ID CLD18_MOUSE Reviewed; 264 AA. AC P56857; Q91ZY9; Q91ZZ0; Q91ZZ1; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 1. DT 08-NOV-2023, entry version 150. DE RecName: Full=Claudin-18; GN Name=Cldn18; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY RP (ISOFORMS A1.1; A1.2; A2.1 AND A2.2), AND ALTERNATIVE SPLICING. RX PubMed=11585919; DOI=10.1128/mcb.21.21.7380-7390.2001; RA Niimi T., Nagashima K., Ward J.M., Minoo P., Zimonjic D.B., Popescu N.C., RA Kimura S.; RT "Claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 RT homeodomain transcription factor, encodes lung- and stomach-specific RT isoforms through alternative splicing."; RL Mol. Cell. Biol. 21:7380-7390(2001). RN [2] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [3] RP FUNCTION (ISOFORM A2.1), SUBCELLULAR LOCATION (ISOFORMS A1.1 AND A2.1), RP TISSUE SPECIFICITY (ISOFORMS A1.1 AND A2.1), AND DISRUPTION PHENOTYPE RP (ISOFORM A2.1). RX PubMed=22079592; DOI=10.1053/j.gastro.2011.10.040; RA Hayashi D., Tamura A., Tanaka H., Yamazaki Y., Watanabe S., Suzuki K., RA Suzuki K., Sentani K., Yasui W., Rakugi H., Isaka Y., Tsukita S.; RT "Deficiency of claudin-18 causes paracellular H+ leakage, up-regulation of RT interleukin-1beta, and atrophic gastritis in mice."; RL Gastroenterology 142:292-304(2012). RN [4] RP FUNCTION, INTERACTION WITH TJP2, TISSUE SPECIFICITY (ISOFORMS A1.1 AND RP A2.1), AND DISRUPTION PHENOTYPE. RX PubMed=22437732; DOI=10.1002/jbmr.1600; RA Linares G.R., Brommage R., Powell D.R., Xing W., Chen S.T., Alshbool F.Z., RA Lau K.H., Wergedal J.E., Mohan S.; RT "Claudin 18 is a novel negative regulator of bone resorption and osteoclast RT differentiation."; RL J. Bone Miner. Res. 27:1553-1565(2012). RN [5] RP FUNCTION, INDUCTION BY 17-BETA-ESTRADIOL, AND DISRUPTION PHENOTYPE. RX PubMed=23299504; DOI=10.1152/ajpendo.00408.2012; RA Kim H.Y., Alarcon C., Pourteymour S., Wergedal J.E., Mohan S.; RT "Disruption of claudin-18 diminishes ovariectomy-induced bone loss in RT mice."; RL Am. J. Physiol. 304:E531-E537(2013). RN [6] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=24588076; DOI=10.1165/rcmb.2013-0353oc; RA Li G., Flodby P., Luo J., Kage H., Sipos A., Gao D., Ji Y., Beard L.L., RA Marconett C.N., DeMaio L., Kim Y.H., Kim K.J., Laird-Offringa I.A., RA Minoo P., Liebler J.M., Zhou B., Crandall E.D., Borok Z.; RT "Knockout mice reveal key roles for claudin 18 in alveolar barrier RT properties and fluid homeostasis."; RL Am. J. Respir. Cell Mol. Biol. 51:210-222(2014). RN [7] RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION RP PHENOTYPE. RX PubMed=24787463; DOI=10.1165/rcmb.2013-0456oc; RA LaFemina M.J., Sutherland K.M., Bentley T., Gonzales L.W., Allen L., RA Chapin C.J., Rokkam D., Sweerus K.A., Dobbs L.G., Ballard P.L., Frank J.A.; RT "Claudin-18 deficiency results in alveolar barrier dysfunction and impaired RT alveologenesis in mice."; RL Am. J. Respir. Cell Mol. Biol. 51:550-558(2014). RN [8] RP FUNCTION, INTERACTION WITH TJP1 AND YAP1, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=29400695; DOI=10.1172/jci90429; RA Zhou B., Flodby P., Luo J., Castillo D.R., Liu Y., Yu F.X., McConnell A., RA Varghese B., Li G., Chimge N.O., Sunohara M., Koss M.N., Elatre W., RA Conti P., Liebler J.M., Yang C., Marconett C.N., Laird-Offringa I.A., RA Minoo P., Guan K., Stripp B.R., Crandall E.D., Borok Z.; RT "Claudin-18-mediated YAP activity regulates lung stem and progenitor cell RT homeostasis and tumorigenesis."; RL J. Clin. Invest. 