P56857 · CLD18_MOUSE
- ProteinClaudin-18
- GeneCldn18
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids264 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Involved in alveolar fluid homeostasis via regulation of alveolar epithelial tight junction composition and therefore ion transport and solute permeability, potentially via downstream regulation of the actin cytoskeleton organization and beta-2-adrenergic signaling (PubMed:24588076).
Required for lung alveolarization and maintenance of the paracellular alveolar epithelial barrier (PubMed:24787463).
Acts to maintain epithelial progenitor cell proliferation and organ size, via regulation of YAP1 localization away from the nucleus and thereby restriction of YAP1 target gene transcription (PubMed:29400695).
Acts as a negative regulator of RANKL-induced osteoclast differentiation, potentially via relocation of TJP2/ZO-2 away from the nucleus, subsequently involved in bone resorption in response to calcium deficiency (PubMed:22437732).
Mediates the osteoprotective effects of estrogen, potentially via acting downstream of estrogen signaling independently of RANKL signaling pathways (PubMed:23299504).
Required for lung alveolarization and maintenance of the paracellular alveolar epithelial barrier (PubMed:24787463).
Acts to maintain epithelial progenitor cell proliferation and organ size, via regulation of YAP1 localization away from the nucleus and thereby restriction of YAP1 target gene transcription (PubMed:29400695).
Acts as a negative regulator of RANKL-induced osteoclast differentiation, potentially via relocation of TJP2/ZO-2 away from the nucleus, subsequently involved in bone resorption in response to calcium deficiency (PubMed:22437732).
Mediates the osteoprotective effects of estrogen, potentially via acting downstream of estrogen signaling independently of RANKL signaling pathways (PubMed:23299504).
Isoform A1.1
Involved in the maintenance of homeostasis of the alveolar microenvironment via regulation of pH and subsequent T-cell activation in the alveolar space, is therefore indirectly involved in limiting C. neoformans infection.
Isoform A2.1
Required for the formation of the gastric paracellular barrier via its role in tight junction formation, thereby involved in the response to gastric acidification.
Miscellaneous
May act as a tumor suppressor, inhibiting the development of AT2 cell-derived lung tumors.
GO annotations
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameClaudin-18
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP56857
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Localizes to tight junctions in epithelial cells.
Isoform A1.1
Isoform A2.1
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-6 | Cytoplasmic | ||||
Sequence: MATTTC | ||||||
Transmembrane | 7-27 | Helical | ||||
Sequence: QVVGLLLSLLGLAGCIAATGM | ||||||
Topological domain | 28-80 | Extracellular | ||||
Sequence: DMWSTQDLYDNPVTAVFQYEGLWRSCVQQSSGFTECRPYFTILGLPAMLQAVR | ||||||
Transmembrane | 81-101 | Helical | ||||
Sequence: ALMIVGIVLGVIGILVSIFAL | ||||||
Topological domain | 102-122 | Cytoplasmic | ||||
Sequence: KCIRIGSMDDSAKAKMTLTSG | ||||||
Transmembrane | 123-143 | Helical | ||||
Sequence: ILFIISGICAIIGVSVFANML | ||||||
Topological domain | 144-176 | Extracellular | ||||
Sequence: VTNFWMSTANMYSGMGGMGGMVQTVQTRYTFGA | ||||||
Transmembrane | 177-197 | Helical | ||||
Sequence: ALFVGWVAGGLTLIGGVMMCI | ||||||
Topological domain | 198-264 | Cytoplasmic | ||||
Sequence: ACRGLTPDDSNFKAVSYHASGQNVAYRPGGFKASTGFGSNTRNKKIYDGGARTEDDEQSHPTKYDYV |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Parenchymal expansion phenotype and overall lung enlargement evident from 18 days post-conception (dpc), as a result of increased lung cellularity, airspace enlargement and increase in the number of AT2 cells in the lung alveolar compartments (PubMed:29400695).
Increase in AT2 cells in S and G2/M phase of the cell cycle with no change in low levels of apoptosis in the lungs (PubMed:29400695).
