BACKGROUND: Shuffling of modular protein domains is an important source of evolutionary innovation. Formins are a family of actin-organizing proteins that share a conserved FH2 domain but their overall domain architecture differs dramatically between opisthokonts (metazoans and fungi) and plants. We performed a phylogenomic analysis of formins in most eukaryotic kingdoms, aiming to reconstruct an evolutionary scenario that may have produced the current diversity of domain combinations with focus on the origin of the angiosperm formin architectures. RESULTS: The Rho GTPase-binding domain (GBD/FH3) reported from opisthokont and Dictyostelium formins was found in all lineages except plants, suggesting its ancestral character. Instead, mosses and vascular plants possess the two formin classes known from angiosperms: membrane-anchored Class I formins and Class II formins carrying a PTEN-like domain. PTEN-related domains were found also in stramenopile formins, where they have been probably acquired independently rather than by horizontal transfer, following a burst of domain rearrangements in the chromalveolate lineage. A novel RhoGAP-related domain was identified in some algal, moss and lycophyte (but not angiosperm) formins that define a specific branch (Class III) of the formin family. CONCLUSION: We propose a scenario where formins underwent multiple domain rearrangements in several eukaryotic lineages, especially plants and chromalveolates. In plants this replaced GBD/FH3 by a probably inactive RhoGAP-like domain, preserving a formin-mediated association between (membrane-anchored) Rho GTPases and the actin cytoskeleton. Subsequent amplification of formin genes, possibly coincident with the expansion of plants to dry land, was followed by acquisition of alternative membrane attachment mechanisms present in extant Class I and Class II formins, allowing later loss of the RhoGAP-like domain-containing formins in angiosperms.

Department of Plant Physiology Faculty of Sciences Charles University Vinièná 5 CZ 128 43 Praha 2 Czech Republic

Zobrazit více v PubMed

Vogel C, Bashton M, Kerrison ND, Chothia C, Teichmann SA. Structure, function and evolution of multidomain proteins. Curr Opin Struct Biol. 2004;14:208–216. doi: 10.1016/j.sbi.2004.03.011. PubMed DOI

Higgs HN. Formin proteins: a domain-based approach. Trends Biochem Sci. 2005;30:342–353. doi: 10.1016/j.tibs.2005.04.014. PubMed DOI

Kovar DR. Molecular details of formin-mediated actin assembly. Curr Opin Cell Biol. 2006;18:11–17. doi: 10.1016/j.ceb.2005.12.011. PubMed DOI

Alberts AS. Diaphanous-related Formin homology proteins. Curr Biol. 2002;12:R796–R796. doi: 10.1016/S0960-9822(02)01309-X. PubMed DOI

Rivero F, Muramoto T, Meyer AK, Urushihara H, Uyeda TQ, Kitayama C. A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa. . BMC Genomics. 2005;6:28. doi: 10.1186/1471-2164-6-28. PubMed DOI PMC

Higgs HN, Peterson KJ. Phylogenetic analysis of the formin homology 2 domain. Mol Biol Cell. 2005;16:1–13. doi: 10.1091/mbc.E04-07-0565. PubMed DOI PMC

Deeks MJ, Hussey P, Davies B. Formins: intermediates in signal transduction cascades that affect cytoskeletal reorganization. Trends Plant Sci. 2002;7:492–498. doi: 10.1016/S1360-1385(02)02341-5. PubMed DOI

Cvrčková F, Novotný M, Pícková D, Zárský V. Formin homology 2 domains occur in multiple contexts in angiosperms. BMC Genomics. 2004;5:44. doi: 10.1186/1471-2164-5-44. PubMed DOI PMC

Cvrčková F. Are plant formins integral membrane proteins? Genome Biology. 2000;1:research 001–007. doi: 10.1186/gb-2000-1-1-research001. PubMed DOI PMC

Banno H, Chua NH. Characterization of the arabidopsis formin-like protein AFH1 and its interacting protein. Plant Cell Physiol. 2000;41:617–626. PubMed

