PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of multi-PDZ-domain protein 1 (MUPP1). MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organisation of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ6 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by ��-strands. This domain is a canonical PDZ domain containing six ��-strands A-F and two ��-helices (��-helix 1 and 2), arranged in the order: ��-strands A, B, C, ��-helix 1, ��-strands D, E, ��-helix 2 and ��-strand F [, , , , , , , , ].
This entry represents the first PDZ domain (PDZ1) found in multi-PDZ domain protein (MPDZ, also known as MUPP1) and protein associated to tight junctions (PATJ, also known as InaD-like protein). Both MPDZ and PATJ are scaffolding proteins that facilitate the localisation of various proteins to the cell membrane and are required for the correct formation of tight junctions [, ]. These host proteins typically share a similar domain architecture, consisting of an N-terminal L27 domain followed by multiple PDZ domains. In MPDZ, this specific first PDZ domain has been shown to interact with the membrane-spanning proteoglycan NG2 [, ].
Multiple PDZ domain protein (MUPP1) and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organisation of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules) [, , , , , , ]. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by ��-strands. This entry represents the ninth PDZ domain (PDZ9) which is a canonical PDZ domain containing six ��-strands A-F and two ��-helices (��-helix 1 and 2), arranged in the order: ��-strands A, B, C, ��-helix 1, ��-strands D, E, ��-helix 2 and ��-strand F.
This entry represents the 13th domain in Multiple PDZ domain protein (MUPP1).Multiple PDZ domain protein (MUPP1) and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organisation of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules) [, , , , , , ]. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by ��-strands. This entry represents the ninth PDZ domain (PDZ9) which is a canonical PDZ domain containing six ��-strands A-F and two ��-helices (��-helix 1 and 2), arranged in the order: ��-strands A, B, C, ��-helix 1, ��-strands D, E, ��-helix 2 and ��-strand F.
Rho guanine nucleotide exchange factor 18 (ARHGEF18, also known as p114RhoGEF) acts as a guanine nucleotide exchange factor (GEF) for RhoA and RAC1 GTPases, but not for CDC42. Its activation induces the formation of actin stress fibres and the production of reactive oxygen species (ROS) [, ]. It is activated by the G protein ��-�� subunits of heterotrimeric G proteins []. ARHGEF18 is required for the regulation of the circumferential actomyosin belt in epithelial cells, interacting with proteins such as EPB41L4B and PATJ []. It also interacts with SEPT9, which may inhibit its GEF activity []. In humans, defects in ARHGEF18 are the cause of retinitis pigmentosa 78 (RP78), an autosomal recessive retinal dystrophy []. The protein typically contains a Dbl homology (DH) domain and a Pleckstrin homology (PH) domain.
