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Details on Person UniProt:P55851 UCP2
| Class:Id | ReferenceGeneProduct:66882 |
|---|---|
| _chainChangeLog | chain:1-309 added on Sat February 7 2015 |
| _displayName | UniProt:P55851 UCP2 |
| _timestamp | 2025-02-21 20:05:11 |
| chain | chain:1-309 |
| checksum | 2E1741391621E3D9 |
| comment | FUNCTION Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. Continuous export of oxaloacetate and related four-carbon dicarboxylates from mitochondrial matrix into the cytosol negatively regulates the oxidation of acetyl-CoA substrates via the Krebs cycle, lowering the ATP/ADP ratio and reactive oxygen species (ROS) production (PubMed:24395786). May mediate inducible proton entry into the mitochondrial matrix affecting ATP turnover as a protection mechanism against oxidative stress. The proton currents are most likely associated with fatty acid flipping across the inner membrane of mitochondria in a metabolic process regulated by free fatty acids and purine nucleotides (By similarity) (PubMed:11171965, PubMed:11278935, PubMed:22524567, PubMed:26182433, PubMed:33373220). Regulates the use of glucose as a source of energy. Required for glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus (VMH). This mitochondrial adaptation mechanism modulates the VMH pool of glucose-excited neurons with an impact on systemic glucose homeostasis (By similarity). Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. Attenuates ROS production in response to IL33 to preserve the integrity of the Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (By similarity). Can unidirectionally transport anions including L-malate, L-aspartate, phosphate and chloride ions (PubMed:22524567, PubMed:24395786, PubMed:26182433). Does not mediate adaptive thermogenesis (By similarity).CATALYTIC ACTIVITY L-aspartate(out) + phosphate(in) + H(+)(in) = L-aspartate(in) + phosphate(out) + H(+)(out)CATALYTIC ACTIVITY oxaloacetate(out) + phosphate(in) + H(+)(in) = oxaloacetate(in) + phosphate(out) + H(+)(out)CATALYTIC ACTIVITY (S)-malate(out) + phosphate(in) + H(+)(in) = (S)-malate(in) + phosphate(out) + H(+)(out)CATALYTIC ACTIVITY malonate(out) + phosphate(in) + H(+)(in) = malonate(in) + phosphate(out) + H(+)(out)CATALYTIC ACTIVITY sulfate(out) + phosphate(in) + H(+)(in) = sulfate(in) + phosphate(out) + H(+)(out)CATALYTIC ACTIVITY (S)-malate(out) = (S)-malate(in)CATALYTIC ACTIVITY L-aspartate(out) = L-aspartate(in)CATALYTIC ACTIVITY phosphate(in) = phosphate(out)CATALYTIC ACTIVITY chloride(in) = chloride(out)CATALYTIC ACTIVITY H(+)(in) = H(+)(out)CATALYTIC ACTIVITY a long-chain fatty acid(out) = a long-chain fatty acid(in)ACTIVITY REGULATION Inhibited by pyridoxal- 5'-phosphate, bathophenanthroline, tannic acid, bromocresol purple, butylmalonate and phenylsuccinate (PubMed:24395786). Proton conductance is activated by cardiolipin and long-chain free fatty acids and inhibited by purine nucleotides ATP and ADP. Chloride ion transporter activity is inhibited by long-chain free fatty acids (PubMed:22524567, PubMed:26182433).SUBUNIT Homotetramer. Adopts an asymmetrical dimer of dimers functional form.INTERACTION Widely expressed in adult human tissues, including tissues rich in macrophages. Most expressed in white adipose tissue and skeletal muscle.DOMAIN The GDP-binding domain is located within the hydrophilic cavity, with GDP phosphates likely forming salt bridges with the charged residues, Lys-141 and Arg-185.DOMAIN The long-chain fatty acid-binding domain consists of an hydrophobic groove between peripheral transmembrane helices 1 and 6 near the matrix side.POLYMORPHISM Genetic variations in UCP2 define the body mass index quantitative trait locus 4 (BMIQ4) [MIM:607447]. A common polymorphism in the promoter of UCP2 has been shown to be associated with a decreased risk of obesity in middle-aged individuals.SIMILARITY Belongs to the mitochondrial carrier (TC 2.A.29) family.CAUTION The role of UCP2/SLC25A8 in mitochondrial proton conductance is a matter of debate. It was initially suggested that it mediates proton leak that increases net proton conductance in response to ROS such as reactive alkenals generated during fatty acid oxidation in mitochondria. By lowering the proton motive force, it would provide for feedback control of mitochondrial ROS metabolism limiting extensive ROS production and protecting cells against oxidative stress. This activity and its potential regulation by ubiquinones and nucleotides was disputed by later studies, which failed to reproduce the effect on proton conductance under physiological conditions. Rather than 'uncoupling' the link between electron transfer and ATP synthesis, it may couple metabolite transport to proton flux to allow for optimal ATP turnover. |
| description | recommendedName: fullName evidence="17"Dicarboxylate carrier SLC25A8 alternativeName: Mitochondrial uncoupling protein 2 shortName: UCP 2 alternativeName: Solute carrier family 25 member 8 alternativeName: UCPH |
| geneName | UCP2 SLC25A8 |
| identifier | P55851 |
| isSequenceChanged | FALSE |
| keyword | Membrane Mitochondrion Mitochondrion inner membrane Proteomics identification Reference proteome Repeat Transmembrane Transmembrane helix Transport |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | UCP2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989302] ENSEMBL:ENSG00000175567 UCP2 [Homo sapiens] |
| secondaryIdentifier | UCP2_HUMAN Q4PJH8 Q53HM3 |
| sequenceLength | 309 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:166392] UCP2 [mitochondrial inner membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P55851 UCP2 (66882)
