Ab initio protein modelling reveals novel human MIT domains.
Database searches can fail to detect all truly homologous sequences, particularly when dealing with short, highly sequence diverse protein families. Here, using microtubule interacting and transport (MIT) domains as an example, we have applied an approach of profile-profile matching followed by ab initio structure modelling to the detection of true homologues in the borderline significant zone of database searches. Novel MIT domains were confidently identified in USP54, containing an apparently inactive ubiquitin carboxyl-terminal hydrolase domain, a katanin-like ATPase KATNAL1, and an uncharacterized protein containing a VPS9 domain. As a proof of principle, we have confirmed the novel MIT annotation for USP54 by in vitro profiling of binding to CHMP proteins.
Rigden
Daniel J
DJ
School of Biological Sciences, University of Liverpool, Liverpool, UK. drigden@liv.ac.uk
Liu
Han
H
Hayes
Sebastian D
SD
Urbé
Sylvie
S
Clague
Michael J
MJ
D000595:Amino Acid Sequence; D001692:Biological Transport; D019295:Computational Biology; D003198:Computer Simulation; D030541:Databases, Genetic; D015870:Gene Expression; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D011506:Proteins