Alternative titles; symbols
HGNC Approved Gene Symbol: TJP3
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:3,708,384-3,750,813 (from NCBI)
TJP3 is a member of the family of membrane-associated guanylate kinase-like proteins (MAGUK) that associate with intracellular junctions (Itoh et al., 1999).
Using a peptide sequence derived from a 130-kD protein that coimmunoprecipitated with TJP1 (601009) in canine kidney cells, Haskins et al. (1998) isolated canine Tjp3, which they called ZO3. The deduced 898-amino acid protein has a predicted molecular mass of 98 kD, although it runs anomalously at 130 kD by SDS PAGE. Canine Tjp3 shares 47% amino acid identity with human TJP1 and TJP2 (607709). The Tjp3 protein contains 3 PDZ domains, an SH3 domain, and a guanylate kinase (GUK) domain with high similarity to TJP1 and TJP2, as well as a unique proline-rich region between PDZ2 and PDZ3. Immunogold electro microscopy localized TJP3 with TJP1 to tight junctions in canine kidney cells.
Itoh et al. (1999) cloned mouse Tjp3 cDNA by database analysis, followed by screening a mouse lung cDNA library. Immunohistochemical studies colocalized Tjp1, Tjp2 (607709), and Tjp3 to the tight junctions of intestinal epithelial cells in occludin (OCLN; 602876)-deficient mice.
Haskins et al. (1998) showed that recombinant Tjp3 binds in vitro translated Tjp1 and binds directly to the cytoplasmic tail of occludin but no binding was detected between Tjp3 and Tjp2.
Using in vitro assays and immunoprecipitation studies, Itoh et al. (1999) showed that the mouse Tjp1, Tjp2, and Tjp3 PDZ1 domains interacted with the C-terminal cytoplasmic domains of Cldn1 (603718) through Cldn8 (611231). The mouse Tjp3 PDZ2 domain interacted with Tjp1 but showed no evidence of interaction with Tjp2. Itoh et al. (1999) concluded that Tjp3 may be recruited to the claudin-positive tight junctions through interactions with Tjp1 or claudin family members.
Roh et al. (2002) determined that Tjp3 interacted with PATJ (INADL; 603199) and that both proteins colocalized to tight junctions in vivo. In vitro studies showed that the sixth and eighth PDZ domains of PATJ mediated interaction with the Tjp3 C-terminal domain and with Cldn1, respectively. Roh et al. (2002) suggested that the TJP3-PATJ interaction plays a role in recruiting PATJ and its associated proteins CRB1 (604210) and MPP5 (606958) to tight junctions.
Gross (2014) mapped the TJP3 gene to chromosome 19p13.3 based on an alignment of the TJP3 sequence (GenBank BC108906) with the genomic sequence (GRCh37).
Gross, M. B. Personal Communication. Baltimore, Md. 5/30/2014.
Haskins, J., Gu, L., Wittchen, E. S., Hibbard, J., Stevenson, B. R. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J. Cell Biol. 141: 199-208, 1998. [PubMed: 9531559] [Full Text: https://doi.org/10.1083/jcb.141.1.199]
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. 147: 1351-1363, 1999. [PubMed: 10601346] [Full Text: https://doi.org/10.1083/jcb.147.6.1351]
Roh, M. H., Liu, C.-J., Laurinec, S., Margolis, B. The carboxyl terminus of zona occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions. J. Biol. Chem. 277: 27501-27509, 2002. [PubMed: 12021270] [Full Text: https://doi.org/10.1074/jbc.M201177200]