Metalloreductase STEAP3 (STEAP3)
The protein contains 488 amino acids for an estimated molecular weight of 54601 Da.
Endosomal ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Participates in erythroid iron homeostasis by reducing Fe(3+) to Fe(2+). Can also reduce of Cu(2+) to Cu(1+), suggesting that it participates in copper homeostasis. Uses NADP(+) as acceptor. May play a role downstream of p53/TP53 to interface apoptosis and cell cycle progression. Indirectly involved in exosome secretion by facilitating the secretion of proteins such as TCTP. (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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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 annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs17013371 |
No binding partner found
Biological Process
Apoptotic process
Cell cycle
Cellular iron ion homeostasis
Copper ion import
Exosomal secretion
Ferric iron import into cell
Iron ion homeostasis
Iron ion import across cell outer membrane
Oxidation-reduction process
Positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Protein secretion
Regulation of apoptotic process
Transferrin transport
Transmembrane transport
The reference OMIM entry for this protein is 609671
Six-transmembrane epithelial antigen of prostate 3; steap3
Tumor suppressor-activated pathway 6; tsap6
CLONING
Passer et al. (2003) cloned human STEAP3, which they called TSAP6, from a pooled-tissue cDNA library. The deduced 488-amino acid protein contains an N-terminal motif associated with oxidoreductases and dehydrogenases and 5 or 6 transmembrane domains. Human TSAP6 shares 87% amino acid identity with mouse Tsap6. Northern blot analysis of human tissues detected a 4.3-kb transcript expressed highly in liver and at a lower level in skeletal muscle. Heart, brain, placenta, lung, kidney, and pancreas expressed little to no TSAP6. Northern blot analysis of mouse tissues detected expression predominantly in heart, spleen, lung, liver, and skeletal muscle. Western blot analysis of mouse and human cell lines detected TSAP6 at an apparent molecular mass of 50 to 55 kD. Using Western blot analysis, Lespagnol et al. (2008) detected Tsap6 proteins of 46 and 52 kD in mouse NIH3T3 cells, and they showed that the larger protein resulted from glycosylation. Confocal microscopy of mouse embryonic fibroblasts showed colocalization of endogenous Tsap6 with the trans-Golgi network maker Tgn38 (TGOLN; 603062). Punctuated cytoplasmic and plasma membrane staining of Tsap6 partially colocalized with transferrin receptor (TFRC; 190010) and Eea1 (605070), suggesting that Tsap6 is expressed in the endosomal compartment.MAPPING
By FISH, Passer et al. (2003) mapped the STEAP3 gene to chromosome 2q14.2. They mapped the mouse Steap3 gene to chromosome 1.GENE FUNCTION
Using Northern blot analysis, Passer et al. (2003) found that p53 (TP53; 191170) upregulated TSAP6 expression in mouse and human cell lines. They identified a p53-responsive element upstream of the first exon of the mouse Tsap6 gene. TSAP6 antisense cDNA decreased the level of p53-induced apoptosis, and TSAP6 small interfering RNA inhibited apoptosis in TSAP6-overexpressing cells. Yeast 2-hybrid analysis, protein pull-down assays, and coimmunoprecipitation analysis revealed that TSAP6 interacted with NIX (BNIP3; 605368), a proapoptotic BCL2 (151430)-related protein, and with MYT1 kinase (602474), a negative regulator of G2/M transition. Moreover, TSAP6 enhanced the susceptibility of cells to apoptosis and cooperated with NIX to exacerbate this effect. Cell cycle studies indicated that TSAP6 could augment MYT1 activity. Passer et al. (2003) concluded that TSAP6 may act downstream of p53 to interface apoptosis and cell cycle progression. Histamine-releasing factor (TPT1; 600763) is a secreted protein that participates in inflammatory responses by promoting the release of histamine. Amzallag et al. (2004) found that secretion of TPT1 proceeded by a nonclassical pathway independent of the endoplasmic reticulum and Golgi apparatus. They determined that TSAP6 interacted with TPT1 in several protein interaction assays, and the 2 proteins codistributed to small vesicles called exosomes at the plasma membrane and around the nucleus in several human cell lines. Overexpression of TSAP6 increased the level of TPT1 in exosome preparations and consistently enhanced TPT1 secretion. Amzallag et al. (2004) concluded that TSAP6 has a role in the export of TPT1 via a nonclassical pathway and suggested that TSAP6 may have a general role in the regulation of vesicular trafficking and secretion.MOLECULAR GENETICS
In 3 sibs with hypochromic microcytic anemia and iron overload (615234), born of nonconsanguineous Pakistani parents, Grandchamp et al. (2011) analyzed 7 candidate ... 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 609671 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed