Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.13.4848· OSTI ID:5161053

McKinley-Grant, L J; Idler, W W; Bernstein, I A; Parry, D A.D.; Cannizzaro, L; Croce, C M; Huebner, K; Lessin, S R; Steinert, P M ^[1]

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1. National Institutes of Health, Bethesda, MD (USA)

Filaggrins are an important class of intermediate filament-associated proteins that interact with keratin intermediate filaments of terminally differentiating mammalian epidermis. They show wide species variations and their aberrant expression has been implicated in a number of keratinizing disorders. The authors have isolated a cDNA clone encoding human filaggrin and used this to demonstrate that the human gene encodes a polyprotein precursor containing numerous tandem filaggrin repeats. This structure is similar to that of mouse; however, the human filaggrin repeat is much longer (972 base pairs; 324 amino acids) and shows little sequence homology to the mouse protein. Also, data presented here reveal that the human filaggrin repeats show considerable sequence variations; such polymorphism is not found in the mouse. Furthermore, chromosomal mapping data revealed that the human gene is located at 1q21, indicating that the polymorphism is confined to a single locus. By peptide mapping, they define a short linker sequence within the human filaggrin repeat that is excised by proteolysis to yield functional molecules. Finally, they show by in situ hybridization that human filaggrin precursor gene expression is tightly regulated at the transcriptional level in terminally differentiating epidermis and that this represents a useful system in which to study intermediate filament-intermediate filament-associated protein interactions as well as disorders of keratinization.

• OSTI ID: 5161053
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:13; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CHROMOSOMES
DAYS LIVING RADIOISOTOPES
DNA
DNA HYBRIDIZATION
DNA SEQUENCING
EPIDERMIS
EPITHELIUM
GENES
GENETIC MAPPING
HETEROCHROMOSOMES
HYBRIDIZATION
HYDROGEN COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
MAPPING
MICE
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHENYLALANINE
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
RECOMBINANT DNA
RODENTS
SCLEROPROTEINS
SKIN
STRUCTURAL CHEMICAL ANALYSIS
TISSUES
TRANSCRIPTION
TRITIUM COMPOUNDS
VERTEBRATES