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FUNCTION Cysteine desulfurase, of the core iron-sulfur cluster (ISC) assembly complex, that catalyzes the desulfuration of L-cysteine to L-alanine, as component of the cysteine desulfurase complex, leading to the formation of a cysteine persulfide intermediate at the active site cysteine residue and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (PubMed:29097656, PubMed:31101807, PubMed:18650437). The persulfide is then transferred on the flexible Cys loop from the catalytic site of NFS1 to the surface of NFS1 (PubMed:29097656). After the NFS1-linked persulfide sulfur is transferred to one of the conserved Cys residues of the scaffold, a reaction assisted by FXN (By similarity). 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 (By similarity).FUNCTION May catalyze the desulfuration of L-cysteine to L-alanine as component of the cysteine desulfurase complex (NFS1:LYRM4), leading to the formation of a cysteine persulfide intermediate (PubMed:18650437, PubMed:16527810). Acts as a sulfur donor for MOCS3 by transferring the sulfur of the cysteine persulfide intermediate on MOCS3 (PubMed:18650437, PubMed:23593335).CATALYTIC ACTIVITY [sulfur carrier]-H + L-cysteine = [sulfur carrier]-SH + L-alanineCATALYTIC ACTIVITY [sulfur carrier]-H + L-cysteine = [sulfur carrier]-SH + L-alanineCATALYTIC ACTIVITY [sulfur-carrier protein]-L-cysteine + L-cysteine = [sulfur-carrier protein]-S-sulfanyl-L-cysteine + L-alanineCOFACTOR Active only in complex with LYRM4.BIOPHYSICOCHEMICAL PROPERTIES Kinetic parameter was determined for the protein lacking the 55 N-terminal amino acids and in a complex with LYRM4.SUBUNIT Homodimer (PubMed:29097656, PubMed:31101807). Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer (Probable). Component of cyteine desulfurase complex composed of NFS1, LYRM4 and NDUFAB1; this complex contributes to the activation of cysteine desulfurase activity and NFS1 stabilization (PubMed:34824239, PubMed:31664822). Interacts (homodimer form) with ISCU (D-state); each monomer interacts with the C-terminal regions of each NFS1 monomer (PubMed:29097656, PubMed:11060020, PubMed:23940031). Interacts with HSPA9 (PubMed:26702583). Interacts (via homodimer form) with FDX2 (PubMed:29097656). Interacts (via homodimer form) with FXN (PubMed:31101807). Interacts with LYRM4 (PubMed:29097656, PubMed:19454487). Component of a complex composed of FXN, NFS1, LYRM4 and ISCU (By similarity).SUBUNIT Monomer (PubMed:16527810). Homodimer (PubMed:16527810, PubMed:18650437, PubMed:23593335). Oligomer (PubMed:18650437). Interacts with ISCU (PubMed:16527810). Component of the cysteine desulfurase complex composed of NFS1 and LYRM4; this complex contributes to the activation of cysteine desulfurase activity (PubMed:18650437). Interacts with MOCS3 (PubMed:18650437, PubMed:23593335).INTERACTION Individual cells may vary AUG utilization in accordance with changes in metabolic status, the cytosolic pH being a strong determinant of this modulation.TISSUE SPECIFICITY Predominantly expressed in heart and skeletal muscle. Also found in brain, liver and pancreas.PTM N-gluconoylated.PTM Cysteine persulfide intermediate is reduced by thiol-containing molecules like glutathione and L-cysteine. Persulfide reduction is a rate-limiting step of cysteine desulfurase catalytic cycle.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.
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