2b3y

Structural highlights

Function

ACOHC_HUMAN Bifunctional iron sensor that switches between 2 activities depending on iron availability (PubMed:1946430, PubMed:1281544, PubMed:8041788). Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization (PubMed:1946430, PubMed:1281544, PubMed:8041788, PubMed:23891004). Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA (PubMed:1946430, PubMed:1281544, PubMed:8041788, PubMed:23891004).^{[1] [2] [3] [4]} Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.^{[5] [6] [7]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Aconitase 3D structures

References

1. ↑ Haile DJ, Rouault TA, Harford JB, Kennedy MC, Blondin GA, Beinert H, Klausner RD. Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11735-9. PMID:1281544 doi:10.1073/pnas.89.24.11735
2. ↑ Kaptain S, Downey WE, Tang C, Philpott C, Haile D, Orloff DG, Harford JB, Rouault TA, Klausner RD. A regulated RNA binding protein also possesses aconitase activity. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10109-13. PMID:1946430
3. ↑ Stehling O, Mascarenhas J, Vashisht AA, Sheftel AD, Niggemeyer B, Rösser R, Pierik AJ, Wohlschlegel JA, Lill R. Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins. Cell Metab. 2013 Aug 6;18(2):187-98. PMID:23891004 doi:10.1016/j.cmet.2013.06.015
4. ↑ Philpott CC, Klausner RD, Rouault TA. The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5. PMID:8041788
5. ↑ Haile DJ, Rouault TA, Harford JB, Kennedy MC, Blondin GA, Beinert H, Klausner RD. Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11735-9. PMID:1281544 doi:10.1073/pnas.89.24.11735
6. ↑ Kaptain S, Downey WE, Tang C, Philpott C, Haile D, Orloff DG, Harford JB, Rouault TA, Klausner RD. A regulated RNA binding protein also possesses aconitase activity. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10109-13. PMID:1946430
7. ↑ Philpott CC, Klausner RD, Rouault TA. The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5. PMID:8041788
8. ↑ Dupuy J, Volbeda A, Carpentier P, Darnault C, Moulis JM, Fontecilla-Camps JC. Crystal structure of human iron regulatory protein 1 as cytosolic aconitase. Structure. 2006 Jan;14(1):129-39. PMID:16407072 doi:10.1016/j.str.2005.09.009