ArticleBiology direct2011
Not all transmembrane helices are born equal: Towards the extension of the sequence homology concept to membrane proteins.
Article in Biology direct, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- A Comprehensive Review on Homology Modelling in Drug Development: Methodologies, Tools, and Evaluation.Mini reviews in medicinal chemistry · 2026Review
- Importance of Computer-aided Drug Design in Modern Pharmaceutical Research.Current drug discovery technologies · 2025Review
- The Pentameric Ligand-Gated Ion Channel Family: A New Member of the Voltage Gated Ion Channel Superfamily?International journal of molecular sciences · 2024Article
- Sequence Similarity among Structural Repeats in the Piezo Family of Mechanosensitive Ion Channels.Microbial physiology · 2023Article
- Discovery and Characterization of the Phospholemman/SIMP/Viroporin Superfamily.Microbial physiology · 2022Article
- Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites.Biology direct · 2021Article
- Expansion of the Major Facilitator Superfamily (MFS) to include novel transporters as well as transmembrane-acting enzymes.Biochimica et biophysica acta. Biomembranes · 2020Article
- Expansion of the Transporter-Opsin-G protein-coupled receptor superfamily with five new protein families.PloS one · 2020Article
- Function of a membrane-embedded domain evolutionarily multiplied in the GPI lipid anchor pathway proteins PIG-B, PIG-M, PIG-U, PIG-W, PIG-V, and PIG-Z.Cell cycle (Georgetown, Tex.) · 2018Article
- Charged residues next to transmembrane regions revisited: "Positive-inside rule" is complemented by the "negative inside depletion/outside enrichment rule".BMC biology · 2017Article
- xHMMER3x2: Utilizing HMMER3's speed and HMMER2's sensitivity and specificity in the glocal alignment mode for improved large-scale protein domain annotation.Biology direct · 2016Article
- The C-terminal region of the non-structural protein 2B from Hepatitis A Virus demonstrates lipid-specific viroporin-like activity.Scientific reports · 2015Article
- dissectHMMER: a HMMER-based score dissection framework that statistically evaluates fold-critical sequence segments for domain fold similarity.Biology direct · 2015Article
- De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods.Biology direct · 2015Article
- On the necessity of dissecting sequence similarity scores into segment-specific contributions for inferring protein homology, function prediction and annotation.BMC bioinformatics · 2014Article
- Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently "orphan" viral proteins.Journal of virology · 2014Article
- Transamidase subunit GAA1/GPAA1 is a M28 family metallo-peptide-synthetase that catalyzes the peptide bond formation between the substrate protein's omega-site and the GPI lipid anchor's phosphoethanolamine.Cell cycle (Georgetown, Tex.) · 2014Article
- Dynamics of domain coverage of the protein sequence universe.BMC genomics · 2012Article
- Transmembrane helix: simple or complex.Nucleic acids research · 2012Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSequence homology considerations widely used to transfer functional annotation to uncharacterized protein sequences require special precautions in the case of non-globular sequence segments including membrane-spanning stretches composed of non-polar residues. Simple, quantitative criteria are desirable for identifying transmembrane helices (TMs) that must be included into or should be excluded from start sequence segments in similarity searches aimed at finding distant homologues.
resultsWe found that there are two types of TMs in membrane-associated proteins. On the one hand, there are so-called simple TMs with elevated hydrophobicity, low sequence complexity and extraordinary enrichment in long aliphatic residues. They merely serve as membrane-anchoring device. In contrast, so-called complex TMs have lower hydrophobicity, higher sequence complexity and some functional residues. These TMs have additional roles besides membrane anchoring such as intra-membrane complex formation, ligand binding or a catalytic role. Simple and complex TMs can occur both in single- and multi-membrane-spanning proteins essentially in any type of topology. Whereas simple TMs have the potential to confuse searches for sequence homologues and to generate unrelated hits with seemingly convincing statistical significance, complex TMs contain essential evolutionary information.
conclusionFor extending the homology concept onto membrane proteins, we provide a necessary quantitative criterion to distinguish simple TMs (and a sufficient criterion for complex TMs) in query sequences prior to their usage in homology searches based on assessment of hydrophobicity and sequence complexity of the TM sequence segments.
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