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Human Molecular Genetics, 2001, Vol. 10, No. 24 2813-2820
© 2001 Oxford University Press

A new sequence motif linking lissencephaly, Treacher Collins and oral–facial–digital type 1 syndromes, microtubule dynamics and cell migration

Richard D. Emes and Chris P. Ponting+

MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK

A previously unidentified sequence motif has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral–facial–digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An additional homologous motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1 homology (LisH) motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD repeat-containing ß-propeller proteins. It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary structure of LisH motifs, and their occurrence in homologues of Gß ß-propeller subunits, suggests that they are analogues of G{gamma} subunits, and might associate with the periphery of ß-propeller domains. The finding of LisH motifs in both treacle and Nopp140 reinforces previous observations of functional similarities between these nucleolar proteins. Uncharacterized LisH motif-containing proteins represent candidates for other diseases associated with aberrant microtubule dynamics and defects of cell migration, nucleokinesis or chromosome segregation.

+ To whom correspondence should be addressed. Tel: +44 1865 272175; Fax: +44 1865 282651; Email: chris.ponting@anat.ox.ac.uk


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