Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol FTH1 contributors: mct/npt - updated : 16-02-2018
HGNC name ferritin, heavy polypeptide 1
HGNC id 3976
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Fth
Homologene
FAMILY
  • the non-heme iron protein family
    • CATEGORY regulatory , storage
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • iron-storage protein, storing iron in a soluble nontoxic, readily available form
  • specific ferroxidase activity allowing rapid uptake of iron
  • functioning (cytoplasmic) acotinase when binding a (4Fe-4S) cluster
  • loss of the cluster transforms the molecules into a iron responsive protein (IRP) repressing translation when cellular iron is low
  • protect the nucleus from oxidative damage (Storr 2009)
  • critical for maintaining iron homeostasis and protecting against iron overload (Sammarco 2008)
  • with TF may serve as redundant mechanisms for the uptake of iron by cells (Li 2010)
  • is the major source of iron for oligodendrocytes
  • FTH1 and DAXX are able to participate in apoptosis pathway through JNK signal molecule and FTH1 can inhibit this pathway
  • can store and release iron, therefore it prevents the cell from damage caused by iron-dioxygen reactions as well as it provides iron for biological processing
  • core subunit of the iron storage protein ferritin and is related to the pathogenesis of malignant diseases
  • has ferroxidase activity that is required for iron incorporation and limiting toxicity
  • protective role of FTH1 and critical role of proximal tubule FTH1 in iron trafficking in acute kidney injury (AKI)
  • has ferroxidase activity (converting Fe(II) to Fe(III)
  • iron binding protein that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis
  • iron-dependent, highly-specific formation of the remarkably stable FTH1-NCOA4 complex may be important for the characterization of the mechanism of ferritinophagy 7)
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism metal
    signaling
    a component
  • heteromultimeric complex with FTL both in various tissue and cell specific proportions, arranged in a hollow shell with a 80A diameter cavity
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • iron Fe2+,Fe3+
    • protein
  • IRP binding to the IRE to the ferritin receptor and erythroid aminolevulinic synthase, enabling tight coordination between cellular iron uptake and the synthesis of ferritin and heme
  • interacting with AAAS (fibroblasts from triple A patients (with known AAAS mutations) lack nuclear FTH1, suggesting that the nuclear translocation of FTH1 is defective) (Storr 2009)
  • TFRC ligand (after binding to TFRC, enters not only endosomes but also lysosomes)(Li 2010)
  • NCOA4 directly binds ferritin heavy chain-1 (FTH1) to target the iron-binding ferritin complex
  • direct association via a key surface arginine in FTH1 and a C-terminal element in NCOA4 is required for delivery of ferritin to the lysosome via autophagosomes
    • cell & other
    REGULATION
    inhibited by low cellular iron
    repressed by C-Myc
    ASSOCIATED DISORDERS
    corresponding disease(s) IRO
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    constitutional       loss of function
    in most cells of the forebrain including cells of the choroid plexus caused accumulation of cerebrospinal fluid in the lateral ventricles and the subarachnoid space
    tumoral     --over  
    is closely related to the development of leukemia/lymphoma, which could have implications for the prevention of malignant hematologic diseases
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a novel and reliable marker for macrophages and early erythroid precursors, and may be of clinical utility in the diagnosis of diseases associated with these two cell types
    • Therapy target
    ANIMAL & CELL MODELS