Atypical dual specificity phosphatase (IPR020417)

Short name: Atypical_DUSP

Overlapping homologous superfamilies

Family relationships


Dual specificity phosphatases (DUSPs) are members of the superfamily of protein tyrosine phosphatases [PMID: 17057753, PMID: 15186772]. They remove the phosphate group from both phospho-tyrosine and phospho-serine/threonine residues. They are structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR [PMID: 8987394,PMID: 7961745,PMID: 8154323]. They are characterized as VHR- [PMID: 9571625,PMID: 8650541] or Cdc25-like [PMID: 7601801,PMID: 8701088].

In general, DUSPs are classified into the following subgroups [PMID: 19228121]:

  • Slingshot phosphatases
  • Phosphatase of regenerating liver (PRL)
  • Cdc14 phosphatases
  • Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-like and myotubularin phosphatases
  • Mitogen-activated protein kinase phosphatases (MKPs)
  • Atypical DUSPs

The atypical DUSPs share a high degree of similarity with the MKP subgroup, but lack the N-terminal regulatory domain, which provides the substrate specificity towards the MAP kinases. These atypical-DUSPs form a heterogeneous group and have in common the presence of a single catalytic PTP domain. VHR was the first characterised member of this subfamily; its crystal structure is known [PMID: 1281549, PMID: 8650541].

The function of many atypical DUSPs remains unknown, although some have been related to regulation of MAP kinase pathways [PMID: 10224087, PMID: 11971192, PMID: 15796912]. VHR has also been related to the control of cell-senescence [PMID: 16604064].

The atypical DUSPs can be subdivided into two groups (termed A and B) on the basis of sequence similarity. Each of these subgroups is characterised by its own distinctive set of motifs, the functions of which are as yet unknown.

This entry also includes DUSP1, DUSP2 and DUSP10 which do not belong to the atypical DUSP family.

GO terms

Biological Process

GO:0006470 protein dephosphorylation

Molecular Function

GO:0008138 protein tyrosine/serine/threonine phosphatase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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