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Symbol UCP3 contributors: mct/ - updated : 26-04-2012
HGNC name uncoupling protein 3 (mitochondrial, proton carrier)
HGNC id 12519
Corresponding disease
OBS4 severe obesity and diabetes mellitus non insulin-dependent
Location 11q13.4      Physical location : 73.711.329 - 73.720.282
Synonym name
  • mitochondrial uncoupling protein 3
  • solute carrier family 25 member 9
  • Synonym symbol(s) SLC25A9
    TYPE functioning gene
    text in 5' of UCP2
    STRUCTURE 8.79 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box) (TATA box)
    Binding site   HRE
    text structure promoter activation requires MYOD and is induced by retinoic acid in muscle cells
    MAPPING cloned Y linked   status confirmed
    Map cen - D11S1883 - D11S913 - DHCR7 - D11S1337 - D11S916 - UCP2 - UCP3 - D11S911 - D11S937 - D11S1362 - D11S901 - qter
    Physical map
    ART2P 11q13 ADP-ribosyltransferase 2 pseudogene (RT6 antigen homolog, rat) PDE2A 11cen-q12.1 phosphodiesterase 2A, cGMP-stimulated CENTD2 11q13.3 centaurin, delta 2 STARD10 11q13 START domain containing 10 FLJ00012 11q13.3 hypothetical protein FLJ00012 KIAA0769 11q13.2 hypothetical protein FLJ00012 P2RY2 11q13.5-q14.1 purinergic receptor P2Y, G-protein coupled, 2 P2RY6 11q13.5 pyrimidinergic receptor P2Y, G-protein coupled, 6 ARHGEF17 11q13.3-q13.5 Rho guanine nucleotide exchange factor (GEF) 17 TNFRSF19L 11q13,3 tumor necrosis factor receptor superfamily, member 19-like LOC387786 11 LOC387786 KIAA0280 11q13.3 KIAA0280 protein PLEKHB1 11q13.5-q14.1 pleckstrin homology domain containing, family B (evectins) member 1 RAB6A 2q14-q21 RAB6A, member RAS oncogene family LOC268276 11q13 musashi 1 pseudogene MRPL48 11q13.2 mitochondrial ribosomal protein L48 E2IG2 11q13.3 E2IG2 protein FLJ11848 11q13.3 hypothetical protein FLJ11848 TSARG6 11q13.3 testis spermatogenesis apoptosis-related protein 6 UCP2 11q13 uncoupling protein 2 (mitochondrial, proton carrier) UCP3 11q13 uncoupling protein 3 (mitochondrial, proton carrier) DKFZP586P0123 11q13.3 DKFZP586P0123 protein PME-1 11q13.3 protein phosphatase methylesterase-1 LOC283208 FLJ32029 KCNE3 11q13-q14 potassium voltage-gated channel, Isk-related family, member 3 HCP27 11q13.3 cytochrome c, somatic pseudogene LOC387787 11 similar to RIKEN cDNA 2610209A20 POLD3 11q14 similar to RIKEN cDNA 2610209A20 BNF1 FLJ22596 11q13.3 hypothetical protein FLJ22596 LOC387788 11 similar to ribosomal protein S12 KIAA1991 11q13.3 hypothetical protein KIAA1991 KIAA0102 11q13.3 hypothetical protein KIAA1991 LOC387789 11 LOC387789 NEU3 11q13.5 sialidase 3 (membrane sialidase) LOC390224 11 similar to olfactory receptor MOR101-2 LOC341152 11q13.3 similar to olfactory receptor MOR101-1 LOC390225 11 similar to olfactory receptor MOR101-2 SLCO2B1 11q13 solute carrier organic anion transporter family, member 2B1 ARRB1 11q13 arrestin, beta 1 RPS3 11q13.3-q13.5 ribosomal protein S3 FLJ33790 11q13.3 hypothetical protein FLJ33790 PP1665 11q13.3 hypothetical protein PP1665 SERPINH1 11q13.5 serine (or cysteine) proteinase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1)
    TRANSCRIPTS type messenger
    text two forms: long and short, missing C terminal 37 residues, UCP3L (full lengh) decrease susceptibility to obesity, UCP3S (truncated)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2239 - 275 - 1999 10066417
  • an extra TM and a putative nucleotide binding domain (Boss)
  • encoding for the longer product
  • also called UCP3L
  • 7 splicing 2438 - 312 skeletal muscle 1999 10066417
  • lacking exon 7
  • encoding for the shorter product
  • also called UCP3S
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly
    Digestiveliver   highly Homo sapiens