Increase in bronchoalveolar lavage fluid leakage as a result of alveolar epithelial cell injury at P3 and four weeks of age, resulting in an increase in AT2 cells in the lungs by four weeks of age (PubMed:24787463).
Increase in expression of Cldn3 and Cldn4 in lungs at P7 (PubMed:24787463).
Fixed alveolar permeability defect and dysregulation of genes involved in lung development in lung tissue, including Areg, Shh, Eln, Vegfa, Fgfr4, and Adm from 4 weeks of age (PubMed:24787463).
Impaired alveolarization and decreased lung surface area at four weeks of age (PubMed:24787463).
Membrane ruffling and splaying is evident at AT1-AT1 cell junctions at 8 weeks of age (PubMed:24787463).
Increase in alveolar fluid clearance and lung permeability (PubMed:24588076).
Increase in sodium/potassium-transporting ATPase activity in lungs, accompanied by an increase in Atp1b1 subunit expression, and decreases in Atp1a2, Atp1b3 and Atp1b2 subunit expression (PubMed:24588076).
Increase in expression of Cldn3 and Cldn4 in lung tissues with a decrease in Ocln and Egr1 expression in lung tissues (PubMed:24588076).
Increase in separation distance between Tjp1/Zo-1 in adjacent cells suggesting tight junction separation (PubMed:24588076).
Cytoskeleton rearrangements as evidenced by increased F-actin localization to the plasma membrane and perinuclear actin aggregates with projected radial fibers to the plasma membrane (PubMed:24588076).
Decrease in sensitivity to lung injury in response to ventilator-induced lung injury (PubMed:24588076).
Increased nuclear localization and protein mobility of Yap1 while phosphorylated Yap1 abundance is decreased in AT2 cells, this results in an increase in Yap1-target genes such as Ccnd1, Areg, Cdk6 and Ccn2/Ctgf at two months of age (PubMed:29400695).
Enlargement of the stomach due to increase in gastric mucosal thickness from 2 months of age (PubMed:29400695).
Enlargement of the duodenum and kidney from 2 months of age (PubMed:29400695).
Histological abnormalities in the gastric mucosa including inflammatory infiltrates and a decrease in the number of well-differentiated gastric chief cells and parietal cells (PubMed:22437732).
Reduced total body bone mineral content, total body bone mineral density (BMD), cortical bone thickness, vertebra BMD and femur BMD by 20-25% from 4 to 26 weeks of age (PubMed:22437732, PubMed:23299504).
Reduced trabecular bone, trabecular thickness and trabecular number decreased by 50%, whereas trabecular spacing is increased by 50% from 4 to 26 weeks of age (PubMed:22437732).
Significant increase in osteoclastogenesis, osteoclast number and number of nuclei in osteoclasts on the surface of the trabecular bone of the proximal tibia (PubMed:22437732).
Decrease in bone mass density in the femur, lumbar and whole body (PubMed:22437732).
Skeletal defects and osteoclast levels were exacerbated significantly by a calcium depleted diet (PubMed:22437732).
Reduction in bone volume to total volume ratio and osteoclast surface to bone surface ratio at 14 weeks of age (PubMed:23299504).
Protection against ovariectomy-induced loss of total body, femur and lumbar bone mass density (PubMed:23299504).
A 68% increase in incidence of tumors in lungs between 18 and 20 months of age, tumors develop after 10 months of age (PubMed:29400695).
Tumors are of a AT2 cell-derived lineage, typically adenocarcinomas with associated alveolar mononuclear cells (PubMed:29400695).
Increase in AT2 cells in S and G2/M phase of the cell cycle with no change in low levels of apoptosis in the lungs (PubMed:29400695).
Increase in bronchoalveolar lavage fluid leakage as a result of alveolar epithelial cell injury at P3 and four weeks of age, resulting in an increase in AT2 cells in the lungs by four weeks of age (PubMed:24787463).
Increase in expression of Cldn3 and Cldn4 in lungs at P7 (PubMed:24787463).
