TJP2 gene exists as a single copy in the human genome; it contains 25 exons and is predicted to span over approximately more than 90 Kb of the genomic DNA.

Five isoforms of TJP2 have been identified:
The A1 isoform (CDS: 3570 nt); lacks exons C and B.
The A2 isoform (CDS: 3129 nt); lacks exons C, B, 20 and 21.
The A3 isoform (CDS: 2979 nt); lacks exons C, B, 20, 21, 22 and 23 and exhibits a longer exon 19 (979 vs 213 bp, with a stop codon at bp 313).
The C1 isoform (CDS: 3501 nt); lacks exon A.
The C2 isoform (CDS: 3057 nt); lacks exons A, 20 and 21.
Northern blot analysis done with different probes for exons A and C reveals two TJP2 transcripts of the same size, approximately 4.5 Kb, that respectively correspond to TJP2A and TJP2C.

Not known.

The full length TJP2 protein consists of 1190 amino acids corresponding to a theoretical molecular weight of 133.958 kDa. This size is 16% smaller than the apparent molecular mass of 160 kDa determined by SDS/PAGE. The high proline content (7.1%) may be responsible for this anomalous electrophoretic migration. The protein contains three PDZ, one SH3 and one GuK domain at its NH2 dlg-like terminal region, followed by a short COOH terminal non dlg-like region that contains an acidic and a proline rich domain. The protein belongs to the MAGUK protein family. At the carboxyl terminal end of TJP2 the type I PDZ binding motif TEL is found. TJP2 is predicted to contain 1 nuclear localization signal (NLS; 106-122 aa) and no exportation signals (NES) following the consensus L/M/IX1-4L/V/IX2-3L/V/IX1-2L/I.
Two isoforms named A and C arise from the activation of different promoters. In the A form the initiation codon located within a unique 5 end 189 bp sequence gives rise to a distinctive 23 aa segment, whereas in the C form the 5 end exhibits a 377 bp sequence that is not translated. In isoforms C translation starts from a codon that corresponds to the second ATG in isoforms A. Isoform A2 is generated by alternative splicing of isoform A1. It lacks amino acids 961-1108.
Isoform A3 is generated by alternative splicing of isoform A1. It lacks amino acids 994-1190 and the sequence from amino acids 961 to 993 differs from isoform A1.
Isoform C2 is generated by alternative splicing of isoform C1. It lacks amino acids 961-1108.

Normal tissue: At the mRNA level the A isoforms are abundant in the heart and brain whereas the C isoforms are expressed at a high level in kidney, pancreas, heart and placenta. In brain and skeletal muscle only the A isoform is detectable, but there is no tissue where TJP2C is solely present. TJP2 protein is strongly expressed in epithelial and endothelial cells. During mouse embryogenesis at the 16 cell stage, TJP2 assembles at the apico-lateral contact site of blastomeres for the first time. The half-life of TJP2 protein varies according to the degree of confluence of the culture, thus in canine kidney MDCK cells half lives correspond to 8.7 and 19.1 hrs in sparse and confluent cultures respectively.

Present at the cytoplasmic side of tight junctions in epithelial and endothelial cells. In proliferating cultures and in cells under environmental stress TJP2 is also present at the nucleus. TJP2 enters the nucleus at the late G1 phase of the cell cycle and departs during mitosis. At the nucleus TJP2 exhibits a speckled distribution and co-localizes with splicing factor SC-35 and the nuclear ribonucleoprotein scaffold attachment factor SAF-B. In fibroblasts TJP2 gives a punctate pattern at the cell borders, and in cardiac muscle cells it is detected at the intercalated discs.

TJP2 is crucial during development as silencing inhibits blastocele formation in mouse embryos and knock out mice die shortly after implantation due to an arrest in early gastrulation.
TJP2 silencing with siRNA delays in epithelial monolayers the arrival of tight junction proteins to the cell membrane, triggers the novo formation of leaky tight junctions and alters cell polarity, thus suggesting that TJP2 is critical for the correct assembly and function of tight junctions. TJP2 and TJP1 are redundant in their role as promoters of claudins polymerization into tight junction strands.
TJP2 inhibits transcription of human cyclin D1 (CD1) gene, decreases CD1 protein levels due to an increased degradation of the protein at the proteosome, blocks cell cycle progression from G1 phase to S and in consequence inhibits cell proliferation. These observations favor the image of TJP2 as a tumor suppressor protein.
Besides the above mentioned, the nuclear function of TJP2 remains elusive. It localizes in speckles with SC-35 and associates to lamin B1, to transcription factors Jun, Fos, C/EBP and Myc, to SAF-B, a chromatin component involved in the assembly of transcriptosome complexes, and enhances the nuclear localization of ARVCF, an Armadillo-repeat protein that associates with classical cadherins in adherens junctions.

TJP2 shares the following homology and identity (in parenthesis) with TJP1: 68% (54%); TJP3: 63% (45%); PSD-95: 40% (25%) and Dlg: 40% (23%).

Mutation 143T-->C, predicted to cause a valine to alanine substitution (V48A) in TJP2 produces the loss of the alpha-helical structure of PDZ1 domain of TJP2.

Not known.

Microarray analysis indicates that in 70% of primary pancreatic cancers TJP2 is aberrantly methylated.