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Symbol UCP2 contributors: mct/npt/pgu - updated : 28-08-2015
HGNC name uncoupling protein 2 (mitochondrial, proton carrier)
HGNC id 12518
Location 11q13.4      Physical location : 73.685.715 - 73.693.889
Synonym name
  • solute carrier family 25 member 8
  • uncoupling protein 2
  • Synonym symbol(s) SLC25A8, UCPH, BMIQ4
    TYPE functioning gene
    text in 3' of UCP3
    STRUCTURE 8.17 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D11S916 - UCP2 - D11S911 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1646 - 309 - 1999 10027754
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Endocrinepancreasislet of Langerhans    Homo sapiens
    Reproductivemale systemtestis   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiacmyocardiumhighly Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Muscularmyocyte Homo sapiens
    cell lineage erythroid cells
    cell lines
    fluid/secretion lymph
    at STAGE
  • three tandemly repeated mitochondrial protein domains
  • an ATP binding site
    intraspecies homolog to UCP1,UCP3,highly
  • mitochondrial anion carrier protein family
  • inner mitochondrial membrane anion-carrier superfamily
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    text expressed most abundantly in mitochondria from spleen, certain regions of the brain, the pancreas, macrophages and mast cells
    basic FUNCTION
  • implicated in bioenergetics and reactive oxygen species (ROS) modulation
  • dissipating the proton electrochemical gradient by uncoupling fuel oxidation from ADP-ATP conversion
  • H+ transporter, fatty acid dependent inhibited by low concentration of nucleotides
  • negative regulator of insulin secretion (beta cells dysfunction)
  • involved in the thermogenesis and variation of energy metabolism with a reduced expression in skeletal muscle and intraperitoneal tissue and in obesity
  • may be protecting cardiomyocytes from oxidative stress-induced cell death by reducing reactive oxygen species (ROS) production in mitochondria
  • may represent an effective weaponry used by germ cells to combat radical oxygen species -induced apoptosis, protecting testicular germ cells from hyperthermia-induced apoptosis
  • mitochondrial protein that impairs glucose-stimulated ATP production and negatively regulates glucose sensing in POMC neurons
  • UCP2-mediated loss of glucose sensing in glucose-excited neurons could be an important pathogenic component of type 2 diabetes
  • negative regulator of insulin secretion in beta-cells and negatively regulates glucose sensing in POMC neurons
  • playing a role in autoimmune diabetes
  • regulator of erythropoiesis and inhibition of UCP2 function may contribute to the development of anemia
  • has a role early in erythropoiesis, specifically during the EPO-dependent phase, where it likely controls the amount of ROS available for the activation of MAPK/ERK pathway and, thus, modulates cell proliferation and maturation
  • being essential for mitochondrial Ca(2+) uptake
  • accumulates rapidly in the inner mitochondrial membrane during mitochondrial reactive oxygen stress in macrophages
  • its activity contributes to beta cell pathogenesis and development of type 2 diabetes
  • transcriptional upregulation of UCP2 in response to oxidative stress in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that maintain vasomotor tone located
  • mitochondrial protein that inhibits insulin secretion from beta cells, possibly through down-regulation of reactive oxygen species production
  • can potentially regulate mast cell activation
  • plays an important role in fat metabolism by promoting fat oxidation and restricts ghrelin-induced lipogenesis
  • modulates myocardial excitation-contraction coupling
  • determinant of fat oxidation pathways that may be involved in the changes seen in the metabolic pathways in thyroid disease
  • UCP2/UCP3 are essential for mitochondrial Ca(2+) uptake but both proteins exhibit distinct activities in regard to the source and mode of Ca(2+) mobilization
  • UCP2 expression increased significantly with follicular development in both control and Polycystic ovary syndrome (PCOS) tissue, with expression in early stage follicles from PCOS patients significantly greater than that in controls
  • UCP2/3 are fundamental for mitochondrial uptake of high Ca2+ domains in mitochondria-ER junctions
  • LETM1 and UCP2/3 independently contribute to two distinct, mitochondrial Ca2+ uptake pathways in intact endothelial cells
  • UCP2 and UCP3 have been postulated to catalyze Ca(2+) entry across the inner membrane of mitochondria
  • may contribute to the regulation of hypoglycemia-induced GCG secretion, which is supported by our current finding that UCP2 expression is increased in nutrient-deprived human islets
    metabolism energetic
    a component
  • uncoupling protein constituent of inner mitochondrial membrane
    small molecule
  • 14.3.3 (YWHx) proteins
  • UCP2-MAPK/ERK interaction in erythropoiesis, with an effect on cell proliferation during the EPO-dependent phase
  • significant correlation between UCP2 and CYP11A1 expression was found in PCOS but not control patients
  • IL22 plays likely a protective role in glucose-stimulated insulin secretion (GSIS) via the down-regulation of UCP2
  • cell & other
    activated by at the protein level by superoxide generated by the mitochondrial respiratory chain in conditions of high glucose metabolism
    Other regulated by PPARA and PPARG in mice, in man by food intake, insulin or fatty acids
    corresponding disease(s)
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in cryptorchidism
    constitutional     --low  
    in skeletal muscle of obese
    constitutional       gain of function
    causally linked to loss of glucose sensing in POMC neurons induced by a high-fat diet
    constitutional   deletion    
    prevents obesity-induced loss of glucose sensing
    constitutional       loss of function
    in anemia
    constitutional     --over  
    associated with testicular mitochondrial dysfunction in agreement with the reported decreased fertility in aged individuals (Amaral 2008)
    constitutional       gain of function
    in pathological states such as heart failure
    constitutional       loss of function
    reported to improve insulin secretion of isolated islets and over-expression inhibits insulin secretion
  • to obesity
  • to lipid levels in patients with type 2 diabetes
  • to hyperglycaemia and insulin resistance in severe sepsis
  • Variant & Polymorphism other
  • G/A polymorphism in promoter decrease risk of obesity in middle-age
  • 866G/A associated with variation of insulin secretion and with dyslipidemia in patients with type 2 diabetes
  • A55V homozygous (Val/Val) genotype increased in spina-bifida
  • common, functional polymorphism in the promoter region of the UCP2 gene is associated with hyperglycaemia and insulin resistance in severe sepsis
  • Candidate gene
    Therapy target
    targeting UCP2 may offer clinical benefit in the treatment of cancer
  • Gck+/- Ucp2-/- mice had improved glucose tolerance compared with Gck+/- mice