CLDN2

Claudin 2
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4YYX​
Identifiers
Symbol	CLDN2
External IDs	OMIM: 300520 MGI: 1276110 HomoloGene: 9621 GeneCards: CLDN2 Gene
Gene ontology Molecular function • structural molecule activity • protein binding • identical protein binding Cellular component • plasma membrane • bicellular tight junction • integral component of membrane • extracellular exosome Biological process • calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9075	12738
Ensembl	ENSG00000165376	ENSMUSG00000047230
UniProt	P57739	O88552
RefSeq (mRNA)	NM_001171092	NM_016675
RefSeq (protein)	NP_001164563	NP_057884
Location (UCSC)	Chr X: 106.9 – 106.93 Mb	Chr X: 139.8 – 139.81 Mb
PubMed search

Claudin-2 is a protein that in humans is encoded by the CLDN2 gene.^[1][2] It belongs to the group of claudins.

Members of the claudin protein family, such as CLDN2, are expressed in an organ-specific manner and regulate the tissue-specific physiologic properties of tight junctions (Sakaguchi et al., 2002).[supplied by OMIM]^[2]

Function

Claudin-2 is expressed in cation-leaky epithelia such as that of the kidney proximal tubule.^[3] Mice that are deficient in claudin-2 have reduced reabsorption of Na⁺ in the proximal tubule, consistent with a role in paracellular transport. Similar results have been obtained with cultured cells, as overexpression in claudin-2 lacking cells leads to increase of permeability for small cations.^[4] Furthermore, claudin-2 has been shown to form paracellular channels for water.^[5]

References

1. Morita K, Furuse M, Fujimoto K, Tsukita S (Mar 1999). "Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands". Proc Natl Acad Sci U S A 96 (2): 511–6. doi:10.1073/pnas.96.2.511. PMC 15167. PMID 9892664.
2. "Entrez Gene: CLDN2 claudin 2".
3. Muto, S.; Hata, M.; Taniguchi, J.; Tsuruoka, S.; Moriwaki, K.; Saitou, M.; Furuse, K.; Sasaki, H.; Fujimura, A.; Imai, M.; Kusano, E.; Tsukita, S.; Furuse, M. (2010). "Claudin-2-deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules". Proceedings of the National Academy of Sciences 107 (17): 8011–8016. doi:10.1073/pnas.0912901107. PMC 2867900. PMID 20385797.
4. Amasheh, S; Meiri, N; Gitter, A. H.; Schöneberg, T; Mankertz, J; Schulzke, J. D.; Fromm, M (2002). "Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells". Journal of Cell Science 115 (Pt 24): 4969–76. doi:10.1242/jcs.00165. PMID 12432083.
5. Rosenthal, R.; Milatz, S.; Krug, S. M.; Oelrich, B.; Schulzke, J. -D.; Amasheh, S.; Gunzel, D.; Fromm, M. (2010). "Claudin-2, a component of the tight junction, forms a paracellular water channel". Journal of Cell Science 123 (11): 1913–1921. doi:10.1242/jcs.060665. PMID 20460438.

Further reading

• Kniesel U, Wolburg H (2000). "Tight junctions of the blood–brain barrier". Cell. Mol. Neurobiol. 20 (1): 57–76. doi:10.1023/A:1006995910836. PMID 10690502.
• Heiskala M, Peterson PA, Yang Y (2001). "The roles of claudin superfamily proteins in paracellular transport". Traffic 2 (2): 93–8. doi:10.1034/j.1600-0854.2001.020203.x. PMID 11247307.
• Tsukita S, Furuse M, Itoh M (2001). "Multifunctional strands in tight junctions". Nat. Rev. Mol. Cell Biol. 2 (4): 285–93. doi:10.1038/35067088. PMID 11283726.
• Tsukita S, Furuse M (2003). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): 531–6. doi:10.1016/S0955-0674(02)00362-9. PMID 12231346.
• González-Mariscal L, Betanzos A, Nava P, Jaramillo BE (2003). "Tight junction proteins". Prog. Biophys. Mol. Biol. 81 (1): 1–44. doi:10.1016/S0079-6107(02)00037-8. PMID 12475568.
• Furuse M, Fujita K, Hiiragi T; et al. (1998). "Claudin-1 and -2: Novel Integral Membrane Proteins Localizing at Tight Junctions with No Sequence Similarity to Occludin". J. Cell Biol. 141 (7): 1539–50. doi:10.1083/jcb.141.7.1539. PMC 2132999. PMID 9647647.
• Itoh M, Furuse M, Morita K; et al. (2000). "Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins". J. Cell Biol. 147 (6): 1351–63. doi:10.1083/jcb.147.6.1351. PMC 2168087. PMID 10601346.
• Sakaguchi T, Gu X, Golden HM; et al. (2002). "Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha". J. Biol. Chem. 277 (24): 21361–70. doi:10.1074/jbc.M110261200. PMID 11934881.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Colegio OR, Van Itallie C, Rahner C, Anderson JM (2003). "Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture". Am. J. Physiol., Cell Physiol. 284 (6): C1346–54. doi:10.1152/ajpcell.00547.2002. PMID 12700140.
• Clark HF, Gurney AL, Abaya E; et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Mankertz J, Hillenbrand B, Tavalali S; et al. (2004). "Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity". Biochem. Biophys. Res. Commun. 314 (4): 1001–7. doi:10.1016/j.bbrc.2003.12.185. PMID 14751232.
• Yamauchi K, Rai T, Kobayashi K; et al. (2004). "Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins". Proc. Natl. Acad. Sci. U.S.A. 101 (13): 4690–4. doi:10.1073/pnas.0306924101. PMC 384808. PMID 15070779.
• Escaffit F, Boudreau F, Beaulieu JF (2005). "Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells". J. Cell. Physiol. 203 (1): 15–26. doi:10.1002/jcp.20189. PMID 15389642.
• Liu F, Koval M, Ranganathan S, Fanayan S, Hancock WS, Lundberg EK, Beavis RC, Lane L, Duek P, McQuade L, Kelleher NL, Baker MS (2015). "A systems proteomics view of the endogenous human claudin protein family". J Proteome Res. doi:10.1021/acs.jproteome.5b00769. PMID 26680015.