Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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GYF Contains conserved Gly-Tyr-Phe residues

SMART accession number:	SM00444
Description:	Proline-binding domain in CD2-binding protein. Contains conserved Gly-Tyr-Phe residues.
Interpro abstract (IPR003169):	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 [(PUBMED:9843987)]. It has been proposed that the GYF domain found in these proteins could also be involved in proline-rich sequence recognition [(PUBMED:10404223)]. 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. 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 [(PUBMED:10404223)]. 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 [(PUBMED:12426371)].
GO function:	protein binding (GO:0005515)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 122 GYF domains in 122 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a GYF domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with GYF domain is also avaliable.

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  Go to specific node: Arabidopsis thaliana, Caenorhabditis elegans, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Freund C, Dotsch V, Nishizawa K, Reinherz EL, Wagner G
  • The GYF domain is a novel structural fold that is involved in lymphoid signaling through proline-rich sequences.
  • Nat Struct Biol. 1999; 6: 656-60
  • Display abstract

  • T cell activation through the CD2 cell surface receptor is transmitted by proline-rich sequences within its cytoplasmic tail. A membrane-proximal proline-rich tandem repeat, involved in cytokine production, is recognized by the intracellular CD2 binding protein CD2BP2. We solved the solution structure of the CD2 binding domain of CD2BP2, which we name the glycine-tyrosine-phenylalanine (GYF) domain. The GYF sequence is part of a structurally unique bulge-helix-bulge motif that constitutes the major binding site for the CD2 tail. A hydrophobic surface patch is created by motif residues that are highly conserved among a variety of proteins from diverse eukaryotic species. Thus, the architecture of the GYF domain may be widely used in protein-protein associations.

  • Nishizawa K, Freund C, Li J, Wagner G, Reinherz EL
  • Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation.
  • Proc Natl Acad Sci U S A. 1998; 95: 14897-902
  • Display abstract

  • An intracellular protein termed CD2 binding protein 2 (CD2BP2), which binds to a site containing two PPPGHR segments within the cytoplasmic region of CD2, was identified. Mutagenesis and NMR analysis demonstrated that the CD2 binding region of CD2BP2 includes a 17-aa motif (GPY[orF]xxxxM[orV]xxWxxx GYF), also found in several yeast and Caenorhabditis elegans proteins of unknown function. In Jurkat T cells, over-expression of the isolated CD2BP2 domain binding to CD2 enhances the production of interleukin 2 on crosslinking of CD2 but not the T cell receptor. Hence, a proline-binding module distinct from SH3 and WW domains regulates protein-protein interactions.

• Structure (3D structures containing this domain)

• 3D Structures of GYF domains in PDB

  PDB code	Main view	Title
  1gyf		Gyf domain from human cd2bp2 protein
  1l2z		Cd2bp2-gyf domain in complex with proline-rich cd2 tail segment peptide
  1syx		The crystal structure of a binary u5 snrnp complex
  1wh2		Solution structure of the gyf domain of a hypothetical protein from arabidopsis thaliana

• Links (links to other resources describing this domain)

• INTERPRO	IPR003169

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