PROSITE documentation PDOC51145

ZU5 domain profile

The ZU5 domain is a domain of ~150 residues present in zona occludens 1 (ZO-1) protein, in unc5-like netrin receptors and in ankyrins. The ZU5 domain is named after the mouse tight junction protein ZO-1 and the C. elegans uncoordinated protein 5 (unc-5) and related Unc5-like netrin receptors. ZU5 domains are found in eukaryotic proteins that in most cases contain a C-terminal death domain (see <PDOC50017>). Other domains which can be found N-terminal to a ZU5 domain are ankyrin repeats (see <PDOC50088>); Ig-like (see <PDOC50835>) and TSP1 repeats (see <PDOC50092>); PDZ (see <PDOC50106>), SH3 (see <PDOC50002>) and guanylate kinase (see <PDOC00670>); or leucine-rich repeats (LRR) [1,2,3,4]. The ZU5 domain is a versatile protein-protein interaction module with more than one interaction surface that acts in different modes to interact with a variety of partners [6].

The ZU5 domain is formed by a compact β-sheet-rich core with a variable number of surface loops and helices (see <PDB:3UD1>). The β-strand-rich core is made of two antiparallel sheets interacting with each other in parallel to form a β-sandwich [6,7].

Some proteins known to contain a ZU5 domain:

• Mammalian zona occludens 1 (ZO-1) or tight junction ZO1 protein, implicated in junction formation. ZO-1 belongs to the membrane-associated guanylate kinase (MAGUK) proteins (see <PDOC00670>).
• Caenorhabditis elegans unc-5, a receptor for netrin (unc-6) required for axon repulsion.
• Vertebrate Unc5 homologues (UNC5H1-4), which are axon guidance receptors that mediate netrin-1-dependent chemorepulsion, and are receptors that mediate netrin-1-independent apoptosis.
• Mammalian ankyrins 1-3, which attach the cytoskeleton to the plasma membrane and organize diverse membrane-spanning proteins, such as ion channels and transporters.
• Caenorhabditis elegans unc-44, an ankyrin-like protein involved in axon guidance.
• Mammalian PIDD (p53-induced protein with a death domain) or LRDD (leucine rich repeat and death domain containing protein), a regulator of apoptosis in response to genotoxic stimuli [4]. PIDD contains two ZU5 domains.
• Vertebrate SH3 domain-binding protein 4 (Sh3bp4), may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes.
• Mammalian metastasis-associated in colon cancer protein 1 (MACC1), acts as a transcription activator for MET and as a key regulator of HGF-MET signaling.
• Vertebrate Death domain-containing protein 1 (DTHD1), contains two ZU5 domains.

The profile we developed covers the entire ZU5 domain.