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Aliases for ISCU Gene

Aliases for ISCU Gene

  • Iron-Sulfur Cluster Assembly Enzyme 2 3 5
  • NifU-Like N-Terminal Domain-Containing Protein 3 4
  • NIFUN 3 4
  • IscU Iron-Sulfur Cluster Scaffold Homolog (E. Coli) 2
  • Iron-Sulfur Cluster Scaffold Homolog (E. Coli) 2
  • IscU Iron-Sulfur Cluster Scaffold Homolog 3
  • NifU-Like N-Terminal Domain Containing 2
  • NifU-Like Protein 4
  • 2310020H20Rik 3
  • HnifU 3
  • ISU2 3
  • NIFU 3
  • HML 3

External Ids for ISCU Gene

Previous HGNC Symbols for ISCU Gene

  • NIFUN

Previous GeneCards Identifiers for ISCU Gene

  • GC12P107458
  • GC12P107459
  • GC12P108956
  • GC12P106020

Summaries for ISCU Gene

Entrez Gene Summary for ISCU 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]

GeneCards Summary for ISCU Gene

ISCU (Iron-Sulfur Cluster Assembly Enzyme) is a Protein Coding gene. Diseases associated with ISCU include Myopathy With Lactic Acidosis, Hereditary and Hereditary Myopathy With Lactic Acidosis Due To Iscu Deficiency. Among its related pathways are Metabolism and Mitochondrial iron-sulfur cluster biogenesis. GO annotations related to this gene include iron ion binding and iron-sulfur cluster binding.

UniProtKB/Swiss-Prot for ISCU Gene

  • 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).

Gene Wiki entry for ISCU Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ISCU Gene

Genomics for ISCU Gene

Regulatory Elements for ISCU Gene

Enhancers for ISCU Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around ISCU on UCSC Golden Path with GeneCards custom track

Promoters for ISCU Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around ISCU on UCSC Golden Path with GeneCards custom track

Genomic Location for ISCU Gene

Chromosome:
12
Start:
108,561,463 bp from pter
End:
108,569,384 bp from pter
Size:
7,922 bases
Orientation:
Plus strand

Genomic View for ISCU Gene

Genes around ISCU on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ISCU Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ISCU Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ISCU Gene

Proteins for ISCU Gene

  • Protein details for ISCU Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H1K1-ISCU_HUMAN
    Recommended name:
    Iron-sulfur cluster assembly enzyme ISCU, mitochondrial
    Protein Accession:
    Q9H1K1
    Secondary Accessions:
    • Q6P713
    • Q99617
    • Q9H1K2

    Protein attributes for ISCU Gene

    Size:
    167 amino acids
    Molecular mass:
    17999 Da
    Quaternary structure:
    • Binds NFS1 (PubMed:11060020). Interacts with HSCB (PubMed:20668094). Interacts with GLRX5 (PubMed:26100117).

    Alternative splice isoforms for ISCU Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ISCU Gene

Proteomics data for ISCU Gene at MOPED

Post-translational modifications for ISCU Gene

  • Ubiquitination at Lys 54, Lys 57, Lys 82, Lys 91, Lys 112, Lys 121, and Lys 147
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for ISCU Gene

Domains & Families for ISCU Gene

Graphical View of Domain Structure for InterPro Entry

Q9H1K1

UniProtKB/Swiss-Prot:

ISCU_HUMAN :
  • Belongs to the NifU family.
Family:
  • Belongs to the NifU family.
genes like me logo Genes that share domains with ISCU: view

No data available for Gene Families for ISCU Gene

Function for ISCU Gene

Molecular function for ISCU Gene

UniProtKB/Swiss-Prot Function:
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).

