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FLASH GENE
Symbol MICU1 contributors: mct - updated : 26-05-2016
HGNC name mitochondrial calcium uptake 1
HGNC id 1530
Corresponding disease
MICU1D MICU1 deficiency
Location 10q22.1      Physical location : -
Synonym name
  • atopy-related autoantigen CALC
  • allergen Hom s 4
  • calcium binding atopy-related autoantigen 1
  • calcium uptake protein 1, mitochondrial
    • Synonym symbol(s) CALC, EFHA3, FLJ12684, hCG_2024621, DKFZp564C246, CBARA1, MPXPS
    DNA
    TYPE functioning gene
    STRUCTURE 258.87 kb     13 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map cen - D10S537 - CBARA1 - D10S218 - P4HA1 - D10S188 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 2506 54 478 - 2010 20693986
    12 - 2500 - 476 - 2010 20693986
    7 - 1850 - 278 - 2010 20693986
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver    
    Lymphoid/Immunespleen   highly
    Nervousbrain   highly
    Reproductivefemale systembreast   
    Respiratorylung    
    Urinarykidney   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two canonical EF hands that are essential for its activity, indicating a role in calcium sensing , and are located in the mitochondrial matrix
    • mono polymer hexamer
    HOMOLOGY
    intraspecies paralog to MICU2
    Homologene
    FAMILY
    CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    text
  • associated with the mitochondrial inner membrane
  • localizes to the mitochondrial matrix side of the inner mitochondrial membrane
    • basic FUNCTION
  • required for high-capacity mitochondrial calcium uptake
  • could act as a Ca2+ sensor via its two canonical EF hands, and gate the activity of a partner channel
  • not involved in LETM1- and UCP2/3-dependent mitochondrial Ca2+ transport in the endothelial cell
  • EF-hand-containing protein that serves as a putative regulator of the uniporter
  • diminution of MICU1 or MCU reduced mitochondrial Ca(2+) uptake in response to d-glucose, whereas d-glucose-triggered cytosolic Ca(2+) oscillations remained unaffected
  • crucial role of MICU1 and MCU in mitochondrial Ca(2+) uptake in pancreatic beta-cells and their involvement in the positive feedback required for sustained insulin secretion
  • is a gatekeeper of MCU-mediated Ca(2+)(m) uptake that is essential to prevent [Ca(2+)](m) overload and associated stress
  • essential role of MICU1 to control Ca2+m uptake and protect cells against deleterious consequences associated with Ca2+m overload
  • is likely a marker for undifferentiated human embryonic stem cells (hESCs) that plays a role in maintaining stemness, cell cycle progression, and proliferation
  • MICU1 physically associates with and is co-expressed with a paralog, MICU2
  • upon Ca(2+) binding, MICU1 undergoes large conformational changes, resulting in the formation of multiple oligomers to activate MCU
  • at higher [Ca(2+)], the stimulatory effect of MICU1 allows the prompt response of mitochondria to Ca(2+) signals generated in the cytoplasm
  • key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (SMDT1) forms the mitochondrial Ca(2+) channel
  • MICU1 is endowed with a specific inhibitory effect on MCU at low [Ca(2+)]c, separate and kinetically different from that of MICU2
  • MICU1 has a double role in MCU regulation, inhibitory at low [Ca(2+)]c and activatory at high [Ca(2+)]c
  • is vital for adaptation to postnatal life and for tissue repair after injury
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • Ca(2+)-free MICU1 forms a hexamer that binds and inhibits MCU
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
    • protein
  • MCU forms oligomers in the mitochondrial inner membrane, physically interacts with CBARA1, and resides within a large molecular weight complex
  • MICU1 interacts with the uniporter pore-forming subunit MCU and sets a Ca2+ threshold for Ca2+m uptake without affecting the kinetic properties of MCU-mediated Ca2+ uptake
  • MICU1 inhibits the mitochondrial Ca2+ channel MCU under resting conditions
  • SMDT1 was required for the interaction of MCU with MICU1 and MICU2
  • MICU1 interacts with MCU to establish the Ca(2+) threshold for mitochondrial Ca(2+) uptake and MCU activity
  • among the interaction partners of CHDCHD4 is MICU1-the regulator of the mitochondrial Ca(2+) uniporter (MCU), which transfers Ca(2+) across the inner membrane
  • SMDT1-dependent regulation of MCU channel activity requires intermembrane space-localized MICU1, MICU2, and cytoplasmic Ca(2+)
  • SMDT1 second function is to maintain tight MICU1, MICU2 regulation of the MCU pore, a role that requires SMDT1 to bind MICU1 using its conserved C-terminal polyaspartate tail
    • cell & other
    REGULATION
    Other both MICU1 and MICU2 are regulated by calcium through their EF-hand domains, thus accounting for the sigmoidal response of MCU to [Ca(2+)] in situ and allowing tight physiological control
    ASSOCIATED DISORDERS
    corresponding disease(s) MICU1D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    results in mitochondrial Ca2+ overload
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS