CLK3(2EU9)

CLK3(2EU9)

CLK3: Human cdc-2 like kinase 3
PDB Code: 2EU9
Description
The Clk family consists in human of four kinases that display so-called dual specificity, i.e., they are capable of phosphorylating both Ser/Thr as well as Tyr residues. CLK homologues have been isolated from a number of organisms including Arabidopsis, Drosophila, mouse and human. The kinase domain of CLK family members is located at the C terminus and contains the family signature motif ‘EHLAMMERILG’, giving rise to the name of these kinases: ‘LAMMER’ kinases.
It has been shown that CLK family members play a pivotal role controlling splicing by regulating members of the SR family of splicing factors. Both CLK3 and CLK1 have been shown to tightly associate with splicing factors and to phosphorylate them at multiple sites. It is therefore not surprising that inactivating mutation in CLK results in drastic phenotypes. In Drosophila mutation in the Lammer kinase DOA (darkener of apricot) alter sexual differentiation and activity of DOA is required for development of embryonic tissues. In addition, non-functional DOA leads to defects in body segmentation, eye formation, and neuronal development.
High levels of CLK3 expression are found in mature spermatozoa where CLK3 is localized in the spermatozoa acrosome and tail. Interestingly CLK3 is released from sperm during the acrosome reaction suggesting that CLK3 may play role in the fertilization process.
Furthermore it has been shown that expression of all CLK family members is up-regulated during hexamethylene bisacetamide induced murine erythroleukemia cell differentiation and a potential therapeutic use of CLK3 has been suggested for the treatment of frontotemporal dementia and parkinsonism linked to chromosome 17.

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