ISCU
entrez
23479
canonical
uniprot
Q9H1K1
canonical
ensembl
ENSG00000136003
resolver
ensp
ENSP00000310623
resolver
ensp
ENSP00000376554
resolver
ensp
ENSP00000411108
resolver
ensp
ENSP00000445598
resolver
ensp
ENSP00000446606
resolver
enst
ENST00000431221
resolver
enst
ENST00000535729
resolver
enst
ENST00000547005
resolver
genesymbol
ISCU
resolver
genesymbol_syn
NIFUN
resolver
hgnc
HGNC:29882
resolver
uniprot
B1P7G3
resolver
uniprot
B3KQ30
resolver
uniprot
B4DNC9
resolver
uniprot
F6S5B4
resolver
uniprot
F6VBT5
resolver
uniprot
Q6P713
resolver
uniprot
Q99617
resolver
uniprot
Q9H1K2
resolver
uniprot_entry
B1P7G3_HUMAN
resolver
uniprot_entry
B3KQ30_HUMAN
resolver
uniprot_entry
B4DNC9_HUMAN
resolver
uniprot_entry
F6S5B4_HUMAN
resolver
uniprot_entry
F6VBT5_HUMAN
resolver
uniprot_entry
ISCU_HUMAN
resolver
uniprot_sec
Q6P713
resolver
uniprot_sec
Q99617
resolver
uniprot_sec
Q9H1K2
resolver
amino_acid_sequence
MAAAGAFRLRRAASALLLRSPRLPARELSAPARLYHKKVVDHYENPRNVGSLDKTSKNVGTGLVGAPACGDVMKLQIQVDEKGKIVDARFKTFGCGSAIASSSLATEWVKGKTVEEALTIKNTDIAKELCLPPVKLHCSMLAEDAIKAALADYKLKQEPKKGEAEKK
uniprot
proteins
disease_involvement
DISEASE: Myopathy with exercise intolerance Swedish type (MEIS) [MIM:255125]: Autosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism. {ECO:0000269|PubMed:18304497}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: [Isoform 1]: 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). {ECO:0000269|PubMed:23940031, ECO:0000269|PubMed:24971490, ECO:0000269|PubMed:29576242, ECO:0000269|PubMed:30031876, ECO:0000269|PubMed:34824239, ECO:0000305|PubMed:23940031}.; FUNCTION: [Isoform 2]: Cytoplasmic scaffold protein, of the cytoplasmic core iron-sulfur cluster (ISC) assembly complex that provides the structural architecture on which the Fe-S clusters are assembled and may be involved in the cytoplasmic iron-sulfur protein biogenesis. {ECO:0000269|PubMed:16517407, ECO:0000269|PubMed:16527810, ECO:0000269|PubMed:29309586}.
uniprot
proteins
mass_dalton
17999
uniprot
proteins
mutagenesis
MUTAGEN 14; /note="S->A: Loss of phosphorylation. Does not affect phosphorylation."; /evidence="ECO:0000269|PubMed:23508953"; MUTAGEN 35; /note="Y->A: Does not affect mitochondrial localization. Loss of iron-sulfur cluster biogenesis. Does not affect reductive cleavage of the ISCU2-bound-persulfide by FDX2."; /evidence="ECO:0000269|PubMed:34824239"; MUTAGEN 69; /note="C->A: Does not affect ISC complex formation. Does not affect the unstimulated cysteine desulfurase activity in the absence of FXN. Does not affect the cysteine desulfurase activity in the presence of FXN. Slightly decreases the cysteine desulfurase activity in the presence of FXN; when associated with A-95. Does not affect iron based stimulation of the cysteine desulfurase activity in the presence of FXN. Does not affect iron based stimulation of the cysteine desulfurase activity in the presence of FXN; when associated with A-95. Loss of the [2Fe-2S] cluster formation."; MUTAGEN 69; /note="C->S: Does not affect the cysteine desulfurase activity in the presence of FXN. Does not affect iron based stimulation of the cysteine desulfurase activity in the presence of FXN."; /evidence="ECO:0000269|PubMed:24971490"; MUTAGEN 71; /note="D->A: Stabilizes the D-state."; /evidence="ECO:0000269|PubMed:23940031"; MUTAGEN 71; /note="D->V: Stabilizes the S-state."; /evidence="ECO:0000269|PubMed:23940031"; MUTAGEN 95; /note="C->A: Does not affect ISC complex formation. Does not affect the unstimulated cysteine desulfurase activity in the absence of FXN. Does not affect the cysteine desulfurase activity in the presence of FXN. Slightly decreases the cysteine desulfurase activity in the presence of FXN; when associated with A-95. Does not affect iron based stimulation of the cysteine desulfurase activity in the presence