ISCU Antibodies

Structure of ISCU

ISCU is an iron-sulfur cluster assembly scaffold protein with a molecular weight of approximately 18.5 kDa, and there are subtle differences among different species.

This protein contains 154 amino acids and forms an iron-sulfur cluster to assemble the core through conserved cysteine residues (Cys37, Cys61, and Cys104 in human ISCUs). Its tertiary structure consists of two α -helices and five β -folds forming hydrophobic pockets, and the electron transfer function is achieved through the coordination of [2Fe-2S] or [4Fe-4S] clusters. It is worth noting that the yeast ISCU protein has an extended N-terminal domain, which is in line with its specific organelle differentiation requirements, while mammals remain completely conserved at the Cys61 site. These structural features reveal the conservation and adaptive variations of the iron-sulfur cluster assembly mechanism during the evolutionary process.

Fig. 1 Peak ratios mapped onto Zn(II)-bound ISCU structure.¹

Key structural properties of ISCU:

• Conservative iron-sulfur cluster assembly scaffold structure
• Cysteine residues form the [2Fe-2S]/[4Fe-4S] cluster coordination centers
• Hydrophobic pockets stabilize the assembly and delivery of iron - sulfur clusters
• Helix-folded alternating domains mediate protein interactions
• Species-specific amino acid variation regulates the binding stability of clusters

Functions of ISCU

The core function of the ISCU gene is to serve as a biosynthetic scaffold for iron-sulfur clusters and simultaneously participate in various cellular metabolic processes:

The transfer efficiency of iron-sulfur clusters in ISCU proteins shows a linear positive correlation, contrary to the synergistic effect of hemoglobin, reflecting its evolutionary conservation as a basal metabolic scaffold protein. This functional characteristic is particularly crucial in tissues that require high energy metabolism, such as myocardium and skeletal muscle, and its functional defect can directly lead to hereditary iron-sulfur cluster deficiency and exercise intolerance syndrome.

Applications of ISCU and ISCU Antibody in Literature

1. Luo, Jialiang, et al. "ISCU-p53 axis orchestrates macrophage polarization to dictate immunotherapy response in esophageal squamous cell carcinoma." Cell Death & Disease 16.1 (2025): 462. https://doi.org/10.1038/s41419-025-07787-7

This study found through single-cell sequencing that in esophageal squamous cell carcinoma, ISCU promotes the polarization of M2-type macrophages and upregulates the expression of xCT and Arg1 by retaining p53 in the cytoplasm, thereby suppressing the immune response. Inhibiting ISCU can reshape the tumor microenvironment and enhance the efficacy of PD-1 inhibitors.

2. Cai, Kai, Ronnie O. Frederick, and John L. Markley. "ISCU interacts with NFU1, and ISCU [4Fe-4S] transfers its Fe-S cluster to NFU1 leading to the production of holo-NFU1." Journal of structural biology 210.2 (2020): 107491. https://doi.org/10.1016/j.jsb.2020.107491

Studies have shown that the human ISCU protein can directly bind to NFU1 with an affinity of 1.1 μM and transfer its [4Fe-4S] cluster to apo-NFU1, while the [2Fe-2S] cluster cannot. This discovery reveals the crucial role of ISCU in the maturation of mitochondrial iron-sulfur proteins.

3. Fox, Nicholas G., et al. "Zinc (II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity." Biochimie 152 (2018): 211-218. https://doi.org/10.1016/j.biochi.2018.07.012

Research has found that human ISCU protein can bind to zinc ions, and this state will inhibit the desulfurizer activity of the NFS1-ISD11-ACP complex. The removal of zinc ions can moderately activate this activity, and frataxin (FXN) can equally activate ISCUs in both zinc-bound and zinc-deficient forms. The study did not observe that the M140 site mutation could bypass the FXN requirement and emphasized the key regulatory role of the zinc ion state in the function of the complex.

4. Rusecka, Joanna M., et al. "Autosomal dominant myopathy caused by a novel ISCU variant." Frontiers in Genetics 16 (2025): 1605440. https://doi.org/10.3389/fgene.2025.1605440

Research has found that the novel heterozygous variant c.399del (P. val134ter) of the ISCU gene can lead to hereditary myopathy accompanied by lactic acidosis. This variation is located in the functional domain. It has been verified by the yeast model to be pathogenic and dominant in inheritance. The clinical manifestations it causes are similar to those of the recessive inherited ISCU deficiency previously.

5. Funauchi, Yuki, et al. "Regulation of iron homeostasis by the p53-ISCU pathway." Scientific reports 5.1 (2015): 16497. https://doi.org/10.1038/srep16497

Research has found that p53 participates in iron metabolism by transcriptional regulation of ISCU expression. The absence of ISCU inhibits the translation of the iron storage protein FTH1, leading to iron accumulation within cells. Both p53-deficient cells and mice showed iron metabolism disorders. Moreover, the low expression of ISCU in human liver cancer was significantly associated with p53 mutations, suggesting that the p53-ISCU pathway plays a key role in maintaining iron homeostasis.

Creative Biolabs: ISCU Antibodies for Research

Creative Biolabs specializes in the production of high-quality ISCU antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom ISCU Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our ISCU antibodies, custom preparations, or technical support, contact us at email.