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A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets. Most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.
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, 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, conceptually similar to the kinase and pseudokinase domain polypeptide structure of the JAK pseudokinases. A complete comparative analysis of human phosphatases and pseudophosphatases has been completed by Manning and colleagues, forming a companion piece to the ground-breaking analysis of the human kinome, which encodes the complete set of ~536 human protein kinases.
Protein tyrosine phosphatases (EC 3.1.3.48, systematic name protein-tyrosine-phosphate phosphohydrolase) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins:
A serine/threonine protein kinase is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human protein kinases are serine/threonine kinases (STK).
A protein kinase inhibitor (PKI) is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that phosphorylate (add a phosphate, or PO4, group) to a protein and can modulate its function.
Mitogen-activated protein kinase 1, also known as ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.
Serine/threonine-protein kinase D1 is an enzyme that in humans is encoded by the PRKD1 gene.
Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode for at least five different isoforms.
Dual specificity protein kinase CLK1 is an enzyme that in humans is encoded by the CLK1 gene.
Dual specificity protein kinase CLK2 is an enzyme that in humans is encoded by the CLK2 gene.
Serine/threonine-protein kinase PRP4 homolog is an enzyme that in humans is encoded by the PRPF4B gene.
Dual specificity tyrosine-phosphorylation-regulated kinase 1B is an enzyme that in humans is encoded by the DYRK1B gene.
Protein phosphorylation is a reversible post-translational modification of proteins in which an amino acid residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. Phosphorylation alters the structural conformation of a protein, causing it to become activated, deactivated, or otherwise modifying its function. Approximately 13,000 human proteins have sites that are phosphorylated.
Fas-activated serine/threonine kinase is an enzyme that in humans is encoded by the FASTK gene.
Maternal embryonic leucine zipper kinase (MELK) is an enzyme that in humans is encoded by the MELK gene. MELK is a serine/threonine kinase belonging to the family of AMPK/Snf1 protein kinases. MELK was first identified present as maternal mRNA in mouse embryos. MELK expression is elevated in a number of cancers and is an active research target for pharmacological inhibition.
Dual specificity protein phosphatase 7 is an enzyme that in humans is encoded by the DUSP7 gene.
Mitogen-activated protein kinase 4 is an enzyme that in humans is encoded by the MAPK4 gene.
Dual specificity tyrosine-phosphorylation-regulated kinase 2 is an enzyme, in particular a dual-specificity kinase, that in humans is encoded by the DYRK2 gene.
Serine/threonine-protein kinase LMTK2 also known as Lemur tyrosine kinase 2 (LMTK2) is an enzyme that in humans is encoded by the LMTK2 gene.
Dual-specificity phosphatase is a form of phosphatase that can act upon tyrosine or serine/threonine residues.
References
- Dhanasekaran N, Premkumar Reddy E (1998). "Signaling by dual specificity kinases". Oncogene. 17 (11 Reviews): 1447–1455. doi: 10.1038/sj.onc.1202251 . PMID 9779990.
- Ali N, Halfter U, Chua NH (1994). "Cloning and biochemical characterization of a plant protein kinase that phosphorylates serine, threonine, and tyrosine". J. Biol. Chem. 269 (50): 31626–9. PMID 7527390.
- Lauze E, Stoelcker B, Luca FC, Weiss E, Schutz AR, Winey M (1995). "Yeast spindle pole body duplication gene MPS1 encodes an essential dual specificity protein kinase". EMBO J. 14 (8): 1655–63. PMC 398258 . PMID 7737118.
- Menegay HJ, Myers MP, Moeslein FM, Landreth GE. "Biochemical characterization and localization of the dual specificity kinase CLK1". J. Cell Sci. 113: 3241–53. PMID 10954422.
- Cleghon V; Sibbet, G; Kinstrie, R; Cleghon, T; Rylatt, M; Morrison, DK; Cleghon, V (2003). "dDYRK2: a novel dual-specificity tyrosine-phosphorylation-regulated kinase in Drosophila". Biochem. J. 374 (Pt 2): 381–91. doi:10.1042/BJ20030500. PMC 1223608 . PMID 12786602.