128:970-984(2018). RN [9] RP FUNCTION (ISOFORM A1.1), AND DISRUPTION PHENOTYPE (ISOFORM A1.1). RX PubMed=34702961; DOI=10.1038/s41598-021-00708-6; RA Sato K., Matsumoto I., Suzuki K., Tamura A., Shiraishi A., Kiyonari H., RA Kasamatsu J., Yamamoto H., Miyasaka T., Tanno D., Miyahara A., Zong T., RA Kagesawa T., Oniyama A., Kawamura K., Kitai Y., Umeki A., Kanno E., RA Tanno H., Ishii K., Tsukita S., Kawakami K.; RT "Deficiency of lung-specific claudin-18 leads to aggravated infection with RT Cryptococcus deneoformans through dysregulation of the microenvironment in RT lungs."; RL Sci. Rep. 11:21110-21110(2021). CC -!- FUNCTION: Involved in alveolar fluid homeostasis via regulation of CC alveolar epithelial tight junction composition and therefore ion CC transport and solute permeability, potentially via downstream CC regulation of the actin cytoskeleton organization and beta-2-adrenergic CC signaling (PubMed:24588076). Required for lung alveolarization and CC maintenance of the paracellular alveolar epithelial barrier CC (PubMed:24787463). Acts to maintain epithelial progenitor cell CC proliferation and organ size, via regulation of YAP1 localization away CC from the nucleus and thereby restriction of YAP1 target gene CC transcription (PubMed:29400695). Acts as a negative regulator of RANKL- CC induced osteoclast differentiation, potentially via relocation of CC TJP2/ZO-2 away from the nucleus, subsequently involved in bone CC resorption in response to calcium deficiency (PubMed:22437732). CC Mediates the osteoprotective effects of estrogen, potentially via CC acting downstream of estrogen signaling independently of RANKL CC signaling pathways (PubMed:23299504). {ECO:0000269|PubMed:22437732, CC ECO:0000269|PubMed:23299504, ECO:0000269|PubMed:24588076, CC ECO:0000269|PubMed:24787463, ECO:0000269|PubMed:29400695}. CC -!- FUNCTION: [Isoform A1.1]: Involved in the maintenance of homeostasis of CC the alveolar microenvironment via regulation of pH and subsequent T- CC cell activation in the alveolar space, is therefore indirectly involved CC in limiting C. neoformans infection. {ECO:0000269|PubMed:34702961}. CC -!- FUNCTION: [Isoform A2.1]: Required for the formation of the gastric CC paracellular barrier via its role in tight junction formation, thereby CC involved in the response to gastric acidification. CC {ECO:0000269|PubMed:22079592}. CC -!- SUBUNIT: Interacts with TJP2/ZO-2 (PubMed:22437732). Interacts with CC TJP1/ZO-1 (PubMed:29400695). Interacts with YAP1 (phosphorylated); the CC interaction sequesters YAP1 away from the nucleus and thereby restricts CC transcription of YAP1 target genes (PubMed:29400695). CC {ECO:0000269|PubMed:22437732, ECO:0000269|PubMed:29400695}. CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction CC {ECO:0000269|PubMed:11585919, ECO:0000269|PubMed:29400695}. Cell CC membrane {ECO:0000269|PubMed:11585919, ECO:0000269|PubMed:29400695}; CC Multi-pass membrane protein {ECO:0000255}. Note=Localizes to tight CC junctions in epithelial cells. {ECO:0000269|PubMed:11585919}. CC -!- SUBCELLULAR LOCATION: [Isoform A1.1]: Cell junction, tight junction CC {ECO:0000269|PubMed:22079592}. CC -!