Human HAD phosphatases: structure, mechanism, and roles in health and disease
Open Access
- 13 June 2012
- journal article
- review article
- Published by Wiley in The FEBS Journal
- Vol. 280 (2), 549-571
- https://doi.org/10.1111/j.1742-4658.2012.08633.x
Abstract
Phosphatases of the haloacid dehalogenase (HAD) superfamily of hydrolases are an ancient and very large class of enzymes that have evolved to dephosphorylate a wide range of low- and high molecular weight substrates with often exquisite specificities. HAD phosphatases constitute approximately one-fifth of all human phosphatase catalytic subunits. While the overall sequence similarity between HAD phosphatases is generally very low, family members can be identified based on the presence of a characteristic Rossmann-like fold and the active site sequence DxDx(V/T). HAD phosphatases employ an aspartate residue as a nucleophile in a magnesium-dependent phosphoaspartyl transferase reaction. Although there is genetic evidence demonstrating a causal involvement of some HAD phosphatases in diseases such as cancer, cardiovascular, metabolic and neurological disorders, the physiological roles of many of these enzymes are still poorly understood. In this review, we discuss the structure and evolution of human HAD phosphatases, and summarize their known functions in health and disease.Keywords
This publication has 103 references indexed in Scilit:
- To live or to die: a matter of processing damaged DNA termini in neuronsEMBO Molecular Medicine, 2011
- Structural and functional analysis of the phosphoryl transfer reaction mediated by the human small C‐terminal domain phosphatase, Scp1Protein Science, 2010
- Markers of fitness in a successful enzyme superfamilyCurrent Opinion in Structural Biology, 2009
- From Promiscuity to Precision: Protein Phosphatases Get a MakeoverMolecular Cell, 2009
- The Structure of Fcp1, an Essential RNA Polymerase II CTD PhosphataseMolecular Cell, 2008
- Mutations in LPIN1 Cause Recurrent Acute Myoglobinuria in ChildhoodAmerican Journal of Human Genetics, 2008
- Essential Phosphatases and a Phospho-Degron Are Critical for Regulation of SRC-3/AIB1 Coactivator Function and TurnoverMolecular Cell, 2008
- A Phenotypic Small-Molecule Screen Identifies an Orphan Ligand-Receptor Pair that Regulates Neural Stem Cell DifferentiationCell Chemical Biology, 2007
- Diversification of function in the haloacid dehalogenase enzyme superfamily: The role of the cap domain in hydrolytic phosphoruscarbon bond cleavageBioorganic Chemistry, 2006
- Determinants for Dephosphorylation of the RNA Polymerase II C-Terminal Domain by Scp1Molecular Cell, 2006