protein degradation

The FHA-domain: a common motif found in nuclear kinases and: "The majority of intracellular protein degradation takes place at the proteasome, a multi-subunit protease present in the cytoplasm and the nucleus of eukaryotic cells. The 20S proteasome forms a barrel-shaped structure, with the active sites of the multiple catalytic subunits facing the central cavity. This core proteasome is typically associated with a 19S cap complex, resulting in a larger assembly termed the 26S proteasome. The 19S cap complex contains several ATPase subunits, which probably act in unfolding the target proteins. In addition, the 19S complex contains at least eleven non-ATPase subunits, which are thought to function in regulation and target recognition. One of these subunits (S5a) binds to ubiquitin, which serves as a universal signal for targeting proteins to the proteasome. Two of the regulatory subunits have recently been shown to share a repeat motif with the cyclosome/APC-complex, which acts in the cell cycle dependent ubiquitination of regulatory proteins. In order to learn more about the potential function of the regulatory proteasome subunits, we set out to identify distantly related proteins by applying the generalised profile method, a sensitive motif-based technique for sequence database searches. We were able to identify two different homology domains, which both occur in multiple components of the regulatory proteasome as well as in several other characterised protein families"