Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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PTBI Phosphotyrosine-binding domain (IRS1-like)

SMART accession number:	SM00310
Description:
Interpro abstract (IPR002404):	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 [(PUBMED:8646778)]. The PTB domain has a compact, 7-stranded beta-sandwich structure, capped by a C-terminal helix. The substrate peptide fits into an L-shaped surface cleft formed from the C-terminal helix and strands 5 and 6 [(PUBMED:8599766)].
GO function:	insulin receptor binding (GO:0005158)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 0 PTBI domains in 0 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a PTBI domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PTBI domain is also avaliable.

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• Cellular role (predicted cellular role)

• Cellular role: signalling
  Binding / catalysis: Phosphotyrosine-binding

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 33.33 map04930 Type II diabetes mellitus 33.33 map04920 Adipocytokine signaling pathway 33.33 map04910 Insulin signaling pathway This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PTBI domain which could be assigned to a KEGG orthologous group, and not all proteins containing PTBI domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of PTBI domains in PDB

  PDB code	Main view	Title
  1irs		Irs-1 ptb domain complexed with a il-4 receptor phosphopeptide, nmr, minimized average structure
  1j0w		Crystal structure analysis of the dok-5 ptb domain
  1p5t		Crystal structure of dok1 ptb domain
  1qqg		Crystal structure of the ph-ptb targeting region of irs-1
  1uef		Crystal structure of dok1 ptb domain complex
  1xr0		Structural basis of snt ptb domain interactions with distinct neurotrophic receptors
  2dlw		Solution structure of the irs domain of human docking protein 2, isoform a
  2v76		Crystal structure of the human dok1 ptb domain
  2ys5		Solution structure of the complex of the ptb domain of snt- and 19-residue peptide (aa 1571-1589) of halk
  2yt2		Solution structure of the chimera of the ptb domain of snt- and 19-residue peptide (aa 1571-1589) of halk

• Links (links to other resources describing this domain)

• INTERPRO	IPR002404

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