Recombinant Human Iron-sulfur cluster assembly enzyme ISCU, mitochondrial (ISCU)

1. identifies an important regulatory role for zinc-bound ISCU in modulation of the human Fe-S assembly system in vitro and reports no 'FXN bypass' effect on mutations at position Met140 in human ISCU PMID: 30031876
2. we report the first heterozygous dominant mutation in ISCU; notably, this alteration resulted in a similar phenotype as the recessive ISCU disease previously described. PMID: 29079705
3. When ISCU was replaced by the fully structured variant ISCU(M108I), the addition of rdFDX2 to the [NIA-ISCU(M108I)-FXN]2 complex led to the release of FXN. Thus, the displacement of FXN by rdFDX2 explains the failure of FXN to stimulate Fe-S cluster assembly on ISCU(M108I). PMID: 29406711
4. We have shown that ASO treatment diminished aberrant splicing and increased ISCU protein levels in both patient fibroblasts and patient myotubes in a concentration dependent fashion. Upon ASO treatment, levels of SDHB in patient myotubular cell lines increased to levels observed in control myotubular cell lines PMID: 28007899
5. The NFS1/ISD11 complex further interacts with scaffold protein ISCU and regulator protein frataxin, thereby forming a quaternary complex for Fe-S cluster formation. PMID: 28271877
6. Molecular dynamics flexible fitting of protein structures docked into the EM map of the model revealed a [FXN(42-210)]24.[NFS1]24.[ISD11]24.[ISCU]24 complex, consistent with the measured 1:1:1:1 stoichiometry of its four components. PMID: 27519411
7. ISCU expression was decreased in the majority of human liver cancer tissues, and its reduced expression was significantly associated with p53 mutation. PMID: 26560363
8. Thus, driven by acquired (hypoxia) or genetic causes, the miR-210-ISCU1/2 regulatory axis is a pathogenic lynchpin causing iron-sulfur deficiency and pulmonary hypertension. PMID: 25825391
9. The core Fe-S biosynthetic enzymatic complex generated [2Fe-2S] cluster intermediates that converted to stable [2Fe-2S] clusters bound to uncomplexed ISCU2. PMID: 26016389
10. IscU is a new substrate of MK2 both in Drosophila cells and in human cells PMID: 25204651
11. Fe-S assembly protein (ISCU2) and frataxin convert substrates l-cysteine, ferrous iron, and electrons into Fe-S clusters. PMID: 24971490
12. the G50E iron-sulfur cluster scaffold protein (ISCU) mutation has a role in mitochondrial myopathy PMID: 24573684
13. NFS1 binds preferentially to the D-state of ISCU while mtHSP70 binds preferentially to the D-state of ISCU and HSC20 binds preferentially to the S-state of ISCU. PMID: 23940031
14. mTORC1 associates with ISCU and phosphorylates ISCU at serine 14. This phosphorylation stabilized ISCU protein. PMID: 23508953
15. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables PMID: 23449350
16. ISCU protein deficiency in patients results from muscle-specific mis-splicing and oxidative stress. PMID: 23035118
17. this study unveiled a signaling axis of HIF-1alpha/miRNA-210/iron-sulfur cluster scaffold protein in a subset of head and neck paragangliomas that could have an impact on SDHB protein stability by a mechanism independent of succinate dehydrogenase mutations PMID: 22977270
18. Photoreactive heterotrifunctional chemical cross-linking confirmed the interaction between frataxin and ISCU in the presence of iron and validated that transient interactions can be covalently trapped with this method. PMID: 22897349
19. iron-sulfur cluster scaffold homologue down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation PMID: 21801864
20. Exchange of [2Fe-2S] centers between glutaredoxin 2 and the cluster scaffold protein ISU, supports a direct link for glutaredoxin 2 and glutathione involvement in ISU promoted Fe-S cluster biosynthesis. PMID: 21437321
21. Data show that the highest level of incorrectly spliced ISCU mRNA was found in skeletal muscle. PMID: 21165651
22. miR-210 mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation PMID: 20436681
23. ISCU and COX10 are target genes of miR-210 related to mitochondrial metabolism PMID: 20498629
24. Data suggest that frataxin may be involved in the biosynthesis of iron-sulphur proteins such as IscU1 not only within the mitochondria, but also in the extramitochondrial compartment. PMID: 16091420
25. Functional analysis of the mitochondrial and cytosolic isoforms of the human Fe-S cluster scaffold protein, ISCU. PMID: 16517407
26. the cytosolic form of ISCS is a functional cysteine desulfurase that can collaborate with cytosolic ISCU to promote de novo iron-sulfur cluster formation PMID: 16527810
27. Intron mutation in the ISCU gene, leading to incorrectly spliced mRNA, is the cause of myopathy with lactic acidosis in this family. PMID: 18296749
28. Gene ISCU was identified as a candidate within a region of shared homozygosity among patients with myopathy with severe exercise intolerance and myoglobinuria. PMID: 18304497
29. the iron-dependent binding affinity of each frataxin derivative to the iron-sulfur cluster scaffold protein ISU is found to be similar to that of native frataxin PMID: 18425540
30. a new ISCU mutation in iron-sulphur cluster deficiency myopathy PMID: 19567699
31. Results identify the iron-sulfur cluster assembly proteins (ISCU1/2) as direct targets for repression by the hypoxia-induced microRNA-210. PMID: 19808020

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HGNC: 29882

OMIM: 255125

KEGG: hsa:23479

STRING: 9606.ENSP00000310623

UniGene: Hs.615131