- SUBCELLULAR LOCATION: [Isoform A2.1]: Cell junction, tight junction CC {ECO:0000269|PubMed:22079592}. Lateral cell membrane CC {ECO:0000269|PubMed:22079592}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=A1.1; Synonyms=Lung-type {ECO:0000303|PubMed:22079592}; CC IsoId=P56857-1; Sequence=Displayed; CC Name=A1.2; CC IsoId=P56857-2; Sequence=VSP_001104, VSP_001105; CC Name=A2.1; Synonyms=Stomach-type {ECO:0000303|PubMed:22079592}; CC IsoId=P56857-3; Sequence=VSP_001103; CC Name=A2.2; CC IsoId=P56857-4; Sequence=VSP_001103, VSP_001104, VSP_001105; CC -!- TISSUE SPECIFICITY: Expressed in the lung (at protein level). CC {ECO:0000269|PubMed:24787463, ECO:0000269|PubMed:29400695}. CC -!- TISSUE SPECIFICITY: [Isoform A1.1]: Expressed in lung (PubMed:11585919, CC PubMed:22437732). Expressed in the stomach (PubMed:22079592). CC {ECO:0000269|PubMed:11585919, ECO:0000269|PubMed:22079592, CC ECO:0000269|PubMed:22437732}. CC -!- TISSUE SPECIFICITY: [Isoform A1.2]: Expressed in lung. CC {ECO:0000269|PubMed:11585919}. CC -!- TISSUE SPECIFICITY: [Isoform A2.1]: Expressed in stomach CC (PubMed:11585919, PubMed:22079592, PubMed:22437732). Expressed in bone CC (PubMed:22437732). {ECO:0000269|PubMed:11585919, CC ECO:0000269|PubMed:22079592, ECO:0000269|PubMed:22437732}. CC -!- TISSUE SPECIFICITY: [Isoform A2.2]: Expressed in stomach. CC {ECO:0000269|PubMed:11585919}. CC -!- DEVELOPMENTAL STAGE: Expressed in the lungs from 19 dpc, expression is CC increased at birth and at four weeks of age. CC {ECO:0000269|PubMed:24787463}. CC -!- INDUCTION: Induced by 17-beta-estradiol in bone marrow stromal cells, CC osteoblasts and osteoclasts. {ECO:0000269|PubMed:23299504}. CC -!- DISRUPTION PHENOTYPE: Parenchymal expansion phenotype and overall lung CC enlargement evident from 18 days post-conception (dpc), as a result of CC increased lung cellularity, airspace enlargement and increase in the CC number of AT2 cells in the lung alveolar compartments CC (PubMed:29400695). Increase in AT2 cells in S and G2/M phase of the CC cell cycle with no change in low levels of apoptosis in the lungs CC (PubMed:29400695). Increase in bronchoalveolar lavage fluid leakage as CC a result of alveolar epithelial cell injury at P3 and four weeks of CC age, resulting in an increase in AT2 cells in the lungs by four weeks CC of age (PubMed:24787463). Increase in expression of Cldn3 and Cldn4 in CC lungs at P7 (PubMed:24787463). Fixed alveolar permeability defect and CC dysregulation of genes involved in lung development in lung tissue, CC including Areg, Shh, Eln, Vegfa, Fgfr4, and Adm from 4 weeks of age CC (PubMed:24787463). Impaired alveolarization and decreased lung surface CC area at four weeks of age (PubMed:24787463). Membrane ruffling and CC splaying is evident at AT1-AT1 cell junctions at 8 weeks of age CC (PubMed:24787463). Increase in alveolar fluid clearance and lung CC permeability (PubMed:24588076). Increase in sodium/potassium- CC transporting ATPase activity in lungs, accompanied by an increase in CC Atp1b1 subunit expression, and decreases in Atp1a2, Atp1b3 and Atp1b2 CC subunit expression (PubMed:24588076). Increase in expression of Cldn3 CC and Cldn4 in lung tissues with a decrease in Ocln and Egr1 expression CC in lung tissues (PubMed:24588076). Increase in separation distance CC between Tjp1/Zo-1 in adjacent cells suggesting tight junction CC separation (PubMed:24588076). Cytoskeleton rearrangements as evidenced CC by increased F-actin localization to the plasma membrane and CC perinuclear actin aggregates with projected radial fibers to the plasma CC membrane (PubMed:24588076). Decrease in sensitivity to lung injury in CC response to ventilator-induced lung injury (PubMed:24588076). Increased CC