Patterns of evolutionary conservation in the nesprin genes highlight probable functionally important protein domains and isoforms.
The nesprins [also known as SYNEs (synaptic nuclear envelope proteins)] are a family of type II transmembrane proteins implicated in the tethering of membrane-bound organelles and in the genetic aetiology of cerebellar ataxia and Emery-Dreifuss muscular dystrophy. They are characterized by a common structure of an SR (spectrin repeat) rod domain and a C-terminal transmembrane KLS (klarsicht)/KASH [klarsicht/ANC-1 (anchorage 1)/SYNE homology] domain which interacts with SUN [Sad1p/UNC (uncoordinated)-84] proteins in the nuclear envelope; most nesprins also have N-terminal actin-binding CH (calponin homology) domains. The genes encoding the three vertebrate nesprins (five in bony fish) and the small transmembrane actin-binding protein calmin are related to each other by ancient duplications and rearrangements. In the present paper, we collate sequence data for nesprins and calmins across the vertebrate clade and use these to study evolutionary constraints acting on their genes. We show that the rod domains of the larger nesprins are composed almost entirely of unbroken SR-like structures (74 in nesprin-1 and 56 in nesprin-2) and that these range from poorly conserved purely structural elements to highly conserved regions with a presumed protein-protein interaction function. The analysis suggests several interesting regions for future study. We also assess the evolutionary and EST (expressed sequence tag) expression support for nesprin isoforms, both known and novel; our findings suggest that substantial reassessment is required.
Simpson
Jennifer G
JG
Department of Medical and Molecular Genetics, King's College London, Tower Wing, Guy's Hospital, London, UK.
Roberts
Roland G
RG
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary
D009419:Nerve Tissue Proteins; D020033:Protein Isoforms