ISCU iron-sulfur cluster scaffold homolog (E. coli) [Homo sapiens (human)] - Gene

Summary

Go to the top of the page Help

Official Symbol: ISCUprovided by HGNC
Official Full Name: iron-sulfur cluster scaffold homolog (E. coli)provided by HGNC
Primary source: HGNC:29882
See related: Ensembl:ENSG00000136003; HPRD:14828; MIM:611911; Vega:OTTHUMG00000168420
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HML; ISU2; NIFU; NIFUN; hnifU; 2310020H20Rik
Summary: Iron-sulfur (Fe-S) clusters are necessary for several mitochondrial enzymes and other subcellular compartment proteins. They contain sulfur and iron, and are created via several steps that include cysteine desulfurases, iron donors, chaperones, and scaffold proteins. This gene encodes the two isomeric forms, ISCU1 and ISCU2, of the Fe-S cluster scaffold protein. Mutations in this gene have been found in patients with myopathy with severe exercise intolerance and myoglobinuria. [provided by RefSeq, Jul 2008]

Genomic context

Go to the top of the page Help

Location :: 12q24.1

Sequence :: Chromosome: 12; NC_000012.11 (108956294..108963160)

See ISCU in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions What's a GeneRIF?

ISCU protein deficiency in patients results from muscle-specific mis-splicing and oxidative stress.
Title: Tissue specificity of a human mitochondrial disease: differentiation-enhanced mis-splicing of the Fe-S scaffold gene ISCU renders patient cells more sensitive to oxidative stress in ISCU myopathy.
this study unveiled a signaling axis of HIF-1alpha/miRNA-210/iron-sulfur cluster scaffold protein in a subset of head and neck paragangliomas that could have an impact on SDHB protein stability by a mechanism independent of succinate dehydrogenase mutations
Title: Identification of a signaling axis HIF-1α/microRNA-210/ISCU independent of SDH mutation that defines a subgroup of head and neck paragangliomas.
Photoreactive heterotrifunctional chemical cross-linking confirmed the interaction between frataxin and ISCU in the presence of iron and validated that transient interactions can be covalently trapped with this method.
Title: Heterotrifunctional chemical cross-linking mass spectrometry confirms physical interaction between human frataxin and ISU.
The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1.
Title: The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1.
iron-sulfur cluster scaffold homologue down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation
Title: miR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies.
Exchange of [2Fe-2S] centers between glutaredoxin 2 and the cluster scaffold protein ISU, supports a direct link for glutaredoxin 2 and glutathione involvement in ISU promoted Fe-S cluster biosynthesis.
Title: Mechanism of glutaredoxin-ISU [2Fe-2S] cluster exchange.
Data show that the highest level of incorrectly spliced ISCU mRNA was found in skeletal muscle.
Title: Tissue-specific splicing of ISCU results in a skeletal muscle phenotype in myopathy with lactic acidosis, while complete loss of ISCU results in early embryonic death in mice.
miR-210 mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation
Title: MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
ISCU and COX10 are target genes of miR-210 related to mitochondrial metabolism
Title: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression.

Submit: New GeneRIF Correction See all (18)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Myopathy with lactic acidosis, hereditary

MIM: 255125

Genetic Testing Registry

Summary from GeneReviews: Myopathy with Deficiency of ISCU

Myopathy with deficiency of ISCU, a mitochondrial myopathy, is characterized by lifelong exercise intolerance in which minor exertion causes tachycardia, shortness of breath, and fatigue and pain of active muscles; episodes of more profound exercise intolerance associated with rhabdomyolysis, myoglobinuria, and weakness that may be severe; and typically full recovery of muscle strength between episodes of rhabdomyolysis. Affected individuals usually have near-normal strength; they can have large calves.

Diagnosis Testing

Diagnosis is based on clinical history and characteristic findings of muscle histochemistry and biochemistry. ISCU, encoding the iron-sulfur cluster assembly enzyme ISCU, is the only gene in which mutations are known to cause myopathy with deficiency of ISCU. Molecular genetic testing is available on a clinical basis.

Genetic Counseling

Myopathy with deficiency of ISCU is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased are possible if the disease-causing mutations in the family have been identified.

References

PMID: 20301757

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description
BioGRID:117038	BioGRID:109072	SFN		BioGRID	PubMed	Affinity Capture-MS
BioGRID:117038	BioGRID:113164	UBC		BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

Go to the top of the page Help

Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Mitochondrial Iron-Sulfur Cluster Biogenesis, organism-specific biosystem (from REACTOME)
Mitochondrial Iron-Sulfur Cluster Biogenesis, organism-specific biosystemIron-sulfur (Fe-S) proteins are localized in the cytosol, nucleus, and mitochondria of mammalian cells (reviewed in Stemmler et al. 2010, Rouault 2012, Bandyopadhyay et al. 2008, Lill 2009, Lill et a...