Fixed alveolar permeability defect and dysregulation of genes involved in lung development in lung tissue, including Areg, Shh, Eln, Vegfa, Fgfr4, and Adm from 4 weeks of age (PubMed:24787463).
Impaired alveolarization and decreased lung surface area at four weeks of age (PubMed:24787463).
Membrane ruffling and splaying is evident at AT1-AT1 cell junctions at 8 weeks of age (PubMed:24787463).
Increase in alveolar fluid clearance and lung permeability (PubMed:24588076).
Increase in sodium/potassium-transporting ATPase activity in lungs, accompanied by an increase in Atp1b1 subunit expression, and decreases in Atp1a2, Atp1b3 and Atp1b2 subunit expression (PubMed:24588076).
Increase in expression of Cldn3 and Cldn4 in lung tissues with a decrease in Ocln and Egr1 expression in lung tissues (PubMed:24588076).
Increase in separation distance between Tjp1/Zo-1 in adjacent cells suggesting tight junction separation (PubMed:24588076).
Cytoskeleton rearrangements as evidenced by increased F-actin localization to the plasma membrane and perinuclear actin aggregates with projected radial fibers to the plasma membrane (PubMed:24588076).
Decrease in sensitivity to lung injury in response to ventilator-induced lung injury (PubMed:24588076).
Increased nuclear localization and protein mobility of Yap1 while phosphorylated Yap1 abundance is decreased in AT2 cells, this results in an increase in Yap1-target genes such as Ccnd1, Areg, Cdk6 and Ccn2/Ctgf at two months of age (PubMed:29400695).
Enlargement of the stomach due to increase in gastric mucosal thickness from 2 months of age (PubMed:29400695).
Enlargement of the duodenum and kidney from 2 months of age (PubMed:29400695).
Histological abnormalities in the gastric mucosa including inflammatory infiltrates and a decrease in the number of well-differentiated gastric chief cells and parietal cells (PubMed:22437732).
Reduced total body bone mineral content, total body bone mineral density (BMD), cortical bone thickness, vertebra BMD and femur BMD by 20-25% from 4 to 26 weeks of age (PubMed:22437732, PubMed:23299504).
Reduced trabecular bone, trabecular thickness and trabecular number decreased by 50%, whereas trabecular spacing is increased by 50% from 4 to 26 weeks of age (PubMed:22437732).
Significant increase in osteoclastogenesis, osteoclast number and number of nuclei in osteoclasts on the surface of the trabecular bone of the proximal tibia (PubMed:22437732).
Decrease in bone mass density in the femur, lumbar and whole body (PubMed:22437732).
Skeletal defects and osteoclast levels were exacerbated significantly by a calcium depleted diet (PubMed:22437732).
Reduction in bone volume to total volume ratio and osteoclast surface to bone surface ratio at 14 weeks of age (PubMed:23299504).
Protection against ovariectomy-induced loss of total body, femur and lumbar bone mass density (PubMed:23299504).
A 68% increase in incidence of tumors in lungs between 18 and 20 months of age, tumors develop after 10 months of age (PubMed:29400695).
Tumors are of a AT2 cell-derived lineage, typically adenocarcinomas with associated alveolar mononuclear cells (PubMed:29400695).
Isoform A1.1
Defective alveolar formation and increased alveolar macrophage counts evident at 6 weeks of age (PubMed:34702961).
Increase in C. neoformans fungal burdens in bronchoalveolar lavage fluids (BALF), lung tissue and alveolar space from 1 day post-infection to 14 days post-infection (PubMed:34702961).
Increase in multiplication of C. neoformans and poor granulomatous responses in the lung at 14 days post-infection with overall higher infection burdens in the brain and lungs to 28 days post-infection (PubMed:34702961).
Increase in neutrophils, alveolar macrophages, inflammatory monocytes, natural killer cells, CD4-positive T-cells, CD8-positive T-cells and natural killer T-cells in BALF 3 days post-C. neoformans infection (PubMed:34702961).
Decrease in IFNG in BALF on days 3 and 7 post-infection, similarly a decrease in Il4 and Il13 in BALF on day 14 and in the lungs on day 3 and day 14 post-infection (PubMed:34702961).
