Tbio ISCU Iron-sulfur cluster assembly enzyme ISCU, mitochondrial

Protein Summary

Description

Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins (PubMed:11060020). First, a [2Fe-2S] cluster is transiently assembled on the scaffold protein ISCU. In a second step, the cluster is released from ISCU, transferred to a glutaredoxin GLRX5, followed by the formation of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters and their target-specific insertion into the recipient apoproteins. Cluster assembly on ISCU depends on the function of the cysteine desulfurase complex NFS1-LYRM4/ISD11, which serves as the sulfur donor for cluster synthesis, the iron-binding protein frataxin as the putative iron donor, and the electron transfer chain comprised of ferredoxin reductase and ferredoxin, which receive their electrons from NADH (By similarity). This gene encodes a component of the iron-sulfur (Fe-S) cluster scaffold. Fe-S clusters are cofactors that play a role in the function of a diverse set of enzymes, including those that regulate metabolism, iron homeostasis, and oxidative stress response. Alternative splicing results in transcript variants encoding different protein isoforms that localize either to the cytosol or to the mitochondrion. Mutations in this gene have been found in patients with hereditary myopathy with lactic acidosis. A disease-associated mutation in an intron may activate a cryptic splice site, resulting in the production of a splice variant encoding a putatively non-functional protein. A pseudogene of this gene is present on chromosome 1. [provided by RefSeq, Feb 2016]

Uniprot Accession IDs

• Q9H1K1
• Q6P713
• Q99617
• Q9H1K2

Gene Name

• ISCU

Ensembl ID

• ENST00000311893
• ENSP00000310623
• ENSG00000136003
• ENST00000392807
• ENSP00000376554

Symbol

• NIFUN
• HML
• ISU2
• NIFU
• NIFUN
• hnifU
• 2310020H20Rik

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	0.95
transcription factor perturbation	0.94
transcription factor binding site profile	0.86
cell type or tissue	0.68
transcription factor	0.66

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 277.66   (req: < 5)

Gene RIFs: 38   (req: <= 3)

Antibodies: 234   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 277.66   (req: >= 5)

Gene RIFs: 38   (req: > 3)

Antibodies: 234   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0