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25  structures 313  species 7  interactions 2128  sequences 62  architectures

Family: IRS (PF02174)

Summary: PTB domain (IRS-1 type)

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This is the Wikipedia entry entitled "Phosphotyrosine-binding domain". More...

Phosphotyrosine-binding domain Edit Wikipedia article

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PTB domain (IRS-1 type) Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002404

Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal pleckstrin homology domain (INTERPRO), followed by an IRS-like phosphotyrosine binding (PTB) domain which has a PH-like fold. 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].

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 [PUBMED:15567406, PUBMED:8646778]. More recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This entry is part of the IRS-like subgroup [PUBMED:8599766, PUBMED:10610414].

The 3D structure of IRS-type PTB domain has been solved [PUBMED: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) [PUBMED:14607833].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(26)
Full
(2128)
Representative proteomes UniProt
(3302)
NCBI
(6661)
Meta
(1)
RP15
(454)
RP35
(944)
RP55
(1658)
RP75
(1958)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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  Seed
(26)
Full
(2128)
Representative proteomes UniProt
(3302)
NCBI
(6661)
Meta
(1)
RP15
(454)
RP35
(944)
RP55
(1658)
RP75
(1958)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(26)
Full
(2128)
Representative proteomes UniProt
(3302)
NCBI
(6661)
Meta
(1)
RP15
(454)
RP35
(944)
RP55
(1658)
RP75
(1958)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: IPR002404
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Mian N
Number in seed: 26
Number in full: 2128
Average length of the domain: 96.00 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 13.60 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 100
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 7 interactions for this family. More...

FERM_N IRS PH FERM_M Integrin_b_cyt Integrin_b_cyt FERM_M

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IRS domain has been found. There are 25 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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