Jump to content

LACTB

From Wikipedia, the free encyclopedia

LACTB
Identifiers
AliasesLACTB, G24, MRPL56, lactamase beta
External IDsOMIM: 608440; MGI: 1933395; GeneCards: LACTB
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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: 66.86 – 66.88 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Structure

[edit]

Gene

[edit]

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

[edit]

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

[edit]

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

[edit]

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

[edit]

References

[edit]
  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000103642 – Ensembl, May 2017
  2. 1 2 3 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): 12–14. doi:10.1006/geno.2001.6643. PMID 11707067.
  6. ↑ "Entrez Gene: LACTB lactamase, beta".
  7. 1 2 Peitsaro N, Polianskyte Z, Tuimala J, Pörn-Ares I, Liobikas J, Speer O, et al. (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 (1) 26. Bibcode:2008BMCEE...8...26P. doi:10.1186/1471-2148-8-26. PMC 2266909. PMID 18226203.
  8. 1 2 Chen Y, Zhu J, Lum PY, Yang X, Pinto S, MacNeil DJ, et al. (March 2008). "Variations in DNA elucidate molecular networks that cause disease". Nature. 452 (7186): 429–435. Bibcode:2008Natur.452..429C. doi:10.1038/nature06757. PMC 2841398. PMID 18344982.
  9. ↑ Eriksson O, Lalowski M, Lindholm D (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. PMC 5462942. PMID 28642719.
  10. 1 2 3 Polianskyte Z, Peitsaro N, Dapkunas A, Liobikas J, Soliymani R, Lalowski M, et al. (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): 18960–18965. Bibcode:2009PNAS..10618960P. 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

[edit]