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J. Biol. Chem., Vol. 265, Issue 4, 1862-1865, Feb, 1990
JA Rothnagel and PM Steinert
Filaggrins are an important class of intermediate filament-associated
proteins that are involved in the organization of keratin filaments in the
terminal stages of mammalian epidermal differentiation. Filaggrins are
initially synthesized as very large polyprotein precursors consisting of
many tandemly arranged repeats that are later liberated by proteolytic
processes to yield many copies of the functional protein. We have recently
characterized a cDNA clone to mouse filaggrin (Rothnagel, J. A., Mehrel.
T., Idler, W. W., Roop, D. R., and Steinert, P. M. (1987) J. Biol. Chem.
262, 15643-15648) which encodes a 750-base pair (250-amino acid) repeating
element having properties consistent with a filaggrin molecule. Southern
blot analysis of total mouse DNA and the mouse gene isolated from a cosmid
library (cosmid clone cFM6.1A2) has also revealed a repeat length of about
750 base pairs. The cosmid clone contains most of the mouse filaggrin gene,
but it is missing the 5'-noncoding sequences and possibly some coding
sequences as well. We report here that cosmid clone cFM6.1A2 contains 20
filaggrin repeats and 15,213 base pairs of coding sequences. Sequence
analysis of this clone has revealed at least two different types of
repeating element. Type B has a repeat length of 750 base pairs (250 amino
acids), whereas type A is 765 base pairs (255 amino acids) long and
contains an additional five amino acids inserted next to an acidic sequence
that delineates the amino and carboxyl termini of the filaggrin repeats. It
is supposed that these additional five amino acids may alter the
proteolytic sensitivity of the acidic linker sequence, thereby affecting
the processing of the precursor. The random distribution of the two types
of repeats in the precursor indicates that the mouse filaggrin gene arose
by a complicated series of duplications and/or rearrangements.
The structure of the gene for mouse filaggrin and a comparison of the repeating units
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
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