title: The third human FER-1-like protein is highly similar to dysferlin.
abstract: Dysferlin, the protein product of the gene mutated in patients with an autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) and a distal muscular dystrophy, Miyoshi myopathy, is homologous to a Caenorhabditis elegans spermatogenesis factor, FER-1. Analysis of fer-1 mutants and of sequence predictions of the FER-1 and dysferlin ORFs has predicted a role in membrane fusion. Otoferlin, another human FER-1-like protein (ferlin), has recently been shown to be responsible for autosomal recessive nonsyndromic deafness (DFNB9). In this report we describe the third human ferlin gene, FER1L3, which maps to chromosome 10q23.3. Expression analysis of the orthologous mouse gene shows ubiquitous expression but predominant expression in the eye, esophagus, and salivary gland. All the ferlins are characterized by sequences corresponding to multiple C2 domains that share the highest level of homology with the C2A domain of rat synaptotagmin III. They are predicted to be Type II transmembrane proteins, with the majority of the protein facing the cytoplasm anchored by the C-terminal transmembrane domain. Sequence and predicted structural comparisons have highlighted the high degree of similarity of dysferlin and FER1L3, which have sequences corresponding to six C2 domains and which share more than 60% amino acid sequence identity.
authors.affiliation: Molecular Genetics Unit, School of Biochemistry and Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, England, NE1 7RU, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Britton
authors.forename: T
authors.initials: T
authors.lastname: Freeman
authors.forename: E
authors.initials: E
authors.lastname: Vafiadaki
authors.forename: S
authors.initials: S
authors.lastname: Keers
authors.forename: R
authors.initials: R
authors.lastname: Harrison
authors.forename: K
authors.initials: K
authors.lastname: Bushby
authors.forename: R
authors.initials: R
authors.lastname: Bashir
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D017124:Conserved Sequence; D003638:Deafness / Q000235:genetics; D000073939:Dysferlin; D005260:Female; D005808:Genes, Recessive; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics*; D016366:Open Reading Frames; D009928:Organ Specificity; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C114839:DYSF protein, human; D000073939:Dysferlin; C106933:FER-1 protein, C elegans; D015801:Helminth Proteins; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; C118457:OTOF protein, human