Disease:


  • OMIM ID: 609691 . 609691
  • OMIM diseaseName:
  • OMIM diseaseClinical_Synopsis:
  • OMIM diseaseText: DESCRIPTION Proteins that contain formin (FMN1; 136535) homology (FH) domains, such as FHOD3, play a role in regulation of the actin cytoskeleton (Kanaya et al., 2005). CLONING By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned FHOD3, which they designated KIAA1695. The deduced protein contains 1,199 amino acids. RT-PCR ELISA detected highest expression in heart, followed by fetal brain and adult skeletal muscle. Intermediate expression was detected in all other whole tissues and specific brain regions examined. By searching for sequences similar to FHOD1 (606881) Katoh and Katoh (2004) identified 3 FHOD3 alternative splice variants. One variant encodes the full-length protein, while the other variants, KIAA1695 and FLJ34580, lack exon 11 and exon 13, respectively. The deduced full-length protein contains 1,439 amino acids and has a central FH1 domain and a C-terminal FH2 domain. FHOD3 shares 52.1% amino acid identity with FHOD1 and 43.9% amino acid identity with the Drosophila FHOD3 ortholog. In addition to the FH1 and FH2 domains, these proteins have conserved N- and C-terminal domains that the authors designated FHDHN and FHDHC, respectively. By searching an EST database for sequences similar to FHOD1, followed by screening a human fetal brain cDNA library, RT-PCR, and 5-prime RACE, Kanaya et al. (2005) cloned FHOD3, which they designated FHOS2. The deduced protein contains 1,422 amino acids. Kanaya et al. (2005) also identified 2 splice variants of mouse Fhos2, designated Fhos2l and Fhos2s, that encode proteins of 1,578 and 1,427 amino acids, respectively, and differ by the presence or absence of a sequence in the N-terminal half. Fhos2s shares 91% amino acid identity with human FHOS2. Northern blot analysis of several mouse tissues detected abundant Fhos2 expression in heart and kidney, much lower expression in brain, and little to no expression in other tissues. Fhos2s was expressed in kidney and brain, whereas Fhos2l predominated in heart. The pattern of FHOS2 expression in human tissues was similar. Immunocytochemical analysis of rat embryonal cardiomyocytes detected colocalization of Fhos2 with nestin (NES; 600915), an intermediate filament protein. In fetal rat brain, Fhos2 localized to radial fibers extending from the ventricle surface to the pial surface. In medulla oblongata, it localized to radial processes extending from the surface of the fourth ventricle. In developing heart, Fhos2 localized to I-band structures. Fhos2 partially localized with nestin in developing brain, but not in developing heart. GENE FUNCTION Kanaya et al. (2005) noted that FHOS1 seems to be normally folded in an inactive form maintained by an intramolecular interaction between its N- and C-terminal regions. Deletion of the N- or C terminal regions activates FHOS1, inducing stress fiber formation. Kanaya et al. (2005) therefore overexpressed C-terminally truncated forms of mouse Fhos2l and Fhos2s in HeLa cells and found that both induced stress fiber formation and cell elongation. C-terminally truncated Fhos2s localized to actin filaments, whereas C-terminally truncated Fhos2l did not. GENE STRUCTURE Katoh and Katoh (2004) determined that the FHOD3 gene contains at least 25 exons. MAPPING By genomic sequence analysis, Katoh and Katoh (2004) mapped the FHOD3 gene to chromosome 18q12.2.
  • OMIM diseaseSee_Also:
  • OMIM diseaseAllelic_Variants:
  • OMIM diseaseCreation_Date: Patricia A. Hartz: 10/27/2005
  • OMIM diseaseEdit_History_Data: wwang: 04/02/2010 mgross: 10/27/2005
  • OMIM diseaseContributors:
  • OMIM diseaseReference: 1. 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 10: 665-678, 2005. 2. Katoh, M.; Katoh, M.: Identification and characterization of human FHOD3 gene in silico. Int. J. Molec. Med. 13: 615-620, 2004. 3. Nagase, T.; Kikuno, R.; Hattori, A.; Kondo, Y.; Okumura, K.; Ohara, O.: Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 347-355, 2000.