NFS1
Description
The NFS1 (NFS1 cysteine desulfurase) is a protein-coding gene located on chromosome 20.
Cysteine desulfurase, mitochondrial is an enzyme that in humans is encoded by the NFS1 gene. Iron-sulfur clusters are required for the function of many cellular enzymes. The protein encoded by this gene supplies inorganic sulfur to these clusters by removing the sulfur from cysteine, creating alanine in the process. This gene uses alternate in-frame translation initiation sites to generate mitochondrial forms and cytoplasmic/nuclear forms. Selection of the alternative initiation sites is determined by the cytosolic pH. The encoded protein belongs to the class-V family of pyridoxal phosphate-dependent aminotransferases.
[Isoform Mitochondrial]: 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). {ECO:0000250|UniProtKB:Q9H1K1, ECO:0000250|UniProtKB:Q9Z1J3, ECO:0000269|PubMed:18650437, ECO:0000269|PubMed:29097656, ECO:0000269|PubMed:31101807}
NFS1 is also known as COXPD52, HUSSY-08, IscS, NIFS.
