Filaggrin

Filaggrin
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4PCW
Identifiers
Symbols	FLG ; ATOD2
External IDs	OMIM: 135940 HomoloGene: 136751 GeneCards: FLG Gene
Gene ontology Molecular function • structural molecule activity • calcium ion binding • protein binding Cellular component • nucleus • intermediate filament • keratohyalin granule Biological process • multicellular organismal development • keratinocyte differentiation • establishment of skin barrier Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2312	14246
Ensembl	ENSG00000143631	ENSMUSG00000091340
UniProt	P20930	P11088
RefSeq (mRNA)	NM_002016	n/a
RefSeq (protein)	NP_002007	n/a
Location (UCSC)	Chr 1: 152.3 – 152.33 Mb	Chr 3: 93.08 – 93.08 Mb
PubMed search	[1]	[2]

Filaggrin is a filament-associated protein that binds to keratin fibers in epithelial cells.

Profilaggrin

Filaggrin monomers are tandemly clustered into a large, 350kDa protein precursor known as profilaggrin. In the epidermis, these structures are present in the keratohyalin granules in cells of the stratum granulosum. Profilaggrin undergoes proteolytic processing to yield individual filaggrin monomers at the transition between the stratum granulosum and the stratum corneum, which may be facilitated by calcium-dependent enzymes.

Function

Filaggrin is essential for the regulation of epidermal homeostasis. Within the stratum corneum, filaggrin monomers can become incorporated into the lipid envelope, which is responsible for the skin barrier function. Alternatively, these proteins can interact with keratin intermediate filaments. Filaggrin undergoes further processing in the upper stratum corneum to release free amino acids that assist in water retention.

Clinical significance

Individuals with truncation mutations in the gene coding for filaggrin are strongly predisposed to a severe form of dry skin, ichthyosis vulgaris, and/or eczema.

It has been shown that almost 50% of all severe cases of eczema may have at least one mutated filaggrin gene. R501X and 2284del4 are not generally found in non-Caucasian individuals, though novel mutations (3321delA and S2554X) that yield similar effects have been found in Japanese populations. Truncation mutations R501X and 2284del4 are the most common mutations in the Caucasian population, with 7 to 10% of the Caucasian population carrying at least one copy of these mutations.

Autoantibodies in rheumatoid arthritis recognizing an epitope of citrullinated peptides are cross-reactive with filaggrin.

The barrier defect seen in filaggrin null carriers also appears to lead to increased asthma susceptibility and exacerbations. Filaggrin deficiency is one of the top genome-wide genetic determinants of asthma, along with the variants found that regulate ORMDL3 expression.

In early infancy, the penetrance of filaggrin mutations may be increased by household exposure to cats.

See also

• Ichthyosis vulgaris
• List of cutaneous conditions caused by mutations in keratins

External links

• Filaggrin at the US National Library of Medicine Medical Subject Headings (MeSH)