Decrease in Il17a in BALF on day 7 and in the lungs on day 14 post-infection (PubMed:34702961).
Increase in K+ ion concentration in BALF, with a decrease in pH which persists 7 days post-infection, resulting in the increased replication of C. neoformans (PubMed:34702961).
Increase in C. neoformans fungal burdens in bronchoalveolar lavage fluids (BALF), lung tissue and alveolar space from 1 day post-infection to 14 days post-infection (PubMed:34702961).
Increase in multiplication of C. neoformans and poor granulomatous responses in the lung at 14 days post-infection with overall higher infection burdens in the brain and lungs to 28 days post-infection (PubMed:34702961).
Increase in neutrophils, alveolar macrophages, inflammatory monocytes, natural killer cells, CD4-positive T-cells, CD8-positive T-cells and natural killer T-cells in BALF 3 days post-C. neoformans infection (PubMed:34702961).
Decrease in IFNG in BALF on days 3 and 7 post-infection, similarly a decrease in Il4 and Il13 in BALF on day 14 and in the lungs on day 3 and day 14 post-infection (PubMed:34702961).
Decrease in Il17a in BALF on day 7 and in the lungs on day 14 post-infection (PubMed:34702961).
Increase in K+ ion concentration in BALF, with a decrease in pH which persists 7 days post-infection, resulting in the increased replication of C. neoformans (PubMed:34702961).
Isoform A2.1
100% incidence of chronic gastritis with atypical distribution of cells in the gastric gland, including fewer parietal and chief cells that are replaced by metaplastic cells with dilated gland lumina (PubMed:22079592).
Lack of increase in stomach lumen acidification with age (PubMed:22079592).
Lack of sensitivity to gastric acidity and an increase in ion permeability of the gastric paracellular barrier (PubMed:22079592).
Spasmolytic polypeptide-expressing metaplasia cells are dominant in the stomach in place of well-differentiated parietal cells and chief cells (PubMed:22079592).
Abundant inflammatory cells in the submucosal region (PubMed:22079592).
Slight decrease in the localization of Cldn18 isoform A1.1 at tight junctions in the gastric superficial mucous epithelial cells (PubMed:22079592).
Upper apical layer of tight junctions in the stomach missing resulting in a decrease in tight junction width (PubMed:22079592).
Increase in proinflammatory markers Il1a and Tnf/Tnf-a, the chemoattractant Cxcl1/Kc and prostaglandin E2 inflammatory marker Ptgs2/Cox2 in gastric tissue (PubMed:22079592).
Lack of increase in stomach lumen acidification with age (PubMed:22079592).
Lack of sensitivity to gastric acidity and an increase in ion permeability of the gastric paracellular barrier (PubMed:22079592).
Spasmolytic polypeptide-expressing metaplasia cells are dominant in the stomach in place of well-differentiated parietal cells and chief cells (PubMed:22079592).
Abundant inflammatory cells in the submucosal region (PubMed:22079592).
Slight decrease in the localization of Cldn18 isoform A1.1 at tight junctions in the gastric superficial mucous epithelial cells (PubMed:22079592).
Upper apical layer of tight junctions in the stomach missing resulting in a decrease in tight junction width (PubMed:22079592).
Increase in proinflammatory markers Il1a and Tnf/Tnf-a, the chemoattractant Cxcl1/Kc and prostaglandin E2 inflammatory marker Ptgs2/Cox2 in gastric tissue (PubMed:22079592).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 14 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000457666 | 1-264 | Claudin-18 | |||
Sequence: MATTTCQVVGLLLSLLGLAGCIAATGMDMWSTQDLYDNPVTAVFQYEGLWRSCVQQSSGFTECRPYFTILGLPAMLQAVRALMIVGIVLGVIGILVSIFALKCIRIGSMDDSAKAKMTLTSGILFIISGICAIIGVSVFANMLVTNFWMSTANMYSGMGGMGGMVQTVQTRYTFGAALFVGWVAGGLTLIGGVMMCIACRGLTPDDSNFKAVSYHASGQNVAYRPGGFKASTGFGSNTRNKKIYDGGARTEDDEQSHPTKYDYV | ||||||
Modified residue | 217 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the lung (at protein level).
