9dvy

Structural highlights

Disease

CLPX_HUMAN The disease may be caused by variants affecting the gene represented in this entry.

Function

CLPX_HUMAN ATP-dependent chaperone that functions as an unfoldase. As part of the ClpXP protease complex, it recognizes specific protein substrates, unfolds them using energy derived from ATP hydrolysis, and then translocates them to the proteolytic subunit (CLPP) of the ClpXP complex for degradation (PubMed:11923310, PubMed:22710082, PubMed:28874591). Thanks to its chaperone activity, it also functions in the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis (PubMed:28874591). This chaperone is also involved in the control of mtDNA nucleoid distribution, by regulating mitochondrial transcription factor A (TFAM) activity (PubMed:22841477).^{[1] [2] [3] [4]}

References

1. ↑ Kang SG, Ortega J, Singh SK, Wang N, Huang NN, Steven AC, Maurizi MR. Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP. J Biol Chem. 2002 Jun 7;277(23):21095-102. PMID:11923310 doi:10.1074/jbc.M201642200
2. ↑ Lowth BR, Kirstein-Miles J, Saiyed T, Brötz-Oesterhelt H, Morimoto RI, Truscott KN, Dougan DA. Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein CLPX. J Struct Biol. 2012 Aug;179(2):193-201. PMID:22710082 doi:10.1016/j.jsb.2012.06.001
3. ↑ Kasashima K, Sumitani M, Endo H. Maintenance of mitochondrial genome distribution by mitochondrial AAA+ protein ClpX. Exp Cell Res. 2012 Nov 1;318(18):2335-43. PMID:22841477 doi:10.1016/j.yexcr.2012.07.012
4. ↑ Yien YY, Ducamp S, van der Vorm LN, Kardon JR, Manceau H, Kannengiesser C, Bergonia HA, Kafina MD, Karim Z, Gouya L, Baker TA, Puy H, Phillips JD, Nicolas G, Paw BH. Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):E8045-E8052. PMID:28874591 doi:10.1073/pnas.1700632114