Mitochondrial fission 1 protein (FIS1)
The protein contains 152 amino acids for an estimated molecular weight of 16938 Da.
Involved in the fragmentation of the mitochondrial network and its perinuclear clustering. Plays a minor role in the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface and mitochondrial fission. Can induce cytochrome c release from the mitochondrion to the cytosol, ultimately leading to apoptosis. Also mediates peroxisomal fission. (updated: March 4, 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.
- 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.
This protein is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Apoptotic process
Autophagy of mitochondrion
Calcium-mediated signaling using intracellular calcium source
Cellular response to glucose stimulus
Cellular response to peptide
Cellular response to thapsigargin
Cellular response to toxic substance
Mitochondrial fission
Mitochondrial fragmentation involved in apoptotic process
Mitochondrial fusion
Mitochondrion morphogenesis
Negative regulation of ATP metabolic process
Negative regulation of endoplasmic reticulum calcium ion concentration
Negative regulation of fatty acid transport
Peroxisome fission
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
Positive regulation of cytosolic calcium ion concentration
Positive regulation of intrinsic apoptotic signaling pathway
Positive regulation of mitochondrial calcium ion concentration
Positive regulation of mitochondrial fission
Positive regulation of neuron apoptotic process
Positive regulation of protein targeting to membrane
Protein homooligomerization
Protein import into peroxisome membrane
Protein targeting to mitochondrion
Regulation of mitochondrion organization
Release of cytochrome c from mitochondria
Response to flavonoid
Response to fluoride
Response to hypobaric hypoxia
Response to muscle activity
Response to nutrient levels
The reference OMIM entry for this protein is 609003
Tetratricopeptide repeat domain-containing protein 11; ttc11
Fis1, s. cerevisiae, homolog of
DESCRIPTION
The balance between fission and fusion regulates the morphology of mitochondria. TTC11 is a component of a mitochondrial complex that promotes mitochondrial fission (James et al., 2003).CLONING
By searching for sequences similar to yeast Fis1, followed by PCR of a liver cDNA library, James et al. (2003) cloned FIS1. The deduced 152-amino acid protein contains a central leucine zipper, a coiled-coil region, and a C-terminal transmembrane domain. It also contains a region showing high interspecies homology and a putative tetratricopeptide repeat. Immunocytochemical analysis of HeLa cells detected endogenous FIS1 expression in mitochondria. Protease treatment indicated that FIS1 is expressed at the outer mitochondrial membrane. Transfection of a C-terminal truncated FIS1 resulted in cytoplasmic expression, indicating that the C terminus is required for mitochondrial localization. Yoon et al. (2003) cloned human FIS1 by PCR. The deduced 152-amino acid protein has a calculated molecular mass of 17 kD.GENE FUNCTION
By overexpression of FIS1 in various cell types, James et al. (2003) found that FIS1 localizes to the outer mitochondrial membrane and induces mitochondrial fission. Fission was inhibited by a dominant-negative mutant of DRP1 (DNM1L; 603850). Fragmentation of the tubular mitochondrial network by FIS1 was followed by the release of cytochrome c and ultimately apoptosis. BCLXL (600039) blocked cytochrome c release and apoptosis, but failed to prevent mitochondrial fragmentation. James et al. (2003) concluded that FIS1 is part of the mammalian fission machinery and that the regulation of mitochondrial fission may be involved in apoptosis. By differential tagging and deletion analysis, Yoon et al. (2003) demonstrated that the C terminus of human FIS1 was essential for mitochondrial localization, and that the cytosolic N terminus was necessary for mitochondrial fission. Increased FIS1 expression promoted mitochondrial fission and the accumulation of fragmented mitochondria. Conversely, cells microinjected with anti-FIS1 antibodies or treated with antisense FIS1 oligonucleotides developed elongated and collapsed mitochondria. Furthermore, FRET and coimmunoprecipitation studies demonstrated that human FIS1 interacted with rat Dnm1l, suggesting that FIS1 participates in mitochondrial fission by recruiting DNM1L from the cytosol. Yoon et al. (2003) concluded that FIS1 is a limiting factor in mitochondrial fission and that the number of FIS1 molecules on the mitochondrial surface determines fission frequency. Frieden et al. (2004) found that the dramatic mitochondrial fragmentation induced by FIS1 overexpression had no effect on the mitochondrial transmembrane potential, pH, or the ability to take up Ca(2+) released from intracellular stores upon agonist stimulation. Malena et al. (2009) tested the hypothesis that altering the balance between mitochondrial fusion and fission could influence the segregation of mutant and wildtype mtDNA variants, because it would modify the number of organelles per cell. Human cells heteroplasmic for the pathologic 3243A-G (MTTL1; 590050.0001) mitochondrial DNA mutation were transfected with constructs designed to silence DRP1 or human FIS1, whose gene products are required for mitochondrial fission. DRP1 and human FIS1 gene silencing were both associated with increased levels of mutant mitochondrial DNA. The authors concluded that the extent of the mitochondrial ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609003 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed