ISOLATION OF AN UBIQUITOUSLY EXPRESSED CDNA-ENCODING HUMAN DYNAMIN-II, A MEMBER OF THE LARGE GTP-BINDING PROTEIN FAMILY

Dynamin (Dyn) is a member of a novel group of GTPases which was initia lly identified as a microtubule-binding protein with a role in vectori al movement. Three distinct Dyn-encoding genes (DYN I, II and III), wi th a neuronal-, ubiquitous or testis-specific expression, respectively , have been identified in rat. In man, only DYN I has so far been char acterized. We have previously isolated a genomic DNA fragment implicat ed in the correction of mitomycin C hypersensitivity of cells from a F anconi anemia patient belonging to genetic complementation group D (FA (D)). Using this probe, we have cloned a human complementary DNA desig nated hDYN II encoding a ubiquitous Dyn isoform. The predicted protein consists of 866 amino acids (97.5 kDa). Dyn proteins exhibit a high d egree of evolutionary conservation: hDyn II is 98% identical to rat Dy n II and 73% identical to hDyn I. A unique 3.6-kb transcript is found in all human tissues examined and it is more abundant in skeletal musc le and heart. This transcript is also expressed in tissue-culture cell s. The hDYN II message is present and not mutated in the FA(D)patient studied. In addition to the GTP-binding domain and motifs associated w ith regulatory function, the hDyn II protein contains a noticeable num ber of consensus motifs for p34Cdc2 kinase phosphorylation which may i ndicate a potential role at the G2/mitosis transition. The sequence re ported here should allow a more complete analysis of Dyn function(s) i n man.