LACTB2

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
Gene location (Human)
Chr.	Chromosome 8 (human) [1]
End	70,669,174 bp [1]
Gene location (Mouse)
Chr.	Chromosome 1 (mouse) [2]
End	13,660,546 bp [2]
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
	51110
	212442
	ENSG00000147592
	ENSMUSG00000025937
	Q53H82
	Q99KR3
	NM_016027
	NM_145381
	NP_057111
	NP_663356
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated April 16, 2019

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

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

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]

Cleavage and polyadenylation specificity factor subunit 3 is a protein that in humans is encoded by the CPSF3 gene.

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]

Related Research Articles

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References

1 2 3 GRCh38: Ensembl release 89: ENSG00000147592 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025937 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
1 2 "Entrez Gene: Lactamase, beta 2" . Retrieved 2015-07-07.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000147592 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025937 - Ensembl, May 2017

[3] "Human PubMed Reference:".

[4] "Mouse PubMed Reference:".

[entrez-5] 1 2 "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.

[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.

[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.