{PDOC00907}
{PS01179; PID}
{BEGIN}
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* Phosphotyrosine interaction domain (PID) 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
(see  <PDOC51064>),  phosphotyrosine-dependent  Shc-like, and phosphotyrosine-
independent   Dab-like   PTBs.   The   last   two  PTBs  have  been  named  as
phosphotyrosine  interaction  domain  (PID  or  PI  domain). PID domain has an
average length of about 160 amino acids [1].

The  Shc-like  PID specifically binds to the Asn-Pro-Xaa-Tyr(P) motif found in
many  tyrosine-phosphorylated  proteins  including growth factor receptors. On
the  other  hand  the Dab-like PID domain binds to non-phosphorylated tyrosine
residue  or even a phenylalanine at the same position [2]. Most of the ligands
for  Shc-like  PID  domains  are  RTK  or  cytokine,  whereas  phosphotyrosine
independent  Dab-like  PID  domains  seems to mediate other types of signaling
pathways,  like  endocytosis/processing  or exocytosis. This domain binds both
peptides  and  headgroups  of  phosphatidylinositides,  utilizing two distinct
binding  motifs  to mediate spatial organization and localization within cells
[1,2,3,4].

The 3D structure of PID domain has been solved (see <PDB:1NTV>) [5]. 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
C-terminal  alpha  helix)  and  a  highly  basic  phospholipid binding "crown"
(largely composed of residues from loop regions near the N terminus). Both Shc
and  Dab1  have two additional alpha helices, one of which is located at the N
terminus and the other between beta 1 and beta 2 strands.

PID has also been found in the proteins listed below.

 - Mammalian  Shc transforming protein which contains one N-terminal PID and a
   C-terminal SH2 domain  (see <PDOC50001>).
 - Human Shc-related protein Sck that shares the same modular architecture.
 - Mammalian protein X11 which is expressed prominently in the nervous system.
   It contains 2 disc homologous regions (DHR) downstream of the PID.
 - Rat    FE65,  a  transcription-factor activator expressed preferentially in
   liver. The  presence  of  a  WW  domain (see <PDOC50020>) as well as 2 PIDs
   indicate a possible role in signal transduction.
 - Drosophila nuclear Numb protein, which is required in determination of cell
   fate during sensory organ formation in Drosophila embryos. It has one PID.
 - Drosophila  protein  disabled  (gene  dab),  which is involved in embryonic
   neural development.  This  cytoplasmic,  tyrosine phosphorylated protein is
   found in CNS axons and body wall muscles. It contains one N-terminal PID.
 - Mouse  mitogen-responsive  phosphoprotein P96 and the human homolog, DOC-2.
   They possess one N-terminal PID.
 - Mammalian regulator of G-protein signalling 12 (RGS12).
 - Caenorhabditis  elegans  hypothetical  protein  F56D2.1  which  contains an
   N-terminal insulinase-type domain (see <PDOC00130>) followed by a PID.

The profile we developed covers the entire PID domain.

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

-Expert(s) to contact by email:
           Bork P.; bork@embl-heidelberg.de
           Margolis B.; margolisb@mcphm0.med.nyu.edu

-Last update: January 2005 / Text revised.

[ 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] Bork P., Margolis B.
     "A phosphotyrosine interaction domain."
     Cell 80:693-694(1995).
     PubMed=7534213
[ 3] Kavanaugh W.M., Williams L.T.
     "An alternative to SH2 domains for binding tyrosine-phosphorylated
     proteins."
     Science 266:1862-1865(1994).
     PubMed=7527937
[ 4] Blaikie P., Immanuel D., Wu J., Li N., Yajnik V., Margolis B.
     "A region in Shc distinct from the SH2 domain can bind
     tyrosine-phosphorylated growth factor receptors."
     J. Biol. Chem. 269:32031-32034(1994).
     PubMed=7798194
[ 5] Stolt P.C., Jeon H., Song H.K., Herz J., Eck M.J., Blacklow S.C.
     "Origins of peptide selectivity and phosphoinositide binding revealed
     by structures of disabled-1 PTB domain complexes."
     Structure 11:569-579(2003).
     PubMed=12737822

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