Protein tyrosine phosphatase sigma

EC number CAS number IntEnz BRENDA ExPASy KEGG MetaCyc metabolic pathway
PRIAM PDB structures PDBsum

Protein tyrosine phosphatases (


Together with tyrosine kinases, PTPs regulate the phosphorylation state of many important signalling molecules, such as the MAP kinase family. PTPs are increasingly viewed as integral components of signal transduction cascades, despite less study and understanding compared to tyrosine kinases.

PTPs have been implicated in regulation of many cellular processes, including, but not limited to:


By mechanism

The PTP superfamily can be divided into four subfamilies.[3][4]

Links to all 107 members of the protein tyrosine phosphatase family can be found in the template at the bottom of this article.

Class I

The class I PTPs, are the largest group of PTPs with 99 members, which can be further subdivided into

  • 38 classical PTPs
    • 21 receptor tyrosine phosphatase
    • 17 nonreceptor-type PTPs
  • 61 VH-1-like or dual-specific phosphatases (DSPs)

Dual-specificity phosphatases (dTyr and dSer/dThr) dual-specificity protein-tyrosine kinase. Dual-specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle.

LEOPARD syndrome, Noonan syndrome, and Metachondromatosis are associated with PTPN11.

Class II

LMW (low-molecular-weight) phosphatases, or acid phosphatases, act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.[5][6]

The class II PTPs contain only one member, low-molecular-weight phosphotyrosine phosphatase (LMPTP).

Class III

Cdc25 phosphatases (dTyr and/or dThr)

The Class III PTPs contains three members, CDC25 A, B, and C

Class IV

pTyr-specific phosphatases

The class IV PTPs contains four members, Eya1-4.

This class is believed to have evolved separately from the other three.[7]

By location

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

  • Receptor-like, which are transmembrane receptors that contain PTPase domains.[8] In terms of structure, all known receptor PTPases are made up of a variable-length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains, or carbonic anhydrase-like domains in their extracellular region. In general, the cytoplasmic region contains two copies of the PTPase domain. The first seems to have enzymatic activity, whereas the second is inactive.
  • Non-receptor (intracellular) PTPases[9]

Common elements

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and possess 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.[10] Functional diversity between PTPases is endowed by regulatory domains and subunits.

Low-molecular-weight phosphotyrosine protein phosphatase
Symbol LMWPc
Pfam InterPro IPR017867
Protein-tyrosine phosphatase
Symbol Y_phosphatase
Pfam Pfam clan InterPro IPR000242
Dual-specificity phosphatase, catalytic domain
Symbol DSPc
Pfam Pfam clan InterPro PROSITE PDOC00323
Protein-tyrosine phosphatase, SIW14-like
Symbol Y_phosphatase2
Pfam Pfam clan InterPro IPR004861
Protein-tyrosine phosphatase-like, PTPLA
Symbol PTPLA
Pfam InterPro IPR007482

Expression pattern

Individual PTPs may be expressed by all cell types, or their expression may be strictly tissue-specific. Most cells express 30% to 60% of all the PTPs, however hematopoietic and neuronal cells express a higher number of PTPs in comparison to other cell types. T cells and B cells of hematopoietic origin express around 60 to 70 different PTPs. The expression of several PTPS is restricted to hematopoietic cells, for example, LYP, SHP1, CD45, and HePTP.[15]


External links

  • Monash University
  • Medical Subject Headings (MeSH)

This article incorporates text from the IPR000106