Cheung AY, Wu H. Overexpression of an Arabidopsis formin stimulates supernumerary actin cable formation from pollen tube cell membrane. Plant Cell. 2004;16:257–269. doi: 10.1105/tpc.016550. PubMed DOI PMC

Favery B, Chelysheva LA, Lebris M, Jammes F, Marmagne A, De Almeida-Engler J, Lecomte P, Vaury C, Arkowitz RA, Abad P. Arabidopsis formin AtFH6 is a plasma membrane-associated protein upregulated in giant cells induced by parasitic nematodes. Plant Cell. 2004;16:2529–2540. doi: 10.1105/tpc.104.024372. PubMed DOI PMC

Deeks MJ, Cvrčková F, Machesky LM, Mikitová V, Ketelaar T, Zárský V, Davies B, Hussey PJ. Arabidopsis group Ie formins localize to specific cell membrane domains, interact with actin-binding proteins and cause defects in cell expansion upon aberrant expression. New Phytologist. 2005;168:529–540. doi: 10.1111/j.1469-8137.2005.01582.x. PubMed DOI

Ingouff M, FitzGerald JN, Guerin C, Robert H, Sorensen MB, Van Damme D, Geelen D, Blanchoin L, Berger F. Plant formin AtFH5 is an evolutionarily conserved actin nucleator involved in cytokinesis. Nat Cell Biol. 2005;7:374–380. doi: 10.1038/ncb1238. PubMed DOI

Yi K, Guo C, Chen D, Zhao B, Yang B, Ren H. Cloning and functional characterization of a formin-like protein (AtFH8) from Arabidopsis. Plant Physiol. 2005;138:1071–1082. doi: 10.1104/pp.104.055665. PubMed DOI PMC

Michelot A, Guerin C, Huang S, Ingouff M, Richard S, Rodiuc N, Staiger CJ, Blanchoin L. The Formin Homology 1 domain modulates the actin nucleation and bundling activity of Arabidopsis FORMIN1. Plant Cell. 2005;17:2296–2313. doi: 10.1105/tpc.105.030908. PubMed DOI PMC

Kim RH, Mak TW. Tumours and tremors: how PTEN regulation underlies both. Brit J Cancer. 2006;94:620–624. PubMed PMC

Li L, Ernsting BR, Wishart MJ, Lohse DL, Dixon JE. A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast. J Biol Chem. 1997;272:29403–29406. doi: 10.1074/jbc.272.47.29403. PubMed DOI

Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 2001;114:2375–2382. PubMed

von Stein W, Ramrath A, Grimm A, Müller-Borg M, Wodarz A. Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. Development. 2005;132:1675–1676. doi: 10.1242/dev.01720. PubMed DOI

Janetopoulos C, Borleis J, Vazquez F, Iijima M, Devreotes P. Temporal and spatial regulation of phosphoinositide signaling mediates cytokinesis. Dev Cell. 2005;8:467–477. doi: 10.1016/j.devcel.2005.02.010. PubMed DOI

Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–1946. doi: 10.1126/science.275.5308.1943. PubMed DOI

Lo SH, Janmey PA, Hartwig JH, Chen LB. Interactions of tensin with actin and identification of its three distinct actin-binding domains. J Cell Biol. 1994;125:1067–1075. doi: 10.1083/jcb.125.5.1067. PubMed DOI PMC

Lo SH. Molecules in focus: tensin. Int J Biochem Cell Biol. 2004;36:31–34. doi: 10.1016/S1357-2725(03)00171-7. PubMed DOI

Lemmon SK. Clathrin uncoating: auxilin comes to life. Curr Biol. 2001;11:R49–R52. doi: 10.1016/S0960-9822(01)00010-0. PubMed DOI

Gupta R, Ting JTL, Sokolov LN, Johnson SA, Luan S. A tumor suppressor homolog, AtPTEN1, is essential for pollen development in Arabidopsis. Plant Cell. 2002;14:2495–2507. doi: 10.1105/tpc.005702. PubMed DOI PMC

