PROSITE documentation PDOC50829
GYF domain profile


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 β-β-α-β-β topology, where the single α-helix is tilted away from the twisted, anti-parallel β-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.

Last update:

May 2003 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

GYF, PS50829; GYF domain profile  (MATRIX)


1AuthorsNishizawa K. Freund C. Li J. Wagner G. Reinherz E.L.
TitleIdentification of a proline-binding motif regulating CD2-triggered T lymphocyte activation.
SourceProc. Natl. Acad. Sci. U.S.A. 95:14897-14902(1998).
PubMed ID9843987

2AuthorsFreund C. Doetsch V. Nishizawa K. Reinherz E.L. Wagner G.
TitleThe GYF domain is a novel structural fold that is involved in lymphoid signaling through proline-rich sequences.
SourceNat. Struct. Biol. 6:656-660(1999).
PubMed ID10404223

3AuthorsFreund C. Kuehne R. Yang H. Park S. Reinherz E.L. Wagner G.
TitleDynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules.
SourceEMBO J. 21:5985-5995(2002).
PubMed ID12426371

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