Protein Kinase Classification

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AGC | ATYPICAL | CAMK | CK1 | CMGC | OTHER | STE | TKL

Link to a list of Dictyostelium protein kinases

Protein Kinase Resources

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AGC

The AGC group of serine/threonine kinases is named after their homology to protein kinases A, G, and C. This includes PKA (e.g. pkaC) and PKG (cyclic nucleotide regulated protein kinases), PKC (diacylglycerol-activated/phospholipid-dependent protein kinase C), and related kinases such as AKT/PKB (phosphoinositide-regulated kinases) (e.g. pkbA), NDR (nuclear Dbf2-related kinases), PDK (phosphoinositide-dependent protein kinases), and RSK (ribosomal S6 kinases).

ATYPICAL

The Atypical kinases (aPKs) have no homology to conventional eukarytic protein kinases (ePKs). The families in this protein kinase group are also unrelated to each other and the only thing in common is the absence of a typical ePK domain.

• The A6 family (Twinfilin/PTK9 family) consists of human Ag and A6r genes, which has homologs in fly, worm, and yeast. However, kinase activity has only been shown for human A6.
• ABC1 domains (kinase-like domains) show a low degree of similarity to ePK domains. Yeast ABC1 is essential for the electron transfer in the BC(1) complex; in E.coli AarF is required for coenzyme Q (ubiquinone) biosynthesis.
• ALPHA kinases include elongation factor 2 (eEF-2) kinase and Dictyostelium myosin heavy chain kinases (MHCKs) (e.g. mhkA). The name 'Alpha kinase' comes from existing evidence that both eEF-2 kinase and mhkA phosphorylate amino acids located within alpha-helices, not within loops or irregular structures like ePKs.
• Best known as a fusion partner of the ABL tyrosine kinase in chronic myelogenous leukemia, BCR (Breakpoint Cluster Region) itself has protein kinase activity.
• BRD (Bromodomain) proteins are found in a variety of eukaryotic DNA-binding proteins and may be involved in protein-protein interactions.
• The G11 family is based on a single human serine/threonine kinase called STK19 or G11. Homologs are found in rat and mouse and a more divergent relative has been identified in zebrafish.
• While histidine phosphorylation has been known to be present in mammals, Histidine Kinases (HISTK) have been identified and studied extensively in bacteria and lower eukaryotes. Here they form a "two-component" signal transduction system, activated by a variety of external signals. In Dictyostelium 14 histidine kinases have been identified (e.g. dhkA).
• The RIO (Right Open reading frame) family has 3 subfamilies, RIO1, -2, and -3, with uncharacterized function. Yeast serine/threonine kinase RIO1 plays a role in cell cycle progression. While the sequences of the RIO family members do not align with the ePK domain, many of the catalytic residues are strongly conserved.
• TAF1 (TATA binding factor associated factor) exists in all fully sequenced eukaryotes and is a component of the basal transcription machinery.
• TIF is a family of three human Transcriptional Intermediary Factor 1 genes, of which TIF1 has been shown to be a protein kinase.

CAMK

CAM kinase stands for Calcium/Calmodulin-dependent kinase, which belong to the serine/threonine kinases. Despite the high sequence similarity of Dictyostelium myosin light chain kinase mlkA (MLCK-A) with calcium/calmodulin-dependent protein kinases including myosin light chain kinases from higher eukaryotes, it was shown that MLCK-A is not activated by calcium/camodulin. However, because of strong similarity, several Dictyostelium CAMK kinases fall into the MLCK family. Other families in the CAMK group include CAMK1 (similar to mammalian CAM kinase type 1), CAMKL (contains AMP kinases, MARK, Kin1 kinases), DAPK (Death Associated Kinase), and RAD53 (similar to mammalian cell cycle checkpoint kinases chk2 and yeast cell cycle arrest kinase RAD53 [Radiation sensitive]).

CK1

Members of the Casein kinase I (CK1) group of serine/threonine kinases are conserved from yeast to man. In Dictyostelium 2 CK1 kinases have been identified: the cloned gene cak1 is highly similar to the yeast and metazoan CK1 family and seems to play a role in DNA repair; the second gene is very similar to the TTBK family (Tau-Tubulin Kinase) of casein kinases, which phosphorylates the microtubule-associated protein tau implicated in Alzheimer's disease.

