Sideroflexin-1 (SFXN1)
The protein contains 322 amino acids for an estimated molecular weight of 35619 Da.
Mitochondrial serine transporter that mediates transport of serine into mitochondria, an important step of the one-carbon metabolism pathway (PubMed:30442778). Mitochondrial serine is converted to glycine and formate, which then exits to the cytosol where it is used to generate the charged folates that serve as one-carbon donors (PubMed:30442778). Transports both D-serine and L-serine (PubMed:30442778). Also able to transport other amino-acids, such as alanine (PubMed:30442778). May be indirectly involved in the transport of a component required for iron utilization into or out of the mitochondria (By similarity). (updated: Feb. 13, 2019)
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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs17065105 | |
| dbSNP:rs34907038 |
Biological Process
D-serine transport
Erythrocyte differentiation
Iron ion homeostasis
Iron ion transport
L-serine transport
Mitochondrial transmembrane transport
One-carbon metabolic process
Serine import into mitochondrion
The reference OMIM entry for this protein is 615569
Sideroflexin 1; sfxn1
CLONING
Fleming et al. (2001) cloned mouse sideroflexin-1 (Sfxn1), which they named after the siderocytic anemia and flexed-tail phenotype of Sfxn1 mutant mice (seeANIMAL MODEL
). The deduced 322-amino acid protein contains 5 transmembrane domains and conserved motifs on either side of transmembrane domain-1. By database analysis, Fleming et al. (2001) identified human SFXN1 and orthologs in C. elegans, Drosophila, and yeast. Northern blot analysis of 12 adult mouse tissues detected highest Sfxn1 expression in kidney and liver, with variable expression in other tissues. Sfxn1 expression in liver was highest during hepatic erythropoiesis in embryonic and neonatal mice. Epitope-tagged Sfxn1 colocalized with a mitochondrial marker in transfected HEK293T cells.MAPPING
Hartz (2013) mapped the SFXN1 gene to chromosome 5q35.2 based on an alignment of the SFXN1 sequence (GenBank GENBANK AF327346) with the genomic sequence (GRCh37). Fleming et al. (2001) mapped the mouse Sfxn1 gene to chromosome 13.ANIMAL MODEL
The flexed-tail (f) mutation in mice results in variable spinal flexions due abnormal development of intervertebral disks. Penetrance of the flexed tail depends upon genetic background. F/f mice also show a fully penetrant transient embryonic and neonatal anemia characterized by appearance of siderocytes with mitochondrial iron accumulation. Fleming et al. (2001) observed that anemia in f/f mice was limited to the time when liver was the major erythropoietic organ. They identified the f mutation as an adenine insertion in exon 2 of the Sfxn1 gene. The insertion occurs after codon 15 and was predicted to cause a frameshift that introduces 17 novel amino acids and a premature stop codon after amino acid 15. Western blot analysis found no expression of the truncated protein in f/f animals. ... More on the omim web site
Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 615569 was added.