Ferritin heavy chain (FTH1)
The protein contains 183 amino acids for an estimated molecular weight of 21226 Da.
Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Cellular iron ion homeostasis
Immune response
Intracellular sequestering of iron ion
Iron ion import
Iron ion transport
Membrane organization
Negative regulation of cell population proliferation
Negative regulation of fibroblast proliferation
Negative regulation of necrotic cell death
Neutrophil degranulation
Post-Golgi vesicle-mediated transport
Receptor-mediated endocytosis
Transmembrane transport
The reference OMIM entry for this protein is 134770
Ferritin heavy chain 1; fth1
Fth
Fhc
Fthl6
DESCRIPTION
The iron storage protein ferritin is a complex of 24 ferritin light chain (FTL; 134790) and ferritin heavy chain (FTH1) subunits in ratios that vary in different cell types. FTH subunits exhibit ferroxidase activity, converting Fe(2+) to Fe(3+), so that iron may be stored in the ferritin mineral core, which prevents undesirable reactions of Fe(2+) with oxygen. FTL subunits are devoid of catalytic activity but are thought to facilitate nucleation and mineralization of the iron center (summary by Sammarco et al., 2008).CLONING
Murray et al. (1987) demonstrated that the rat has a single H-subunit gene. Near the cap region of the 5-prime untranslated region, this subunit shows a 28-nucleotide sequence that is almost totally conserved in human, bullfrog, and chicken H mRNA and is also faithfully represented in the rat and human L-subunit mRNAs. This sequence is a prime candidate for involvement in the known translational regulation of both subunits by iron, which induces synthesis of the subunits by causing latent mRNAs present in the cytosol to become polyribosome-associated and translationally active. Hentze et al. (1986) isolated a genomic phage clone containing a full-length copy of the gene for ferritin heavy chain. The functionality of the gene was demonstrated by the fact that both transient transfectants and stable transformants of mouse fibroblasts actively transcribed human ferritin heavy-chain mRNA.GENE STRUCTURE
Hentze et al. (1986) determined that the FTH1 gene consists of 4 exons and spans approximately 3 kb. From genomic analysis, using a cDNA clone, Boyd et al. (1984) concluded that the ferritin heavy chains are either encoded by a multigene family or that the gene has an unusually large number of exons. Faniello et al. (2006) summarized the major regulatory elements of the FTH1 gene. They noted that the promoter region of FTH1 spans approximately 150 bp upstream from the transcription start site. The promoter has an A box at position -132 and a B box at position -62. The A box is a canonical GC box that is recognized by SP1 (189906). The B box is an inverted CAAT box that is recognized by the B box-binding factor (Bbf), a complex that contains the trimeric transcription factor NFY (see NFYB, 189904), EP300 (602700), and P/CAF (KAT2B; 602303).MAPPING
By study of hamster-human and mouse-human hybrid cells, some with translocations involving chromosome 19, Worwood et al. (1985) concluded that light subunits of ferritin (rich in human spleen ferritin) are coded by a gene in segment 19q13.3-qter and that the gene for the heavy subunit (rich in human heart ferritin) is located on chromosome 11. By study of DNA extracted from rodent-human cell hybrids, Cragg et al. (1985) found sequences homologous to a probe for the H subunit of human ferritin on at least 8 chromosomes: 1, 2, 3, 6p21-6cen, 11, 14, 20, and Xq23-Xqter. Only the gene on chromosome 11 appeared to be expressed in these hybrids. Hentze et al. (1986) assigned the human FTH1 gene to chromosome 11 by analysis of genomic DNA from rodent-human cell hybrids. Gatti et al. (1987) concluded that the heavy-subunit family includes 15 to 20 genes or pseudogenes and that the light-subunit family includes at least 3 genes. They confirmed and extended the chromosomal localization of the heavy-subunit 'genes' to chromosomes 1-6, 8, 9, 11, 13, 14, 17, and X. They identified and characterized a BamHI RFLP of FTH located on chromo ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 134770 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed