LIG_PTB_2
ELM server details
ELM
blue dot
Functional site class:
 PTB ligand
Functional site description:
 Phosphotyrosine binding (PTB) domains mostly recognize small motifs contaning a phosphorylated Tyrosine residue
ELM(s): LIG_PTB_2, LIG_PTB_1
LIG_PTB_2 description: LIG_PTB_2 is a NPXY PTB domain binding motif whose tyrosine is non-phosphorylated
Pattern: NP.Y.
Present in taxon(s): Metazoa  
Not represented in taxon(s):

o Abstract

Phosphotyrosine binding (PTB) domains are structurally conserved modules found in protein involved in numerous biological processes including signaling through cell-surface receptors and protein trafficking. The PTB domain was first identified in the Shc signaling protein and insulin receptor substrate 1 (IRS-1), as modular domain that recognize phosphorylated Asn-Pro-Xxx-pTyr-containing protein.
Recently it has been discovered that not all PTB domains recognize pTyr-containning proteins. In particular, the PTB domains of X11 bind to non-phopsphorylated targets. These peptide sequences lack pTyr but contain the canonical NPXY sequence motif, which has been shown to form ß turn in the binding site in structures of the X11 PTB domain-ßAPP complex.
Studies of the Numb PTB domain have been surprisingly demonstrating that peptides with little sequence similarity to the NPxY motif can bind PTB domains and that not all interacting peptides maintain a similar structure.

o Selected references

Borg JP, Ooi J, Levy E, Margolis B
The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein.
Mol Cell Biol 1996 Nov;16(11) : 6229-41.
PMID: 8887653

Forman-Kay JD, Pawson T
Diversity in protein recognition by PTB domains.
Curr Opin Struct Biol 1999 Dec;9(6) : 690-5.
PMID: 10607674

Howell BW, Lanier LM, Frank R, Gertler FB, Cooper JA
The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids.
Mol Cell Biol 1999 Jul;19(7) : 5179-88.
PMID: 10373567

Tanahashi H, Tabira T
Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's beta-amyloid precursor protein.
Neurosci Lett 1999 Feb 19;261(3) : 143-6.
PMID: 10081969

Yan KS, Kuti M, Zhou MM
PTB or not PTB -- that is the question.
FEBS Lett 2002 Feb 20;513(1) : 67-70.
PMID: 11911882

Zambrano N, Buxbaum JD, Minopoli G, Fiore F, De Candia P, De Renzis S, Faraonio R, Sabo S, Cheetham J, Sudol M, Russo T
Interaction of the phosphotyrosine interaction/phosphotyrosine binding-related domains of Fe65 with wild-type and mutant Alzheimer's beta-amyloid precursor proteins.
J Biol Chem 1997 Mar 7;272(10) : 6399-405.
PMID: 9045663

Zhang Z, Lee CH, Mandiyan V, Borg JP, Margolis B, Schlessinger J, Kuriyan J
Sequence-specific recognition of the internalization motif of the Alzheimer's amyloid precursor protein by the X11 PTB domain.
EMBO J 1997 Oct 15;16(20) : 6141-50.
PMID: 9321393

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

Biological Process
Cellular Component
  cytosol
Molecular Function
  Binding
  protein binding
  protein domain specific binding

 

o Instances for LIG_PTB_2

No instances annotated