NFS1
Function
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:18650437, PubMed:29097656, PubMed:31101807). 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 (NFS1NDUFAB1) 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).
Isoform Cytoplasmic
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:16527810, PubMed:18650437). Acts as a sulfur donor for MOCS3 by transferring the sulfur of the cysteine persulfide intermediate on MOCS3 (PubMed:18650437, PubMed:23593335).
Involvement in disease
Combined oxidative phosphorylation deficiency 52
COXPD52
An autosomal recessive mitochondrial disorder with onset in infancy, characterized by lactic acidemia, hypotonia, respiratory chain complex II and III deficiency, multisystem organ failure and abnormal mitochondria.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-gluconoylated.
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.
Sequence Similarities
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.
Tissue Specificity
Predominantly expressed in heart and skeletal muscle. Also found in brain, liver and pancreas.
Cellular localization
- Isoform Mitochondrial
- Mitochondrion
- Isoform Cytoplasmic
- Cytoplasm
- Nucleus
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
Alternative names
NIFS, HUSSY-08, NFS1, Cysteine desulfurase