Simpson AG, Roger AJ. The real 'kingdoms' of eukaryotes. Curr Biol. 2004;14:R693–R696. doi: 10.1016/j.cub.2004.08.038. PubMed DOI

Schultz J, Milpetz F, Bork P, Ponting CP. SMART, a simple modular architecture research tool: Identification of signalling domains. Proc Natl Acad Sci U S A. 1998;95:5857–5864. doi: 10.1073/pnas.95.11.5857. PubMed DOI PMC

Letunic I, Copley RR, Pils B, Pinkert S, Schultz J, Bork P. SMART 5: domains in the context of genomes and networks. Nucleic Acids Res. 2006;34:D257–D260. doi: 10.1093/nar/gkj079. PubMed DOI PMC

Johnston JJ, Copeland JW, Fasnacht M, Etchberger JF, Liu J, Honig B, Hobert O. An unusual Zn-finger/FH2 domain protein controls a left/right asymmetric neuronal fate decision in C. elegans. Development. 2006;133:3317–3328. doi: 10.1242/dev.02494. PubMed DOI

Scheffzek K, Ahmadian MR, Kabsch W, Wiesmueller L, Lautwein A, Schmitz F, Wittinghofer A. The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science. 1997;277:333–338. doi: 10.1126/science.277.5324.333. PubMed DOI

Fidyk NJ, Cerione RA. Understanding the catalytic mechanism of GTPase-activating proteins: demonstration of the importance of switch domain stabilization in the stimulation of GTP hydrolysis. Biochemistry. 2000;41:15644–15653. doi: 10.1021/bi026413p. PubMed DOI

Daumke O, Weyand M, Chakrabarti PP, Vetter IR, Wittinghofer A. The GTPase-activating protein Rap1GAP uses a catalytic asparagine. Nature. 2004;429:197–201. doi: 10.1038/nature02505. PubMed DOI

Brandao MM, Silva-Brandao KL, Costa FF, Saad ST. Phylogenetic analysis of RhoGAP domain-containing proteins. Genomics Proteomics Bioinformatics. 2006;4:182–188. doi: 10.1016/S1672-0229(06)60031-4. PubMed DOI PMC

Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–3402. doi: 10.1093/nar/25.17.3389. PubMed DOI PMC

Barford D, Flint AJ, Tonks NK. Crystal structure of human protein tyrosine phosphatase 1B. Science. 1994;263:1397–1404. doi: 10.1126/science.8128219. PubMed DOI

Stuckey JA, Schubert HL, Fauman EB, Zhang ZY, Dixon JE, Saper MA. Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate. Nature. 1994;370:571–575. doi: 10.1038/370571a0. PubMed DOI

Rivero F, Cvrčková F. In: Eukaryotic membranes and cytoskeleton: origins and evolution. Jekely G, editor. New York, Springer Science + Business Media, LLC, Landes Bioscience; 2007. Origins and evolution of the actin cytoskeleton; pp. 97–110.http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=eurekah.chapter.66387 PubMed

Richards TA, Cavalier-Smith T. Myosin domain evolution and the primary divergence of eukaryotes. Nature. 2005;436:1113–1118. doi: 10.1038/nature03949. PubMed DOI

Burki F, Shalchian-Tabrizi K, Minge M, Skjaeveland A, Nikolaev SI, Jakobsen KS, Pawlowski J. Phylogenomics reshuffles the eukaryotic supergroups. PLOS One. 2007;2:e790. doi: 10.1371/journal.pone.0000790. PubMed DOI PMC

Hackett JD, Yoon HS, Li S, Reyes-Prieto A, Rummele SE, Bhattacharya D. Phylogenomic analysis supports the monophyly of cryptophytes and haptophytes and the association of rhizaria with chromalveolates. Mol Biol Evol. 2007;24:1702–1713. doi: 10.1093/molbev/msm089. PubMed DOI

de la Pompa JL, James D, Zeller R. The limb deformity proteins during avian neurulation and sense organ development. Dev Dyn. 1995;204:156–167. PubMed

