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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
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
  • 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