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 .
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
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
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 . 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
Vertebrate Death domain-containing protein 1 (DTHD1), contains two ZU5
The profile we developed covers the entire ZU5 domain.
The ZU5 domain is also known as ZU-5 domain.
February 2017 / Profile and text revised.
PROSITE method (with tools and information) covered by this documentation:
Leonardo E.D., Hinck L., Masu M., Keino-Masu K., Ackerman S.L., Tessier-Lavigne M.
Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors.
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