Westendorf JJ, Mernaugh R, Hiebert SW. Identification and characterization of a protein containing formin homology (FH1/FH2) domains. Gene. 1999;232:173–182. doi: 10.1016/S0378-1119(99)00127-4. PubMed DOI

Leader B, Leder P. Formin-2, a novel formin homology protein of the cappuccino subfamily, is highly expressed in the developing and adult central nervous system. Mech Dev. 2000;93:221–231. doi: 10.1016/S0925-4773(00)00276-8. PubMed DOI

Kanaya H, Takeya R, Takeuchi K, Watanabe N, Jing N, Sumimoto H. Fhos2, a novel formin-related actin-organizing protein, probably associates with the nestin intermediate filament. Genes Cells. 2005;10:665–678. doi: 10.1111/j.1365-2443.2005.00867.x. PubMed DOI

Afshar K, Stuart B, Wasserman SA. Functional analysis of the Drosophila diaphanous FH protein in early embryonic development. Development. 2000;127:1887–1897. PubMed

Gill MB, Roecklein-Canfield J, Sage DR, Zambela-Soediono M, Longtine N, Uknis M, Fingeroth JD. EBV attachment stimulates FHOS/FHOD1 redistribution and co-aggregation with CD21: formin interactions with the cytoplasmic domain of human CD21. J Cell Sci. 2004;117:2709–2720. doi: 10.1242/jcs.01113. PubMed DOI

Carramusa L, Ballestrem C, Zilberman Y, Bershadsky AD. Mammalian diaphanous-related formin Dia1 controls the organization of E-cadherin-mediated cell-cell junctions. J Cell Sci. 2007;120:3870–3882. doi: 10.1242/jcs.014365. PubMed DOI

Van Damme D, Bouget FY, Van Poucke K, Inze D, Geelen D. Molecular dissection of plant cytokinesis and phragmoplast structure: a survey of GFP-tagged proteins. Plant J. 2004;40:386–398. doi: 10.1111/j.1365-313X.2004.02222.x. PubMed DOI

Vogel C, Chothia C. Protein famly expansions and biological complexity. PLOS Comput Biol. 2006;2:e48. doi: 10.1371/journal.pcbi.0020048. PubMed DOI PMC

Kitayama C, Uyeda TQP. ForC, a novel type of formin family protein lacking an FH1 domain, is involved in multicellular development in Dictyostelium discoideum. J Cell Sci. 2003;116:711–723. doi: 10.1242/jcs.00265. PubMed DOI

Keeling PJ, Inagaki Y. A class of eukaryotic GTPase with a punctate distribution suggesting multiple functional replacements of translation elongation factor alpha. Proc Natl Acad Sci U S A. 2004;101:15380–15385. doi: 10.1073/pnas.0404505101. PubMed DOI PMC

Gough J. Convergent evolution of domain architectures (is rare) Bioinformatics. 2005;21:1464–1471. doi: 10.1093/bioinformatics/bti204. PubMed DOI

Zheng Y, Hart MJ, Shinjo K, Evans T, Bender A, Cerione RA. Biochemical comparisons of the Saccharomyces cerevisiae Bem2 and Bem3 proteins. Delineation of a limit Cdc42 GTPase-activating protein domain. J Biol Chem. 1993;268:24629–24634. PubMed

Peck J, Douglas G, Wu CH, Burbelo PD. Human RhoGAP domain-containing proteins: structure, function and evolutionary relationships. FEBS Letters. 2002;528:27–34. doi: 10.1016/S0014-5793(02)03331-8. PubMed DOI

Hart MJ, Callow MG, Souza B, Polakis P. IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. EMBO J. 1996;15:2997–3005. PubMed PMC

Kuroda S, Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A, Kaibuchi K. Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1. J Biol Chem. 1996;271:23363–23367. doi: 10.1074/jbc.271.38.23363. PubMed DOI

