UCP2

UCP2

Target · Mitochondrial carrier

UCP2 Uncoupling protein 2 · Dicarboxylate carrier SLC25A8

UCP2 (uncoupling protein 2, also known as SLC25A8 and BMIQ4) is a mitochondrial inner membrane carrier of the solute carrier family 25. UniProt annotates it as an antiporter that exports Krebs cycle dicarboxylates and influences glucose use and redox balance. Browse Assay Genie's current range of UCP2 research reagents below, or read on for the biology behind the target.

Mitochondrial inner membraneDicarboxylate antiporterExpressed most in skeletal muscle
309 aa
Protein length
~33 kDa
Molecular weight
11q13.4
Gene locus
SLC25 carrier
Protein family
Target information

What is UCP2 (uncoupling protein 2)?

UCP2 sits in the inner mitochondrial membrane, where UniProt describes it as an antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton. The process is driven by the mitochondrial motive force and affects glycolysis, glutaminolysis and glutathione-dependent redox balance. Continuous export of oxaloacetate and related four-carbon dicarboxylates from the matrix into the cytosol negatively regulates oxidation of acetyl-CoA substrates through the Krebs cycle, which lowers the ATP/ADP ratio and reactive oxygen species (ROS) production. UCP2 can also unidirectionally transport anions including L-malate, L-aspartate, phosphate and chloride, and may mediate inducible proton entry into the matrix as protection against oxidative stress. The annotation states that it does not mediate adaptive thermogenesis.

The UCP2 gene belongs to the mitochondrial carrier family (TC 2.A.29) and the solute carrier family 25 group. As with other uncoupling proteins, it contains the three homologous domains typical of mitochondrial anion carrier proteins. NCBI Gene reports that it is expressed in many tissues, with the greatest expression in skeletal muscle, and that the exact way uncoupling proteins transfer H+/OH- is not known. The chromosomal order is 5'-UCP3-UCP2-3'. Mouse and rat both have a Ucp2 ortholog.

Beyond bioenergetics, UniProt reports that UCP2 is required for glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus, with an effect on systemic glucose homeostasis. It also regulates ROS levels and metabolic reprogramming in macrophages during the resolution of inflammation, attenuating ROS production in response to IL33 so that itaconate production and GATA3-dependent differentiation of alternatively activated macrophages can continue. Earlier literature placed it in nonshivering thermogenesis, obesity and diabetes, and the symbol BMIQ4 derives from the previous name body mass index QTL 4.

Mitochondrial metabolism

UCP2 exports Krebs cycle dicarboxylates in exchange for phosphate and a proton, linking carbon flux to the ATP/ADP ratio and ROS production.

Glucose homeostasis

UCP2 regulates glucose use and is required for glucose-induced mitochondrial fission and neuron activation in the ventromedial hypothalamus.

Oxidative stress and redox

UCP2 may mediate inducible proton entry that protects against oxidative stress and affects glutathione-dependent redox balance.

Macrophage and inflammation biology

UCP2 controls ROS and metabolic reprogramming in macrophages during resolution of inflammation, supporting itaconate production and GATA3-dependent differentiation.

Background

UCP2 frequently asked questions

What does UCP2 do?

UCP2 is an inner mitochondrial membrane antiporter that exports Krebs cycle dicarboxylates, such as oxaloacetate, in exchange for phosphate plus a proton. This lowers the ATP/ADP ratio and ROS production, and it regulates glucose use. UniProt notes that it does not mediate adaptive thermogenesis.

What other names does UCP2 go by?

The HGNC full name is uncoupling protein 2. The gene is also known as SLC25A8 and BMIQ4, and UniProt names the protein dicarboxylate carrier SLC25A8. Earlier names include body mass index QTL 4 and uncoupling protein 2 (mitochondrial, proton carrier).

Is UCP2 conserved, and how is it related to UCP1 and UCP3?

Mouse and rat both carry a Ucp2 ortholog. UCP2 is a member of the mitochondrial carrier family and, like other uncoupling proteins, has three homologous domains. In the genome, UCP3 lies directly upstream of UCP2 in the order 5'-UCP3-UCP2-3'. Check the datasheet of any product for its validated reactivity.

Explore

Related targets

Other uncoupling proteins and mitochondrial carrier family members relevant to mitochondrial proton leak and metabolism.

Gene and protein annotations from HGNC, NCBI Gene and UniProt P55851; product specifications from Assay Genie datasheets.

UCP2 Product listing