Protein tyrosine phosphatases (EC 3.1.3.48, systematic name protein-tyrosine-phosphate phosphohydrolase) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins:
[a protein]-tyrosine phosphate + H2O = [a protein]-tyrosine + phosphate
Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability, and regulate enzyme activity. As a consequence, 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, transformation, and synaptic plasticity.
Functions
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: Cell growth Cellular differentiation Mitotic cycles Oncogenic transformation Receptor endocytosis
Classification
By mechanism
PTP activity can be found in four protein families.
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 phosphatases 17 nonreceptor-type PTPs 61 VH-1-like or dual-specific phosphatases (DSPs) 11 MAPK phosphatases (MPKs) 3 Slingshots 3 PRLs 4 CDC14s 19 atypical DSPs 5 phosphatase and tensin homologs (PTENs) 16 myotubularins
Dual-specificity phosphatases (dTyr and dSer/dThr) 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 the serine/threonine or the tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a 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.
Elevated levels of activated PTPN5 negatively affects synaptic stability and plays a role in Alzheimer's disease, Fragile X syndrome, schizophrenia, and Parkinson's disease. Decreased levels of PTPN5 has been implicated in Huntington's disease, brain ischemia, alcohol use disorder, and stress disorders. Together these findings indicate that only at optimal levels of PTPN5 is synaptic function unimpaired.
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.
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
These are members of the HAD fold and superfamily, and include phosphatases specific to pTyr and pSer/Thr as well as small molecule phosphatases and other enzymes. The subfamily EYA (eyes absent) is believed to be pTyr-specific, and has four members in human, EYA1, EYA2, EYA3, and EYA4. This class has a distinct catalytic mechanism from the other three classes.