Cvrčková F, Bavlnka B, Rivero F. Evolutionarily conserved modules in actin nucleation: lessons from Dictyostelium discoideum and plants. Protoplasma. 2004;224:15–31. doi: 10.1007/s00709-004-0058-2. PubMed DOI

Hall A. Rho GTPases and the control of cell behaviour. Biochem Soc Trans. 2005;33:891–895. doi: 10.1042/BST20050891. PubMed DOI

Ridley AJ. Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 2006;16:522–529. doi: 10.1016/j.tcb.2006.08.006. PubMed DOI

Erickson JW, Cerione RA, Hart MJ. Identification of an actin cytoskeletal complex that includes IQGAP and the Cdc42 GTPase. J Biol Chem. 1997;272:24443–24447. doi: 10.1074/jbc.272.39.24443. PubMed DOI

Brill S, Li S, Lyman CW, Church DM, Wasmuth JJ, Weissbach L, Bernards A, Snijders AJ. The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases. Mol Cell Biol. 1996;16:4869–4878. PubMed PMC

Noritake J, Fukata M, Sato K, Nakagawa M, Watanabe T, Izumi N, Wang S, Fukata Y, Kaibuchi K. Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact. Mol Biol Cell. 2004;15:1056–1076. doi: 10.1091/mbc.E03-08-0582. PubMed DOI PMC

Rodriguez-Espeleta N, Brinkmann H, Burey SC, Roure B, Burger G, Loffelhardt W, Bohnert HJ, Philippe H, Lang BF. Monophyly of primary photosynthetic eukaryotes:green plants, red algae, and glaucophytes. Curr Biol. 2005;15:1325–1330. doi: 10.1016/j.cub.2005.06.040. PubMed DOI

Merchant SS, Prochnik SE, Vallon O, Harris EH, Karpowicz SJ, Witman GB, Terry A, Salamov A, Fritz-Laylin LK, Maréchal-Drouard L. et al.The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science. 2007;318:245–250. doi: 10.1126/science.1143609. PubMed DOI PMC

Itoh M, Nacher JC, Kuma K, Goto S, Kanehisa M. Evolutionary history and functional implications of protein domains and their combinations in eukaryotes. Genome Biology. 2007;8:R121. doi: 10.1186/gb-2007-8-6-r121. PubMed DOI PMC

NCBI Entrez. http://www.ncbi.nlm.nih.gov

The US Department of Energy Joint Genome Institute . http://www.jgi.doe.gov

The Arabidopsis Information Resource. http://www.arabidopsis.org

Rhee SY, Beavis W, Berardini TZ, Chen G, Dixon D, Doyle A, Garcia-Hernandez M, Huala E, Lander G, Montoya M, Miller N, Mueller LA, Mundodi S, Reiser L, Tacklind J, Weems DC, Wu Y, Yoo D, Yoon J, Zhang P. The Arabidopsis Information Resource (TAIR): a model organism database providing a centralized, curated gateway to Arabidopsis biology, research materials and community. Nucleic Acids Res. 2003;31:224–225. doi: 10.1093/nar/gkg076. PubMed DOI PMC

Genoscope French National Sequencing Center Database. http://www.genoscope.cns.fr

Selaginella Genomics. http://selaginella.genomics.purdue.edu

The Rice Annotation Project Database . http://rapdb.dna.affrc.go.jp

Ohyanagi H, Tanaka T, Sakai H, Shigemoto Y, Yamaguchi K, Habara T, Fujii Y, Antonio BA, Nagamura Y, Imanishi T, Ikeo K, Itoh T, Gojobori T, Sasaki T. The rice annotation project database (RAP-DB): hub for Oryza sativa ssp. japonica genome information. Nucleic Acids Res. 2006;34:D741–D744. doi: 10.1093/nar/gkj094. PubMed DOI PMC

