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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 Lactic Acidosis. Among its related pathways are Metabolism and Mitochondrial iron-sulfur cluster biogenesis. Gene Ontology (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

Additional gene information for ISCU Gene

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

Genomics for ISCU Gene

GeneHancer (GH) Regulatory Elements for ISCU Gene

Promoters and enhancers for ISCU Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J108559 Promoter/Enhancer 2.5 EPDnew Ensembl ENCODE dbSUPER 667.4 +4.1 4112 12.4 CLOCK FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 ZNF548 SART3 ISCU PWP1 FICD UBE3B PRDM4 GC12P108558 TMEM119 GC12M108565 GC12P108510
GH12J108663 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 11.5 +104.6 104554 5.8 HDGF PKNOX1 FOXA2 SMAD1 ARNT ARID4B SIN3A DMAP1 IRF4 YY1 CORO1C SELPLG SSH1 ISCU SART3 ENSG00000257221 MVK ACACB RNU7-169P GC12P108669
GH12J108514 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 8.3 -45.8 -45761 2.3 HDGF PKNOX1 ARID4B SIN3A ZNF2 YY1 POLR2B E2F8 ZNF143 FOS FICD PWP1 SART3 KCTD10 LOC101929162 ALKBH2 UBE3B ISCU GC12P108510 PIR52944
GH12J108540 Enhancer 0.9 Ensembl ENCODE 17.2 -20.0 -20019 2.4 HDGF BMI1 E4F1 ZNF143 ATF7 RCOR1 FOS IKZF2 CHD2 SMARCA5 FICD ISCU LINC01498 GC12M108547 SART3 PIR52944 GC12P108510
GH12J108626 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 4.6 +77.4 77401 24.2 HDGF PKNOX1 SMAD1 ARNT FEZF1 IRF4 YY1 POLR2B ZNF766 CBX5 SELPLG PWP1 SART3 PRDM4 UBE3B RNU4-32P CORO1C FICD LOC101929162 TMEM119
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ISCU on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ISCU gene promoter:
  • CUTL1
  • AML1a
  • C/EBPalpha
  • NCX
  • E4BP4
  • Evi-1
  • Pax-5
  • FOXO4
  • XBP-1

Genomic Locations for ISCU Gene

Genomic Locations for ISCU Gene
chr12:108,561,463-108,569,384
(GRCh38/hg38)
Size:
7,922 bases
Orientation:
Plus strand
chr12:108,956,294-108,963,160
(GRCh37/hg19)
Size:
6,867 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). Interacts with HSPA9 (PubMed:26702583).

    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 isoforms=2147, Lys121, Lys112, isoforms=291, Lys82, isoforms=257, and isoforms=254
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for ISCU Gene

Domains & Families for ISCU Gene

Gene Families for ISCU Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

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

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).

Phenotypes From GWAS Catalog for ISCU Gene

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-containing complex scaffold activity 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

Clone 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

Subcellular locations from the

Human Protein Atlas (HPA)

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,IBA --
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:0016226 iron-sulfur cluster assembly TAS,IEA 11060020
GO:0044281 small molecule metabolic process TAS --
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

(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: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Fe2+
  • FE (II) ion
  • Fe(II)
  • Fe(2+)
  • Ferrous ion
  • Iron ion(2+)
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:

Clone 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 CGAP 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, 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.

Evidence on tissue expression from TISSUES for ISCU Gene

  • Nervous system(4.9)
  • Heart(4.5)
  • Liver(4.3)
  • Muscle(3)
  • Adrenal gland(2.3)
  • Kidney(2.1)
  • Thyroid gland(2.1)
  • Eye(2)
  • Lymph node(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ISCU Gene

