Protein tyrosine phosphatase

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CAS number 79747-53-8
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Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. 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; 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, transformation, and synaptic strengthening.[1][2][3][4]


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[edit]

The PTP superfamily can be divided into four subfamilies.[6][7]

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[edit]

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

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 (EC and tyrosine-specific protein phosphatase (EC 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,[3] Fragile X Syndrome[4] schizophrenia,[8] and Parkinson’s disease.[9] Decreased levels of PTPN5 has been implicated in Huntington's disease,[10][11] cerebral ischemia[12] alcohol abuse,[13][14] and stress disorders.[15][16] Together these findings indicate that only at optimal levels of PTPN5 is synaptic function unimpaired.

Class II[edit]

LMW (low-molecular-weight) phosphatases, or acid phosphatases, act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.[17][18]

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

Class III[edit]

Cdc25 phosphatases (dTyr and/or dThr)

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

Class IV[edit]

pTyr-specific phosphatases

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

This class is believed to have evolved separately from the other three.[19]

By location[edit]

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

Common elements[edit]

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.[22] Functional diversity between PTPases is endowed by regulatory domains and subunits.

Low-molecular-weight phosphotyrosine protein phosphatase
PDB 1phr EBI.jpg
Structure of a low-molecular-weight phosphotyrosine protein phosphatase.[23]
Symbol LMWPc
Pfam PF01451
InterPro IPR017867
SCOP 1phr
Protein-tyrosine phosphatase
PDB 1ypt EBI.jpg
Structure of Yersinia protein tyrosine phosphatase.[24]
Symbol Y_phosphatase
Pfam PF00102
Pfam clan CL0031
InterPro IPR000242
SCOP 1ypt
Dual-specificity phosphatase, catalytic domain
PDB 1vhr EBI.jpg
Structure of the dual-specificity protein phosphatase VHR.[25]
Symbol DSPc
Pfam PF00782
Pfam clan CL0031
InterPro IPR000340
SCOP 1vhr
Protein-tyrosine phosphatase, SIW14-like
PDB 1xri EBI.jpg
Structure of a putative phosphoprotein phosphatase from Arabidopsis thaliana.[26]
Symbol Y_phosphatase2
Pfam PF03162
Pfam clan CL0031
InterPro IPR004861
Protein-tyrosine phosphatase-like, PTPLA
Symbol PTPLA
Pfam PF04387
InterPro IPR007482

Expression pattern[edit]

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.[27] The expression of PTPN5 is restricted to the brain. Differential expression of PTPN5 is found in many brain regions, with no expression in the cerebellum.[28][29][30]


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External links[edit]