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Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains

Fidler, DR; Murphy, SE; Courtis, K; Antonoudiou, P; El-Tohamy, R; Ient, J; Levine, TP; (2016) Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains. Traffic , 17 (11) pp. 1214-1226. 10.1111/tra.12432. Green open access

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Abstract

Advances in membrane cell biology are hampered by the relatively high proportion of proteins with no known function. Such proteins are largely or entirely devoid of structurally significant domain annotations. Structural bioinformaticians have developed profile-profile tools such as HHsearch (online version called HHpred), which can detect remote homologies that are missed by tools used to annotate databases. Here we have applied HHsearch to study a single structural fold in a single model organism as proof of principle. In the entire clan of protein domains sharing the pleckstrin homology domain fold in yeast, systematic application of HHsearch accurately identified known PH-like domains. It also predicted 16 new domains in 13 yeast proteins many of which are implicated in intracellular traffic. One of these was Vps13p, where we confirmed the functional importance of the predicted PH-like domain. Even though such predictions require considerable work to be corroborated, they are useful first steps. HHsearch should be applied more widely, particularly across entire proteomes of model organisms, to significantly improve database annotations.

Type: Article
Title: Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/tra.12432
Publisher version: http://doi.org/10.1111/tra.12432
Language: English
Additional information: © 2016 The Authors. Traffic published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: GRAM domains, Saccharomyces cerevisiae, TBC1D15, YJL016W, YJL181C, YJR030C, Gyp7p, Vid27p, Vps13p, pleckstrin homology (PH) domains, profile-profile search, secondary structure prediction, structural bioinformatics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1514558
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