This page provides information on PI (phosphotyrosine interaction)
  domains.  Please forward suggestions/comments/correction to
  Peer Bork  or Ben Margolis

        Peer.Bork@EMBL.ORG or BEN.MARGOLIS@mcccm.med.nyu.edu

• alignment
• 1D cartoon showing the location of PI domains in the respective proteins

Documentation - PROSITE description

Beside SH2,the phosphotyrosine interaction domain (PI domain or PID)[3] is the
second phosphotyrosine-binding  domain  found  in the transforming protein Shc
[1,2].  Shc couples activated growth factor receptors to a signalling  pathway 
that regulates the proliferation of mammalian cells  and  it might participate
in the transforming activity of oncogenic tyrosine kinases. 
The PI domain specifically binds to the Asn-Pro-Xaa-Tyr(p) motif found in many
tyrosine-phosphorylated proteins  including  growth  factor receptors. PID has
also been  found  in  the  Shc  related  protein Sck [1] and several otherwise
unrelated regulatory proteins [3] which are listed below.

 - Mammalian  Shc  (46  kD  and 52 kD isoforms) contains one N-terminal PID, a
   collagen-like domain and a C-terminal SH2 domain.
 - Human Shc related protein Sck contains one PI domain and a SH2 domain. 
 - Mammalian X11 is expressed prominently in the nervous system. It contains 2
   disc homologous regions (DHR) of about 100 AA downstream of the PID.
 - Drosophila  nuclear  Numb protein is required in determination of cell fate
   during sensory organ formation in drosophila embryos. It has one PID.
 - Caenorhabditis   hypothetical   protein   F56D2.1  contains  an  N-terminal
   metalloproteinase domain followed by one PID.
 - Rat FE65. The WW domain as well as the 2 PIDs found in the sequence of FE65
   indicate that this protein is probably involved in signal transduction.
 - Drosophila  protein  disabled  is  a  cytoplasmic,  tyrosine phosphorylated
   protein found  in  CNS  axons  and  body  wall  muscles.  It is involved in
   embryonic neural development. It contains one N-terminal PI domain.
 - Mouse mitogen responsive phosphoprotein isoforms P96, P93 and P67 which are
   produced by  alternative splicing, contain one N-terminal PID. This is also
   true for the differentially expressed human ortholog Doc-2.
 - Human EST05045 protein fragment has one PID.

PID has an average length of about 160 amino acids. It is a probably globular
domain with an antiparallel beta sheet. The PID is predicted to be involved in
protein/protein interactions. Therefore it is speculated that proteins which 
contain PID are involved in the tyrosine kinase signaling pathway [2].

-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.
-Last update: June 1995 / First entry.

[ 1] Kavanaugh W.M., Williams L.T.
     Science 266:1862-1865(1994)
[ 2] Blaiki, P. et al.,
     J.Biol.Chem. 269, 32031-32034 (1994)
[ 3] Bork P., Margolis B. 
     Cell 80, in press

• creation date: March 1, 1995
• last sequence update:
• last modicication: March 25, 1995