Gene Ontology (GO) - Molecular Function for ISCU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16527810
GO:0051539 4 iron, 4 sulfur cluster binding IBA --
genes like me logo Genes that share ontologies with ISCU: view
genes like me logo Genes that share phenotypes with ISCU: view

Human Phenotype Ontology for ISCU Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

miRNA for ISCU Gene

miRTarBase miRNAs that target ISCU

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for ISCU Gene

Localization for ISCU Gene

Subcellular locations from UniProtKB/Swiss-Prot for ISCU Gene

Isoform 1: Mitochondrion.
Isoform 2: Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ISCU Gene COMPARTMENTS Subcellular localization image for ISCU gene
Compartment Confidence
cytosol 5
mitochondrion 5
nucleus 4

No data available for Gene Ontology (GO) - Cellular Components for ISCU Gene

Pathways & Interactions for ISCU Gene

genes like me logo Genes that share pathways with ISCU: view

Pathways by source for ISCU Gene

2 Reactome pathways for ISCU Gene

SIGNOR curated interactions for ISCU Gene

Is activated by:

Gene Ontology (GO) - Biological Process for ISCU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0009399 nitrogen fixation TAS 8875867
GO:0097428 protein maturation by iron-sulfur cluster transfer IBA --
genes like me logo Genes that share ontologies with ISCU: view

Drugs & Compounds for ISCU Gene

(2) Drugs for ISCU Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for ISCU Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
15438-31-0
genes like me logo Genes that share compounds with ISCU: view

Transcripts for ISCU Gene

Unigene Clusters for ISCU Gene

Iron-sulfur cluster scaffold homolog (E. coli):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ISCU Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8a · 8b · 8c · 8d
SP1: - - - - - -
SP2: - - - - - -
SP3: - - - - - -
SP4: - - - - - - -
SP5: - - -
SP6: - -
SP7: - - -
SP8:

Relevant External Links for ISCU Gene

GeneLoc Exon Structure for
ISCU
ECgene alternative splicing isoforms for
ISCU

Expression for ISCU Gene

mRNA expression in normal human tissues for ISCU Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ISCU Gene

This gene is overexpressed in Peripheral blood mononuclear cells (11.1) and Heart (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for ISCU Gene



SOURCE GeneReport for Unigene cluster for ISCU Gene Hs.615131

mRNA Expression by UniProt/SwissProt for ISCU Gene

Q9H1K1-ISCU_HUMAN
Tissue specificity: Detected in heart, liver, skeletal muscle, brain, pancreas, kidney, lung and placenta.
genes like me logo Genes that share expression patterns with ISCU: view

Protein tissue co-expression partners for ISCU Gene

- Elite partner

Primer Products

No data available for mRNA differential expression in normal tissues for ISCU Gene

Orthologs for ISCU Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ISCU Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia ISCU 35
  • 90.02 (n)
  • 97.6 (a)
ISCU 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LOC477527 35
  • 93.41 (n)
  • 98.8 (a)
ISCU 36
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Iscu 35
  • 87.55 (n)
  • 96.39 (a)
Iscu 16
Iscu 36
  • 95 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia ISCU 35
  • 99.6 (n)
  • 99.4 (a)
-- 36
  • 99 (a)
OneToMany
NIFUN 36
  • 99 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Iscu 35
  • 88.22 (n)
  • 97.01 (a)
oppossum
(Monodelphis domestica)
Mammalia ISCU 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ISCU 36
  • 56 (a)
OneToOne
chicken
(Gallus gallus)
Aves ISCU 35
  • 75 (n)
  • 85.53 (a)
ISCU 36
  • 78 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ISCU 36
  • 81 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia iscu 35
  • 78.45 (n)
  • 84.96 (a)
African clawed frog
(Xenopus laevis)
Amphibia nifu-pending-prov 35
zebrafish
(Danio rerio)
Actinopterygii iscub 35
  • 73.43 (n)
  • 86.47 (a)
wufj08f02 35
ISCU (2 of 2) 36
  • 77 (a)
OneToMany
iscub 36
  • 71 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005813 35
  • 69.08 (n)
  • 80.43 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG9836 35
  • 68.28 (n)
  • 79.31 (a)
CG9836 36
  • 75 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea Y45F10D.4 35
  • 63.7 (n)
  • 71.23 (a)
Y45F10D.4 36
  • 68 (a)
OneToOne
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR112C 35
  • 60.69 (n)
  • 66.21 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D07161g 35
  • 64.49 (n)
  • 71.74 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ISU2 35
  • 65.9 (n)
  • 72.31 (a)
ISU1 36
  • 60 (a)
OneToMany
ISU2 36
  • 62 (a)
OneToMany
ISU2 38
thale cress
(Arabidopsis thaliana)
eudicotyledons ISU3 35
  • 65.15 (n)
  • 74.24 (a)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.6801 35
rice
(Oryza sativa)
Liliopsida Os01g0662600 35
  • 65.91 (n)
  • 77.27 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4350 35
bread mold
(Neurospora crassa)
Ascomycetes NCU05778 35
  • 59.33 (n)
  • 68 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes isu1 35
  • 62.93 (n)
  • 71.2 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 70 (a)
OneToOne
Species with no ortholog for ISCU:
  • Actinobacteria (Mycobacterium tuberculosis)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ISCU Gene

