PROSITE documentation PDOC51064
IRS-type phosphotyrosine binding domain (PTB) profile


Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or scaffolds to organize the signaling complexes involved in wide-ranging physiological processes including neural development, immunity, tissue homeostasis and cell growth. Due to structural differences, PTB domains are divided into three groups represented by phosphotyrosine-dependent IRS-like, phosphotyrosine-dependent Shc-like (see <PDOC00907>), and phosphotyrosine-independent Dab-like PTBs (see <PDOC00907>).

IRS-type PTB domain has an average length of about 100 amino acids. It binds to the insulin receptor through the Asn-Pro-Xaa-Tyr(P) motif found in many tyrosine-phosphorylated proteins. This domain is found in IRS/Dok/SNT proteins that are the major adapters for RTK and cytokine signaling. This domain binds both peptides and headgroups of phosphatidylinositides, utilizing two distinct binding motifs to mediate spatial organization and localization within cells. The IRS-type PTB domain is found alone or in association with the PH domain (see <PDOC50003>) [1,2].

The 3D structure of IRS-type PTB domain has been solved (see <PDB:1P5T>) [3]. It shares a folding pattern commonly referred to as the PH-domain "superfold". The core "superfold" consists of seven antiparallel β strands forming two orthogonal β sheets. This β sandwich is capped at the C terminus by an α helix. It contains a peptide binding pocket (formed by the β strand 5 and the C-terminal α helix) and a highly basic phospholipid binding "crown" (largely composed of residues from loop regions near the N terminus) [3].

IRS-type PTB domain has also been found in the proteins listed below.

  • Mammalian insulin receptor substrate (IRS-1 and IRS-2) proteins.
  • Mammalian docking proteins (DOK1, DOK2 and DOK5) which interact with receptor tyrosine kinases.
  • Mammalian FGFR signalling adaptor (SNT-1 and SNT-2).

The profile we developed covers the entire IRS-type PTB domain.


Talin proteins may contain an IRS-type PTB domain. This family is however too divergent to be detected by this profile.

Last update:

January 2005 / First entry.


Technical section

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

IRS_PTB, PS51064; IRS-type PTB domain profile  (MATRIX)


1AuthorsUhlik M.T. Temple B. Bencharit S. Kimple A.J. Siderovski D.P. Johnson G.L.
TitleStructural and evolutionary division of phosphotyrosine binding (PTB) domains.
SourceJ. Mol. Biol. 345:1-20(2005).
PubMed ID15567406

2AuthorsEck M.J. Dhe-Paganon S. Trub T. Nolte R.T. Shoelson S.E.
TitleStructure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor.
SourceCell 85:695-705(1996).
PubMed ID8646778

3AuthorsShi N. Ye S. Bartlam M. Yang M. Wu J. Liu Y. Sun F. Han X. Peng X. Qiang B. Yuan J. Rao Z.
TitleStructural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain.
SourceJ. Biol. Chem. 279:4962-4969(2004).
PubMed ID14607833

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