LACTB

Serine beta-lactamase-like protein LACTB, mitochondrial is an enzyme that in humans is encoded by the LACTB gene.[5][6] 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. [7] It is involved in the regulation of the metabolic circuitry. A causal association has been found between LACTB and obesity.[8] In breast cancer, LACTB has a tumor suppressor function by modulating lipid metabolism.[9]

LACTB
Identifiers
AliasesLACTB, G24, MRPL56, lactamase beta
External IDsOMIM: 608440 MGI: 1933395 HomoloGene: 12755 GeneCards: LACTB
Gene location (Human)
Chr.Chromosome 15 (human)[1]
Band15q22.2Start63,121,833 bp[1]
End63,142,061 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

114294

80907

Ensembl

ENSG00000103642

ENSMUSG00000032370

UniProt

P83111

Q9EP89

RefSeq (mRNA)

NM_001288585
NM_032857
NM_171846

NM_030717

RefSeq (protein)

NP_001275514
NP_116246
NP_741982

NP_109642

Location (UCSC)Chr 15: 63.12 – 63.14 MbChr 9: 66.96 – 66.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[7][10]

Function

LACTB is widely expressed in different mammalian tissues, with the predominant expression in human skeletal muscle. It localizes in the mitochondrial intermembrane space.[10] 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.[10]

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.[8] LACTB has also been identified to be a tumor suppressor through its effect on mitochondrial phospholipid metabolism and modulation of cell differentiation state.[11]

Interactions

References
  1. GRCh38: Ensembl release 89: ENSG00000103642 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000032370 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Smith TS, Southan C, Ellington K, Campbell D, Tew DG, Debouck C (November 2001). "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. doi:10.1006/geno.2001.6643. PMID 11707067.
  6. "Entrez Gene: LACTB lactamase, beta".
  7. Peitsaro N, Polianskyte Z, Tuimala J, Pörn-Ares I, Liobikas J, Speer O, Lindholm D, Thompson J, Eriksson O (2008). "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. doi:10.1186/1471-2148-8-26. PMC 2266909. PMID 18226203.
  8. 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 (March 2008). "Variations in DNA elucidate molecular networks that cause disease". Nature. 452 (7186): 429–35. doi:10.1038/nature06757. PMC 2841398. PMID 18344982.
  9. Eriksson, Ove; Lalowski, Maciej; Lindholm, Dan (2017). "Commentary: LACTB is a tumour suppressor that modulates lipid metabolism and cell state". Frontiers in Physiology. 8: 396. doi:10.3389/fphys.2017.00396. ISSN 1664-042X. PMC 5462942. PMID 28642719.
  10. 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 (November 2009). "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. doi:10.1073/pnas.0906734106. PMC 2767363. PMID 19858488.
  11. Keckesova et al. 2017. LACTB is a tumour suppressor that modulates lipid metabolism and cell state. Nature 543:681-686
  12. Lu JB, Yao XX, Xiu JC, Hu YW (January 2016). "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. doi:10.1016/j.abb.2015.11.007. PMID 26603571.

Further reading


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