Overview
| Uniprot ID | Q9H1K1 |
|---|
| Protein Name | Iron-sulfur cluster assembly enzyme ISCU |
|---|
| Gene Name | ISCU |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 82 |
LQIQVDEKGKIVDAR |
Function
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)
Protein Sequence
10
MAAAGAFRLR
20
RAASALLLRS
30
PRLPARELSA
40
PARLYHKKVV
50
DHYENPRNVG
60
SLDKTSKNVG
70
TGLVGAPACG
80
DVMKLQIQVD
90
EKGKIVDARF
100
KTFGCGSAIA
110
SSSLATEWVK
120
GKTVEEALTI
130
KNTDIAKELC
140
LPPVKLHCSM
150
LAEDAIKAAL
160
ADYKLKQEPK
KGEAEKK
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0099128 |
mitochondrial [2Fe-2S] assembly complex |
| Cellular Component |
GO:0005759 |
mitochondrial matrix |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0051537 |
2 iron, 2 sulfur cluster binding |
| Molecular Function |
GO:0008198 |
ferrous iron binding |
| Molecular Function |
GO:0005506 |
iron ion binding |
| Molecular Function |
GO:0140132 |
iron-sulfur cluster chaperone activity |
| Molecular Function |
GO:0060090 |
molecular adaptor activity |
| Molecular Function |
GO:0042803 |
protein homodimerization activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0044571 |
[2Fe-2S] cluster assembly |
| Biological Process |
GO:0044572 |
[4Fe-4S] cluster assembly |
| Biological Process |
GO:0006879 |
intracellular iron ion homeostasis |
| Biological Process |
GO:0016226 |
iron-sulfur cluster assembly |
| Biological Process |
GO:1904439 |
negative regulation of iron ion import across plasma membrane |
| Biological Process |
GO:1902958 |
positive regulation of mitochondrial electron transport, NADH to ubiquinone |
Reference
[1] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.