Matsuzaki M, Misumi O, Shin-I T, Maruyama S, Takahara M, Miyagishima SY, Mori T, Nishida K, Yagisawa F, Nishida K. et al.Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature. 2004;428:653–657. doi: 10.1038/nature02398. PubMed DOI

The Cyanidioschyzon merolae Genome Project Database. http://merolae.biol.s.u-tokyo.ac.jp

The Sanger Institute GeneDB database. http://www.genedb.org

A Database for the Model Organism Paramecium tetraurelia. http://paramecium.cgm.cnrs-gif.fr

Eisen JA, Coyne RS, Wu M, Wu D, Thiagarajan M, Wortman JR, Badger JH, Ren Q, Amedeo P, Jones KM. et al.Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLOS Biology. 2007;4:e286. doi: 10.1371/journal.pbio.0040286. PubMed DOI PMC

The Tetrahymena Genome Database. http://www.ciliate.org

The J. Craig Venter Institute. http://www.tigr.org

McGinnis S, Madden TL. BLAST: at the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res. 2004;32:W20–W25. doi: 10.1093/nar/gkh435. PubMed DOI PMC

Letunic I, Goodstadt L, Dickens NJ, Doerks T, Schultz J, Mott R, Ciccarelli F, Copley RR, Ponting C, Bork P. Recent improvements to the SMART domain-based sequence annotation resource. Nucleic Acids Res. 2002;30:242–244. doi: 10.1093/nar/30.1.242. PubMed DOI PMC

Lomsadze A, Ter-Hovhannisyan V, Chernoff Y, Borodovsky M. Gene identification in novel eukaryotic genomes by self-training algorithm. Nucleic Acids Res. 2005;33:6494–6506. doi: 10.1093/nar/gki937. PubMed DOI PMC

Salamov AA, Solovyev VV. Ab initio gene finding in Drosophila genomic DNA. Genome Res. 2000;10:516–522. doi: 10.1101/gr.10.4.516. PubMed DOI PMC

Softberry, Inc. . http://www.softberry.com

Hu P, Brent MR. Using Twinscan to predict gene structures in genomic DNA sequences. Current Protocols in Bioinformatics. 2003. pp. 4.8.1–4.8.19. PubMed

Burge C, Karlin S. Prediction of complete gene structures in human genomic DNA. J Mol Biol. 1997;268:78–94. doi: 10.1006/jmbi.1997.0951. PubMed DOI

Birney E, Clamp R, Durbin R. GeneWise and Genomewise. Genome Res. 2004;14:988–995. doi: 10.1101/gr.1865504. PubMed DOI PMC

Schuler GD, Altschul SF, Lipman DJ. A workbench for multiple alignment construction analysis. Prot Struct Funct Genet. 1991;9:180–190. doi: 10.1002/prot.340090304. PubMed DOI

Stothard P. The Sequence Manipulation Suite: JavaScript programs for analyzing and formatting protein and DNA sequences. Biotechniques. 2000;28:1102–1104. http://www.biotechniques.com/article.asp?id=6120008 PubMed

The Pfam database. http://pfam.janelia.org

Finn RD, Mistry J, Schuster-Bockler B, Griffiths-Jones S, Hollich V, Lassmann T, Moxon S, Marshall M, Khanna A, Durbin R, Eddy SR, Sonnhammer EL, Bateman A. Pfam: clans, web tools and services. Nucl Acids Res. 2006;34:D247–D251. doi: 10.1093/nar/gkj149. PubMed DOI PMC

Nielsen H, Krogh A. Prediction of signal peptides and signal anchors by a hidden Markov model. Proc Int Conf Intell Syst Mol Biol. 1998;6:122–130. PubMed

Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol. 2001;305:567–580. doi: 10.1006/jmbi.2000.4315. PubMed DOI

Emanuelsson O, Brunak S, von Heijne G, Nielsen H. Locating proteins in the cell using TargetP, SignalP, and related tools. Nature Protocols. 2007;2:953–971. doi: 10.1038/nprot.2007.131. PubMed DOI

