Protein phosphatase

A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein. Protein phosphorylation is one of the most common forms of reversible protein posttranslational modification (PTM), with up to 30% of all proteins being phosphorylated at any given time. Protein kinases (PKs) are the effectors of phosphorylation and catalyse the transfer of a γ-phosphate from ATP to specific amino acids on proteins. Several hundred PKs exist in mammals and are classified into distinct super-families. Proteins are phosphorylated predominantly on Ser, Thr and Tyr residues, which account for 79.3, 16.9 and 3.8% respectively of the phosphoproteome, at least in mammals. In contrast, protein phosphatases (PPs) are the primary effectors of dephosphorylation and can be grouped into three main classes based on sequence, structure and catalytic function. The largest class of PPs is the phosphoprotein phosphatase (PPP) family comprising PP1, PP2A, PP2B, PP4, PP5, PP6 and PP7, and the protein phosphatase Mg2+- or Mn2+-dependent (PPM) family, composed primarily of PP2C. The protein Tyr phosphatase (PTP) super-family forms the second group,[1] and the aspartate-based protein phosphatases the third. The protein pseudophosphatases form part of the larger phosphatase family, and in most cases are thought to be catalytically inert, instead functioning as phosphate-binding proteins, integrators of signalling or subcellular traps. Examples of membrane-spanning protein phosphatases containing both active (phosphatase) and inactive (pseudophosphatase) domains linked in tandem are known,[1] conceptually similar to the kinase and pseudokinase domain polypeptide structure of the JAK pseudokinases.[2][3] A complete comparative analysis of human phosphatases and pseudophosphatases has been completed by Manning and colleagues,[4] forming a companion piece to the ground-breaking analysis of the human kinome, which encodes the complete set of ~536 human protein kinases.[5]

  1. ^ a b Tonks NK (November 2006). "Protein tyrosine phosphatases: from genes, to function, to disease". Nature Reviews. Molecular Cell Biology. 7 (11): 833–46. doi:10.1038/nrm2039. PMID 17057753. S2CID 1302726.
  2. ^ Reiterer V, Eyers PA, Farhan H (September 2014). "Day of the dead: pseudokinases and pseudophosphatases in physiology and disease". Trends in Cell Biology. 24 (9): 489–505. doi:10.1016/j.tcb.2014.03.008. PMID 24818526.
  3. ^ Mendrola JM, Shi F, Park JH, Lemmon MA (August 2013). "Receptor tyrosine kinases with intracellular pseudokinase domains". Biochemical Society Transactions. 41 (4): 1029–36. doi:10.1042/BST20130104. PMC 3777422. PMID 23863174.
  4. ^ Cite error: The named reference ChenManning was invoked but never defined (see the help page).
  5. ^ Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (December 2002). "The protein kinase complement of the human genome". Science. 298 (5600): 1912–34. Bibcode:2002Sci...298.1912M. doi:10.1126/science.1075762. PMID 12471243. S2CID 26554314.