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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
  • Iron-Sulfur Cluster Assembly Enzyme ISCU, Mitochondrial 3
  • 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 Myopathy With Deficiency Of Iron-Sulfur Cluster Assembly Enzyme. 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 Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH12F108559 1.4 Ensembl ENCODE 17.4 +4.1 4112 12.4 HDGF PKNOX1 ARNT CREB3L1 WRNIP1 ARID4B SIN3A FEZF1 DMAP1 ZNF2 PWP1 FICD ISCU ENSG00000256139 SART3 UBE3B PRDM4 TMEM119
GH12F108663 1.6 FANTOM5 Ensembl ENCODE 11.5 +104.8 104793 6.3 HDGF PKNOX1 ARNT WRNIP1 ARID4B SIN3A DMAP1 YY1 ELK1 ZNF143 CORO1C SELPLG SSH1 SART3 ISCU MIR4496 MVK ACACB RNU7-169P GC12P108645
GH12F108540 1 Ensembl ENCODE 17.2 -20.0 -20019 2.4 HDGF ASH2L BMI1 ZBTB40 CBX5 FOS ZNF639 MTA2 ZNF740 BHLHE40 FICD ISCU LINC01498 GC12M108547 PIR52944
GH12F108575 0.9 Ensembl ENCODE 11.4 +15.0 15015 1.9 HDGF TBP ZNF664 POLR2H RAD51 ZNF366 IKZF1 ZNF512 NBN MLLT1 ISCU FICD TMEM119
GH12F108525 0.8 ENCODE 12.1 -34.7 -34671 3.2 SOX13 CTCF ZMYM3 EBF1 ZNF644 YY1 ZKSCAN1 ZEB1 ZFHX2 ADNP FICD ISCU ALKBH2 PIR52944 GC12M108547
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

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
ENSR00000173918 537 4001 HDGF PKNOX1 ARNT CREB3L1 WRNIP1 ARID4B SIN3A FEZF1 DMAP1 ZNF2

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).

    Three dimensional structures from OCA and Proteopedia for ISCU Gene

    Alternative splice isoforms for ISCU Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ISCU Gene

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:0005506 iron ion binding TAS 11060020
GO:0005515 protein binding IPI 16527810
GO:0008198 ferrous iron binding IBA --
GO:0032947 protein complex scaffold IDA 16527810
GO:0036455 iron-sulfur transferase activity 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

Inhibitory RNA Products

Flow Cytometry Products

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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ISCU gene
Compartment Confidence
mitochondrion 5
cytosol 5
nucleus 4

Gene Ontology (GO) - Cellular Components for ISCU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS 16527810
GO:0005737 cytoplasm IEA,IDA 11060020
GO:0005739 mitochondrion IEA,IDA 11060020
GO:0005759 mitochondrial matrix TAS --
GO:0005829 cytosol IDA 16527810
genes like me logo Genes that share ontologies with ISCU: view

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:0006879 cellular iron ion homeostasis IBA --
GO:0009399 nitrogen fixation TAS 8875867
GO:0016226 iron-sulfur cluster assembly IEA,TAS 11060020
GO:0044281 small molecule metabolic process TAS --
GO:0044571 [2Fe-2S] cluster assembly IBA --
genes like me logo Genes that share ontologies with ISCU: view

Drugs & Compounds for ISCU Gene

(3) Drugs for ISCU Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

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

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:

Inhibitory RNA Products

Flow Cytometry Products

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 from GTEx, Illumina, BioGPS, and SAGE 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, MaxQB, and MOPED for ISCU Gene



Protein tissue co-expression partners for ISCU Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ISCU Gene:

ISCU

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

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
chimpanzee
(Pan troglodytes)
Mammalia ISCU 34
  • 99.6 (n)
-- 35
  • 99 (a)
OneToMany
NIFUN 35
  • 99 (a)
OneToMany
dog
(Canis familiaris)
Mammalia ISCU 35
  • 99 (a)
OneToOne
LOC477527 34
  • 93.41 (n)
cow
(Bos Taurus)
Mammalia ISCU 34 35
  • 90.02 (n)
rat
(Rattus norvegicus)
Mammalia Iscu 34
  • 88.22 (n)
mouse
(Mus musculus)
Mammalia Iscu 34 16 35
  • 87.55 (n)
oppossum
(Monodelphis domestica)
Mammalia ISCU 35
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ISCU 35
  • 56 (a)
OneToOne
chicken
(Gallus gallus)
Aves ISCU 34 35
  • 75 (n)
lizard
(Anolis carolinensis)
Reptilia ISCU 35
  • 81 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia iscu 34
  • 78.45 (n)
African clawed frog
(Xenopus laevis)
Amphibia nifu-pending-prov 34
zebrafish
(Danio rerio)
Actinopterygii ISCU (2 of 2) 35
  • 77 (a)
OneToMany
iscub 34 35
  • 73.43 (n)
wufj08f02 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005813 34
  • 69.08 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG9836 34 35
  • 68.28 (n)
worm
(Caenorhabditis elegans)
Secernentea Y45F10D.4 34 35
  • 63.7 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ISU2 34 35 37
  • 65.9 (n)
ISU1 35
  • 60 (a)
OneToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D07161g 34
  • 64.49 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR112C 34
  • 60.69 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons ISU3 34
  • 65.15 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.6801 34
rice
(Oryza sativa)
Liliopsida Os01g0662600 34
  • 65.91 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 70 (a)
OneToOne
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes isu1 34
  • 62.93 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU05778 34
  • 59.33 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4350 34
Species where no ortholog for ISCU was found in the sources mined by GeneCards:
  • 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
rs267607190 Pathogenic 108,564,313(+) CGTGG(A/G)GTCCC nc-transcript-variant, reference, missense
rs767000507 Pathogenic 108,567,650(+) TCTTT(C/G)ATTTC intron-variant
rs558084375 Uncertain significance 108,562,632(+) CGGCG(C/G)CTGGG nc-transcript-variant, upstream-variant-2KB, reference, missense, utr-variant-5-prime
rs863224044 Uncertain significance 108,562,722(+) CCCGA(C/T)TCTAT nc-transcript-variant, upstream-variant-2KB, reference, missense, utr-variant-5-prime
rs112552261 Benign 108,562,673(+) CTGCT(A/G)CTGCG nc-transcript-variant, upstream-variant-2KB, reference, synonymous-codon, utr-variant-5-prime

Structural Variations from Database of Genomic Variants (DGV) for ISCU Gene

Variant ID Type Subtype PubMed ID
nsv560112 CNV loss 21841781

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
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ISCU

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot 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
  • iron-sulfur cluster deficiency myopathy
myopathy with deficiency of iron-sulfur cluster assembly enzyme
  • myopathy with deficiency of iscu
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. 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 4 22 64
  2. 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 22 64
  3. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. (PMID: 18304497) Mochel F. … Haller R.G. (Am. J. Hum. Genet. 2008) 3 4 22 64
  4. Functional analysis of GLRX5 mutants reveals distinct functionalities of GLRX5 protein. (PMID: 26100117) Liu G. … Nie G. (J. Cell. Biochem. 2016) 3 4 64
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson S.L. … O'Brien S.J. (PLoS ONE 2010) 3 46 64

Products for ISCU Gene

Sources for ISCU Gene

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