ZO 2


Gene Symbol: ZO 2
Description: tight junction protein 2
Alias: ZO-2, tight junction protein ZO-2, Tight junction protein ZO-2 (Zonula occludens 2 protein) (Zona occludens 2 protein) (Tight junction protein 2), zona occludens protein 2, zonula occludens protein 2
Species: mouse
Products:     ZO 2

Top Publications

  1. Yates L, Schnatwinkel C, Murdoch J, Bogani D, Formstone C, Townsend S, et al. The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis. Hum Mol Genet. 2010;19:2251-67 pubmed publisher
  2. Xu J, Kausalya P, Phua D, Ali S, Hossain Z, Hunziker W. Early embryonic lethality of mice lacking ZO-2, but Not ZO-3, reveals critical and nonredundant roles for individual zonula occludens proteins in mammalian development. Mol Cell Biol. 2008;28:1669-78 pubmed publisher
    ..Thus, ZO-2 is required for mouse embryonic development, but ZO-3 is dispensable. This is to our knowledge the first report showing that an individual ZO protein plays a nonredundant and critical role in mammalian development. ..
  3. Umeda K, Ikenouchi J, Katahira Tayama S, Furuse K, Sasaki H, Nakayama M, et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell. 2006;126:741-54 pubmed
    ..When NZO-1 was forcibly recruited to lateral membranes and dimerized, claudins were dramatically polymerized. These findings indicate that ZO-1 and ZO-2 can independently determine whether and where claudins are polymerized. ..
  4. Umeda K, Matsui T, Nakayama M, Furuse K, Sasaki H, Furuse M, et al. Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. J Biol Chem. 2004;279:44785-94 pubmed
    ..Finally, we discussed advantageous aspects of the gene knock-out system with cultured epithelial cells in epithelial cell biology. ..
  5. Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol. 1999;147:1351-63 pubmed
    ..In good agreement, PDZ1 and PDZ2 domains of ZO-1/ZO-2/ZO-3 were also recruited to claudin-based TJs, when introduced into cultured epithelial cells. The possible molecular architecture of TJ plaque structures is discussed. ..
  6. Wang H, Ding T, Brown N, Yamamoto Y, Prince L, Reese J, et al. Zonula occludens-1 (ZO-1) is involved in morula to blastocyst transformation in the mouse. Dev Biol. 2008;318:112-25 pubmed publisher
    ..These results provide the first evidence that ZO-1 is involved in blastocyst formation from the morula by regulating accumulation of fluid and differentiation of nonpolar blastomeres to polar trophoblast cells...
  7. Katsuno T, Umeda K, Matsui T, Hata M, Tamura A, Itoh M, et al. Deficiency of zonula occludens-1 causes embryonic lethal phenotype associated with defected yolk sac angiogenesis and apoptosis of embryonic cells. Mol Biol Cell. 2008;19:2465-75 pubmed publisher
    ..In conclusion, ZO-1 may be functionally important for cell remodeling and tissue organization in both the embryonic and extraembryonic regions, thus playing an essential role in embryonic development...
  8. Itoh M, Morita K, Tsukita S. Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin. J Biol Chem. 1999;274:5981-6 pubmed
    ..These findings indicated that ZO-2 forms a complex with ZO-1/occludin or ZO-1/alpha catenin to establish TJ or AJ domains, respectively. ..
  9. Sheth B, Nowak R, Anderson R, Kwong W, Papenbrock T, Fleming T. Tight junction protein ZO-2 expression and relative function of ZO-1 and ZO-2 during mouse blastocyst formation. Exp Cell Res. 2008;314:3356-68 pubmed publisher
    ..In contrast, ZO-1 knockdown, or combined ZO-1 and ZO-2 knockdown, generated a more severe inhibition of blastocoel formation indicating distinct roles for ZO proteins in blastocyst morphogenesis. ..

More Information


  1. Yamazaki Y, Umeda K, Wada M, Nada S, Okada M, Tsukita S, et al. ZO-1- and ZO-2-dependent integration of myosin-2 to epithelial zonula adherens. Mol Biol Cell. 2008;19:3801-11 pubmed publisher
    ..Fluorescence resonance energy transfer analyses revealed that spatiotemporal Rho-activation occurred in a ZO-1/2-dependent way to establish ZA from primordial forms in epithelial cells. ..
