title: Identification of divergent WH2 motifs by HMM-HMM alignments.
abstract: BACKGROUND
  The actin cytoskeleton is a hallmark of eukaryotic cells. Its regulation as well as its interaction with other proteins is carefully orchestrated by actin interaction domains. One of the key players is the WH2 motif, which enables binding to actin monomers and filaments and is involved in the regulation of actin nucleation. Contrasting conserved domains, the identification of this motif in protein sequences is challenging, as it is short and poorly conserved.
  
  
  RESULTS
  To identify divergent members, we combined Hidden-Markov-Model (HMM) to HMM alignments with orthology predictions. Thereby, we identified nearly 500 proteins containing so far not annotated WH2 motifs. This included shootin-1, an actin binding protein involved in neuron polarization. Among others, WH2 motifs of 'proximal to raf' (ptr)-orthologs, which are described in the literature, but not annotated in genome databases, were identified.
  
  
  CONCLUSIONS
  In summary, we increased the number of WH2 motif containing proteins substantially. This identification of candidate regions for actin interaction could steer their experimental characterization. Furthermore, the approach outlined here can easily be adapted to the identification of divergent members of further domain families.
authors.affiliation: Department of Bioinformatics, Biozentrum, University Würzburg, Am Hubland, 97074, Würzburg, Germany. clemens.weiss@stud-mail.uni-wuerzburg.de.
authors.forename: Clemens Leonard
authors.initials: CL
authors.lastname: Weiß
authors.affiliation: Department of Bioinformatics, Biozentrum, University Würzburg, Am Hubland, 97074, Würzburg, Germany. Joerg.Schultz@biozentrum.uni-wuerzburg.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schultz
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D056893:Alveolata / Q000737:chemistry / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry / Q000378:metabolism; D056898:Euglenozoa / Q000737:chemistry / Q000378:metabolism; D005658:Fungi / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D016415:Sequence Alignment / Q000379:methods / Q000706:statistics & numerical data*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D014452:Ubiquitins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D014452:Ubiquitins; C583651:shootin 1 protein, mouse; C402385:spir protein, Drosophila; C047192:thymosin beta(1); D013947:Thymosin