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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
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
  • PTBP1 acts as a dominant repressor of ISCU mis-splicing
    • 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