View source for Kinase Family COL4A3BP

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[[kinase classification|Kinase Classification]]: [[Kinase_Group_SAPPK|Group SAPPK]]: [[Kinase_Family_COL4A3BP|Family COL4A3BP]]

Col4A3BP is a human putative protein kinase that lacks sequence similarity to any other kinases.

====Evolution====
Col4A3BP is found in animals and choanoflagellates, usually as a single copy.

====Domain Structure====
Col4A3BP has PH (lipid association) and START (lipid transport) domains, but nothing related to any known kinase domain.

====Function====
This binding protein for Collagen COL4A3 (Goodpasture antigen) is involved in intracellular transport of ceramide in the ER/Golgi.  Affinity purified, FLAG-tagged protein from yeast and 293 cells was found to bind and phosphorylate COL4A3 <cite>Raya</cite>. The kinase activity was validated by renaturation: SDS-PAGE produced a major band of 89kDa, which gave kinase activity when blotted and renatured, though the band was broad, and one other band was seen on the gel presented. In unpublished data, kinase activity was seen in deletion mutants that migrated at different sizes, and the kinase activity again matched the size of the protein. Excision of the 89 kDa band of the blot before running the assay (to prevent contamination of a kinase that might migrate in-blot), showed that the kinase activity mapped specifically to that region. Bovine COL4A3 could not be phosphorylated by COL4A3BP under similar conditions, despite 97% AA identity to human and conservation of Ser9 and absolute conservation of the first 21 AA which form the substrate site in the assay. The yeast-derived protein was already phosphorylated on Ser, Thr, and Tyr. The human protein is a target of CK1g2 and PKD kinases, which may regulate ceramide transport, and it is known to interact with the MARK2 and CK1g2 kinases in large scale protein-interaction screens (so it is weakly possible that one of these is copurifying in the biochemical assay). The kinase-associated region has not been mapped.

Another group, using a similar immunoprecipitation and kinase assay, showed that another SAPPK, BLVRA, could bind Col4A4BP and downreglate its kinase activity <cite>Miralem</cite>.

While the biochemical validation is strong, the lack of follow-on studies, or mapping of the kinase activity within the protein all leave some question as to whether this protein is an intrinsic kinase, or has a tightly-bound, copurifying kinase partner.

====References====
<biblio>
#Miralem pmid=20177069
#Raya pmid=10212244
</biblio>