of FXN. Does not affect iron based stimulation of the cysteine desulfurase activity in the presence of FXN; when associated with A.69. Loss of the [2Fe-2S] cluster formation."; /evidence="ECO:0000269|PubMed:24971490"; MUTAGEN 95; /note="C->S: Slightly decrease the cysteine desulfurase activity in the presence of FXN. Does not affect iron based stimulation of the cysteine desulfurase activity in the presence of FXN."; /evidence="ECO:0000269|PubMed:24971490"; MUTAGEN 122; /note="N->A: Stabilizes the S-state."; /evidence="ECO:0000269|PubMed:23940031"; MUTAGEN 130; /note="C->S: Does not affect the unstimulated cysteine desulfurase activity in the absence of FXN. Does not affect the cysteine desulfurase activity in the presence of FXN. Does not affect iron based stimulation of the cysteine desulfurase activity in the presence of FXN. Does not affect the [2Fe-2S] cluster assembly."; /evidence="ECO:0000269|PubMed:24971490"; MUTAGEN 137; /note="H->A: Stabilizes the D-state."; /evidence="ECO:0000269|PubMed:23940031"; MUTAGEN 138; /note="C->A: Does not affect ISC complex formation. Does not affect the unstimulated cysteine desulfurase activity in the absence of FXN. Loss of iron-based stimulation of the cysteine desulfurase activity in the presence of FXN. Loss of the [2Fe-2S] cluster formation."; /evidence="ECO:0000269|PubMed:24971490"; MUTAGEN 138; /note="C->S: Loss of iron-based stimulation of the cysteine desulfurase activity in the presence of FXN."; /evidence="ECO:0000269|PubMed:24971490"; MUTAGEN 140; /note="M->I: Does not affect the SDA complex formation. Abolishes desulfurase activity of SDA complex when zinc ion is bound. Activated by FXN when component of SDAU complex."; /evidence="ECO:0000269|PubMed:30031876"; MUTAGEN 140; /note="M->L: Does not affect the SDA complex formation. Abolishes desulfurase activity of SDA complex when zinc ion is bound. Activated by FXN when component of SDAU complex."; /evidence="ECO:0000269|PubMed:30031876"; MUTAGEN 140; /note="M->V: Does not affect the SDA complex formation. Abolishes desulfurase activity of SDA complex when zinc ion is bound. Activated by FXN when component of SDAU complex."; /evidence="ECO:0000269|PubMed:30031876
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-14 is required for ISCU protein stabilization in the cytosol, whereas dephosphorylation of Ser-14, due to the inhibition of mTORC1 (mammalian target of rapamycin complex 1) complex, leads to degradation of the precursor form and ultimately to a decrease in the mitochondrial mature form. {ECO:0000269|PubMed:23508953}.; PTM: Cysteine persulfide is reduced by thiol-containing molecules such as glutathione and L-cysteine. {ECO:0000250|UniProtKB:Q9D7P6}.
uniprot
proteins
protein_family
NifU family
uniprot
proteins
pubmed
11060020
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16517407
uniprot
proteins
pubmed
16527810
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
18304497
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20668094
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21298097
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23508953
uniprot
proteins
pubmed
23940031
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24971490
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26100117
uniprot
proteins
pubmed
26702583
uniprot
proteins
pubmed
29097656
uniprot
proteins
pubmed
29309586
uniprot
proteins
pubmed
29576242
uniprot
proteins
pubmed
30031876
uniprot
proteins
pubmed
31101807
uniprot
proteins
pubmed
34824239
uniprot
proteins
pubmed
8875867
uniprot
proteins
sequence_length
167
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion {ECO:0000269|PubMed:11060020, ECO:0000269|PubMed:26702583}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Nucleus {ECO:0000269|PubMed:11060020}.
uniprot
proteins