uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Topology based identification and comprehensive classification of four-transmembrane helix containing proteins (4TMs) in the human genome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Show others and affiliations
2016 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 17, 268Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

Background: Membrane proteins are key components in a large spectrum of diverse functions and thus account for the major proportion of the drug-targeted portion of the genome. From a structural perspective, the a-helical transmembrane proteins can be categorized into major groups based on the number of transmembrane helices and these groups are often associated with specific functions. When compared to the well-characterized seven-transmembrane containing proteins (7TM), other TM groups are less explored and in particular the 4TM group. In this study, we identify the complete 4TM complement from the latest release of the human genome and assess the 4TM structure group as a whole. We functionally characterize this dataset and evaluate the resulting groups and ubiquitous functions, and furthermore describe disease and drug target involvement.

Results: We classified 373 proteins, which represents similar to 7 % of the human membrane proteome, and includes 69 more proteins than our previous estimate. We have characterized the 4TM dataset based on functional, structural, and/or evolutionary similarities. Proteins that are involved in transport activity constitute 37 % of the dataset, 23 % are receptor-related, and 13 % have enzymatic functions. Intriguingly, proteins involved in transport are more than double the 15 % of transporters in the entire human membrane proteome, which might suggest that the 4TM topological architecture is more favored for transporting molecules over other functions. Moreover, we found an interesting exception to the ubiquitous intracellular N- and C-termini localization that is found throughout the entire membrane proteome and 4TM dataset in the neurotransmitter gated ion channel families. Overall, we estimate that 58 % of the dataset has a known association to disease conditions with 19 % of the genes possibly involved in different types of cancer.

Conclusions: We provide here the most robust and updated classification of the 4TM complement of the human genome as a platform to further understand the characteristics of 4TM functions and to explore pharmacological opportunities.

Place, publisher, year, edition, pages
2016. Vol. 17, 268
Keyword [en]
Human proteome, Four transmembrane, 4TM, Function, Topology prediction, Structure function, Cancer, Drug targets
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:uu:diva-295564DOI: 10.1186/s12864-016-2592-7ISI: 000373559700001PubMedID: 27030248OAI: oai:DiVA.org:uu-295564DiVA: diva2:934299
Funder
Swedish Research CouncilNovo Nordisk
Available from: 2016-06-08 Created: 2016-06-08 Last updated: 2017-11-30Bibliographically approved

Open Access in DiVA

fulltext(2694 kB)170 downloads
File information
File name FULLTEXT01.pdfFile size 2694 kBChecksum SHA-512
9a04bef3798a2cfc298d54de6b63842686a89f933b8636d712ce9ea17c7165cadee9b07ba9ec08fb9746eba020767ce6ab2dac6ca21c829c8eabe72fa8839fae
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Attwood, Misty M.Krishnan, ArunkumarSchiöth, Helgi B.

Search in DiVA

By author/editor
Attwood, Misty M.Krishnan, ArunkumarSchiöth, Helgi B.
By organisation
Functional Pharmacology
In the same journal
BMC Genomics
Medical Biotechnology

Search outside of DiVA

GoogleGoogle Scholar
Total: 170 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 475 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf