ELM Details - LIG

LIG_GYF

Functional site class:	GYF ligand
Functional site description:	Proline-rich sequences recognized by GYF domains - involved in lymphoid signaling
ELM(s):	LIG_GYF
LIG_GYF description:	LIG_GYF is a proline-rich sequence specifically recognized by GYF domains. Known cases so far involve the CD2 binding protein CD2BP2, which specifically recognizes the cytoplasmic tail of CD2 surface receptor. The LIG_GYF sequence is generally composed of a pair of similar proline-rich sequences and has been shown to compete in vitro with the SH3 domain of the src-family FYN kinase. Each proline-rich sequence is spanned by positively charged residues that have complementary binding partners on the GYF domain. Due to the limited experimental data available, the current pattern is certainly overdetermined and a better description should be possible in future.
Pattern:	[QHR].{0,1}P[PL]PP[GS]H[RH]
Present in taxon(s):	Homo sapiens Eukaryota Mus musculus Rattus norvegicus
Not represented in taxon(s):

See instances for LIG_GYF

Abstract

The glycine-tyrosine-phenylalanine, or GYF, domain has been identified at the N-term of a number of proteins in organisms ranging from S.pombe to H.sapiens with fairly conserved sequence. It interacts with proline-rich sequences and, in humans, it has been shown to recognize specifically two PPPPGHR repeats at the C-term of the CD2 cell surface receptor. Despite functioning as a proline-rich peptide binding domain, the GYF fold is structurally unrelated to the SH3 or WW domains.
The NMR structure of the GYF domain of the CD2BP2 protein has been solved in complex with a proline-rich peptide (PDB code: 1L2Z) and the residues of the domain involved in binding have been identified. The binding pocket is very hydrophobic with a relatively smooth, concave surface. The GYF tripeptide (conserved at the C term of the domain sequence) is involved in the binding.

Selected references

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 Jul;6(7) : 656-60.

PMID: 10404223

Freund C, Kuhne R, Yang H, Park S, Reinherz EL, Wagner G

Dynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules.

EMBO J 2002 Nov 15;21(22) : 5985-95.

PMID: 12426371

This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process

  signal transduction

GO:0007165

Cellular Component

  cytosol

GO:0005829

Molecular Function

  receptor (2090)

GO:0004872

Instances for LIG_GYF

Sequence	Position	Subsequence (Click for evidence information)	PDB	Gene Name	Protein Description	Organism
CD2_HUMAN	281-289	PATSQHPPPPPGHRSQAPSH	1L2Z	Name=CD2; Synonyms=SRBC;	T-cell surface antigen CD2 precursor (T-cell surface antigen T11/Leu- 5) (LFA-2) (LFA-3 receptor) (Erythrocyte receptor) (Rosette receptor) (CD2 antigen).	Homo sapiens (Human).