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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21.

Filaggrins are an important class of intermediate filament-associated proteins that interact with keratin intermediate filaments of terminally differentiating mammalian epidermis. They show wide species variations and their aberrant expression has been implicated in a number of keratinizing disorders. We have isolated a cDNA clone encoding human filaggrin and used this to demonstrate that the human gene encodes a polyprotein precursor containing numerous tandem filaggrin repeats. This structure is similar to that of mouse; however, the human filaggrin repeat is much longer (972 base pairs; 324 amino acids) and shows little sequence homology to the mouse protein. Also, data presented here reveal that the human filaggrin repeats show considerable sequence variations; such polymorphism is not found in the mouse. Furthermore, chromosomal mapping data revealed that the human gene is located at 1q21, indicating that the polymorphism is confined to a single locus. By peptide mapping, we define a short linker sequence within the human filaggrin repeat that is excised by proteolysis to yield functional molecules. Finally, we show by in situ hybridization that human filaggrin precursor gene expression is tightly regulated at the transcriptional level in terminally differentiating epidermis and that this represents a useful system in which to study intermediate filament-intermediate filament-associated protein interactions as well as disorders of keratinization.[1]


  1. Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21. McKinley-Grant, L.J., Idler, W.W., Bernstein, I.A., Parry, D.A., Cannizzaro, L., Croce, C.M., Huebner, K., Lessin, S.R., Steinert, P.M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
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