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FLASH GENE
Symbol ISCU contributors: mct/npt - updated : 26-01-2013
HGNC name iron-sulfur cluster scaffold homolog (E. coli)
HGNC id 29882
Corresponding disease
MPEI1 myopathy, with progressive exercice intolerance 1
Location 12q23.3      Physical location : 108.956.293 - 108.963.158
Synonym name
  • IscU iron-sulfur cluster scaffold homolog
  • NifU-like N-terminal domain containing
  • nitrogen fixation cluster-like
  • iron-sulfur cluster assembly enzyme ISCU, mitochondrial
  • NifU-like protein
  • Synonym symbol(s) ISU1, ISU2, MGC74517, NIFU, NIFUN, hnifU, 2310020H20Rik, ISCU2
    DNA
    TYPE functioning gene
    STRUCTURE 6.87 kb     6 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 1189 15.1 142 - 2006 16527810
  • also called variant 1 or ISCU1
  • found in the cytosol and nucleus
  • have a role similar to that of its mitochondrial counterpart in Fe&
  • 8722;S cluster formation in the cytosol (PMID: 20481466)
    5 splicing 1093 17.9 167 - 2006 16527810
  • also called variant 2 or ISCU2
  • found in the mitochondrion
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiensAdult
    Endocrineneuroendocrinepituitary  highly
     parathyroid   highly
    Hearing/Equilibriumear   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac   Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • the first beta-strand of ISCU provides potentially the binding interface for the ISCU-HSCB interaction
  • conserved 99LPPVK103 motif
  • mono polymer monomer
    HOMOLOGY
    interspecies homolog to E;Coli Iscu
    Homologene
    FAMILY
  • nifU family
  • CATEGORY enzyme , storage
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • involved in respiratory chain biogenesis
  • functional cysteine desulfurase that can collaborate with cytosolic ISCU to promote de novo iron-sulfur cluster formation
  • being important in iron homeostasis and, among other functions, essential for aconitase activity
  • are thought to assemble Fe/S clusters for mitochondrial aconitase and for lipoate synthase, the enzyme producing lipoate for pyruvate dehydrogenase complex (PDC)
  • ISCU and FXN stimulate NFS1 and LYRM4 cysteine desulfurase activity
  • play an important role in cellular iron homeostasis
  • ISCU assembled [Fe-S] clusters appear to be preferentially channeled to aconitase and complex II
  • scaffold protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis and transfer
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complex SDU and SDUF comprised of NFS1, LYRM4, and ISCU and NFS1, LYRM4, ISCU, and FXN, respectively (SDUF is capable of synthesizing Fe/S cluster)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with extra-mitochondrial frataxin
  • interaction between ISCU and HSCB is critical for successful assembly of iron-sulfur clusters
  • ISCU (iron-sulfur cluster scaffold homolog) and COX10 (cytochrome c oxidase assembly protein), two important factors of the mitochondria electron transport chain and the tricarboxylic acid cycle have been identified as potential targets of MIR210
  • interaction with NFU1 (NFU1 could function as an alternate scaffold to ISCU for assembly of [Fe-S] proteins, thus providing parallel pathways)
  • 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
  • HSCB interacts with multiple proteins involved in ISC biogenesis including the ISCU ISC biogenesis complex and the HSPA9 ISC chaperone
  • modulation of the degradation of ISCU by the PIM1 protease is a regulatory mechanism serving to rapidly help balance the cell need for critical iron-requiring processes under changing environmental conditions
  • NFS1 alone could catalyze Fe-S cluster assembly on ISCU and that the addition of LYRM4 increased the Fe-S cluster assembly rate
  • ISCU suppressor mimics the frataxin effects on NFS1, explaining the bypassing activity
  • FXN accelerates persulfide formation on NFS1 and favors a helix-to-coil interconversion on ISCU that facilitates the transfer of sulfur from NFS1 to ISCU as an initial step in Fe-S cluster biosynthesis
  • cell & other
    REGULATION
    repressed by iron deprivation
    ASSOCIATED DISORDERS
    corresponding disease(s) MPEI1
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • complete loss of Iscu in mice results in early embryonic death