GYF domain

{{Infobox protein family

| Symbol = GYF

| Name = GYF

| image = PDB 1syx EBI.jpg

| width =

| caption = the crystal structure of a binary u5 snrnp complex

| Pfam = PF02213

| Pfam_clan =

| InterPro = IPR003169

| SMART = GYF

| PROSITE =

| MEROPS =

| SCOP = 1gyf

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD = cd00072

}}

In molecular biology, the GYF domain (glycine-tyrosine-phenylalanine domain) is an approximately 60-amino acid protein 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.{{cite journal |vauthors=Nishizawa K, Freund C, Li J, Wagner G, Reinherz EL | title = Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 25 | pages = 14897–902 |date=December 1998 | pmid = 9843987 | pmc = 24547 | doi = 10.1073/pnas.95.25.14897| bibcode = 1998PNAS...9514897N | doi-access = free }} It has been proposed that the GYF domain found in these proteins could also be involved in proline-rich sequence recognition.{{cite journal |vauthors=Freund C, Dotsch V, Nishizawa K, Reinherz EL, Wagner G | title = The GYF domain is a novel structural fold that is involved in lymphoid signaling through proline-rich sequences | journal = Nat. Struct. Biol. | volume = 6 | issue = 7 | pages = 656–60 |date=July 1999 | pmid = 10404223 | doi = 10.1038/10712 | s2cid = 19688996 }} 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. 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.{{cite journal |vauthors=Freund C, Kuhne R, Yang H, Park S, Reinherz EL, Wagner G | title = Dynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules | journal = EMBO J. | volume = 21 | issue = 22 | pages = 5985–95 |date=November 2002 | pmid = 12426371 | pmc = 137194 | doi = 10.1093/emboj/cdf602}}