{PDOC50001}
{PS50001; SH2}
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* Src homology 2 (SH2) domain profile *
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The Src  homology  2  (SH2) domain is a protein domain of about 100 amino-acid
residues first   identified   as  a  conserved  sequence  region  between  the
oncoproteins Src and Fps [1]. Similar sequences were later found in many other
intracellular signal-transducing   proteins   [2].  SH2  domains  function  as
regulatory modules  of  intracellular  signalling cascades by interacting with
high affinity  to  phosphotyrosine-containing  target  peptides in a sequence-
specific and strictly phosphorylation-dependent manner [3,4,5,6].

The SH2  domain  has  a conserved 3D structure consisting of two alpha helices
and six  to  seven  beta-strands.  The  core  of  the  domain  is  formed by a
continuous beta-meander composed of two connected beta-sheets [7].

So far, SH2 domains have been identified in the following proteins:

 - Many  vertebrate,  invertebrate  and  retroviral cytoplasmic (non-receptor)
   protein tyrosine kinases. In particular in the Src, Abl, Bkt, Csk and ZAP70
   families of kinases.
 - Mammalian phosphatidylinositol-specific phospholipase C gamma-1 and -2. Two
   copies of  the  SH2  domain  are  found  in  those  proteins in between the
   catalytic 'X-' and 'Y-boxes' (see <PDOC50007>).
 - Mammalian phosphatidyl inositol 3-kinase regulatory p85 subunit.
 - Some vertebrate and invertebrate protein-tyrosine phosphatases.
 - Mammalian Ras GTPase-activating protein (GAP).
 - Adaptor  proteins  mediating binding of guanine nucleotide exchange factors
   to growth  factor  receptors: vertebrate GRB2, Caenorhabditis elegans sem-5
   and Drosophila DRK.
 - Mammalian  Vav  oncoprotein,  a  guanine-nucleotide  exchange factor of the
   CDC24 family.
 - Miscellanous   proteins   interacting   with  vertebrate  receptor  protein
   tyrosine kinases: oncoprotein Crk, mammalian cytoplasmic proteins Nck, Shc.
 - STAT proteins (signal transducers and activators of transcription).
 - Chicken tensin.
 - Yeast transcriptional control protein SPT6.

The profile developed to detect SH2 domains is based on a structural alignment
consisting of  8  gap-free  blocks  and  7  linker  regions  totaling 92 match
positions.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: protein tyrosine  kinases JAK1  and
 JAK2.

-Expert(s) to contact by email:
           Zvelebil M.; marketa@ludwig.ucl.ac.uk

-Last update: November 1995 / First entry.

[ 1] Sadowski I., Stone J.C., Pawson T.
     "A noncatalytic domain conserved among cytoplasmic protein-tyrosine
     kinases modifies the kinase function and transforming activity of
     Fujinami sarcoma virus P130gag-fps."
     Mol. Cell. Biol. 6:4396-4408(1986).
     PubMed=3025655
[ 2] Russel R.B., Breed J., Barton G.J.
     FEBS Lett. 304:15-20(1992).
[ 3] Marangere L.E.M., Pawson T.
     J. Cell Sci. Suppl. 18:97-104(1994).
[ 4] Pawson T., Schlessingert J.
     "SH2 and SH3 domains."
     Curr. Biol. 3:434-442(1993).
     PubMed=15335710
[ 5] Mayer B.J., Baltimore D.
     "Signalling through SH2 and SH3 domains."
     Trends Cell Biol. 3:8-13(1993).
     PubMed=14731533
[ 6] Pawson T.
     "Protein modules and signalling networks."
     Nature 373:573-580(1995).
     PubMed=7531822; DOI=10.1038/373573a0
[ 7] Kuriyan J., Cowburn D.
     Curr. Opin. Struct. Biol. 3:828-837(1993).

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