title: The left-right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulin.
abstract: All vertebrates have a left-right body axis with invariant asymmetries of the heart and the positions of the abdominal viscera. Major advances have recently been made in defining molecular components of the pathway specifying the vertebrate left-right axis, but our knowledge of the early determinants is extremely limited. In the invmouse the left-right axis is consistently reversed, unlike other vertebrate mutants where randomisation of situs is apparent. The gene disrupted in this mouse encodes a 1062-amino-acid protein, inversin. We previously reported 16 tandem ankyrin repeats, spanning amino acids 13-557, and two putative nuclear localisation sequences, but otherwise the sequence offered few clues to the possible function. In order to identify regions likely to be functionally important, we have identified and characterised orthologous sequences in several species, including chick, Xenopus and zebrafish. Sequence comparisons show strong conservation of the ankyrin repeat region and also a lysine-rich domain spanning amino acids 558-604. Further analysis identified a highly conserved IQ calmodulin-binding domain in the latter region and another such domain in an otherwise poorly conserved C-terminal region. A yeast two-hybrid screen identified calmodulin in one third of the positive clones, and we confirmed this interaction by immunoprecipitation.
authors.affiliation: Institute of Human Genetics, University of Newcastle, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Morgan
authors.forename: Judith
authors.initials: J
authors.lastname: Goodship
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Essner
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Vogan
authors.forename: Lee
authors.initials: L
authors.lastname: Turnpenny
authors.forename: H Joseph
authors.initials: HJ
authors.lastname: Yost
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
authors.forename: Tom
authors.initials: T
authors.lastname: Strachan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins; D001483:Base Sequence; D002147:Calmodulin / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
chemical_list: D017487:Ankyrins; D002147:Calmodulin; D017931:DNA Primers; C114503:INVS protein, human; C491947:Invs protein, mouse; D011506:Proteins; D014157:Transcription Factors