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The extended human PTPome: a growing tyrosine phosphatase family

AutorAlonso, Andrés ; Pulido, Rafael
Palabras claveAsp phosphatase
Lipid phosphatase
His phosphatase
Tyr phosphatase
Dephosphorylation
Fecha de publicación2016
EditorJohn Wiley & Sons
Federation of European Biochemical Societies
CitaciónFEBS Journal 283(8): 1404-1429 (2016)
ResumenTyr phosphatases are, by definition, enzymes that dephosphorylate phospho-Tyr (pTyr) from proteins. This activity is found in several structurally diverse protein families, including the protein Tyr phosphatase (PTP), arsenate reductase, rhodanese, haloacid dehalogenase (HAD) and His phosphatase (HP) families. Most of these families include members with substrate specificity for non-pTyr substrates, such as phospho-Ser/phospho-Thr, phosphoinositides, phosphorylated carbohydrates, mRNAs, or inorganic moieties. A Cys is essential for catalysis in PTPs, rhodanese and arsenate reductase enzymes, whereas this work is performed by an Asp in HAD phosphatases and by a His in HPs, via a catalytic mechanism shared by all of the different families. The category that contains most Tyr phosphatases is the PTP family, which, although it received its name from this activity, includes Ser, Thr, inositide, carbohydrate and RNA phosphatases, as well as some inactive pseudophosphatase proteins. Here, we propose an extended collection of human Tyr phosphatases, which we call the extended human PTPome. The addition of new members (SACs, paladin, INPP4s, TMEM55s, SSU72, and acid phosphatases) to the currently categorized PTP group of enzymes means that the extended human PTPome contains up to 125 proteins, of which ~ 40 are selective for pTyr. We set criteria to ascribe proteins to the extended PTPome, and summarize the more important features of the new PTPome members in the context of their phosphatase activity and their relationship with human disease. Dephosphorylation of phospho-Tyr from proteins is exerted by several protein families, including Cys-, Asp-, and His-based PTPs, and several PTPs display substrate specificity towards non-phospho-Tyr substrates, such as phospho-Ser/Thr or phospho-inositides, among others. Here, we define criteria to ascribe proteins to the Tyr phosphatase family (extended PTPome), present an open list of PTPome members, and summarize their more important features and their relation with human disease.
URIhttp://hdl.handle.net/10261/157790
DOI10.1111/febs.13600
Identificadoresdoi: 10.1111/febs.13600
issn: 1742-464X
e-issn: 1742-4658
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