ISCU

Isoform 1

Mitochondrial scaffold protein, of the core iron-sulfur cluster (ISC) assembly complex, that provides the structural architecture on which the [2Fe-2S] clusters are assembled (PubMed:34824239). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (Probable) (PubMed:24971490, PubMed:29576242, PubMed:30031876, PubMed:34824239). Exists as two slow interchanging conformational states, a structured (S) and disordered (D) form (PubMed:23940031). May modulate NFS1 desulfurase activity in a zinc-dependent manner (PubMed:30031876). Modulates the interaction between FXN and the cysteine desulfurase complex (PubMed:29576242).

Isoform 2

Cytoplasmic scaffold protein, of the cytoplasmic core iron-sulfur cluster (ISC) assembly complex that provides the structural architecture on which the Fe-S clusters are assembled and may be involved in the cytoplasmic iron-sulfur protein biogenesis.

Myopathy with exercise intolerance Swedish type

MEIS

Autosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism.

None

The disease is caused by variants affecting the gene represented in this entry.

Phosphorylation at Ser-14 is required for ISCU protein stabilization in the cytosol, whereas dephosphorylation of Ser-14, due to the inhibition of mTORC1 (mammalian target of rapamycin complex 1) complex, leads to degradation of the precursor form and ultimately to a decrease in the mitochondrial mature form.

Cysteine persulfide is reduced by thiol-containing molecules such as glutathione and L-cysteine.

Belongs to the NifU family.

Detected in heart, liver, skeletal muscle, brain, pancreas, kidney, lung and placenta.

• Isoform 1
• Mitochondrion
• Isoform 2
• Cytoplasm
• Nucleus

NIFUN, ISCU, Iron-sulfur cluster assembly enzyme ISCU, NifU-like N-terminal domain-containing protein, NifU-like protein

• entrezGene:23479
• omim:611911
• swissprot:Q9H1K1

Proteins

Metabolism

17999Da