CMGC

CMGC kinases are mostly serine/threonine kinases. This group includes the CDK family (Cyclin-Dependent Kinase), the MAPK family (Mitogen-Activated Protein Kinase), the GSK family (Glycogen Synthase Kinase), the DYRK family (Dual specificity Tyrosine Regulated Kinase), and the dual specificity CLK family (CDC2-Like Kinase).

OTHER

The Other kinase group consists of many diverse families, most of which are serine/threonine protein kinases. These conserved families do not share significant levels of homology with any other kinase group, and therefore are classified together in the irregular Other group.

• Members of the Aurora (AUR) kinase family are known to play a role in mitotic spindle formation. In mammals, three Aurora kinases are present: aurA, aurB, and aurC. Only one Aurora family kinase, aurB, appears to be present in the Dictyostelium genome.
• BUD32 kinase in Saccharomyces cerevisiae is involved in bud formation, while its mammalian homolog, p53-related protein kinase, functions in tumor suppression.
• CK2 (Casein kinase II) family members have been shown to phosphorylate numerous substrates. Two CK2 alpha subunits join with two beta subunits to form a tetrameric complex; the alpha chain casK in Dictyostelium has been previously characterized.
• The IRE (Inositol-requiring) family of serine/threonine protein kinases plays a role in the unfolded protein response. IRE kinases (named ERN, ER to nucleus signaling, in humans) contain an endoribonuclease domain in addition to a protein kinase domain.
• The NAK (Numb-associated kinase) family of serine/threonine protein kinases were originally identified in Drosophila melanogaster, where NAK interacts with the neuronal differentiation protein Numb. Members of the NAK family are involved in many different biological processes, including tissue differentiation, endocytosis, and cell signaling.
• NEK family kinases are related to the NimA (Never in mitosis) kinase found in Aspergillus nidulans. In Dictyostelium, 10 putative NEK family kinases have been identified in addition to nek2, which has been previously charaterized.
• The GCN2 (an acronym for General Control Non-derepressible) proteins, also known as PEK (Pancreatic Eukaryotic initiation factor-2alpha Kinase), inhibit translation via phosphorylation of eIF2 (eukaryotic Initiation Factor 2). Two members of this family have been previously identified in Dictyostelium: ifkA and ifkB.
• PLK (Polo-like kinase) family members play a role in formation of the mitotic spindle. One PLK has been described in Dictyostelium, however, its function in mitosis has yet to be determined.
• SCY1 protein kinase is also known as NTKL (N-terminal kinase-like). Human NTKL is found in the cytoplasm and localizes to the centrosomes during mitosis.
• The TTK gene family encodes dual-specificity kinases. The TTK family kinase mps1 was originally identified in Saccharomyces cerevisiae as a monopolar spindle mutant defective in centrosomal duplication during cell division.
• Members of the VPS (Vacuolar Protein Sorting) family of serine/threonine protein kinases regulate the phosphatidylinositol 3 kinase VPS34. Orthologs include p150 in humans and VPS15 in budding yeast.
• The WEE kinases regulate progression through the cell cycle via phosphorylation of CDKs (cyclin-dependent kinases). Three WEE kinases are present in Schizosaccharomyces pombe and in animals; interestingly, three putative members of the WEE family have been identified in Dictyostelium.

STE

The name STE stands for "Sterile," serine/threonine kinases originally identified in yeast where they are involved in the mating signalling pathway. Families include the kinases of Mitogen-Activated Protein Kinase (MAPK): STE7 (includes MAPKK, MAP2K), STE11 (includes MAP2K and MAPKKK, MAP3K), and the largest family, STE20, which has several subfamilies (e.g. PAKA, PAKB, YSK, SLK; includes MAPKKKK, MAP4K).

TKL

The Dictyostelium genome does not contain 'mono-specific' tyrosine kinases or receptor tyrosine kinases, however, there is a high number of TKL(Tyrosine Kinase-Like) kinases. TKL is a diverse group of families that resemble both serine/threonine and tyrosine kinases, and often function as dual-specifity kinases. It consists of the MLK (Mixed Lineage Kinases), LISK (sub-families LIMK (LIM kinase) and TESK (Testicular protein Kinase)), RAF (name from the retroviral oncogene v-raf), and LRRK (Leucine Rich Repeat Kinase) families.

PROTEIN KINASE RESOURCES

The Protein Kinase Resource (PKR)
Kinase.com
KinG: Kinases in Genomes
Histidine Protein Kinases (HPKs)
MAPK Resource Home page
InterPro: Protein kinase
EC 2.7.1