    Reproductivefemale systembreastmammary gland lowly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal predominantly
    cell lineage
    cell lines
    at STAGE
    physiological period fetal, pregnancy
    Text specifically, in skeletal muscle during development
  • three mitochondrial tandemly repeated protein domains
  • an ATP binding site
  • five transmembrane segments (5'TM) UCP35
  • distinct sites in the IML2 (intermembrane loop 2) of UCP3 effecting mitochondrial uptake of high and low Ca(2+) signals
    interspecies homolog to rattus Ucp3 (87.34 pc)
    homolog to murine UCP3 (86.69 pc)
  • mitochondrial anion carriers protein family (MACP)
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • dissipating the proton electrochemical gradient by uncoupling fuel oxidation from ADP-ATP conversion
  • H+ transporter, fatty acid dependent, mitochondrial
  • involved in the variation of energy metabolism, obesity and in modulation of tissue respiratory control
  • possible mediator of adaptive thermogenesis and energy balance
  • playing an unique role in the regulation of fatty acid during fasting
  • playing a physiological role in facilitating outward transport of long-chain fatty acid anions, which cannot be oxidized, from the mitochondrial matrix
  • may having a role in modulating lipotoxicity
  • may be functioning by modulating mitochondrial inner membrane proton conductance resulting in the alteration in reactive oxygen species (ROS) production
  • in liver modulates gene expression and oxidative metabolism in response to fatty acids, and sensitizes mitochondria to permeability transition
  • turned over rapidly in multiple cell types in a proteasome-dependent manner
  • can affect ROS production through a membrane potential-independent mechanism
  • 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
  • being essential for mitochondrial Ca(2+) uptake
  • required for the HK2-mediated decrease in mitochondrial ROS emission)
  • 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
  • negatively modulates the activity of ATP2A1 by limiting mitochondrial ATP production
  • may have a role in the protection of mitochondria against lipid-induced mitochondrial dysfunction, but only after long-term exposure to high-fat
    PHYSIOLOGICAL PROCESS mitochondrial transport
    text energy transfer
    metabolism energetic
    a component
  • uncoupling protein constituent of inner mitochondrial membrane
    small molecule
  • 14.3.3 (YWHx) proteins
  • major repressor of UCP3 gene expression in response to glucocorticoids
  • cell & other
    activated by coenzyme Q (ubiquinone)
    thyroid hormones
    induced by hypoxia in skeletal muscle and this induction is sustained for up to 48 h
    inhibited by low concentration of nucleotides
    repressed by SIRT1, in response to glucocorticoids (has multiple implications in relation to the molecular mechanisms of control of UCP3 gene transcription and the physiological control of muscle cell function)
    Other regulated by nutritional factors
    regulated by PPARA and PPARG in mice
    dysregulated in states of insulin resistance
    corresponding disease(s) OBS4
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    dysregulation of protein expressionincreased expression in function of obesity and in type 2 diabetes (NIDDM)
    constitutional     --over  
    in skeletal muscle might protect against fat-induced insulin resistance in muscle by conversion of intramyocellular fat into thermal energy
    Variant & Polymorphism
    Candidate gene
    Therapy target
    increasing mitochondrial UCP3 in skeletal muscle may be an excellent therapeutic target for type 2 diabetes mellitus
    Ucp3 knockout mice indeed have elevated mitochondrial ROS production after short-term (8 weeks) high-fat feeding