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-specificity 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, 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.
By location Based on their cellular localization, PTPases are also classified as: • Receptor-like, which are
transmembrane receptors that contain PTPase
domains. 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
Common elements All PTPases, other than those of the EYA family, 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. Functional diversity between PTPases is endowed by regulatory domains and subunits. ==Expression pattern==