STEAP3
Metalloreductase STEAP3 is an enzyme that in humans is encoded by the STEAP3 gene.[1][2]
STEAP3 is a metalloreductase, capable of coverting iron from an insoluble ferric (Fe3+) to a soluble ferrous (Fe2+) form.[3]
The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80% of the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism for iron uptake in which iron loaded transferrin (Tf) binds to the transferrin receptor (TfR) at the cell surface. The Tf:TfR complex then enters the endosome via receptor-mediated endocytosis. Upon endosomal acidification, iron is released from Tf, reduced to Fe2+ by Steap3, and transported across the endosomal membrane by divalent metal ion transporter 1. Steap3 is composed of an N-terminal cytosolic oxidoreductase domain and a C-terminal heme-containing transmembrane domain. The NADPH/flavin binding domain of Steap3 differs significantly from those in other eukaryotic reductases. Steap3 shows remarkable, although limited homology to FNO, an archaeal oxidoreductase. We have determined the crystal structure of the human-Steap3 oxidoreductase domain in the absence and presence of NADPH (PDB-ID 2vns and 2vq3). The structure of the oxidoreductase domain reveals an unexpected dimer interface and substrate binding sites that are well positioned to direct electron transfer from the cytosol to a transmembrane heme moiety. [4]
Interactions
STEAP3 has been shown to interact with BNIP3L[1] and PKMYT1.[1]
References
- ^ a b c Passer BJ, Nancy-Portebois V, Amzallag N, Prieur S, Cans C, Roborel de Climens A, Fiucci G, Bouvard V, Tuynder M, Susini L, Morchoisne S, Crible V, Lespagnol A, Dausset J, Oren M, Amson R, Telerman A (Mar 2003). "The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase". Proc Natl Acad Sci U S A 100 (5): 2284–9. doi:10.1073/pnas.0530298100. PMC 151332. PMID 12606722. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151332.
- ^ "Entrez Gene: STEAP3 STEAP family member 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55240.
- ^ Ohgami RS, Campagna DR, McDonald A, Fleming MD (August 2006). "The Steap proteins are metalloreductases". Blood 108 (4): 1388–94. doi:10.1182/blood-2006-02-003681. PMC 1785011. PMID 16609065. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1785011.
- ^ Anoop K. Sendamarai, Robert S. Ohgami, Mark D. Fleming, and C. Martin Lawrence (May 2008). "Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle". Proc Natl Acad Sci U S A 105 (21): 7410–5. doi:10.1073/pnas.0801318105. PMC 2396704. PMID 18495927. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2396704.
Further reading
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311072.
- Korkmaz KS, Elbi C, Korkmaz CG, et al. (2002). "Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer.". J. Biol. Chem. 277 (39): 36689–96. doi:10.1074/jbc.M202414200. PMID 12095985.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Amzallag N, Passer BJ, Allanic D, et al. (2004). "TSAP6 facilitates the secretion of translationally controlled tumor protein/histamine-releasing factor via a nonclassical pathway.". J. Biol. Chem. 279 (44): 46104–12. doi:10.1074/jbc.M404850200. PMID 15319436.
- Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528930.
- Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1347501.