Tight junction protein 2 (TJP2) (ZO-2)

Tight junction protein 2 (TJP2), also known as Zonula occludens protein 2 (ZO-2), is a crucial scaffolding protein within the membrane-associated guanylate kinase (MAGUK) family (UniProt: Q9UDY2) [1]. It is primarily located at the cytoplasmic face of tight junctions in epithelial and endothelial cells, where it organizes transmembrane proteins like claudins and occludin to regulate paracellular transport (PMID: 21458445) [2]. The protein contains three PDZ domains, which serve as specialized binding modules for the C-terminal motifs of various signaling and structural partners (PMID: 30154016) [4]. Beyond its structural role, ZO-2 can shuttle to the nucleus to influence gene expression and cell cycle progression, acting as a potential tumor suppressor in several contexts (PMID: 21458445) [2]. Clinically, mutations in TJP2 are the primary cause of progressive familial intrahepatic cholestasis type 4 (PFIC4), a condition characterized by impaired bile flow and liver failure (PMID: 24508231) [3]. Although no drugs targeting ZO-2 PDZ domains are currently in clinical use, these domains are significant research targets for drug delivery strategies aimed at modulating the blood-brain barrier or treating epithelial-derived cancers (PMID: 30154016) [4].

Other names

Zonula occludens protein 2TJP2X104

Modulation of protein-protein interactions (PPI) mediated by PDZ domains