ACO1 explained
Aconitase 1, soluble is a protein that in humans is encoded by the ACO1 gene.[1]
Function
The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5' UTR of ferritin mRNA, and in the 3' UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants.[1]
Further reading
- Wang W, Di X, D'Agostino RB, Torti SV, Torti FM . Excess capacity of the iron regulatory protein system . The Journal of Biological Chemistry . 282 . 34 . 24650–9 . Aug 2007 . 17604281 . 10.1074/jbc.M703167200 . free .
- Martelli A, Salin B, Dycke C, Louwagie M, Andrieu JP, Richaud P, Moulis JM . Folding and turnover of human iron regulatory protein 1 depend on its subcellular localization . The FEBS Journal . 274 . 4 . 1083–92 . Feb 2007 . 17244191 . 10.1111/j.1742-4658.2007.05657.x . 8412580 . free .
- Hu J, Connor JR . Demonstration and characterization of the iron regulatory protein in human brain . Journal of Neurochemistry . 67 . 2 . 838–44 . Aug 1996 . 8764614 . 10.1046/j.1471-4159.1996.67020838.x. 35872879 .
- Popovic Z, Templeton DM . Inhibition of an iron-responsive element/iron regulatory protein-1 complex by ATP binding and hydrolysis . The FEBS Journal . 274 . 12 . 3108–19 . Jun 2007 . 17521334 . 10.1111/j.1742-4658.2007.05843.x . 22629034 . free .
- Wang J, Fillebeen C, Chen G, Biederbick A, Lill R, Pantopoulos K . Iron-dependent degradation of apo-IRP1 by the ubiquitin-proteasome pathway . Molecular and Cellular Biology . 27 . 7 . 2423–30 . Apr 2007 . 17242182 . 1899896 . 10.1128/MCB.01111-06 .
- Liu CY, Liu YF, Zeng L, Zhang SG, Xu H . [The expression of TfR1 mRNA and IRP1 mRNA in the placenta from different maternal iron status] . Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi . 28 . 4 . 255–8 . Apr 2007 . 17877204 .
- Zimmer M, Lamb J, Ebert BL, Lynch M, Neil C, Schmidt E, Golub TR, Iliopoulos O . The connectivity map links iron regulatory protein-1-mediated inhibition of hypoxia-inducible factor-2a translation to the anti-inflammatory 15-deoxy-delta12,14-prostaglandin J2 . Cancer Research . 70 . 8 . 3071–9 . Apr 2010 . 20354189 . 2861799 . 10.1158/0008-5472.CAN-09-2877 .
- Gu JM, Lim SO, Oh SJ, Yoon SM, Seong JK, Jung G . HBx modulates iron regulatory protein 1-mediated iron metabolism via reactive oxygen species . Virus Research . 133 . 2 . 167–77 . May 2008 . 18262302 . 10.1016/j.virusres.2007.12.014 .
- Popovic Z, Templeton DM . Iron accumulation and iron-regulatory protein activity in human hepatoma (HepG2) cells . Molecular and Cellular Biochemistry . 265 . 1–2 . 37–45 . Oct 2004 . 15543932 . 10.1023/b:mcbi.0000044313.19574.c6. 19363206 .
Notes and References
- Web site: Entrez Gene: Aconitase 1, soluble .