View source for Kinase Family STK33

__NOTOC__
[[kinase classification|Kinase Classification]]: [[Kinase_Group_CAMK|Group CAMK]]: [[Kinase_Family_STK33|Family STK33]]

STK33 is a CAMK-like kinase implicated in cancer growth pathways.

====Evolution====
STK33 is found in animals and some fungi (chytrids) but is lost in both Drosophila and C. elegans and related species (all nematodes, and almost all Dipteran insects).

====Domain Structure====
STK33 is about 500 AA long, with a kinase domain in the middle, and unannotated sequences on either side that are poorly conserved in vertebrates and absent from many invertebrate gene predictions. A short region of ~15 AA is conserved at the N-terminal edge of the kinase and ~11 AA on the C-terminal edge. Alphafold shows no structure outside of the kinase domain other than a short predicted helix, and InterProscan predicts disorder in most of the terminal regions.

===Expression===
Human STK33 is most highly expressed in testis, but is found in all tissues, particularly in ciliated cells (Proteinatlas). It is found in the cytoplasm, nucleoplasm and nucleoli.

====Functions====
STK33 has been implicated in development of many cancers. STK33 overexpression drove proliferation, migration and EMT and knockdown inhibited growth and activated apoptosis in cell lines from several cancers, including pancreatic <cite>Kong</cite>, small cell lung cancer <cite>Sun</cite>, gastric <cite>Kong2</cite>, hepatocellular carcinoma (HCC) <cite>Yang</cite>, large cell lung cancer <cite>Wang</cite>, as well as in mouse models of HCC.

Molecularly, STK33 is known to autophosphorylate  <cite>Brauksiepe</cite>, to bind and phosphorylated ERK2 <cite>Zhang</cite>, and to bind to and activate c-myc in liver cells <cite>Yang</cite>, both of which may be pro-oncogenic. It also binds to and phosphorylates the N-terminal portion of vimentin <cite>Brauksiepe </cite>. 

STK33 is induced by HIF1a in pancreatic cancer <cite>Kong</cite>, and it binds and is stabilized by the HSP90/CDC37 chaperone complex <cite>Azoitei</cite>. An initial report indicating a synthetic lethal role in Kras-driven cancers <cite>Scholl</cite> has since been refuted <cite>Babji</cite>. In SCLC cells, it activated S6K1/BAD signaling <cite>Sun</cite>. In NSCLC cell lines and tissue, the micro-RNA miR-107 suppresses growth and downregulates STK33<cite>Wei</cite>.

The STK33 locus has also been implicated by GWAS with obesity <cite>Rask-Andersen</cite>, and in tyrosine metabolism: STK33 phosphorylates HPD (4-hydroxyphenylpyruvic acid dioxygenase) on T382, recruiting the FHA domain-containing PELI1, which induces ubiquitin-mediated degradation of HPD <cite>Xie</cite>.

====References====
<biblio>
#Scholl pmid=19490892
#Babji pmid=21742770
#Kong pmid=29038348
#Sun pmid=28895411
#Rask-Andersen pmid=23967198
#Zhang pmid=30760631
#Kong2 pmid=29367428
#Yang pmid=25398772
#Wang pmid=25662617
#Azoitei pmid=22451720
#Xie pmid=31537781
#Brauksiepe pmid=18811945
#Wei pmid=32395291
</biblio>