Recombinant Human Ferritin heavy chain (FTH1)

Function

Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation (PubMed:9003196). Also plays a role in delivery of iron to cells (By similarity). Mediates iron uptake in capsule cells of the developing kidney (By similarity). Delivery to lysosomes is mediated by the cargo receptor NCOA4 for autophagic degradation and release of iron (PubMed:24695223, PubMed:26436293)

Subcellular Location

Cytoplasm; Lysosome; Cytoplasmic vesicle, autophagosome

Disease Association

Hemochromatosis 5 (HFE5) : A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading. [The disease is caused by variants affecting the gene represented in this entry. In a Japanese family affected by HFE5, a single point mutation has been detected in the iron-responsive element (IRE) in the 5'-UTR of FTH1 mRNA. This mutation leads to an increased binding affinity for iron regulatory protein and thereby to the efficient suppression of mRNA translation] | Neurodegeneration with brain iron accumulation 9 (NBIA9) : An autosomal dominant neurodegenerative disorder associated with iron accumulation, primarily in the basal ganglia. It is characterized by global developmental delay apparent from infancy, and progressive decline of motor and cognitive skills. Clinical features include delayed walking or inability to walk, spasticity with hyperreflexia, ataxia, dystonia, and poor or absent language. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in the liver

Subunit

Oligomer of 24 subunits (PubMed:9159481). There are two types of subunits: L (light) chain and H (heavy) chain (PubMed:9159481). The major chain can be light or heavy, depending on the species and tissue type. In the human liver, the heavy chain is predominant (PubMed:9159481). The functional molecule forms a roughly spherical shell with a diameter of 12 nm and contains a central cavity into which the insoluble mineral iron core is deposited (PubMed:9159481). Interacts with NCOA4; NCOA4 promotes targeting of the iron-binding ferritin complex to autolysosomes following starvation or iron depletion (PubMed:24695223)

• Costanzo F. et al. Cloning and sequencing of a full length cDNA coding for a human apoferritin H chain: evidence for a multigene family. — EMBO J. (1984)
• Boyd D. et al. Structural and functional relationships of human ferritin H and L chains deduced from cDNA clones. — J. Biol. Chem. (1985)
• Chou C.-C. et al. Structure and expression of ferritin genes in a human promyelocytic cell line that differentiates in vitro. — Mol. Cell. Biol. (1986)
• Costanzo F. et al. Structure of gene and pseudogenes of human apoferritin H. — Nucleic Acids Res. (1986)
• Hentze M.W. et al. Cloning, characterization, expression, and chromosomal localization of a human ferritin heavy-chain gene. — Proc. Natl. Acad. Sci. U.S.A. (1986)
• Dhar M. et al. Sequence of a cDNA encoding the ferritin H-chain from an 11-week-old human fetal brain. — Gene (1993)
• Chauthaiwale V.M. et al. Cloning of a novel full length cDNA for ferritin heavy chain from normal adult human and Alzheimer's brain. (JUL-)
• Franco A.V. et al. Detection of ferritin heavy chain by SEREX: a multifunctional molecule in malignant tumour cells. (AUG-)