  2. Ciolofan C, Li X, Olson C, Kamasawa N, Gebhardt B, Yasumura T, et al. Association of connexin36 and zonula occludens-1 with zonula occludens-2 and the transcription factor zonula occludens-1-associated nucleic acid-binding protein at neuronal gap junctions in rodent retina. Neuroscience. 2006;140:433-51 pubmed
  3. Nakatsu D, Kano F, Taguchi Y, Sugawara T, Nishizono T, Nishikawa K, et al. JNK1/2-dependent phosphorylation of angulin-1/LSR is required for the exclusive localization of angulin-1/LSR and tricellulin at tricellular contacts in EpH4 epithelial sheet. Genes Cells. 2014;19:565-81 pubmed publisher
  4. Kurakin A, Wu S, Bredesen D. Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening. J Biol Chem. 2003;278:34102-9 pubmed
    ..A direct interaction of synaptojanin 1 and PAK2 with CIN85 SH3 domains was confirmed by Far Western blotting. ..
  5. Stamatovic S, Keep R, Kunkel S, Andjelkovic A. Potential role of MCP-1 in endothelial cell tight junction 'opening': signaling via Rho and Rho kinase. J Cell Sci. 2003;116:4615-28 pubmed
    ..These data are the first to strongly suggest that MCP-1, via CCR2 present on brain endothelial cells, contributes to increased brain endothelial permeability. ..
  6. Unda F, Perez Nanclares G, Le Morvan V, Hernandez C, Vilaxa A, de la Fuente M, et al. Dynamic assembly of tight junction-associated proteins ZO-1, ZO-2, ZO-3 and occludin during mouse tooth development. Histol Histopathol. 2003;18:27-38 pubmed publisher
    ..The occurrence and relation during tooth development of tight junction proteins ZO-1, ZO-2 and occludin, but not ZO-3, suggests a combinatory assembly in tooth morphogenesis and cell differentiation. ..
  7. Kopecki Z, Yang G, Arkell R, Jackson J, Melville E, Iwata H, et al. Flightless I over-expression impairs skin barrier development, function and recovery following skin blistering. J Pathol. 2014;232:541-52 pubmed publisher
    ..These results therefore demonstrate an important role for Flii in the development and regulation of the epidermal barrier, which may contribute to the impaired healing and skin fragility of EB patients. ..
  8. Chen H, Chen C, Chen W, Wang S, Chen Y. A promising protein responsible for overactive bladder in ovariectomized mice. Taiwan J Obstet Gynecol. 2017;56:196-203 pubmed publisher
    ..This exploratory study estimated changes in protein expression and composition in the bladder of OVX mice. These changes may be associated with the molecular mechanisms of OAB. ..
  9. Yates L, Schnatwinkel C, Hazelwood L, Chessum L, Paudyal A, Hilton H, et al. Scribble is required for normal epithelial cell-cell contacts and lumen morphogenesis in the mammalian lung. Dev Biol. 2013;373:267-80 pubmed publisher
    ..Thus we reveal novel and important roles for Scrib in lung development operating via the PCP pathway, and in regulating junctional complexes and cell cohesion. ..
  10. Yogo K, Mizutamari M, Mishima K, Takenouchi H, Ishida Kitagawa N, Sasaki T, et al. Src homology 2 (SH2)-containing 5'-inositol phosphatase localizes to podosomes, and the SH2 domain is implicated in the attenuation of bone resorption in osteoclasts. Endocrinology. 2006;147:3307-17 pubmed
    ..These results demonstrate that c-Src enhances the translocation of SHIP to podosomes and regulates its function there through the SH2 domain, leading to an attenuation of bone resorption. ..
  11. Wang H, Luan L, Ding T, Brown N, Reese J, Paria B. Dynamics of zonula occludens-2 expression during preimplantation embryonic development in the hamster. Theriogenology. 2011;76:678-86 pubmed publisher
  12. Hubmacher D, Wang L, Mecham R, Reinhardt D, Apte S. Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia--a novel mouse model providing insights into geleophysic dysplasia. Dis Model Mech. 2015;8:487-99 pubmed publisher
    ..Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2(-/-) mice cannot be reversed by TGFβ neutralization, and thus might be mediated by other mechanisms. ..
