LACTB2

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

LACTB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4AD9
Identifiers
Aliases	LACTB2, CGI-83, lactamase beta 2
External IDs	MGI: 2442551; HomoloGene: 9349; GeneCards: LACTB2; OMA:LACTB2 - orthologs
Gene ___location (Human) Chr. Chromosome 8 (human)[1] Band 8q13.3 Start 70,635,318 bp[1] End 70,669,185 bp[1]
Gene ___location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 A3 Start 13,693,554 bp[2] End 13,730,770 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal gland right adrenal cortex kidney tubule left adrenal gland jejunal mucosa left adrenal cortex right ventricle right lobe of liver left testis right testis Top expressed in right kidney left lobe of liver human kidney proximal tubule brown adipose tissue sternocleidomastoid muscle morula intercostal muscle triceps brachii muscle digastric muscle More reference expression data BioGPS n/a
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
Orthologs Species Human Mouse Entrez 51110 212442 Ensembl ENSG00000147592 ENSMUSG00000025937 UniProt Q53H82 Q99KR3 RefSeq (mRNA) NM_016027 NM_145381 RefSeq (protein) NP_057111 NP_663356 Location (UCSC) Chr 8: 70.64 – 70.67 Mb Chr 1: 13.69 – 13.73 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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 ^[6] MBL ribonucleases are responsible for RNA processing, generating the 3' end of tRNA,(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

1. GRCh38: Ensembl release 89: ENSG00000147592 – Ensembl, May 2017
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.
5. "Entrez Gene: Lactamase, beta 2". Retrieved 2015-07-07.
6. Dominski Z (2007-03-01). "Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA metabolism". Critical Reviews in Biochemistry and Molecular Biology. 42 (2): 67–93. doi:10.1080/10409230701279118. PMID 17453916. S2CID 26906168.
7. Vogel A, Schilling O, Späth B, Marchfelder A (December 2005). "The tRNase Z family of proteins: physiological functions, substrate specificity and structural properties". Biological Chemistry. 386 (12): 1253–64. doi:10.1515/BC.2005.142. PMID 16336119. S2CID 22522356.
8. Albrecht TR, Wagner EJ (March 2012). "snRNA 3' end formation requires heterodimeric association of integrator subunits". Molecular and Cellular Biology. 32 (6): 1112–23. doi:10.1128/MCB.06511-11. PMC 3295014. PMID 22252320.
9. Levy S, Allerston CK, Liveanu V, Habib MR, Gileadi O, Schuster G (February 2016). "Identification of LACTB2, a metallo-β-lactamase protein, as a human mitochondrial endoribonuclease". Nucleic Acids Research. 44 (4): 1813–32. doi:10.1093/nar/gkw050. PMC 4770246. PMID 26826708.
10. Yu J, Wu WK, Liang Q, Zhang N, He J, Li X, Zhang X, Xu L, Chan MT, Ng SS, Sung JJ (January 2016). "Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer". Oncogene. 35 (2): 187–95. doi:10.1038/onc.2015.72. PMC 4717154. PMID 25823027.