Filaggrin
FLG | |||
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Molecular function | |||
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Sources:Amigo / QuickGO |
Ensembl |
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UniProt |
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RefSeq (mRNA) |
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RefSeq (protein) |
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Location (UCSC) | Chr 1: 152.3 – 152.33 Mb | n/a | |||||||
PubMed search | [2] | n/a |
View/Edit Human |
Filaggrin (filament aggregating protein) is a filament-associated protein that binds to keratin fibers in epithelial cells. Ten to twelve filaggrin units are post-translationally hydrolyzed from a large profilaggrin precursor protein during terminal differentiation of epidermal cells.[3] In humans, profilaggrin is encoded by the FLG gene, which is part of the S100 fused-type protein (SFTP) family within the epidermal differentiation complex on chromosome 1q21.[4]
Profilaggrin
Filaggrin monomers are tandemly clustered into a large, 350kDa protein precursor known as profilaggrin. In the
Structure
Filaggrin is characterized by a particularly high isoelectric point due to the relatively high presence of histidine in its primary structure.[6] It is also relatively low in the sulfur-containing amino acids methionine and cysteine.
Function
Filaggrin is essential for the regulation of epidermal homeostasis. Within the
Some studies attribute an important role to filaggrin in maintaining the physiological acidic pH of the skin, through a breaking-down mechanism to form histidine and subsequently trans-urocanic acid.[7] However, others have shown that the filaggrin–histidine–urocanic acid cascade is not essential for skin acidification.[8]
Clinical significance
Individuals with truncation
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.[11] 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.[9]
The barrier defect seen in filaggrin null carriers also appears to lead to increased asthma susceptibility and exacerbations.[13][14][15] Filaggrin deficiency is one of the top genome-wide genetic determinants of asthma, along with the variants found that regulate ORMDL3 expression.[16]
In early infancy, the penetrance of filaggrin mutations may be increased by household exposure to cats.[17]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000143631 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8417356.
- S2CID 5435031.
- ^ PMID 19726197.
- PMID 6195345.
- S2CID 24679127.
- PMID 20376063.
- ^ S2CID 2500278.
- PMID 16815158.
- PMID 17291859.
- PMID 9421490.
- S2CID 8105444.
- PMID 17531295.
- PMID 18325573.
- PMID 18395550.
- PMID 18578563.
External links
- Filaggrin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)