title: ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins.
abstract: BACKGROUND
  Annotations of completely sequenced genomes reveal that nearly half of the genes identified are of unknown function, and that some belong to uncharacterized gene families. To help resolve such issues, information can be obtained from the comparative analysis of homologous genes in model organisms.
  
  
  RESULTS
  While characterizing genes from the retinitis pigmentosa locus RP26 at 2q31-q33, we have identified a new gene, ORMDL1, that belongs to a novel gene family comprising three genes in humans (ORMDL1, ORMDL2 and ORMDL3), and homologs in yeast, microsporidia, plants, Drosophila, urochordates and vertebrates. The human genes are expressed ubiquitously in adult and fetal tissues. The Drosophila ORMDL homolog is also expressed throughout embryonic and larval stages, particularly in ectodermally derived tissues. The ORMDL genes encode transmembrane proteins anchored in the endoplasmic reticulum (ER). Double knockout of the two Saccharomyces cerevisiae homologs leads to decreased growth rate and greater sensitivity to tunicamycin and dithiothreitol. Yeast mutants can be rescued by human ORMDL homologs.
  
  
  CONCLUSIONS
  From protein sequence comparisons we have defined a novel gene family, not previously recognized because of the absence of a characterized functional signature. The sequence conservation of this family from yeast to vertebrates, the maintenance of duplicate copies in different lineages, the ubiquitous pattern of expression in human and Drosophila, the partial functional redundancy of the yeast homologs and phenotypic rescue by the human homologs, strongly support functional conservation. Subcellular localization and the response of yeast mutants to specific agents point to the involvement of ORMDL in protein folding in the ER.
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain. roser@bio.ub.es
authors.forename: Lars
authors.initials: L
authors.lastname: Hjelmqvist
authors.forename: Miquel
authors.initials: M
authors.lastname: Tuson
authors.forename: Gemma
authors.initials: G
authors.lastname: Marfany
authors.forename: Enric
authors.initials: E
authors.lastname: Herrero
authors.forename: Susana
authors.initials: S
authors.lastname: Balcells
authors.forename: Roser
authors.initials: R
authors.lastname: Gonzàlez-Duarte
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D017124:Conserved Sequence / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000737:chemistry*; D020869:Gene Expression Profiling / Q000379:methods; D018390:Gene Targeting / Q000379:methods; D049452:Green Fluorescent Proteins; D006801:Humans; D017403:In Situ Hybridization; D007425:Intracellular Membranes / Q000737:chemistry*; D007814:Larva / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D016415:Sequence Alignment / Q000379:methods; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; C464400:ORMDL protein, Drosophila; C464259:ORMDL1 protein, human; C464279:ORMDL2 protein, human; C464399:ORMDL3 protein, human; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins