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FLASH GENE
Symbol UCP1 contributors: mct - updated : 28-03-2018
HGNC name uncoupling protein 1 (mitochondrial, proton carrier)
HGNC id 12517
Location 4q31.1      Physical location : 141.481.051 - 141.489.959
Synonym name
  • thermogenin
  • mitochondrial brown fat uncoupling protein
  • solute carrier family 25 member 7
    • Synonym symbol(s) SLC25A7, UCP
    DNA
    TYPE functioning gene
    STRUCTURE 8.91 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    Binding site   enhancer
    text structure
  • a new regulatory motif in the promoter that binds NR4As to stimulate UCP1 gene transcription
  • binding sites for KLF11 and KLF15 in the UCP1 promoter, and cooperative action of KLF11 and KLF15 on the UCP1 promoter was essential for induction of UCP1 in the process of brown adipocyte differentiation of mesenchymal stem cells
  • regulatory CREs in the UCP1 enhancer
    • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1000 - 307 - 2008 11317671
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadiposebrown highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three tandemly repeated mitochondrial protein domains
  • an ATP binding site
  • three matrix loops involved in the control of transport
    • conjugated PhosphoP
    mono polymer dimer
    HOMOLOGY
    Homologene
    FAMILY
  • mitochondrial carrier family
    • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    text
  • localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT)
  • integral membrane protein found in the mitochondrial inner membrane of brown adipose tissue
    • basic FUNCTION
  • dissipating the proton electrochemical gradient and uncoupling fuel oxidation from ADP-ATP conversion
  • H+ transporter, fatty acid dependent
  • BAT-specific protein present only in the inner mitochondorial membrane of brown adipocytes
  • phosphoprotein, and cold-acclimation increases the proportion of UCP1 that is serine phosphorylated
  • identified as a second protein propagating basal proton leak, lending support to the hypothesis that basal leak pathways are perpetrated by members of the mitochondrial anion carrier family but not by other mitochondrial inner membrane proteins
  • adipose tissue-specific UCP1 expression potentially involves demethylation of CpG dinucleotides found in regulatory CREs in the UCP1 enhancer, as well as modification of histone tails
  • catalyzes the dissipation of mitochondrial proton motive force as heat
  • potently reduces mitochondrial superoxide production after cold acclimation and during fatty acid oxidation
  • can affect reactive oxygen containing species production by isolated mitochondria from brown adipose tissue
  • catalyzes proton leak across the mitochondrial inner membrane to disengage substrate oxidation from ATP production
  • UCP1 is a hallmark of BAT, being the pivotal player for cold-induced thermogenesis
  • contributes to thermogenesis, and its expression is regulated at the transcriptional level, and is also regulated post-transcriptionally
  • is the established mediator of brown adipose tissue-dependent thermogenesis
  • is certainly a unique mitochondrial transporter able to uncouple respiration from ADP phosphorylation in mitochondria
  • UCP1 has retained all of the key features of mitochondrial carriers, indicating that it operates by a conventional carrier-like mechanism
  • generates heat by causing proton leak across the mitochondrial inner membrane that requires fatty acid (FA)
  • differences in molecular mechanisms of the inhibition between the highly homologous transporters UCP1 and UCP3 indicate that UCP3 has adapted to fulfill a different role and possibly another transport function in brown adipose tissue (BAT)
  • expression of UCP1 in brown adipose tissue (BAT) is essential for mammalian thermogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS mitochondrial transport
    text energy transfer
    PATHWAY
    metabolism energetic
    signaling
    a component
  • uncoupling protein constituent of inner mitochondrial membrane
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • concomitant MYOD1 and IGF2 inactivation accelerates differentiation of a brown preadipocyte cell line and induces lipid accumulation and increased UCP1 and PRDM16 expression
  • fatty acids induce a conformational change in UCP1
  • UCP1 expression is differently affected by RARA in mouse and human adipocytes (PMUID: 24059847)
  • PRDM16 is recruited to the UCP1 enhancer
  • cardiolipin stabilizes UCP1, as demonstrated by reconstitution experiments and thermostability assays, indicating that the lipid has an integral role in the functioning of the protein, similar to other mitochondrial carriers
  • KDM1A interacts with ZNF516 to Promote UCP1 transcription and brown fat program
  • TENM2 deficiency induces UCP1 expression in differentiating human fat cells
  • CLK2 is likely a regulatory component of diet-induced thermogenesis in brown adipose tissue (BAT) through increased CREB-dependent expression of UCP1
  • reduced UCP1 expression under inflammation is mediated by the increased expression of CCAR2, which inhibits SIRT1 activity
  • stress activated kinase MAP2K6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure
    • cell & other
    REGULATION
    activated by coenzyme Q (ubiquinone)
    by fatty acids
    induced by BMP7
    inhibited by low concentration of nucleeotides
    purine nucleotides
    repressed by
  • SESN2 and antioxidants that inhibit UCP1 expression through suppressing ROS-mediated MAPK14 activation, implying a critical role of ROS in proper BAT metabolism
    • Other regulated by PPARA and PPARG in mice
    ASSOCIATED DISORDERS
    corresponding disease(s)
    related resource MITOP database
    Susceptibility obesity, diabetes
    Variant & Polymorphism SNP
  • a minor role of the 5'utr polymorphism in obesity and diabetes
  • SNP in type 2 diabetes mellitus (allele GG)
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • transgenic mice with muscular overexpression of uncoupling protein 1 (Ucp1), a potent mitochondrial uncoupler, displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology