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FLASH GENE
Symbol CISD2 contributors: mct - updated : 01-09-2018
HGNC name CDGSH iron sulfur domain 2
HGNC id 24212
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Endocrineadrenal gland   highly
Urinarybladder   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal anchor sequence tethers the protein to the outer membrane
  • a single -adrenergic receptor kinase site at amino acids 25-29
  • 21 two PKA/PKC kinase motifs at amino acids 32-34 and 67-69
  • a single CK2 (formerly, casein kinase 2)
  • a two iron-two sulphur coordinating domain within its cytosolic region, which is necessary, but not sufficient for interaction with BCL2
  • a 39-amino-acid single zinc-finger domain of the CDGSH type, with a CCHH finger, located close to the carboxy terminus, oriented toward the cytoplasm
  • HOMOLOGY
    Homologene
    FAMILY
  • CISD protein family, NEET proteins family
  • CATEGORY transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • detected both in endoplasmic reticulum (ER) and mitochondrial outer membrane
  • basic FUNCTION
  • may function in Fe-S cluster shuttling and/or in redox reactions
  • important iron-containing protein involved in the control of maximal mitochondrial respiratory rates
  • endoplasmic reticulum (ER) IFN stimulator, which is a strong type I IFN stimulator and plays a pivotal role in response to both non–self-cytosolic RNA and dsDNA (Sun 2009)
  • is involved in mammalian lifespan control (pMID: 20649540)
  • endoplasmic reticulum (ER) BCL-2-interacting protein, which functions to mediate the ability of ER BCL-2 to antagonize BECN1 -dependent autophagy and depress ER calcium stores
  • is required for homeostatic maintenance of skeletal muscle
  • protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism
  • regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis
  • key player in regulating autophagy
  • physiological role for CISD1, CISD2 in promoting mitochondrial function in cancer cells
  • plays likely an important role in intracellular Ca(2+) homeostasis, which is required for the differentiation and functioning of adipocytes as well as the regulation of glucose homeostasis
  • may function as an autophagy regulator involved in the BCL2 mediated regulation of autophagy
  • regulates mitochondrial function, proliferation, intracellular Ca(2+) homeostasis, and Wnt pathway signaling
  • is known to have roles in calcium metabolism, anti-apoptosis, and longevity
  • exerts anti-apoptotic and anti-inflammatory effects in neural cells
  • functions to control mammalian life span and regulates human cells proliferation
  • play an important role in promoting proliferation and enhanced progression of HCC (hepatocellular carcinoma)
  • is a redox-sensitive gene critical for normal development and mitochondrial integrity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • interact with GIMAP5 on the mitochondrial and ER membranes and thereby modulate mitochondrial Ca(2+) uptake associated with the maintenance of intracellular Ca(2+) homeostasis in adipocytes
  • regulates Ca(2+) homeostasis and Ca(2+) has been proposed to have an important regulatory role in autophagy
  • protein
  • is required in this pathway for BCL2 at the ER to functionally antagonize Beclin 1-dependent autophagy
  • cell & other
    REGULATION
    activated by dimerization, induced by innate immune challenges, leads to the activation of CISD2 and, in turn, the downstream components (Sun 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s) WFS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in cervical cancer cells at both the mRNA and protein levels
    tumoral       gain of function
    in lung adenocarcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • CISD2 expression might be an independent prognostic indicator for the survival of patients with early-stage cervical cancer, and might be a novel biomarker for early-stage cervical cancer progression
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    promising mitochondrial targets for cancer therapy
    diabete  
    cellular target for anti-diabetic drugs
    neuromuscularmyopathy 
    novel therapeutic target for treating certain muscle pathologies (PMID: 22343142)
    cancerdigestiveliver
    may serve as a therapeutic target for HCC
    ANIMAL & CELL MODELS
  • Cisd2 deficiency shortens lifespan resulting in premature aging in mice
  • Naf-1 null mice display discernable clinical signs of degeneration at 2-3 months of age, with early evidence of significant defects in the structure and performance of skeletal muscle