{PDOC51145}
{PS51145; ZU5}
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* ZU5 domain profile *
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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) [1-4]. 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 beta-sheet-rich core with a variable
number of  surface  loops  and  helices (see <PDB:3UD1>). The beta-strand-rich
core is  made  of  two  antiparallel  sheets  interacting  with  each other in
parallel to form a beta-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: The ZU5 domain is also known as ZU-5 domain.

-Last update: February 2017 / Profile and text revised.

[ 1] 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."
     Nature 386:833-838(1997).
     PubMed=9126742
[ 2] Ackerman S.L., Kozak L.P., Przyborski S.A., Rund L.A., Boyer B.B.,
     Knowles B.B.
     "The mouse rostral cerebellar malformation gene encodes an UNC-5-like
     protein."
     Nature 386:838-842(1997).
     PubMed=9126743
[ 3] Zhang J., Xu L.G., Han K.J., Shu H.B.
     "Identification of a ZU5 and death domain-containing inhibitor of
     NF-kappaB."
     J. Biol. Chem. 279:17819-17825(2004).
     PubMed=14769797; DOI=10.1074/jbc.M310737200
[ 4] Tinel A., Tschopp J.
     "The PIDDosome, a protein complex implicated in activation of
     caspase-2 in response to genotoxic stress."
     Science 304:843-846(2004).
     PubMed=15073321; DOI=10.1126/science.1095432
[ 5] Mohler P.J., Yoon W., Bennett V.
     "Ankyrin-B targets beta2-spectrin to an intracellular compartment in
     neonatal cardiomyocytes."
     J. Biol. Chem. 279:40185-40193(2004).
     PubMed=15262991; DOI=10.1074/jbc.M406018200
[ 6] Yasunaga M., Ipsaro J.J., Mondragon A.
     "Structurally similar but functionally diverse ZU5 domains in human
     erythrocyte ankyrin."
     J. Mol. Biol. 417:336-350(2012).
     PubMed=22310050; DOI=10.1016/j.jmb.2012.01.041
[ 7] Wang C., Yu C., Ye F., Wei Z., Zhang M.
     "Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals
     interaction surfaces  necessary for ankyrin function."
     Proc. Natl. Acad. Sci. U.S.A. 109:4822-4827(2012).
     PubMed=22411828; DOI=10.1073/pnas.1200613109

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