View source for Kinase Group Atypical

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[[kinase classification|Kinase Classification]]: [[Kinase_Group_Atypical|Atypical Group]]

The Atypical protein kinases (aPK) group is now split into several structural categories. All aPKs lack sequence similarity to the ePK domain HMM profile, but have been shown experimentally to have protein kinase activity or are clear homologs of other aPKs. All eukaryotic aPK families are small, several having just one member in vertebrates, and none in invertebrates. Other aPK families may remain to be discovered by biochemical methods, but since most atypical families are small, and most biochemically-discovered kinases are ePKs, it is unlikely that many new atypical kinases will be discovered. Conversely, some of these aPKs may be false positives, if the reports of kinase activity are not correct.  


==Structural homologs of ePKs==
Several kinases previously defined as "Atypical" are now known to share the same [[PKL]] fold and catalytic mechanism as ePKs. These have been reclassified to a new group, called [[Kinase_Group_PKL|PKL]].


==Structural Homologs of other kinase enzymes==

====[[Kinase_Family_PDHK|PDHK]]: Pyruvate Dehydrogenase Kinases====
This family of mitochondrial kinases contains a domain which is similar to prokaryotic histidine kinases, but has been shown biochemically to phosphorylate serine rather than histidine. Crystal structures confirm that the PDHK domain fold is similar to that of histidine kinases, distinct from the ePK domain <cite>Machius, Steussy</cite>.

====[[Kinase_Group_NDK|NDK]]: Nucleoside diphosphate Kinases====
This universal group is known to phosphorylate NDPs to make NTPs, using a phospho-histidine intermediate, but has also been reported to have protein kinase activity in mammals, Drosophila and ciliates.

====[[Kinase_Group_PyK|PyK]]: Pyruvate Kinase====
Human Pyruvate Kinase M2 (PKM2) phosphorylates ADP in a key step of glycolysis. Recent findings indicate that PKM2 also has protein tyrosine kinase activity, and possibly histidine kinase activity that is tied to cell proliferation regulation in cancer. No other form of pyruvate kinase has been implicated as a protein kinase.


==[[Kinase_Group_SAPPK|SAPPK]]: Structurally Atypical Putative Protein Kinases==
Several proteins have reported protein kinase biochemical activity but are not members of any known kinase fold or have a known mechanism of phosphotransfer. Most have only one or a few papers supporting their kinase activity. Since some proteins (see below) are now thought to be non-kinases, despite initial supporting evidence, it may be that many of these proteins are not bona fide kinases, but can bind tightly to other kinases and so show activity. Many are known to autophosphorylate but not transphosphorylate, suggesting that if they are kinases, they have a limited substrate range.



=== References ===
<biblio>
#Machius pmid=11562470
#Steussy pmid=11483605
</biblio>