Protein-tyrosine phosphatase, non-receptor type-1/2 (IPR012265)

Short name: Ptpn1/Ptpn2

Overlapping homologous superfamilies

Family relationships



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; EC: 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 [PMID: 9818190, PMID: 14625689]. The PTP superfamily can be divided into four subfamilies [PMID: 12678841]:

  • (1) pTyr-specific phosphatases
  • (2) dual specificity phosphatases (dTyr and dSer/dThr)
  • (3) Cdc25 phosphatases (dTyr and/or dThr)
  • (4) LMW (low molecular weight) phosphatases

Based on their cellular localisation, PTPases are also classified as:

  • Receptor-like, which are transmembrane receptors that contain PTPase domains [PMID: 16672235]
  • Non-receptor (intracellular) PTPases [PMID: 8948575]

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 [PMID: 9646865]. Functional diversity between PTPases is endowed by regulatory domains and subunits.

This entry represents non-receptor PTPase types 1 and 2 (also known as T-cell PTPase). These types appear to have different biological functions: in knock-out mice, type1 knock-outs showed increased insulin sensitivity but a normal lifespan, while type 2 knock-outs died when only a few weeks old [PMID: 10066179, PMID: 9271584]. Substrate-trapping experiments suggest that these types recognise different cellular targets, though it is not known if this is due to sequence differences or to other regulatory mechanisms. Regulation of function and activity can occur at the transcriptional, alternative splicing, proteolytic processing and covalent modification levels. For example, T-cell PTPase has two different isoforms generated by alternative splicing, one of which recognises nuclear substrates, while the other recognises cytoplasmic substrates. These proteins adopt an alpha-beta-alpha fold where the active site is located in a deep cleft located on the surface of the protein [PMID: 11907034, PMID: 9553104].

GO terms

Biological Process

GO:0006470 protein dephosphorylation

Molecular Function

GO:0004725 protein tyrosine phosphatase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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