nuclear localization and protein mobility of Yap1 while phosphorylated CC Yap1 abundance is decreased in AT2 cells, this results in an increase CC in Yap1-target genes such as Ccnd1, Areg, Cdk6 and Ccn2/Ctgf at two CC months of age (PubMed:29400695). Enlargement of the stomach due to CC increase in gastric mucosal thickness from 2 months of age CC (PubMed:29400695). Enlargement of the duodenum and kidney from 2 months CC of age (PubMed:29400695). Histological abnormalities in the gastric CC mucosa including inflammatory infiltrates and a decrease in the number CC of well-differentiated gastric chief cells and parietal cells CC (PubMed:22437732). Reduced total body bone mineral content, total body CC bone mineral density (BMD), cortical bone thickness, vertebra BMD and CC femur BMD by 20-25% from 4 to 26 weeks of age (PubMed:22437732, CC PubMed:23299504). Reduced trabecular bone, trabecular thickness and CC trabecular number decreased by 50%, whereas trabecular spacing is CC increased by 50% from 4 to 26 weeks of age (PubMed:22437732). CC Significant increase in osteoclastogenesis, osteoclast number and CC number of nuclei in osteoclasts on the surface of the trabecular bone CC of the proximal tibia (PubMed:22437732). Decrease in bone mass density CC in the femur, lumbar and whole body (PubMed:22437732). Skeletal defects CC and osteoclast levels were exacerbated significantly by a calcium CC depleted diet (PubMed:22437732). Reduction in bone volume to total CC volume ratio and osteoclast surface to bone surface ratio at 14 weeks CC of age (PubMed:23299504). Protection against ovariectomy-induced loss CC of total body, femur and lumbar bone mass density (PubMed:23299504). A CC 68% increase in incidence of tumors in lungs between 18 and 20 months CC of age, tumors develop after 10 months of age (PubMed:29400695). Tumors CC are of a AT2 cell-derived lineage, typically adenocarcinomas with CC associated alveolar mononuclear cells (PubMed:29400695). CC {ECO:0000269|PubMed:22437732, ECO:0000269|PubMed:23299504, CC ECO:0000269|PubMed:24588076, ECO:0000269|PubMed:24787463, CC ECO:0000269|PubMed:29400695}. CC -!- DISRUPTION PHENOTYPE: [Isoform A1.1]: Defective alveolar formation and CC increased alveolar macrophage counts evident at 6 weeks of age CC (PubMed:34702961). Increase in C. neoformans fungal burdens in CC bronchoalveolar lavage fluids (BALF), lung tissue and alveolar space CC from 1 day post-infection to 14 days post-infection (PubMed:34702961). CC Increase in multiplication of C. neoformans and poor granulomatous CC responses in the lung at 14 days post-infection with overall higher CC infection burdens in the brain and lungs to 28 days post-infection CC (PubMed:34702961). Increase in neutrophils, alveolar macrophages, CC inflammatory monocytes, natural killer cells, CD4-positive T-cells, CC CD8-positive T-cells and natural killer T-cells in BALF 3 days post-C. CC neoformans infection (PubMed:34702961). Decrease in IFNG in BALF on CC days 3 and 7 post-infection, similarly a decrease in Il4 and Il13 in CC BALF on day 14 and in the lungs on day 3 and day 14 post-infection CC (PubMed:34702961). Decrease in Il17a in BALF on day 7 and in the lungs CC on day 14 post-infection (PubMed:34702961). Increase in K(+) ion CC concentration in BALF, with a decrease in pH which persists 7 days CC post-infection, resulting in the increased replication of C. neoformans CC (PubMed:34702961). {ECO:0000269|PubMed:34702961}. CC -!