  13. D Atri F, Nadalutti F, Citi S. Evidence for a functional interaction between cingulin and ZO-1 in cultured cells. J Biol Chem. 2002;277:27757-64 pubmed
  14. Paudyal A, Damrau C, Patterson V, Ermakov A, Formstone C, Lalanne Z, et al. The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear. BMC Dev Biol. 2010;10:87 pubmed publisher
    ..This mutant provides a useful tool to allow future studies aimed at understanding the molecular function of Ptk7. ..
  15. Tsukita S, Katsuno T, Yamazaki Y, Umeda K, Tamura A, Tsukita S. Roles of ZO-1 and ZO-2 in establishment of the belt-like adherens and tight junctions with paracellular permselective barrier function. Ann N Y Acad Sci. 2009;1165:44-52 pubmed publisher
  16. Oka T, Remue E, Meerschaert K, Vanloo B, Boucherie C, Gfeller D, et al. Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling. Biochem J. 2010;432:461-72 pubmed publisher
    ..The present paper is the first report on a PDZ-based nuclear translocation mechanism. Moreover, since the Hippo pathway acts as a tumour suppressor pathway, the YAP2-ZO-2 complex could represent a target for cancer therapy. ..
  17. Kaźmierczak M, Harris S, Kazmierczak P, Shah P, Starovoytov V, Ohlemiller K, et al. Progressive Hearing Loss in Mice Carrying a Mutation in Usp53. J Neurosci. 2015;35:15582-98 pubmed publisher
    ..We demonstrate that USP53 is a catalytically inactive deubiquitinating enzyme and a novel component of tight junctions that is necessary for sensory hair cell survival and inner ear homeostasis. ..
  18. Xu J, Anuar F, Ali S, Ng M, Phua D, Hunziker W. Zona occludens-2 is critical for blood-testis barrier integrity and male fertility. Mol Biol Cell. 2009;20:4268-77 pubmed publisher
    ..The critical role of ZO-2 for male fertility and blood-testis barrier integrity thus provides a first example for a nonredundant role of an individual ZO protein in adult mice. ..
  19. Gladden A, Hebert A, Schneeberger E, McClatchey A. The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex. Dev Cell. 2010;19:727-39 pubmed publisher
    ..Our studies reveal that Merlin can associate directly with ?-catenin and link it to Par3, thereby providing an essential link between the AJ and the Par3 polarity complex during junctional maturation. ..
  20. Kanazawa T, Ichii O, Otsuka S, Namiki Y, Hashimoto Y, Kon Y. Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial transition in developing kidneys of C57BL/6 mice. J Vet Med Sci. 2011;73:601-7 pubmed
    ..These results, and those of previous findings, indicate that Hnf4? protein is associated with the initiation of MET in early nephrogenesis. ..
  21. Linares G, Brommage R, Powell D, Xing W, Chen S, Alshbool F, et al. Claudin 18 is a novel negative regulator of bone resorption and osteoclast differentiation. J Bone Miner Res. 2012;27:1553-65 pubmed publisher
    ..In conclusion, we demonstrate that Cldn-18 is a novel negative regulator of bone resorption and osteoclast differentiation. ..
  22. Saito K, Enya K, Oneyama C, Hikita T, Okada M. Proteomic identification of ZO-1/2 as a novel scaffold for Src/Csk regulatory circuit. Biochem Biophys Res Commun. 2008;366:969-75 pubmed
    ..These results suggest novel roles for ZO proteins as Src/Csk scaffolds potentially involved in the regulation of Src transformation. ..
  23. Grego Bessa J, Hildebrand J, Anderson K. Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains. Development. 2015;142:1305-14 pubmed publisher
    ..The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization. ..
  24. Monteiro A, Sumagin R, Rankin C, Leoni G, Mina M, Reiter D, et al. JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Mol Biol Cell. 2013;24:2849-60 pubmed publisher
    ..These results suggest that JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton. ..