Germ Layers:
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • respiratory
  • skeletal muscle
  • urinary
Regions:
Head and neck:
  • ear
Thorax:
  • heart
  • heart valve
Abdomen:
  • kidney
General:
  • blood
  • bone marrow
  • red blood cell
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 33
  • 99.6 (n)
-- 34
  • 99 (a)
OneToMany
NIFUN 34
  • 99 (a)
OneToMany
dog
(Canis familiaris)
Mammalia ISCU 34
  • 99 (a)
OneToOne
LOC477527 33
  • 93.41 (n)
cow
(Bos Taurus)
Mammalia ISCU 34 33
  • 90.02 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Iscu 33
  • 88.22 (n)
mouse
(Mus musculus)
Mammalia Iscu 16 34 33
  • 87.55 (n)
oppossum
(Monodelphis domestica)
Mammalia ISCU 34
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ISCU 34
  • 56 (a)
OneToOne
chicken
(Gallus gallus)
Aves ISCU 34 33
  • 75 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ISCU 34
  • 81 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia iscu 33
  • 78.45 (n)
African clawed frog
(Xenopus laevis)
Amphibia nifu-pending-prov 33
zebrafish
(Danio rerio)
Actinopterygii ISCU (2 of 2) 34
  • 77 (a)
OneToMany
iscub 34 33
  • 73.43 (n)
OneToMany
wufj08f02 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005813 33
  • 69.08 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG9836 34 33
  • 68.28 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea Y45F10D.4 34 33
  • 63.7 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ISU2 36 34 33
  • 65.9 (n)
ISU1 34
  • 60 (a)
OneToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D07161g 33
  • 64.49 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR112C 33
  • 60.69 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons ISU3 33
  • 65.15 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.6801 33
rice
(Oryza sativa)
Liliopsida Os01g0662600 33
  • 65.91 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 70 (a)
OneToOne
Cin.4350 33
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes isu1 33
  • 62.93 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU05778 33
  • 59.33 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4350 33
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)
Aminode:
Evolutionary constrained regions (ECRs) for ISCU: view image

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 Variation AA Info Type
rs267607190 pathogenic, Myopathy with lactic acidosis, hereditary 108,564,313(+) G/A/C coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs767000507 pathogenic, Myopathy with lactic acidosis, hereditary 108,567,650(+) G/C intron_variant
rs1064797174 likely-benign, not provided 108,568,835(+) G/A 3_prime_UTR_variant, coding_sequence_variant, non_coding_transcript_variant, stop_gained, synonymous_variant
rs368028981 likely-benign, not specified 108,564,308(+) C/T coding_sequence_variant, non_coding_transcript_variant, synonymous_variant
rs767846973 likely-benign, not specified 108,564,403(+) T/A/C intron_variant

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)

Additional Variant Information for ISCU Gene

Human Gene Mutation Database (HGMD)
ISCU
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ISCU

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ISCU Gene

Disorders for ISCU Gene

MalaCards: The human disease database

(6) MalaCards diseases for ISCU Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
myopathy with lactic acidosis, hereditary
  • hml
lactic acidosis
  • acidosis lactic
infantile cerebellar-retinal degeneration
  • icrd
siderosis
  • pulmonary siderosis
myopathy
  • muscular diseases
- 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.

Additional Disease Information for ISCU

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 WH … Rouault T (The EMBO journal 2000) 2 3 4 22 58
  2. A modular domain of NifU, a nitrogen fixation cluster protein, is highly conserved in evolution. (PMID: 8875867) Hwang DM … Liew CC (Journal of molecular evolution 1996) 2 3 4 22 58
  3. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. (PMID: 18304497) Mochel F … Haller RG (American journal of human genetics 2008) 3 4 22 58
  4. Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-sulfur cluster assembly. (PMID: 26702583) Shan Y … Cortopassi G (Mitochondrion 2016) 3 4 58
  5. Functional Analysis of GLRX5 Mutants Reveals Distinct Functionalities of GLRX5 Protein. (PMID: 26100117) Liu G … Nie G (Journal of cellular biochemistry 2016) 3 4 58

Products for ISCU Gene

Sources for ISCU Gene

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