Histone Serine/threonine/tyrosine kinases

Protein phosphorylation is the function of members of protein kinase superfamily. They harbour a characteristic kinase domain. This kinase domain catalyses the transfer of gamma-phosphate group from a donor like ATP/GTP, specifically to the serine, threonine or tyrosine residues of the protein substrates. There are a large number of protein kinases and their classification is difficult.

Protein kinases are broadly classified into:

AGC (Cyclic nucleotide-regulated protein kinase) group: These are basic amino acid directed enzymes. There substrates have serine/threonine rediues in proximity to arginine or lysine residues. Examples of some families: PKC, RAC, beta-ARK, RhK, ribosomal S6 kinase.

CaMK (Ca+/Calmodulin regulated kinases) group: These are also basic amino acid directed enzymes like AGC. Most of these enzymes are activated by Calcium or calmodulin binding to the C terminal end of the catalytic domain. Examples of some families: CaMK1/2/4, EF2K, PhK, MLCK, Snf1/AMPK.

CMGC (cyclin-dependent kinases; CDKs) group: Enzymes in this large group mostly have affinity for substrates that have target site within a proline rich environment. A characteristic of this group is the large kinase domain due to insertions. Examples of some families: cdc2, cdk2, Erk/MAP kinase, GSK3.

Protein-Tyrosine Kinase group: The members of this group are capable of exclusively phosphorylating tyrosine residues. Glutamic acid on the amino or carboxyl end of the acceptor is majorly the preferred site. They play a significant role in signal transduction. A number of enzymes in this group are membrane bound receptors. Examples of some families: HRI, PKR/Tik, Gcn2.

Others include protein kinases with dual specificity. They are capable of phosphorylating Serine/threonine as well as Tyrosine residues. Examples of some families: MEK/Ste7, Wee1/Mik1 families.

Here we list 29 unique kinases found in humans through literature that show specificity towards histones in in vitro and in vivo conditions. Protein kinases have very important role in signal transduction and are critical components of multiple signalling pathways that exist in eukaryotic cells. Hence, protein kinases are heavily implicated in many cellular processes. DNAPK, ATM, ATR, MST1 are important kinases that mediate DNA damage response by phosphorylation of histone H2AX. IKK alpha, MSK1 and MST1 directly or indirectly regulate NF-kB signalling. Other processes include DNA repair pathways, cell cycle progression, transcriptional regulation of Hox genes and E2F target genes, nuclear hormone signalling and chromatin remodelling. Protein kinases are also implicated in many cancers like prostrate cancers, gastric cancers, types of blood cancers, breast cancers. Of particular interest is WSTF that bears no homology to any tyrosine kinase fold but still catalyses tyrosine phosphorylation.

Further reading: PMID: 7768349.

Cytogenetic map of Serine/threonine/tyrosine kinases coding genes
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Different histone Serine/threonine/tyrosine kinases
Enzyme (UniprotKB recommended name) Coding gene/s Site of histone modification
Cyclin-dependent kinase 17CDK17
Cyclin-dependent kinase 3CDK3
Cyclin-dependent kinase 5CDK5
Death-associated protein kinase 3DAPK3H3T11ph
DNA-dependent protein kinase catalytic subunitPRKDCH2AS139ph
Glycogen synthase kinase-3 betaGSK3BH1T10ph
Inhibitor of nuclear factor kappa-B kinase subunit alphaCHUKH3S10ph
LIM domain kinase 2LIMK2
Microtubule-associated serine/threonine-protein kinase-likeMASTL
Mitogen-activated protein kinase kinase kinase 8MAP3K8H3S10ph
Mitogen-activated protein kinase kinase kinase MLTUnknownH3S28ph
Mitotic checkpoint serine/threonine-protein kinase BUB1BUB1H2AT120ph
Protein kinase C beta typePRKCBH3T6ph
Protein kinase C delta typePRKCDH3T45ph
Ribosomal protein S6 kinase alpha-4RPS6KA4H3S28ph
Ribosomal protein S6 kinase alpha-5RPS6KA5H2AS1ph, H3S10ph, H3S28ph
Serine-protein kinase ATMATMH2AS139ph
Serine/threonine-protein kinase 10STK10
Serine/threonine-protein kinase 12AURKBH3S10ph, H3S6ph, H3S28ph
Serine/threonine-protein kinase 4STK4H2BS14ph, H2AS139
Serine/threonine-protein kinase ATRATRH2AS139ph
Serine/threonine-protein kinase haspinGSG2H3T3ph
Serine/threonine-protein kinase N1PKN1H3T11ph
Serine/threonine-protein kinase Nek6NEK6
Serine/threonine-protein kinase Nek9NEK9
Serine/threonine-protein kinase PAK 2PAK2H3S10ph
Serine/threonine-protein kinase tousled-like 1TLK1H3S10ph
Tyrosine-protein kinase BAZ1BBAZ1BH2AY142ph
Tyrosine-protein kinase JAK2JAK2H3Y41ph