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      <page pageid="2410" ns="0" title="Standard Kinase Classification Scheme">
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          <rev contentformat="text/x-wiki" contentmodel="wikitext" xml:space="preserve">The standard protein kinase classification scheme &lt;cite&gt;Manning2002a, Manning2002b&lt;/cite&gt; classifies protein kinases into groups, families, and subfamilies, on the basis of their functions, their sequence and structural similarity, and their evolutionary history.  The system is highly curated and designed to be of maximal practical value, rather than created by absolute rules. '''Groups''' generally relate to broad substrate site specificity (e.g. TKs phosphorylate on tyrosine, and CMGC usually phosphorylate residues next to proline), '''Families''' group related kinases by both sequence similarity and broad biological function, and some but not all families are subdivided into '''Subfamilies''' that have finer sequence and functional similarity and are generally still conserved at least between multiple phyla. 


===History of Kinase Classification===
This kinase classification was first published by Manning and colleagues from Sugen in 2002 in papers covering the human kinome &lt;cite&gt;Manning2002a&lt;/cite&gt; and the yeast, worm, and fly kinomes &lt;cite&gt;Manning2002b&lt;/cite&gt;. This scheme was largely built on and early 1995 scheme by Hanks and Hunter &lt;cite&gt;Hanks&lt;/cite&gt;, extending it from 5 groups, 44 families and 51 subfamilies to 9 groups, 134 families and 196 subfamilies.

The classification has been continuously revised since then, largely by the [http://manninglab.org Manning lab] at the Salk Institute. A few notable changes are: 

* The Atypical group used to cover all kinases not in the ePK superfamily. This has now been split into [[PKL]] (kinases that share a fold with [[ePK]]s but are in different superfamilies), HisK (histidine kinase fold kinases), NDK (nucleoside diphosphate kinases), and the remaining Atypical kinases that belong to several structural folds that are not known to generally have kinase activity.

* Extensive additional subfamilies have been added for non-human species.

* Additional subfamilies have been created for kinases that have distinct orthologs across multiple phyla


===Additional Notes===
* Several publications use this classification but have mixed up the classification levels, in particular referring to groups as families or families as subfamilies.

* The scheme is not completely monophyletic, and relies on several &quot;left-over&quot; groups to simplify the classification: in particular, [[Kinase_Group_Atypical|Atypical]] includes many unrelated kinases; the [[Kinase_Group_PKL|PKL group]] contains all PKL-fold kinases that are not ePKs, and the [[Kinase_Group_Other|Other]] group includes all ePKs that do not fit into any other group. 


===References===
&lt;biblio&gt;
#Hanks pmid=7768349
#Manning2002a pmid=12471243
#Manning2002b pmid=12368087
&lt;/biblio&gt;</rev>
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      <page pageid="1361" ns="0" title="TKL-Sp1 Draft Analysis">
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          <rev contentformat="text/x-wiki" contentmodel="wikitext" xml:space="preserve">__NOTOC__
[[kinase classification|Kinase Classification]]: [[Kinase_Group_TKL|Group TKL]]: [[Kinase_Family_TKL-Sp1|Family TKL-Sp1]]: [[TKL-Sp1 Draft Analysis]]

====Draft Analysis of TKL-Sp1====
This data is preliminary, incomplete, and may even be incorrect in areas. It is presented here to share early unpublished results that might otherwise languish. Please use with caution and credit the Manning lab if you wish to publish this data or conclusions from it.

====Sequences and Phylogeny====

=====Vertebrate Members=====
TKL-Sp1 is found in all fish and one amphibian. One member from Danio is published as 'CBL-interacting protein kinase 26-like' (XP_002665081.2). It, and a Medaka homolog are fully covered by ESTs apart from the C-terminal end. Genomic predictions show homologs in Stickleback (2 copies), Fugu and Tetraodon. A single EST from the amphibian axolotl (gb|CO779758.1) is also clearly orthologous, but not other evidence of tetrapod homologs could be found (Aug 2011).

The conserved start of the fish members is supported by some upstream EST coverage in Danio which is not conserved and the presence of an upstream stop in a trout EST.

=====Other Deuterostomes=====
Independent expansions of the TKL-Sp1 family are seen in the hemichordate Saccoglossus, with 4 members (two very similar pairs) and the sea urchin (echinoderm) Strongylocentrotus purpuratus, with 10 members. Many of the urchin members have putative upstream regions, some composed of ankyrin repeats (common in many urchin kinases), though these sequences have no EST coverage. A single homolog is seen in the chordate Branchiostoma, and none is seen in either Ciona genome.

=====Other Animals=====
Searches of genome predictions, NRAA and EST databases show two orphan members of TKL-Sp1, in widely divergent species: the wasp, Nasonia vitripennis, and the Cnidarian, Nematostella vectensis. These have no homologs in other insects or other cnidarians, respectively.

====Sequences and Alignments====
An initial alignment of the above sequences is found at [http://kinase.com/wikifiles/tkl-sp1.aln tkl-sp1.aln].

[[User:Gerard|Gerard]] 07:10, 4 August 2011 (PDT)</rev>
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