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The left-right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulin

Lookup NU author(s): Professor Judith Goodship, Lee Turnpenny, Professor Tom Strachan

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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 inv mouse 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. © Springer-Verlag 2002.


Publication metadata

Author(s): Goodship J; Strachan T; Turnpenny L; Morgan D; Essner JJ; Vogan KJ; Yost HJ; Tabin CJ

Publication type: Article

Publication status: Published

Journal: Human Genetics

Year: 2002

Volume: 110

Issue: 4

Pages: 377-384

ISSN (print): 0340-6717

ISSN (electronic): 1432-1203

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00439-002-0696-4

DOI: 10.1007/s00439-002-0696-4

PubMed id: 11941489


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