{PDOC50829}
{PS50829; GYF}
{BEGIN}
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* GYF domain profile *
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The  glycine-tyrosine-phenylalanine  (GYF)  domain  is an around 60-amino acid
domain which  contains  a  conserved  GP[YF]xxxx[MV]xxWxxx[GN]YF motif. It was
identified in  the  human  intracellular  protein termed CD2 binding protein 2
(CD2BP2), which  binds  to a site containing two tandem PPPGHR segments within
the cytoplasmic  region  of  CD2.  Binding experiments and mutational analyses
have demonstrated  the  critical  importance  of  the GYF tripeptide in ligand
binding. A  GYF  domain  is also found in several other eukaryotic proteins of
unknown function  [1]. It has been proposed that the GYF domain found in these
proteins could also be involved in proline-rich sequence recognition [2].

Resolution of  the  structure  of  the  CD2BP2  GYF domain by NMR spectroscopy
revealed a compact domain with a beta-beta-alpha-beta-beta topology, where the
single alpha-helix  is  tilted away from the twisted, anti-parallel beta-sheet
(see <PDB:1GYF>). The conserved residues of the GYF domain create a contiguous
patch of  predominantly hydrophobic nature which forms an integral part of the
ligand-binding site [2]. There is limited homology within the C-terminal 20-30
amino acids  of various GYF domains, supporting the idea that this part of the
domain is structurally but not functionally important [3].

The profile we developed spans the entire GYF domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: May 2003 / First entry.

[ 1] Nishizawa K., Freund C., Li J., Wagner G., Reinherz E.L.
     "Identification of a proline-binding motif regulating CD2-triggered T
     lymphocyte activation."
     Proc. Natl. Acad. Sci. U.S.A. 95:14897-14902(1998).
     PubMed=9843987
[ 2] Freund C., Doetsch V., Nishizawa K., Reinherz E.L., Wagner G.
     "The GYF domain is a novel structural fold that is involved in
     lymphoid signaling through proline-rich sequences."
     Nat. Struct. Biol. 6:656-660(1999).
     PubMed=10404223; DOI=10.1038/10712
[ 3] Freund C., Kuehne R., Yang H., Park S., Reinherz E.L., Wagner G.
     "Dynamic interaction of CD2 with the GYF and the SH3 domain of
     compartmentalized effector molecules."
     EMBO J. 21:5985-5995(2002).
     PubMed=12426371

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