ENSEMBL:
Gene Tree for ISCU (if available)
TreeFam:
Gene Tree for ISCU (if available)

Paralogs for ISCU Gene

Pseudogenes.org Pseudogenes for ISCU Gene

genes like me logo Genes that share paralogs with ISCU: view

No data available for Paralogs for ISCU Gene

Variants for ISCU Gene

Sequence variations from dbSNP and Humsavar for ISCU Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
VAR_060728 -
rs2014219 -- 108,569,220(+) AGTGC(A/G)TAAGT downstream-variant-500B, utr-variant-3-prime
rs2014226 -- 108,569,153(+) TTTGA(A/T)TTGTG downstream-variant-500B, utr-variant-3-prime
rs2014227 -- 108,569,151(+) ATTTT(A/G)AATTG downstream-variant-500B, utr-variant-3-prime
rs7133224 -- 108,569,490(+) AACAA(A/G)GACAA downstream-variant-500B

Variation tolerance for ISCU Gene

Residual Variation Intolerance Score: 45.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.30; 25.83% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ISCU Gene

Human Gene Mutation Database (HGMD)
ISCU

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for ISCU Gene

Disorders for ISCU Gene

MalaCards: The human disease database

(7) MalaCards diseases for ISCU Gene - From: OMIM, ClinVar, GeneTests, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
myopathy with lactic acidosis, hereditary
  • myopathy with exercise intolerance, swedish type
hereditary myopathy with lactic acidosis due to iscu deficiency
  • iron-sulfur cluster deficiency myopathy
myopathy with deficiency of iscu
  • iron-sulfur cluster deficiency myopathy
lactic acidosis
  • acidosis lactic
infantile cerebellar-retinal degeneration
  • icrd
- elite association - COSMIC cancer census association via MalaCards
Search ISCU in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ISCU_HUMAN
  • 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 mutations affecting the gene represented in this entry.

Relevant External Links for ISCU

Genetic Association Database (GAD)
ISCU
Human Genome Epidemiology (HuGE) Navigator
ISCU
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
ISCU
genes like me logo Genes that share disorders with ISCU: view

No data available for Genatlas for ISCU Gene

Publications for ISCU Gene

  1. A modular domain of NifU, a nitrogen fixation cluster protein, is highly conserved in evolution. (PMID: 8875867) Hwang D.M. … Liew C.-C. (J. Mol. Evol. 1996) 2 3 4 23 67
  2. Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. (PMID: 11060020) Tong W.-H. … Rouault T. (EMBO J. 2000) 2 3 23
  3. Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. (PMID: 19567699) Kollberg G. … Holme E. (Brain 2009) 3 23
  4. Antisense oligonucleotide therapeutics for iron-sulphur cluster deficiency myopathy. (PMID: 19846308) Kollberg G. … Holme E. (Neuromuscul. Disord. 2009) 3 23
  5. Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. (PMID: 18296749) Olsson A. … Holmberg M. (Hum. Mol. Genet. 2008) 3 23

Products for ISCU Gene

Sources for ISCU Gene

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