General gene information

Go to the top of the page Help

Markers

RH25375 (e-PCR)
- UniSTS:89125

G20365 (e-PCR)
- UniSTS:63822

A005N44 (e-PCR)
- UniSTS:63823

D12S1907 (e-PCR)
- UniSTS:67736

Genotypes

Related pseudogene(s)

1 found Review record(s) in Gene

Homology

Homologs of the ISCU gene: The ISCU gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

MGC74517

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
iron ion binding	TAS Traceable Author Statement more info	PubMed
iron-sulfur cluster binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein complex scaffold	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
iron-sulfur cluster assembly	TAS Traceable Author Statement more info	PubMed
nitrogen fixation	TAS Traceable Author Statement more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info
cytosol	IDA Inferred from Direct Assay more info	PubMed
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
nucleus	TAS Traceable Author Statement more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: iron-sulfur cluster assembly enzyme ISCU, mitochondrial

Names: iron-sulfur cluster assembly enzyme ISCU, mitochondrial; nifU-like protein; NifU-like N-terminal domain containing; IscU iron-sulfur cluster scaffold homolog; nifU-like N-terminal domain-containing protein

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011857.1 RefSeqGene

Range

5001..11867

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_014301.3 → NP_055116.1 iron-sulfur cluster assembly enzyme ISCU, mitochondrial isoform ISCU1

Status: REVIEWED

Description

Transcript Variant: This variant contains an alternate segment in the 5' coding region and uses a downstream start codon, compared to variant 2. Isoform ISCU1 has a shorter and distinct N-terminus, compared to isoform ISCU2. Isoform ISCU1 was found in the cytosol and nucleus.

Source sequence(s)

AY009127, BI597126, BQ002528, BQ020993, DB095495, DB493673

Consensus CDS

CCDS9118.1

UniProtKB/Swiss-Prot

Q9H1K1

Related

ENSP00000376554, OTTHUMP00000238764, ENST00000392807, OTTHUMT00000399695

Conserved Domains (2) summary

COG0822
Location:11 – 133
Blast Score: 343

IscU; NifU homolog involved in Fe-S cluster formation [Energy production and conversion]

cd06664
Location:13 – 124
Blast Score: 379

IscU_like; Iron-sulfur cluster scaffold-like proteins
NM_213595.2 → NP_998760.1 iron-sulfur cluster assembly enzyme ISCU, mitochondrial isoform ISCU2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the longer protein (isoform ISCU2). Isoform ISCU2 is found in the mitochondrion.

Source sequence(s)

BI597126, BP378051, BQ002528, BQ020993, DB095495, DB493673

Consensus CDS

CCDS44966.1

UniProtKB/Swiss-Prot

Q9H1K1

Related

ENSP00000310623, OTTHUMP00000238762, ENST00000311893, OTTHUMT00000399693

Conserved Domains (2) summary

COG0822
Location:33 – 158
Blast Score: 359

IscU; NifU homolog involved in Fe-S cluster formation [Energy production and conversion]

cd06664
Location:34 – 149
Blast Score: 397

IscU_like; Iron-sulfur cluster scaffold-like proteins

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p10 Primary Assembly

Range

108956294..108963160

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

106020849..106027716

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018923.1 Alternate CHM1_1.0

Range

108797792..108804660

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01053133.1 (8041..14908)	None
genomic	AC008119.6 (110698..117459)	None
genomic	AMYH01004731.1 (87316..94184)	None
genomic	CH471054.1	EAW97818.1
		EAW97819.1
		EAW97820.1
		EAW97821.1
		EAW97822.1
genomic	EU334585.1	ACA52543.1
genomic	FJ695196.1	None
mRNA	AK000574.1	None
mRNA	AK022758.1	None
mRNA	AK057251.1	BAG51892.1
mRNA	AK293202.1	BAG56742.1
mRNA	AK297862.1	BAG60191.1
mRNA	AY009127.1	AAG37427.1
mRNA	AY009128.1	AAG37428.1
mRNA	BC003522.1	None
mRNA	BC011906.2	AAH11906.1
mRNA	BC061903.1	AAH61903.1
mRNA	BG621612.1	None
mRNA	BI597126.1	None
mRNA	BM423850.1	None
mRNA	BM921073.1	None
mRNA	BP378051.1	None
mRNA	BQ002528.1	None
mRNA	BQ020993.1	None
mRNA	BU602914.1	None
mRNA	DB095495.1	None
mRNA	DB493673.1	None
mRNA	EU329002.1	ACA34743.1
mRNA	U47101.1	AAC50885.1
other-genetic	DQ896294.2	ABM87293.1
other-genetic	EU176420.1	ABW03871.1