Biology:LACTB
 Generic protein structure example |
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]
References
- ↑ "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. doi:10.1006/geno.2001.6643. PMID 11707067.
- ↑ "Entrez Gene: LACTB lactamase, beta". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=114294.
- ↑ 3.0 3.1 "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. doi:10.1186/1471-2148-8-26. PMID 18226203.
- ↑ 4.0 4.1 "Variations in DNA elucidate molecular networks that cause disease". Nature 452 (7186): 429–35. March 2008. doi:10.1038/nature06757. PMID 18344982. Bibcode: 2008Natur.452..429C.
- ↑ Eriksson, Ove; Lalowski, Maciej; Lindholm, Dan (2017). "Commentary: LACTB is a tumour suppressor that modulates lipid metabolism and cell state" (in en). Frontiers in Physiology 8: 396. doi:10.3389/fphys.2017.00396. ISSN 1664-042X. PMID 28642719.
- ↑ 6.0 6.1 6.2 "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. doi:10.1073/pnas.0906734106. PMID 19858488. Bibcode: 2009PNAS..10618960P.
- ↑ Keckesova et al. 2017. LACTB is a tumour suppressor that modulates lipid metabolism and cell state. Nature 543:681-686
- ↑ "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. doi:10.1016/j.abb.2015.11.007. PMID 26603571.
Further reading
- "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. doi:10.1177/1087057107301499. PMID 17517902.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. November 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- "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. doi:10.1101/gr.1293003. PMID 12975309.
- "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. doi:10.1046/j.1523-1747.2002.01793.x. PMID 12164938.
- "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. doi:10.1074/jbc.M106510200. PMID 11551941.
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