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45  structures 105  species 2  interactions 923  sequences 28  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

Phosphotyrosine-binding domain
PDB 1wvh EBI.jpg
Structure of the PTB domain of tensin1.[1]
Identifiers
Symbol PTB
Pfam PF08416
InterPro IPR013625
CDD cd00934
PTB domain (IRS-1 type)
PDB 1irs EBI.jpg
irs-1 ptb domain complexed with a il-4 receptor phosphopeptide, nmr, minimized average structure
Identifiers
Symbol IRS
Pfam PF02174
InterPro IPR002404
SMART PTBI
SCOP 1cli
SUPERFAMILY 1cli
CDD cd01204

In molecular biology, Phosphotyrosine-binding domains are protein domains which bind to phosphotyrosine.

The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (Pfam PF00017) domain and a region similar to the tumour suppressor PTEN.[2] The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.[3]

The phosphotyrosine-binding domain of insulin receptor substrate-1 is not related to the phosphotyrosine-binding domain of tensin. Insulin receptor substrate-1 proteins contain both a pleckstrin homology domain and a phosphotyrosine binding (PTB) domain. The PTB 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 an 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.[4] 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.[5]

Human proteins containing these domains[edit]

APBA1; APBA2; APBA3; EPS8; EPS8L1; EPS8L2; EPS8L3; TENC1; TNS; TNS1; TNS3; TNS4; DOK1; DOK2; DOK3; DOK4; DOK5; DOK6; DOK7; FRS2; FRS3; IRS1; IRS2; IRS4; TLN1; TLN2

References[edit]

  1. ^ McCleverty CJ, Lin DC, Liddington RC (June 2007). "Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions". Protein Sci. 16 (6): 1223–9. doi:10.1110/ps.072798707. PMC 2206669. PMID 17473008. 
  2. ^ Chen H, Ishii A, Wong WK, Chen LB, Lo SH (October 2000). "Molecular characterization of human tensin". Biochem. J. 351 (2): 403–11. PMC 1221376. PMID 11023826. 
  3. ^ Lo SH (January 2004). "Tensin". Int. J. Biochem. Cell Biol. 36 (1): 31–4. doi:10.1016/S1357-2725(03)00171-7. PMID 14592531. 
  4. ^ Eck MJ, Dhe-Paganon S, Trub T, Nolte RT, Shoelson SE (May 1996). "Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor". Cell 85 (5): 695–705. doi:10.1016/S0092-8674(00)81236-2. PMID 8646778. 
  5. ^ Zhou MM, Huang B, Olejniczak ET, Meadows RP, Shuker SB, Miyazaki M, Trub T, Shoelson SE, Fesik SW (April 1996). "Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain". Nat. Struct. Biol. 3 (4): 388–93. doi:10.1038/nsb0496-388. PMID 8599766. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR013625

This article incorporates text from the public domain Pfam and InterPro IPR002404


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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PTB domain (IRS-1 type) Provide feedback

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002404

Insulin receptor substrate-1 proteins contain both a pleckstrin homology domain (INTERPRO) 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].

Gene Ontology

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Domain organisation

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Alignments

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(32)
Full
(923)
Representative proteomes NCBI
(834)
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(1)
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(117)
RP35
(160)
RP55
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RP75
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  Seed
(32)
Full
(923)
Representative proteomes NCBI
(834)
Meta
(1)
RP15
(117)
RP35
(160)
RP55
(311)
RP75
(552)
Alignment:
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  Seed
(32)
Full
(923)
Representative proteomes NCBI
(834)
Meta
(1)
RP15
(117)
RP35
(160)
RP55
(311)
RP75
(552)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Curation and family details

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Seed source: IPR002404
Previous IDs: none
Type: Domain
Author: Bateman A, Mian N
Number in seed: 32
Number in full: 923
Average length of the domain: 96.60 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 10.89 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.1 21.1
Noise cut-off 20.6 20.6
Model length: 100
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

PH IRS

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 45 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 seqence.

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