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FLASH GENE

Symbol

FTH1

contributors: mct/npt - updated : 16-02-2018

HGNC name	ferritin, heavy polypeptide 1
HGNC id	3976

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002032 4 - 1245 NP_002023 21 183 - 2017 28754384

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Nervous brain         Visual eye anterior segment cornea

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune macrophage Homo sapiens Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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