IRS-type PTB domain (IPR002404)

Short name: IRS_PTB

Domain relationships


Insulin receptor substrate-1 proteins contain both a pleckstrin homology domain (IPR001849) and a phosphotyrosine binding (PTB) domain. These domains facilitate interaction with the activated tyrosine-phosphorylated insulin receptor. The PTB domain is situated towards the N terminus. Two arginines in this domain are responsible for hydrogen bonding phosphotyrosine residues on a Ac-LYASSNPApY-NH2 peptide in the juxtamembrane region of the insulin receptor. Further interactions via `bridged' water molecules are coordinated by residues an Asn and a Ser residue [PMID: 8646778].

PTB domains function as adaptors or scaffolds to organise the signalling 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, and phosphotyrosine-independent Dab-like PTBs.

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 organisation and localization within cells. The IRS-type PTB domain is found alone or in association with the PH domain [PMID: 15567406, PMID: 8646778].

The 3D structure of IRS-type PTB domain has been solved [PMID: 14607833]. It shares a folding pattern commonly referred to as the PH-domain "superfold". The core "superfold" consists of seven antiparallel beta strands forming two orthogonal beta sheets. This beta sandwich is capped at the C terminus by an alpha helix. It contains a peptide binding pocket (formed by the beta strand 5 and the C-terminal alpha helix) and a highly basic phospholipid binding "crown" (largely composed of residues from loop regions near the N terminus) [PMID: 14607833].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0005158 insulin receptor binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles