOCATION: [Isoform A2]: Cell junction, tight junction file:human/CLDN18/CLDN18-uniprot.txt Lateral cell membrane |
| GO:0016338 calcium-independent cell-cell adhesion | ISS GO_REF:0000024 | ACCEPT | Summary: Claudin-18 mediates calcium-independent adhesion between epithelial cells through trans interaction of its extracellular loops. Reason: Claudin trans-interaction is how tight-junction strands join adjacent cells; the term fits the structural function and is transferred from the characterized orthologue. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Note=Localizes to tight junctions in epithelial cells. |
| GO:0035265 organ growth | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse claudin-18 restrains organ growth by sequestering phosphorylated YAP1 away from the nucleus. Reason: An organism-level outcome of the junctional scaffolding function, inferred from the mouse orthologue; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Acts to maintain epithelial progenitor cell proliferation |
| GO:0035265 organ growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse claudin-18 restrains organ growth by sequestering phosphorylated YAP1 away from the nucleus. Reason: An organism-level outcome of the junctional scaffolding function, inferred from the mouse orthologue; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Acts to maintain epithelial progenitor cell proliferation |
| GO:0042045 epithelial fluid transport | IEA GO_REF:0000107 | ACCEPT | Summary: Claudin-18 controls alveolar epithelial fluid and solute permeability. Reason: Loss of the mouse orthologue disrupts alveolar fluid homeostasis through altered tight-junction composition; this paracellular barrier role is the principal physiological function of the lung isoform. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Involved in alveolar fluid homeostasis via regulation of |
| GO:0042045 epithelial fluid transport | ISS GO_REF:0000024 | ACCEPT | Summary: Claudin-18 controls alveolar epithelial fluid and solute permeability. Reason: Loss of the mouse orthologue disrupts alveolar fluid homeostasis through altered tight-junction composition; this paracellular barrier role is the principal physiological function of the lung isoform. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Involved in alveolar fluid homeostasis via regulation of |
| GO:0042802 identical protein binding | ISS GO_REF:0000024 | ACCEPT | Summary: Claudin-18 self-associates, as claudins do when polymerizing into strands. Reason: Homotypic claudin interaction, in cis within a membrane and in trans across the junction, is the mechanism of strand formation; inferred from the characterized orthologue. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Note=Localizes to tight junctions in epithelial cells. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | UNDECIDED | Summary: Ortholog-transferred response to ethanol, from rat. Reason: An expression or barrier response reported in rat; no human or mouse experimental support was available here and the source study could not be assessed. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Required for lung alveolarization and |
| GO:0048286 lung alveolus development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Claudin-18 is required for normal lung alveolarization. Reason: A developmental outcome of the barrier and YAP-regulatory functions, inferred from the mouse knockout; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Required for lung alveolarization and |
| GO:0048286 lung alveolus development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Claudin-18 is required for normal lung alveolarization. Reason: A developmental outcome of the barrier and YAP-regulatory functions, inferred from the mouse knockout; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Required for lung alveolarization and |
| GO:0050673 epithelial cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Claudin-18 loss increases alveolar epithelial progenitor proliferation. Reason: Downstream of YAP1 sequestration at the junction rather than a direct activity; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Acts to maintain epithelial progenitor cell proliferation |
| GO:0050673 epithelial cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Claudin-18 loss increases alveolar epithelial progenitor proliferation. Reason: Downstream of YAP1 sequestration at the junction rather than a direct activity; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Acts to maintain epithelial progenitor cell proliferation |
| GO:0070160 tight junction | IEA GO_REF:0000107 | ACCEPT | Summary: Claudin-18 is a component of epithelial tight junctions. Reason: Its two extracellular loops interact in trans across the paracellular space to form the seal; this is the defining location of a claudin and is supported by the phylogenetic assignment and the mouse orthologue. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Note=Localizes to tight junctions in epithelial cells. file:human/CLDN18/CLDN18-uniprot.txt Cell junction, tight junction |
| GO:0071391 cellular response to estrogen stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Claudin-18 mediates osteoprotective effects attributed to estrogen signalling in mouse. Reason: An ortholog-transferred, tissue-specific physiological role some distance from the junctional function; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Mediates the osteoprotective |
| GO:0071391 cellular response to estrogen stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Claudin-18 mediates osteoprotective effects attributed to estrogen signalling in mouse. Reason: An ortholog-transferred, tissue-specific physiological role some distance from the junctional function; retained as non-core. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Mediates the osteoprotective |
| GO:0120192 tight junction assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Claudin-18 participates in the assembly and organization of tight junctions. Reason: As a strand-forming claudin that recruits ZO scaffolds through its PDZ-binding motif, it builds the junction rather than merely residing in it; the PAINT assignment covers the family. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Required for the formation of the gastric file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0120193 tight junction organization | IEA GO_REF:0000107 | ACCEPT | Summary: Claudin-18 participates in the assembly and organization of tight junctions. Reason: As a strand-forming claudin that recruits ZO scaffolds through its PDZ-binding motif, it builds the junction rather than merely residing in it; the PAINT assignment covers the family. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Required for the formation of the gastric file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:0120193 tight junction organization | ISS GO_REF:0000024 | ACCEPT | Summary: Claudin-18 participates in the assembly and organization of tight junctions. Reason: As a strand-forming claudin that recruits ZO scaffolds through its PDZ-binding motif, it builds the junction rather than merely residing in it; the PAINT assignment covers the family. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Required for the formation of the gastric file:human/CLDN18/CLDN18-uniprot.txt Interacts with TJP2/ZO-2 (By similarity). Interacts with |
| GO:1900181 negative regulation of protein localization to nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Claudin-18 restricts nuclear localization of YAP1 and ZO-2. Reason: Sequestration of partners at the junction is a consequence of its scaffolding interactions; supported for the mouse orthologue and retained as non-core for human. Supporting Evidence: file:human/CLDN18/CLDN18-uniprot.txt Interacts with YAP1 (phosphorylated); the file:human/CLDN18/CLDN18-uniprot.txt interaction sequesters YAP1 away from the nucleus and thereby restricts |
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Download this section (compressed HTML)Q: How do the CLDN18.1 and CLDN18.2 first extracellular loops differ in trans-interaction partners and in ion/water selectivity of the strands they form?
Q: Is the YAP1-sequestering activity of the claudin-18 tail direct in human cells, and does loss of CLDN18.2 in gastric cancer contribute to tumour growth by releasing YAP1?
Experiment: Express each isoform, and loop-swapped chimeras, in claudin-deficient MDCK cells and measure transepithelial resistance and ion and small-solute permeability, with freeze-fracture or super-resolution imaging of strand architecture.
Hypothesis: The two CLDN18 isoforms build strands with different paracellular selectivity because of their divergent first extracellular loop.
Experiment: Test the interaction in human gastric epithelial cells by co-immunoprecipitation and proximity ligation with and without the C-terminal tail, and quantify nuclear YAP1 and target gene expression on CLDN18 knockout and tail-deletion rescue.
Hypothesis: Human CLDN18.2 directly retains phosphorylated YAP1 at the junction.
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