ISCU

Protein identityUniProt · HPA

UniProt accession

Q9H1K1

Gene

ISCU

Ensembl

ENSG00000136003

Chromosome

12

Canonical length

167 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Mitochondria,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

167 residues, UniProt reviewed canonical sequence.

>Q9H1K1|ISCU
     1  MAAAGAFRLR RAASALLLRS PRLPARELSA PARLYHKKVV DHYENPRNVG SLDKTSKNVG
    61  TGLVGAPACG DVMKLQIQVD EKGKIVDARF KTFGCGSAIA SSSLATEWVK GKTVEEALTI
   121  KNTDIAKELC LPPVKLHCSM LAEDAIKAAL ADYKLKQEPK KGEAEKK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ISCU can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

487 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ISCU.

Disease | AllUniProt

Conditions ISCU is implicated in, by any mechanism.

• Myopathy with exercise intolerance Swedish type (MEIS) MIM:255125

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 202 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary myopathy with lactic acidosis due to ISCU deficiency

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.16

gnomAD pLI

0.04

gnomAD missense Z

0.21

DepMap mean gene effect

-1.97

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• [2Fe-2S] cluster assembly
• [4Fe-4S] cluster assembly
• intracellular iron ion homeostasis
• iron-sulfur cluster assembly
• positive regulation of mitochondrial electron transport, NADH to ubiquinone
• negative regulation of iron ion import across plasma membrane

Molecular functions

• 2 iron, 2 sulfur cluster binding
• ferrous iron binding
• iron ion binding
• molecular adaptor activity
• protein homodimerization activity
• zinc ion binding
• iron-sulfur cluster chaperone activity

Cellular components

• cytoplasm
• cytosol
• iron-sulfur cluster assembly complex
• mitochondrial [2Fe-2S] assembly complex
• mitochondrial matrix
• mitochondrion
• nucleus

Protein domainsUniProt · Pfam · InterPro

• NIF system FeS cluster assembly, NifU, N-terminal
• Iron-sulfur cluster assembly scaffold protein IscU
• NifU-like N terminal domain

KeywordsUniProt

• Cytoplasm
• Iron
• Metal-binding
• Mitochondrion
• Nucleus
• Phosphoprotein
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of ISCU in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FXN
• GLRX5
• HSCB
• NFS1
• HSPA9
• LYRM4