  25. Walsh T, Pierce S, Lenz D, Brownstein Z, Dagan Rosenfeld O, Shahin H, et al. Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51. Am J Hum Genet. 2010;87:101-9 pubmed publisher
  26. Morita K, Furuse M, Yoshida Y, Itoh M, Sasaki H, Tsukita S, et al. Molecular architecture of tight junctions of periderm differs from that of the maculae occludentes of epidermis. J Invest Dermatol. 2002;118:1073-9 pubmed
  27. Mahaffey J, Grego Bessa J, Liem K, Anderson K. Cofilin and Vangl2 cooperate in the initiation of planar cell polarity in the mouse embryo. Development. 2013;140:1262-71 pubmed publisher
    ..We propose that Vangl2 and cofilin cooperate to target Rab11(+) vesicles containing PCP proteins to the apical membrane during the initiation of planar cell polarity. ..
  28. Lee J, Silva Gagliardi N, Tepass U, McGlade C, Anderson K. The FERM protein Epb4.1l5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo. Development. 2007;134:2007-16 pubmed
    ..We propose that mouse Lulu (Epb4.1l5) helps anchor the actin-myosin contractile machinery to the membrane to allow the dynamic rearrangements of epithelia that mediate embryonic morphogenesis. ..
  29. Traweger A, Fuchs R, Krizbai I, Weiger T, Bauer H, Bauer H. The tight junction protein ZO-2 localizes to the nucleus and interacts with the heterogeneous nuclear ribonucleoprotein scaffold attachment factor-B. J Biol Chem. 2003;278:2692-700 pubmed
    ..Interestingly, no association of SAF-B with ZO-1 was found, which supports the notion that junctional MAGUKs serve nonredundant functions. ..
  30. Bautista García P, Reyes J, Martin D, Namorado M, Chavez Munguia B, Soria Castro E, et al. Zona occludens-2 protects against podocyte dysfunction induced by ADR in mice. Am J Physiol Renal Physiol. 2013;304:F77-87 pubmed publisher
    ..These results suggest that ZO-2 could be a new target for the regulation of hyperactive Wnt/?-catenin signaling in proteinuric kidney diseases. ..
  31. Harrelson Z, Kaestner K, Evans S. Foxa2 mediates critical functions of prechordal plate in patterning and morphogenesis and is cell autonomously required for early ventral endoderm morphogenesis. Biol Open. 2012;1:173-81 pubmed publisher
    ..Loss of Foxa2 in ventral endoderm resulted in reduced expression of Sox17, Gata4, and ZO proteins, accounting at least in part for observed lack of foregut fusion, cardia bifida, and increased apoptosis of ventral endoderm. ..
  32. Wu R, Zeng Y, Pan I, Wu M. Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis. Mol Endocrinol. 2015;29:1334-46 pubmed publisher
    ..Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development. ..
  33. Phua D, Xu J, Ali S, Boey A, Gounko N, Hunziker W. ZO-1 and ZO-2 are required for extra-embryonic endoderm integrity, primitive ectoderm survival and normal cavitation in embryoid bodies derived from mouse embryonic stem cells. PLoS ONE. 2014;9:e99532 pubmed publisher
    ..The null embryoid bodies thus give an insight into how the two ZO proteins influence early mouse embryogenesis and possible mechanisms underlying the embryonic lethal phenotype. ..
  34. Zimmerman S, Hueschen C, Malide D, Milgram S, Playford M. Sorting nexin 27 (SNX27) associates with zonula occludens-2 (ZO-2) and modulates the epithelial tight junction. Biochem J. 2013;455:95-106 pubmed publisher
    ..Our results also indicate a role for SNX27-ZO-2 interactions in tight junction maintenance and function. ..
  35. Kokai E, Voss F, Fleischer F, Kempe S, Marinkovic D, Wolburg H, et al. Myc regulates embryonic vascular permeability and remodeling. Circ Res. 2009;104:1151-9 pubmed publisher
    ..Thus, the net outcome of an excess of vascular endothelial growth factor-A and angiopoietin-2 in the face of an elevated cellular turnover appears to be a defect in vascular integrity. ..