TESK1 is a 65.1 kDa dual specificity protein kinase from the TESK superfamily. It phosphorylates serine, threonine and tyrosine. It has a role in actin cytoskeleton organisation by phosphorylation Ser-3 in Cofilin to cause inhibition of TESK1 and when mutated can lead to tumour growth and dysregulation. It is ubiquitous but is expressed highly in testicular tissue giving the hypothesis that it may play a role in spermatogenesis and developmental processes. TESK1 is crucial for actin reorganisation and actin functions in motility, adhesion, secretion, cytokinesis, and morphological change. Expression was also found to be high in the Adrenal Cortex, Lung, Heart, and NK cells.

 

As well as inhibiting Cofilin it inhibits TAOK. Additionally, if Tao1 binds to Spread1, TESK1 activity is inhibited regulating expression levels. TESK1 can also bind to actopaxin and 14-3-3 allow the regulation of actin and microtubules.

 

In humans there are three isoforms that show some sequence comparison. TESK1 has 12 subdomains with a conserved VIB subdomain within which is an uncommon ‘DLTSKN’ sequence motif. The gene for TESK1 in homo sapiens is found on chromosome 9 at position 9p13.

The TESK1 gene is conserved in humans, chimpanzees, Rhesus monkeys, dogs, cows, mice, rats, and zebrafish.

 

Overall quaternary structure of TESK1 has not been determined yet by NMR or X-ray crystallography. However secondary and tertiary structure predicting prgrammes and domain analysis can help to predict the structure of TESK1.

 

The PHYRE analysis of TESK1 showed mostly disordered regions and alpha helical secondary structure, however this is limited as there is a large proportion of disordered regions. The most confident prediction was the protein kinase domain (40-330 residues). However the Ramanchandran Plot suggests this is not an accurate prediction of the whole structure of TESK1. The Kyte-Doolittle shows that TESK1 is very hydrophilic and this suggests it is a cytosolic protein and mostly likely is due to its involvement in regulating cellular functions. From the Pfam analysis, it is shown that the protein contains only one conserved functional domain, the Protein Kinase domain (57-311 residues).

 

However, the predictive software used is rather unreliable and only takes into account certain variables, yielding inconclusive results. For example, compartments predicts the TESK1 to reside in the cytoplasm and the Phobius prediction did not. 

 

To conlude, it is clear that TESK1 possesses a Kinase domain. However, none of the analytical methods employed were successful in predicting the structure or function of the rest of TESK1's sequence. Despite this, it is clear that TESK1 plays an important role in cytoskeletal remodelling through interacting with other proteins. This fact leads to the postulation that perhaps the domain/s from residues 300-626 are involved in the binding of proteins such as SPRY1. But the mechanism of this interaction is unclear. Overall, it is unlikely that bioinformatical analysis will yield a more conclusive picture of TESK1’s structure/domains/function. Further experimentation is needed to elucidate its precise nature within the cell.