CBS Prediction Servers. http://cbs.dtu.dk/services/

Lassmann T, Sonnhammer EL. Kalign, Kalignvu and Mumsa: web servers for multiple sequence alignment. Nucl Acids Res. 2006;34:W596–W599. doi: 10.1093/nar/gkl191. PubMed DOI PMC

Multiple Sequence Alignment Server. http://msa.cgb.ki.se/cgi-bin/msa.cgi

Do CB, Mahabhashyam MSP, Brudno M, Batzoglou S. PROBCONS: Probabilistic Consistency-based Multiple Sequence Alignment. . Genome Res. 2005;15:330–340. doi: 10.1101/gr.2821705. PubMed DOI PMC

Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser. 1999;41:95–98.

Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis. 1997;18:2714–2723. doi: 10.1002/elps.1150181505. PubMed DOI

Guindon S, Gascuel O. A simple, fast an accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol. 2003;52:696–704. doi: 10.1080/10635150390235520. PubMed DOI

Tamura K, Dudley J, Nei M, Kumar S. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. . Mol Biol Evol. 2007;24:1596–1599. doi: 10.1093/molbev/msm092. PubMed DOI

Schwede T, Kopp J, Guex N, Peitsch MC. SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res. 2003;31:3381–3385. doi: 10.1093/nar/gkg520. PubMed DOI PMC

Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling. Bioinformatics. 2006;22:195–201. doi: 10.1093/bioinformatics/bti770. PubMed DOI

CPHmodels 2.0: X3M a Computer Program to Extract 3D Models. http://www.cbs.dtu.dk/services/CPHmodels/

Bennett-Lovsey RM, Herbert AD, Sternberg MJ, Kelley LA. Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre. Proteins. 2007. in press . PubMed

The Imperial College Phyre Server. http://www.sbg.bio.ic.ac.uk/phyre/

DeepViewSwiss-PdbViewer. http://www.expasy.org/spdbv

Hooft RW, Vriend G, Sander C, Abola EE. Errors in protein structures. Nature. 1996;381:272–272. doi: 10.1038/381272a0. PubMed DOI

Rodriguez R, Chinea G, Lopez N, Pons T, Vriend G. Homology modeling, model and software evaluation: three related resources. Bioinformatics. 1998;14:523–528. doi: 10.1093/bioinformatics/14.6.523. PubMed DOI

The WHAT IF Web Interface. http://swift.cmbi.ru.nl

Green plants. Version 01 January 1996 (under construction) The Tree of Life Web Project. http://tolweb.org/Green_plants/2382/1996.01.01

Graham LE, Cook ME, Busse JS. The origin of plants: Body plan changes contributing to a major evolutionary radiation. Proc Natl Acad Sci U S A. 2000;97:4535–4540. doi: 10.1073/pnas.97.9.4535. PubMed DOI PMC

Transmembrane formins as active cargoes of membrane trafficking

Bundling up the Role of the Actin Cytoskeleton in Primary Root Growth

The Arabidopsis thaliana Class II Formin FH13 Modulates Pollen Tube Growth

Division of Labor Between Two Actin Nucleators-the Formin FH1 and the ARP2/3 Complex-in Arabidopsis Epidermal Cell Morphogenesis

Arabidopsis Class II Formins AtFH13 and AtFH14 Can Form Heterodimers but Exhibit Distinct Patterns of Cellular Localization

Formins: linking cytoskeleton and endomembranes in plant cells

Formins and membranes: anchoring cortical actin to the cell wall and beyond

Invasive cells in animals and plants: searching for LECA machineries in later eukaryotic life

AtFH1 formin mutation affects actin filament and microtubule dynamics in Arabidopsis thaliana

Formins: emerging players in the dynamic plant cell cortex

Evolution of the land plant exocyst complexes

Turnover of Phosphatidic Acid through Distinct Signaling Pathways Affects Multiple Aspects of Pollen Tube Growth in Tobacco