{PDOC51064}
{PS51064; IRS_PTB}
{BEGIN}
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* IRS-type phosphotyrosine binding domain (PTB) profile *
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Proteins  encoding  phosphotyrosine binding (PTB) domains function as adaptors
or  scaffolds  to  organize  the  signaling complexes involved in wide-ranging
physiological   processes   including  neural  development,  immunity,  tissue
homeostasis  and  cell  growth. Due to structural differences, PTB domains are
divided  into  three groups represented by phosphotyrosine-dependent IRS-like,
phosphotyrosine-dependent  Shc-like  (see  <PDOC00907>),  and phosphotyrosine-
independent Dab-like PTBs (see <PDOC00907>).

IRS-type  PTB  domain has an average length of about 100 amino acids. It binds
to  the  insulin  receptor  through the Asn-Pro-Xaa-Tyr(P) motif found in many
tyrosine-phosphorylated proteins. This domain is found in IRS/Dok/SNT proteins
that  are the major adapters for RTK and cytokine signaling. This domain binds
both peptides and headgroups of phosphatidylinositides, utilizing two distinct
binding  motifs to mediate spatial organization and localization within cells.
The  IRS-type  PTB  domain is found alone or in association with the PH domain
(see <PDOC50003>) [1,2].

The  3D structure of IRS-type PTB domain has been solved (see <PDB:1P5T>) [3].
It shares a folding pattern commonly referred to as the PH-domain "superfold".
The  core  "superfold" consists of seven antiparallel beta strands forming two
orthogonal  beta  sheets. This beta sandwich is capped at the C terminus by an
alpha helix. It contains a peptide binding pocket (formed by the beta strand 5
and  the  C-terminal  alpha  helix)  and  a  highly basic phospholipid binding
"crown"  (largely  composed of residues from loop regions near the N terminus)
[3].

IRS-type PTB domain has also been found in the proteins listed below.

 - Mammalian insulin receptor substrate (IRS-1 and IRS-2) proteins.
 - Mammalian  docking  proteins (DOK1,  DOK2  and  DOK5)  which  interact with
   receptor tyrosine kinases.
 - Mammalian FGFR signalling adaptor (SNT-1 and SNT-2).

The profile we developed covers the entire IRS-type PTB domain.

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

-Note: Talin  proteins  may contain  an  IRS-type  PTB domain.  This family is
 however too divergent to be detected by this profile.

-Last update: January 2005 / First entry.

[ 1] Uhlik M.T., Temple B., Bencharit S., Kimple A.J., Siderovski D.P.,
     Johnson G.L.
     "Structural and evolutionary division of phosphotyrosine binding (PTB)
     domains."
     J. Mol. Biol. 345:1-20(2005).
     PubMed=15567406; DOI=10.1016/j.jmb.2004.10.038
[ 2] Eck M.J., Dhe-Paganon S., Trub T., Nolte R.T., Shoelson S.E.
     "Structure of the IRS-1 PTB domain bound to the juxtamembrane region
     of the insulin receptor."
     Cell 85:695-705(1996).
     PubMed=8646778
[ 3] Shi N., Ye S., Bartlam M., Yang M., Wu J., Liu Y., Sun F., Han X.,
     Peng X., Qiang B., Yuan J., Rao Z.
     "Structural basis for the specific recognition of RET by the Dok1
     phosphotyrosine binding domain."
     J. Biol. Chem. 279:4962-4969(2004).
     PubMed=14607833; DOI=10.1074/jbc.M311030200

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