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- Almén, Markus Sällman, et al.
(author)
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Mapping the human membrane proteome : a majority of the human membrane proteins can be classified according to function and evolutionary origin
- 2009
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In: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 7, s. 50-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Membrane proteins form key nodes in mediating the cell's interaction with the surroundings, which is one of the main reasons why the majority of drug targets are membrane proteins. RESULTS: Here we mined the human proteome and identified the membrane proteome subset using three prediction tools for alpha-helices: Phobius, TMHMM, and SOSUI. This dataset was reduced to a non-redundant set by aligning it to the human genome and then clustered with our own interactive implementation of the ISODATA algorithm. The genes were classified and each protein group was manually curated, virtually evaluating each sequence of the clusters, applying systematic comparisons with a range of databases and other resources. We identified 6,718 human membrane proteins and classified the majority of them into 234 families of which 151 belong to the three major functional groups: receptors (63 groups, 1,352 members), transporters (89 groups, 817 members) or enzymes (7 groups, 533 members). Also, 74 miscellaneous groups with 697 members were determined. Interestingly, we find that 41% of the membrane proteins are singlets with no apparent affiliation or identity to any human protein family. Our results identify major differences between the human membrane proteome and the ones in unicellular organisms and we also show a strong bias towards certain membrane topologies for different functional classes: 77% of all transporters have more than six helices while 60% of proteins with an enzymatic function and 88% receptors, that are not GPCRs, have only one single membrane spanning alpha-helix. Further, we have identified and characterized new gene families and novel members of existing families. CONCLUSION: Here we present the most detailed roadmap of gene numbers and families to our knowledge, which is an important step towards an overall classification of the entire human proteome. We estimate that 27% of the total human proteome are alpha-helical transmembrane proteins and provide an extended classification together with in-depth investigations of the membrane proteome's functional, structural, and evolutionary features.
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| 2. |
- Nordström, Karl J V, et al.
(author)
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Critical evaluation of the FANTOM3 non-coding RNA transcripts
- 2009
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In: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 94:3, s. 169-176
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Journal article (peer-reviewed)abstract
- We studied the genomic positions of 38,129 putative ncRNAs from the RIKEN dataset in relation to protein-coding genes. We found that the dataset has 41% sense, 6% antisense, 24% intronic and 29% intergenic transcripts. Interestingly, 17,678 (47%) of the FANTOM3 transcripts were found to potentially be internally primed from longer transcripts. The highest fraction of these transcripts was found among the intronic transcripts and as many as 77% or 6929 intronic transcripts were both internally primed and unspliced. We defined a filtered subset of 8535 transcripts that did not overlap with protein-coding genes, did not contain ORFs longer than 100 residues and were not internally primed. This dataset contains 53% of the FANTOM3 transcripts associated to known ncRNA in RNAdb and expands previous similar efforts with 6523 novel transcripts. This bioinformatic filtering of the FANTOM3 non-coding dataset has generated a lead dataset of transcripts without signs of being artefacts, providing a suitable dataset for investigation with hybridization-based techniques.
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