The Ferritin-Heavy-Polypeptide-Like-17 (FTHL17) gene encodes a ferritin with low stability and no ferroxidase activity and with a partial nuclear localization.
BACKGROUND
Three functional ferritin genes have been identified so far in mammals, and they encode the cytosolic Heavy (FTH) and Light chain (FTL) and the mitochondrial ferritin. The expression of a transcript by a fourth ferritin-like gene (Ferritin-Heavy-Polypeptide-Like-17, FTHL17) on the X chromosome was reported in mouse spermatogonia and in early embryonic cells.


METHODS
The intronless human FTHL17 gene encodes a protein with 64% identity to human FTH with substitution of key residues of the ferroxidase center. The gene was cloned into vectors for expression in Escherichia coli and mammalian cells, linked to a flag-tag.


RESULTS
The recombinant FTHL17 from E. coli purified as an assembled 24-mer ferritin devoid of ferroxidase activity and with a reduced physical stability. When transiently expressed in mammalian cells the flag-FTHL17 assembled in ferritin shells that showed reduced stability to denaturants compared with flag H and L ferritins. Immunocytochemistry with anti-flag antibody decorated the nuclei of flag-FTHL17 transfected COS cells, but not those of the cells transfected with flag-FTH or flag-FTL.


CONCLUSIONS
We concluded that FTHL17 encodes a ferritin-like protein without ferroxidase activity. Its restricted embryonic expression and partial nuclear localization suggest that this novel ferritin type may have functions other than iron storage.


CONCLUSIONS
The work confirms the presence of a fourth functional human ferritin gene with properties distinct from the canonical cytosolic ones.
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Paola
P
Ruzzenenti
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Michela
M
Asperti
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Stefania
S
Mitola
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Elisabetta
E
Crescini
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Federica
F
Maccarinelli
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Magdalena
M
Gryzik
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Maria
M
Regoni
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Dario
D
Finazzi
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy. Electronic address: paolo.arosio@unibs.it.
Paolo
P
Arosio
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
Maura
M
Poli
D000595:Amino Acid Sequence; D000818:Animals; D001052:Apoferritins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D053595:Embryonic Stem Cells / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011489:Protein Denaturation; D055550:Protein Stability; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
C000600683:FTHL17 protein, mouse; D011994:Recombinant Proteins; D001052:Apoferritins
Embryonic cell; Ferritin; Ferroxidase center; Protein stability