- DISRUPTION PHENOTYPE: [Isoform A2.1]: 100% incidence of chronic CC gastritis with atypical distribution of cells in the gastric gland, CC including fewer parietal and chief cells that are replaced by CC metaplastic cells with dilated gland lumina (PubMed:22079592). Lack of CC increase in stomach lumen acidification with age (PubMed:22079592). CC Lack of sensitivity to gastric acidity and an increase in ion CC permeability of the gastric paracellular barrier (PubMed:22079592). CC Spasmolytic polypeptide-expressing metaplasia cells are dominant in the CC stomach in place of well-differentiated parietal cells and chief cells CC (PubMed:22079592). Abundant inflammatory cells in the submucosal region CC (PubMed:22079592). Slight decrease in the localization of Cldn18 CC isoform A1.1 at tight junctions in the gastric superficial mucous CC epithelial cells (PubMed:22079592). Upper apical layer of tight CC junctions in the stomach missing resulting in a decrease in tight CC junction width (PubMed:22079592). Increase in proinflammatory markers CC Il1a and Tnf/Tnf-a, the chemoattractant Cxcl1/Kc and prostaglandin E2 CC inflammatory marker Ptgs2/Cox2 in gastric tissue (PubMed:22079592). CC {ECO:0000269|PubMed:22079592}. CC -!- MISCELLANEOUS: May act as a tumor suppressor, inhibiting the CC development of AT2 cell-derived lung tumors. CC {ECO:0000269|PubMed:29400695}. CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF221068; AAF26447.1; -; mRNA. DR EMBL; AF349450; AAL15635.1; -; mRNA. DR EMBL; AF349451; AAL15636.1; -; mRNA. DR EMBL; AF349453; AAL15638.1; -; mRNA. DR CCDS; CCDS23437.1; -. [P56857-1] DR CCDS; CCDS57692.1; -. [P56857-2] DR CCDS; CCDS57693.1; -. [P56857-4] DR CCDS; CCDS57694.1; -. [P56857-3] DR RefSeq; NP_001181850.1; NM_001194921.1. [P56857-3] DR RefSeq; NP_001181851.1; NM_001194922.1. [P56857-2] DR RefSeq; NP_001181852.1; NM_001194923.1. [P56857-4] DR RefSeq; NP_062789.1; NM_019815.3. [P56857-1] DR AlphaFoldDB; P56857; -. DR SMR; P56857; -. DR DIP; DIP-48956N; -. DR IntAct; P56857; 2. DR STRING; 10090.ENSMUSP00000035048; -. DR TCDB; 1.H.1.1.8; the claudin tight junction (claudin1) family. DR iPTMnet; P56857; -. DR PhosphoSitePlus; P56857; -. DR MaxQB; P56857; -. DR PaxDb; 10090-ENSMUSP00000035048; -. DR ProteomicsDB; 285482; -. [P56857-1] DR ProteomicsDB; 285483; -. [P56857-2] DR ProteomicsDB; 285484; -. [P56857-3] DR ProteomicsDB; 285485; -. [P56857-4] DR Antibodypedia; 4575; 274 antibodies from 30 providers. DR DNASU; 56492; -. DR Ensembl; ENSMUST00000035048; ENSMUSP00000035048; ENSMUSG00000032473. [P56857-1] DR Ensembl; ENSMUST00000112882; ENSMUSP00000108503; ENSMUSG00000032473. [P56857-3] DR Ensembl; ENSMUST00000131922; ENSMUSP00000117382; ENSMUSG00000032473. [P56857-4] DR Ensembl; ENSMUST00000136429; ENSMUSP00000115782; ENSMUSG00000032473. [P56857-2] DR GeneID; 56492; -. DR KEGG; mmu:56492; -. DR UCSC; uc009rep.2; mouse. [P56857-1] DR UCSC; uc009req.2; mouse. [P56857-2] DR UCSC; uc009rer.2; mouse. [P56857-4] DR UCSC; uc009res.2; mouse. [P56857-3] DR AGR; MGI:1929209; -. DR CTD; 51208; -. DR MGI; MGI:1929209; Cldn18. DR VEuPathDB; HostDB:ENSMUSG00000032473; -. DR eggNOG; ENOG502QTRB; Eukaryota. DR GeneTree; ENSGT00940000158655; -. DR HOGENOM; CLU_076370_2_1_1; -. DR InParanoid; P56857; -. DR OMA; TICQVMG; -. DR OrthoDB; 5346296at2759; -. DR PhylomeDB; P56857; -. DR TreeFam; TF331936; -. DR BioGRID-ORCS; 56492; 1 hit in 78 CRISPR screens. DR PRO; PR:P56857; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; P56857; Protein. DR