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Filaggrin (FLG)
Function:
- promotes production of natural moisturizing factors & the lipid matrix, which acts like mortar, keeping keratinocytes in the horny layer together [3]
- aggregates keratin intermediate filaments & promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis
- filaggrin is initially synthesized as a large, insoluble, highly phosphorylated precursor containing many tandem copies of 324 AA, which are not separated by large linker sequences
- during terminal differentiation it is dephosphorylated & proteolytically cleaved
- the N-terminal of the mature protein is heterogeneous, & is blocked by the formation of pyroglutamate
- undergoes deimination of some Arg (citrullination)
Structure:
- belongs to the S100-fused protein family
- contains 2 EF-hand domains
- contains 23 filaggrin repeats
Expression:
- keratohyalin granules
- produced by upper-layer epidermal keratinocytes
Pathology:
- defects in FLG are the cause of ichthyosis vulgaris
- defects in FLG may be the cause of susceptibility to atopic dermatitis type 2
- loss-of-function mutation in FLG perturbs the skin barrier
- increasing transepidermal water loss, resulting in xerosis
- the lack of epidermal lipids also reduces production of antimicrobial peptides & facilitates allergen penetration of the skin inducing allergic sensitization
Related
Filaggrin (FLG)
General
Ca+2 binding protein
phosphoprotein
Properties
SIZE: entity length = 4061 aa
MW = 435 kD
MOTIF: EF hand
SITE: 6-43
EF hand
SITE: 49-84
MOTIF: Ca+2-binding site
SITE: 62-73
coiled coil {186-216}
Filaggrin {258-306}
serine-rich region {260-3955}
MOTIF: serine residue (SEVERAL)
Filaggrin {374-428}
Filaggrin {579-630}
Ser phosphorylation site {S695}
Filaggrin {698-753}
Filaggrin {904-955}
Filaggrin {1023-1077}
Filaggrin {1228-1279}
Filaggrin {1347-1401}
Filaggrin {1552-1603}
Filaggrin {1671-1725}
Filaggrin {1876-1927}
Filaggrin {1995-2050}
Filaggrin {2201-2252}
Filaggrin {2320-2374}
Ser phosphorylation site {S2514}
Thr phosphorylation site {T2517}
Filaggrin {2525-2576}
Filaggrin {2644-2698}
Filaggrin {2849-2900}
Filaggrin {2968-3022}
Filaggrin {3173-3224}
Filaggrin {3292-3346}
Ser phosphorylation site {S3371}
Ser phosphorylation site {S3376}
Ser phosphorylation site {S3473}
Filaggrin {3497-3548}
Filaggrin {3616-3670}
Filaggrin {3821-3872}
Database Correlations
OMIM correlations
MORBIDMAP 135940
UniProt P20930
PFAM correlations
Entrez Gene 2312
Kegg hsa:2312
References
- UniProt :accession P20930
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=FLG
- Rothaus C
Atopic Dermatitis.
NEJM Resident 360. March 24, 2021
https://resident360.nejm.org/clinical-pearls/atopic-dermatitis-7
- Stander S
Atopic Dermatitis.
N Engl J Med 2021; 384:1136-1143. March 25 (Review article)
PMID: 33761208
https://www.nejm.org/doi/full/10.1056/NEJMra2023911