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Protein Domain : IPR000340

Name  Dual specificity phosphatase, catalytic domain Short Name  Dual-sp_phosphatase_cat-dom
Type  Domain Description  Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; ) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [, ]. The PTP superfamily can be divided into four subfamilies []:(1) pTyr-specific phosphatases(2) dual specificity phosphatases (dTyr and dSer/dThr)(3) Cdc25 phosphatases (dTyr and/or dThr)(4) LMW (low molecular weight) phosphatasesBased on their cellular localisation, PTPases are also classified as:Receptor-like, which are transmembrane receptors that contain PTPase domains []Non-receptor (intracellular) PTPases []All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif []. Functional diversity between PTPases is endowed by regulatory domains and subunits. This entry represents dual specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual specificity phosphatases are a group of enzymes with both Ser/Thr () and tyrosine specific protein phosphatase () activity able to remove both the serine/threonine or tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylatedunder the action of a kinase. Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. The crystal structure of a human DSP, vaccinia H1-related phosphatase (or VHR), has been determined at 2.1 angstrom resolution []. A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine. Positively charged crevices near the active site may explain the enzyme's preference for substrates with two phosphorylated residues. The VHR structure defines a conserved structural scaffold for both DSPs and PTPs. A "recognition region" connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between VHR, the PTPs, and other DSPs.These proteins may also have inactive phosphatase domains, and dependent on the domain composition this loss of catalytic activity has different effects on protein function. Inactive single domain phosphatases can still specifically bind substrates, and protect again dephosphorylation, while the inactive domains of tandem phosphatases can be further subdivided into two classes. Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. The second class shows a release of evolutionary constraint for the sites around the catalytic centre, which emphasises a difference in function from the first group. There is a region of higher conservation common to both classes, suggesting a new regulatory centre [].

Publication Counts Displayer

0 Child Features

2 Contains

DB identifier Name Short Name Type
IPR000387 Protein-tyrosine/Dual specificity phosphatase Tyr/Dual-sp_Pase Domain
IPR016130 Protein-tyrosine phosphatase, active site Tyr_Pase_AS Active_site

1 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PF00782 PFAM IPR000340

3 Data Sets

Name URL
TrEMBL data set http://www.ebi.ac.uk/trembl/
InterPro data set  
InterPro GO Annotation data set  

7 Found In

DB identifier Name Short Name Type
IPR017074 mRNA capping enzyme, bifunctional mRNA_cap_enz_bifunc Family
IPR020417 Atypical dual specificity phosphatase Atypical_DUSP Family
IPR008343 Mitogen-activated protein (MAP) kinase phosphatase MKP Family
IPR016278 Dual specificity protein phosphatase 12 DUSP12 Family
IPR020405 Atypical dual specificity phosphatase, subfamily A Atypical_DUSP_famA Family
IPR017361 Bifunctional phosphatidylinositol trisphosphate phosphatase/dual specificity phosphatase PTEN Bifunc_PIno_P3_Pase/Pase_PTEN Family
IPR020420 Atypical dual specificity phosphatase, subfamily B Atypical_DUSP_famB Family

2 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Dual specificity phosphatase, catalytic domain   GO:0008138 protein tyrosine/serine/threonine phosphatase activity
Dual specificity phosphatase, catalytic domain   GO:0006470 protein dephosphorylation

2 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Dual specificity phosphatase, catalytic domain   GO:0008138 protein tyrosine/serine/threonine phosphatase activity
Dual specificity phosphatase, catalytic domain   GO:0006470 protein dephosphorylation

1 Parent Features

DB identifier Name Short Name Type
IPR029021 Protein-tyrosine phosphatase-like Prot-tyrosine_phosphatase-like Domain

207 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0074510 Q9VWF4 Drosophila melanogaster
FBpp0074420 Q9VWN2 Drosophila melanogaster
FBpp0111917 A8JUQ2 Drosophila melanogaster
FBpp0083844 Q86BN8 Drosophila melanogaster
FBpp0080414 O61722 Drosophila melanogaster
FBpp0290828 Q6NN85 Drosophila melanogaster
FBpp0087183 Q8SX38 Drosophila melanogaster
FBpp0075565 Q8IQK0 Drosophila melanogaster
FBpp0075564 Q8IQK1 Drosophila melanogaster
FBpp0075562 Q9VU80 Drosophila melanogaster
FBpp0290827 E1JIW2 Drosophila melanogaster
FBpp0074802 Q9VVW5 Drosophila melanogaster
FBpp0081288 Q9VHV8 Drosophila melanogaster
FBpp0088843 Q7KMQ6 Drosophila melanogaster
FBpp0088844 Q9V3L4 Drosophila melanogaster
FBpp0088841 Q9Y0B6 Drosophila melanogaster
FBpp0310519 Q9NGL1 Drosophila melanogaster
FBpp0303925 M9PI51 Drosophila melanogaster
FBpp0079115 Q9VLW7 Drosophila melanogaster
FBpp0290546 E1JHB2 Drosophila melanogaster
FBpp0290545 Q5U0V6 Drosophila melanogaster
FBpp0073739 Q9VY44 Drosophila melanogaster
FBpp0303122 M9PG13 Drosophila melanogaster
FBpp0292332 B3DNI0 Drosophila melanogaster
FBpp0288363 Q29H78 Drosophila pseudoobscura
FBpp0282103 Q299A1 Drosophila pseudoobscura
FBpp0273478 Q29IU9 Drosophila pseudoobscura
FBpp0274773 Q29GD4 Drosophila pseudoobscura
FBpp0279410 Q29P39 Drosophila pseudoobscura
FBpp0280157 Q29N01 Drosophila pseudoobscura