Bgee; ENSMUSG00000032473; Expressed in mucous cell of stomach and 25 other tissues. DR Genevisible; P56857; MM. DR GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB. DR GO; GO:0016328; C:lateral plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0070160; C:tight junction; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0070830; P:bicellular tight junction assembly; IBA:GO_Central. DR GO; GO:0016338; P:calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules; ISS:UniProtKB. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0048565; P:digestive tract development; IMP:MGI. DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:MGI. DR GO; GO:2001205; P:negative regulation of osteoclast development; IMP:MGI. DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IDA:MGI. DR GO; GO:0034504; P:protein localization to nucleus; IDA:MGI. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0120192; P:tight junction assembly; IMP:UniProtKB. DR GO; GO:0071847; P:TNFSF11-mediated signaling pathway; IMP:MGI. DR Gene3D; 1.20.140.150; -; 1. DR InterPro; IPR006187; Claudin. DR InterPro; IPR003928; Claudin18. DR InterPro; IPR017974; Claudin_CS. DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin. DR PANTHER; PTHR12002; CLAUDIN; 1. DR PANTHER; PTHR12002:SF9; CLAUDIN-18; 1. DR Pfam; PF00822; PMP22_Claudin; 1. DR PRINTS; PR01077; CLAUDIN. DR PRINTS; PR01448; CLAUDIN18. DR PROSITE; PS01346; CLAUDIN; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell junction; Cell membrane; Membrane; KW Phosphoprotein; Reference proteome; Tight junction; Transmembrane; KW Transmembrane helix. FT CHAIN 1..264 FT /note="Claudin-18" FT /id="PRO_0000457666" FT TOPO_DOM 1..6 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 7..27 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 28..80 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 81..101 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 102..122 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 123..143 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 144..176 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 177..197 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 198..264 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 198..264 FT /note="Required for role in regulation of RANKL-induced FT osteoclast differentiation" FT /evidence="ECO:0000269|PubMed:22437732" FT REGION 241..264 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 244..264 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 217 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT VAR_SEQ 1..69 FT /note="MATTTCQVVGLLLSLLGLAGCIAATGMDMWSTQDLYDNPVTAVFQYEGLWRS FT CVQQSSGFTECRPYFTI -> MSVTACQGLGFVVSLIGFAGIIAATCMDQWSTQDLYNN FT PVTAVFNYQGLWRSCVRESSGFTECRGYFTL (in isoform A2.1 and FT isoform A2.2)" FT /evidence="ECO:0000305" FT /id="VSP_001103" FT VAR_SEQ 208 FT /note="N -> K (in isoform A1.2 and isoform A2.2)" FT /evidence="ECO:0000305" FT /id="VSP_001104" FT VAR_SEQ 209..264 FT /note="Missing (in isoform A1.2 and isoform A2.2)" FT /evidence="ECO:0000305" FT /id="VSP_001105" SQ SEQUENCE 264 AA; 28122 MW; 3CA0D441C4705653 CRC64; MATTTCQVVG LLLSLLGLAG CIAATGMDMW STQDLYDNPV TAVFQYEGLW RSCVQQSSGF TECRPYFTIL GLPAMLQAVR ALMIVGIVLG VIGILVSIFA LKCIRIGSMD DSAKAKMTLT SGILFIISGI CAIIGVSVFA NMLVTNFWMS TANMYSGMGG MGGMVQTVQT RYTFGAALFV GWVAGGLTLI GGVMMCIACR GLTPDDSNFK AVSYHASGQN VAYRPGGFKA STGFGSNTRN KKIYDGGART EDDEQSHPTK YDYV //