LACTB

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Template:Short description Template:Infobox gene Serine beta-lactamase-like protein LACTB, mitochondrial is an enzyme that in humans is encoded by the LACTB gene.[1][2] This gene encodes a 54 kDa protein sharing significant sequence similarity to serine proteases of the penicillin binding protein and beta-lactamase superfamily occurring in bacteria. [3] It is involved in the regulation of the metabolic circuitry. A causal association has been found between LACTB and obesity.[4] In breast cancer, LACTB has a tumor suppressor function by modulating lipid metabolism.[5]

Structure

Gene

The LACTB gene is located at chromosome 15q22.1, consisting of 8 exons. Alternative splicing results in multiple transcript variants encoding different protein isoforms.

Protein

LACTB shares sequence similarity to the beta-lactamase/penicillin-binding protein family of serine proteases that are involved in bacterial cell wall metabolism. The N-terminal 97 amino acid segment of LACTB does not form part of the conserved penicillin-binding protein domain and may therefore be responsible for organelle targeting.[3][6]

Function

LACTB is widely expressed in different mammalian tissues, with the predominant expression in human skeletal muscle. It localizes in the mitochondrial intermembrane space.[6] LACTB can polymerize into stable filaments occupying the mitochondrial intermembrane space. These filaments are speculated to play a role in submitochondrial organization and therefore possibly affect mitochondrial metabolon organization.[6]

Clinical significance

It has been found LACTB could cause obesity through gene co-expression analysis based on data integrated from multiple sources. This has been validated in vivo through LACTB overexpression in transgenic mice, which resulted in an obese phenotype.[4] LACTB has also been identified to be a tumor suppressor through its effect on mitochondrial phospholipid metabolism and modulation of cell differentiation state.[7]

Interactions

References

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  7. Keckesova et al. 2017. LACTB is a tumour suppressor that modulates lipid metabolism and cell state. Nature 543:681-686
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Further reading

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