title: A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa.
abstract: BACKGROUND
  Formins are multidomain proteins defined by a conserved FH2 (formin homology 2) domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1) domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes.
  
  
  RESULTS
  We present a detailed sequence analysis of the 10 formins (ForA to J) identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells.
  
  
  CONCLUSIONS
  Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism.
authors.affiliation: Center for Biochemistry and Center for Molecular Medicine, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Köln, Germany. francisco.rivero@uni-koeln.de
authors.forename: Francisco
authors.initials: F
authors.lastname: Rivero
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Muramoto
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Meyer
authors.forename: Hideko
authors.initials: H
authors.lastname: Urushihara
authors.forename: Taro Q P
authors.initials: TQ
authors.lastname: Uyeda
authors.forename: Chikako
authors.initials: C
authors.lastname: Kitayama
mesh_terms: D008841:Actin Cytoskeleton; D000199:Actins / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D002352:Carrier Proteins / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D030562:Databases, Protein; D004023:Dictyostelium / Q000378:metabolism*; D004330:Drosophila; D005656:Fungal Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: D000199:Actins; D002352:Carrier Proteins; D018076:DNA, Complementary; D005656:Fungal Proteins; D008840:Microfilament Proteins; D020033:Protein Isoforms
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