Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase
dc.contributor.author | Szklarczyk, R | |
dc.contributor.author | Wanschers, BFJ | |
dc.contributor.author | Cuypers, TD | |
dc.contributor.author | Esseling, JJ | |
dc.contributor.author | Riemersma, M | |
dc.contributor.author | van den Brand, MAM | |
dc.contributor.author | Gloerich, J | |
dc.contributor.author | Lasonder, E | |
dc.contributor.author | van den Heuvel, LP | |
dc.contributor.author | Nijtmans, LG | |
dc.contributor.author | Huynen, MA | |
dc.date.accessioned | 2016-07-11T15:05:01Z | |
dc.date.available | 2016-07-11T15:05:01Z | |
dc.date.issued | 2012 | |
dc.identifier.issn | 1465-6906 | |
dc.identifier.issn | 1474-760X | |
dc.identifier.other | ARTN R12 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/5045 | |
dc.description.abstract |
BACKGROUND: Orthology is a central tenet of comparative genomics and ortholog identification is instrumental to protein function prediction. Major advances have been made to determine orthology relations among a set of homologous proteins. However, they depend on the comparison of individual sequences and do not take into account divergent orthologs. RESULTS: We have developed an iterative orthology prediction method, Ortho-Profile, that uses reciprocal best hits at the level of sequence profiles to infer orthology. It increases ortholog detection by 20% compared to sequence-to-sequence comparisons. Ortho-Profile predicts 598 human orthologs of mitochondrial proteins from Saccharomyces cerevisiae and Schizosaccharomyces pombe with 94% accuracy. Of these, 181 were not known to localize to mitochondria in mammals. Among the predictions of the Ortho-Profile method are 11 human cytochrome c oxidase (COX) assembly proteins that are implicated in mitochondrial function and disease. Their co-expression patterns, experimentally verified subcellular localization, and co-purification with human COX-associated proteins support these predictions. For the human gene C12orf62, the ortholog of S. cerevisiae COX14, we specifically confirm its role in negative regulation of the translation of cytochrome c oxidase. CONCLUSIONS: Divergent homologs can often only be detected by comparing sequence profiles and profile-based hidden Markov models. The Ortho-Profile method takes advantage of these techniques in the quest for orthologs. | |
dc.format.extent | R12-R12 | |
dc.format.medium | Electronic | |
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.subject | Amino Acid Sequence | |
dc.subject | Computational Biology | |
dc.subject | Electron Transport Complex IV | |
dc.subject | Humans | |
dc.subject | Membrane Proteins | |
dc.subject | Mitochondria | |
dc.subject | Mitochondrial Proteins | |
dc.subject | Molecular Sequence Data | |
dc.subject | Protein Biosynthesis | |
dc.subject | Saccharomyces cerevisiae | |
dc.subject | Saccharomyces cerevisiae Proteins | |
dc.subject | Schizosaccharomyces | |
dc.subject | Sequence Homology, Amino Acid | |
dc.title | Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase | |
dc.type | journal-article | |
dc.type | Article | |
plymouth.author-url | https://www.ncbi.nlm.nih.gov/pubmed/22356826 | |
plymouth.issue | 2 | |
plymouth.volume | 13 | |
plymouth.publication-status | Published | |
plymouth.journal | Genome Biology | |
dc.identifier.doi | 10.1186/gb-2012-13-2-r12 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
dc.publisher.place | England | |
dcterms.dateAccepted | 2012-02-22 | |
dc.identifier.eissn | 1474-760X | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1186/gb-2012-13-2-r12 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2012-02-22 | |
rioxxterms.type | Journal Article/Review |