LACTB explained

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

• MiR-125b-5p^[8]

Further reading

• Hallis TM, Kopp AL, Gibson J, Lebakken CS, Hancock M, Van Den Heuvel-Kramer K, Turek-Etienne T . An improved beta-lactamase reporter assay: multiplexing with a cytotoxicity readout for enhanced accuracy of hit identification . Journal of Biomolecular Screening . 12 . 5 . 635–44 . August 2007 . 17517902 . 10.1177/1087057107301499 . free .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . free .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–70 . October 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
• Hell-Pourmojib M, Neuner P, Fischer H, Rezaie S, Kindås-Mügge I, Knobler R, Trautinger F . Differential expression of a novel gene in response to hsp27 and cell differentiation in human keratinocytes . The Journal of Investigative Dermatology . 119 . 1 . 154–9 . July 2002 . 12164938 . 10.1046/j.1523-1747.2002.01793.x . free .
• Koc EC, Burkhart W, Blackburn K, Moyer MB, Schlatzer DM, Moseley A, Spremulli LL . The large subunit of the mammalian mitochondrial ribosome. Analysis of the complement of ribosomal proteins present . The Journal of Biological Chemistry . 276 . 47 . 43958–69 . November 2001 . 11551941 . 10.1074/jbc.M106510200 . free .

Notes and References

1. Smith TS, Southan C, Ellington K, Campbell D, Tew DG, Debouck C . Identification, genomic organization, and mRNA expression of LACTB, encoding a serine beta-lactamase-like protein with an amino-terminal transmembrane domain . Genomics . 78 . 1–2 . 12–4 . November 2001 . 11707067 . 10.1006/geno.2001.6643 .
2. Web site: Entrez Gene: LACTB lactamase, beta.
3. Peitsaro N, Polianskyte Z, Tuimala J, Pörn-Ares I, Liobikas J, Speer O, Lindholm D, Thompson J, Eriksson O . Evolution of a family of metazoan active-site-serine enzymes from penicillin-binding proteins: a novel facet of the bacterial legacy . BMC Evolutionary Biology . 8 . 26 . 2008 . 1 . 18226203 . 2266909 . 10.1186/1471-2148-8-26 . 2008BMCEE...8...26P . free .
4. Chen Y, Zhu J, Lum PY, Yang X, Pinto S, MacNeil DJ, Zhang C, Lamb J, Edwards S, Sieberts SK, Leonardson A, Castellini LW, Wang S, Champy MF, Zhang B, Emilsson V, Doss S, Ghazalpour A, Horvath S, Drake TA, Lusis AJ, Schadt EE . Variations in DNA elucidate molecular networks that cause disease . Nature . 452 . 7186 . 429–35 . March 2008 . 18344982 . 10.1038/nature06757 . 2841398. 2008Natur.452..429C .
5. Eriksson. Ove. Lalowski. Maciej. Lindholm. Dan. 2017. Commentary: LACTB is a tumour suppressor that modulates lipid metabolism and cell state. Frontiers in Physiology. en. 8. 396. 10.3389/fphys.2017.00396. 28642719. 5462942. 1664-042X. free.
6. Polianskyte Z, Peitsaro N, Dapkunas A, Liobikas J, Soliymani R, Lalowski M, Speer O, Seitsonen J, Butcher S, Cereghetti GM, Linder MD, Merckel M, Thompson J, Eriksson O . LACTB is a filament-forming protein localized in mitochondria . Proceedings of the National Academy of Sciences of the United States of America . 106 . 45 . 18960–5 . November 2009 . 19858488 . 10.1073/pnas.0906734106 . 2767363. 2009PNAS..10618960P . free .
7. [Zuzana Kečkéšová|Keckesova]
8. Lu JB, Yao XX, Xiu JC, Hu YW . MicroRNA-125b-5p attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production by targeting inhibiting LACTB in THP-1 macrophages . Archives of Biochemistry and Biophysics . 590 . 64–71 . January 2016 . 26603571 . 10.1016/j.abb.2015.11.007 .