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Human FEZ1 interacts with Protein Kinase C (PKC) and several regulatory proteins involved in functions ranging from microtubule associated transport to transcriptional regulation. Theoretical prediction, circular dichroism, fluorescence spectroscopy, and limited proteolysis of recombinant FEZ1 suggest that it contains disordered regions, especially in its N\u2010terminal region, and that it may belong to the group of natively unfolded proteins. Small angle X\u2010ray scattering experiments indicated a mainly disordered conformation, proved that FEZ1 is a dimer of elongated shape and provided overall dimensional parameters for the protein. <jats:italic>In vitro<\/jats:italic> pull down experiments confirmed these results and demonstrated that dimerization involves the N\u2010terminus. <jats:italic>Ab\u2010initio<\/jats:italic> 3D low resolution models of the full\u2010length conformation of the dimeric constructs 6xHis\u2010FEZ1(1\u2010392) and 6xHis\u2010FEZ1(1\u2010227) were obtained. Furthermore, we performed <jats:italic>in vitro<\/jats:italic> phosphorylation assays of FEZ1 with PKC. The phosphorylation occurred mainly in its C\u2010terminal region, and does not cause any significant conformational changes, but nonetheless inhibited its interaction with the FEZ1 interacting domain of the protein CLASP2 <jats:italic>in vitro<\/jats:italic>. The C terminus of FEZ1 has been reported to bind to several interacting proteins. This suggests that FEZ1 binding and transport function of interacting proteins may be subject to regulation by phosphorylation. Proteins 2009. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.22135","type":"journal-article","created":{"date-parts":[[2008,7,9]],"date-time":"2008-07-09T20:46:34Z","timestamp":1215636394000},"page":"104-121","source":"Crossref","is-referenced-by-count":32,"title":["Human FEZ1 has characteristics of a natively unfolded protein and dimerizes in solution"],"prefix":"10.1002","volume":"74","author":[{"given":"Daniel C. F.","family":"Lanza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio C.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana M.","family":"Assmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre J. 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