LACTB2

LACTB2
Available structures
Gene ontology
Molecular function	metal ion binding; hydrolase activity; protein binding; nuclease activity; endoribonuclease activity; RNA binding; zinc ion binding; single-stranded RNA binding; endonuclease activity;
Cellular component	mitochondrion; mitochondrial matrix;
Biological process	RNA phosphodiester bond hydrolysis, endonucleolytic;
	Sources:Amigo / QuickGO
	ENSG00000147592
	ENSMUSG00000025937
	Q53H82
	Q99KR3
	NM_016027
	NM_145381
	NP_057111
	NP_663356
	Wikidata
View/Edit Human	View/Edit Mouse

Lactamase, beta 2 is a protein that in humans is encoded by the LACTB2 gene.^[5]

Structure

LACTB2 is located on the 8th chromosome, with its specific location being 8q13.3. The gene contains 7 exons.^[5]

The LACTB2 protein has a metallo β-lactamase (MBL) fold, with two zinc ions in the active site.

Function

The metallo beta-lactamases were first identified in bacteria; they give some strains antibiotic resistance by degrading beta-lactam antibiotics (such as penicillins). However, the protein family includes many members that are ribonucleases (RNases), deoxyribonucleases (DNases) and other metabolic enzymes

RNase Z^[7]) eukaryotic mRNA (CPSF-73) and snRNA molecules ^[8] LACTB2 is a mitochondrial endoribonuclease which may have a role in degrading mitochondrial mRNAs.^[9]

Clinical significance

A tumor-specific LACTB2-NCOA2 fusion originating from intra-chromosomal rearrangement of chromosome 8 has been identified at both DNA and RNA levels. Unlike conventional oncogenic chimeric proteins, the fusion product lacks functional domain from respective genes, indicative of an amorphic rearrangement. This chimeric LACTB2-NCOA2 transcript was detected in 6 out of 99 (6.1%) colorectal cancer (CRC) cases, where NCOA2 was significantly downregulated. Enforced expression of wild-type

NCOA2 but not the LACTB2-NCOA2 fusion protein impaired the pro-tumorigenic phenotypes of CRC cells, whereas knockdown of endogenous NCOA2 in normal colonocytes had opposite effects. Mechanistically, NCOA2 inhibited Wnt/β-catenin signaling through simultaneously upregulating inhibitors and downregulating stimulators of Wnt/β-catenin pathway. NCOA2 is a novel negative growth regulatory gene repressing the Wnt/β-catenin pathway in CRC, where recurrent fusion with LACTB2 contributes to its disruption.^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000147592 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000025937 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: Lactamase, beta 2". Retrieved 2015-07-07.
S2CID 26906168
.

S2CID 22522356
.

PMID 22252320
.

PMID 26826708
.

PMID 25823027
.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000147592 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000025937 – 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.

[entrez-5] "Entrez Gene: Lactamase, beta 2". Retrieved 2015-07-07.

[6] S2CID 26906168
.

[7] S2CID 22522356
.

[8] PMID 22252320
.

[9] PMID 26826708
.

[10] PMID 25823027
.

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