The reference OMIM entry for this protein is 135940

Filaggrin; flg profilaggrin, included

DESCRIPTION

Profilaggrin is a major protein component of the keratohyalin granules of mammalian epidermis. It is initially expressed as a large polyprotein precursor which is subsequently proteolytically processed into individual functional filaggrin molecules. The filaggrins show wide species variations and their aberrant expression has been implicated in a number of keratinizing disorders (Baden et al., 1974; Holbrook et al., 1982; Sybert et al., 1985). Deimination of FLG arginine residues by peptidylarginine deiminases (see PADI1, 607934) results in the dissociation of FLG from the matrix and promotes its degradation into free amino acids that are important for retaining water in the stratum corneum and for UV protection (summary by Hsu et al., 2011).

CLONING

McKinley-Grant et al. (1989) isolated a cDNA clone encoding human filaggrin. They demonstrated that the human gene encodes a polyprotein precursor containing numerous tandem filaggrin repeats. This structure is similar to that of the mouse; however, the human filaggrin repeat is much longer (972 basepairs; 324 amino acids) and shows little sequence homology to the mouse protein. They found furthermore that the human filaggrin repeats show considerable sequence variations; such polymorphism is not found in the mouse. By peptide mapping, they defined a short linker sequence within the human filaggrin repeat that is excised by proteolysis to yield functional molecules. They showed by in situ hybridization that the expression of the gene for the human filaggrin precursor is tightly regulated at the transcriptional level in terminally differentiating epidermis. Gan et al. (1990) isolated genomic DNA and cDNA clones encoding the 5-prime and 3-prime ends of the human gene and mRNA. They found evidence of likely CAT and TATA sequences, an intron in the 5-prime untranslated region, and several potential regulatory sequences. The gene is made up of repeats, all of the same length. Sequences showed considerable variation, most attributable to single-base changes. Thus, human filaggrin consists of a heterogeneous population of molecules of different sizes, charges, and sequences. Amino acid sequences encoding the amino and carboxyl termini were more conserved, as were the 5-prime and 3-prime DNA sequences flanking the coding portions of the gene. The presence of unique restriction enzyme sites in these conserved flanking sequences enabled Gan et al. (1990) to calculate the size of the full-length gene and the number of repeats in it; depending on the source of genomic DNA, the gene contains 10, 11, or 12 filaggrin repeats that segregate in families in a normal mendelian manner. Thus, the human profilaggrin gene is polymorphic with respect to size due to simple allelic differences between individuals. Using RT-PCR, Wu et al. (2009) detected FLG expression in all normal tissues examined.

GENE STRUCTURE

The FLG gene comprises 3 exons (Presland et al., 1992).

MAPPING

Using a cDNA clone as a probe in the study of a panel of mouse-human somatic cell hybrids retaining overlapping subsets of human chromosomal regions and for chromosomal in situ hybridization, McKinley-Grant et al. (1989) demonstrated that the human filaggrin gene maps to 1q21. Rothnagel et al. (1994) mapped the homologous gene to mouse chromosome 3 by PCR analyses of DNAs isolated from mouse/Chinese hamster somatic cell hybrids. Genes of 3 protein families that are specifically expressed ... More on the omim web site

Subscribe to this protein entry history

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 135940 was added.