Isoform A1.1
Isoform A1.2
Expressed in lung.
Isoform A2.1
Expressed in stomach (PubMed:11585919, PubMed:22079592, PubMed:22437732).
Expressed in bone (PubMed:22437732).
Expressed in bone (PubMed:22437732).
Isoform A2.2
Expressed in stomach.
Induction
Induced by 17-beta-estradiol in bone marrow stromal cells, osteoblasts and osteoclasts.
Developmental stage
Expressed in the lungs from 19 dpc, expression is increased at birth and at four weeks of age.
Gene expression databases
Interaction
Subunit
Interacts with TJP2/ZO-2 (PubMed:22437732).
Interacts with TJP1/ZO-1 (PubMed:29400695).
Interacts with YAP1 (phosphorylated); the interaction sequesters YAP1 away from the nucleus and thereby restricts transcription of YAP1 target genes (PubMed:29400695).
Interacts with TJP1/ZO-1 (PubMed:29400695).
Interacts with YAP1 (phosphorylated); the interaction sequesters YAP1 away from the nucleus and thereby restricts transcription of YAP1 target genes (PubMed:29400695).
Isoform A2.1
Interacts with CLDN19.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 198-264 | Required for role in regulation of RANKL-induced osteoclast differentiation | ||||
Sequence: ACRGLTPDDSNFKAVSYHASGQNVAYRPGGFKASTGFGSNTRNKKIYDGGARTEDDEQSHPTKYDYV | ||||||
Region | 241-264 | Disordered | ||||
Sequence: KKIYDGGARTEDDEQSHPTKYDYV | ||||||
Compositional bias | 244-264 | Basic and acidic residues | ||||
Sequence: YDGGARTEDDEQSHPTKYDYV |
Sequence similarities
Belongs to the claudin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
P56857-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameA1.1
- SynonymsLung-type
- Length264
- Mass (Da)28,122
- Last updated2000-05-30 v1
- Checksum3CA0D441C4705653
P56857-2
- NameA1.2
P56857-3
- NameA2.1
- SynonymsStomach-type
- Differences from canonical
- 1-69: MATTTCQVVGLLLSLLGLAGCIAATGMDMWSTQDLYDNPVTAVFQYEGLWRSCVQQSSGFTECRPYFTI → MSVTACQGLGFVVSLIGFAGIIAATCMDQWSTQDLYNNPVTAVFNYQGLWRSCVRESSGFTECRGYFTL
P56857-4
- NameA2.2
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_001103 | 1-69 | in isoform A2.1 and isoform A2.2 | |||
Sequence: MATTTCQVVGLLLSLLGLAGCIAATGMDMWSTQDLYDNPVTAVFQYEGLWRSCVQQSSGFTECRPYFTI → MSVTACQGLGFVVSLIGFAGIIAATCMDQWSTQDLYNNPVTAVFNYQGLWRSCVRESSGFTECRGYFTL | ||||||
Alternative sequence | VSP_001104 | 208 | in isoform A1.2 and isoform A2.2 | |||
Sequence: N → K | ||||||
Alternative sequence | VSP_001105 | 209-264 | in isoform A1.2 and isoform A2.2 | |||
Sequence: Missing | ||||||
Compositional bias | 244-264 | Basic and acidic residues | ||||
Sequence: YDGGARTEDDEQSHPTKYDYV |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF221068 EMBL· GenBank· DDBJ | AAF26447.1 EMBL· GenBank· DDBJ | mRNA | ||
AF349450 EMBL· GenBank· DDBJ | AAL15635.1 EMBL· GenBank· DDBJ | mRNA | ||
AF349451 EMBL· GenBank· DDBJ | AAL15636.1 EMBL· GenBank· DDBJ | mRNA | ||
AF349453 EMBL· GenBank· DDBJ | AAL15638.1 EMBL· GenBank· DDBJ | mRNA |