GLS2

GLS2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4BQM
Identifiers
Aliases	GLS2 , GA, GLS, LGA, hLGA, glutaminase 2
External IDs	OMIM: 606365 MGI: 2143539 HomoloGene: 40861 GeneCards: GLS2
Gene location (Human)
Chr.	Chromosome 12 (human)
End	56,488,414 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	128,045,873 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; cerebellar hemisphere; ; body of pancreas; ; oocyte; ; Brodmann area 9; ; middle temporal gyrus; ; Brodmann area 10; ; orbitofrontal cortex; ; pituitary gland; ; cingulate gyrus;
	Top expressed in
	left lobe of liver; ; visual cortex; ; cerebellar cortex; ; anterior horn of spinal cord; ; facial motor nucleus; ; superior frontal gyrus; ; medial vestibular nucleus; ; morula; ; supraoptic nucleus; ; dorsal tegmental nucleus;
	More reference expression data
	n/a
Gene ontology
Molecular function	hydrolase activity ; protein binding ; glutaminase activity ;
Cellular component	mitochondrial matrix ; mitochondrion ;
Biological process	regulation of apoptotic process ; glutamate secretion ; cellular amino acid metabolic process ; glutamine metabolic process ; cellular amino acid biosynthetic process ; glutamate biosynthetic process ; glutamine catabolic process ; reactive oxygen species metabolic process ;
	Sources:Amigo / QuickGO
Orthologs
	27165
	216456
	ENSG00000135423
	ENSMUSG00000044005
	Q9UI32
	Q571F8
	NM_001280796 ; NM_001280797 ; NM_001280798 ; NM_013267 ; NM_138566 Contents Structure ; Function ; Clinical significance ; References ; Further reading ;
	NM_001033264 ; NM_001285777 ; NM_001285779
	NP_001267725 ; NP_001267726 ; NP_001267727 ; NP_037399
	NP_001028436 ; NP_001272706 ; NP_001272708
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 12, 2022

Glutaminase 2 (liver, mitochondrial) is a protein that in humans is encoded by the GLS2 gene.^[5]

Structure

The GLS2 gene is on the 12th chromosome in humans, with its specific location being 12q13.3. It contains 19 exons.^[5]

Function

GLS2 is a part of the glutaminase family. The protein encoded by this gene is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. Originally thought to be liver-specific, this protein has been found in other tissues as well. Alternative splicing results in multiple transcript variants that encode different isoforms.

Clinical significance

GLS2 has interesting molecular relationships with tumor progression and cancer. Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma.^[6] Additionally, silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells.^[7]

Related Research Articles

Chemokine ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils. CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells towards the epithelial cells surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the chemokine receptor CCR6.

CD133 antigen, also known as prominin-1, is a glycoprotein that in humans is encoded by the PROM1 gene. It is a member of pentaspan transmembrane glycoproteins, which specifically localize to cellular protrusions. When embedded in the cell membrane, the membrane topology of prominin-1 is such that the N-terminus extends into the extracellular space and the C-terminus resides in the intracellular compartment. The protein consists of five transmembrane segments, with the first and second segments and the third and fourth segments connected by intracellular loops while the second and third as well as fourth and fifth transmembrane segments are connected by extracellular loops. While the precise function of CD133 remains unknown, it has been proposed that it acts as an organizer of cell membrane topology.

<span class="mw-page-title-main">Glutaminase</span>

Glutaminase is an amidohydrolase enzyme that generates glutamate from glutamine. Glutaminase has tissue-specific isoenzymes. Glutaminase has an important role in glial cells.

Hepatic lipase (HL), also called hepatic triglyceride lipase (HTGL) or LIPC, is a form of lipase, catalyzing the hydrolysis of triacylglyceride. Hepatic lipase is coded by chromosome 15 and its gene is also often referred to as HTGL or LIPC. Hepatic lipase is expressed mainly in liver cells, known as hepatocytes, and endothelial cells of the liver. The hepatic lipase can either remain attached to the liver or can unbind from the liver endothelial cells and is free to enter the body's circulation system. When bound on the endothelial cells of the liver, it is often found bound to HSPG, heparan sulfate proteoglycans (HSPG), keeping HL inactive and unable to bind to HDL or IDL. When it is free in the bloodstream, however, it is found associated with HDL to maintain it inactive. This is because the triacylglycerides in HDL serve as a substrate, but the lipoprotein contains proteins around the triacylglycerides that can prevent the triacylglycerides from being broken down by HL.

Transcription factor jun-B is a protein that in humans is encoded by the JUNB gene. Transcription factor jun-B is a transcription factor involved in regulating gene activity following the primary growth factor response. It binds to the DNA sequence 5'-TGA[CG]TCA-3'.

Transcription factor E2F3 is a protein that in humans is encoded by the E2F3 gene.

Alpha-1-syntrophin is a protein that in humans is encoded by the SNTA1 gene. Alpha-1 syntrophin is a signal transducing adaptor protein and serves as a scaffold for various signaling molecules. Alpha-1 syntrophin contains a PDZ domain, two Pleckstrin homology domain and a 'syntrophin unique' domain.

Protein NDRG2 is a protein that in humans is encoded by the NDRG2 gene.

Oligodendrocyte transcription factor (OLIG2) is a basic helix-loop-helix (bHLH) transcription factor encoded by the Olig2 gene. The protein is of 329 amino acids in length, 32 kDa in size and contains one basic helix-loop-helix DNA-binding domain. It is one of the three members of the bHLH family. The other two members are OLIG1 and OLIG3. The expression of OLIG2 is mostly restricted in central nervous system, where it acts as both an anti-neurigenic and a neurigenic factor at different stages of development. OLIG2 is well known for determining motor neuron and oligodendrocyte differentiation, as well as its role in sustaining replication in early development. It is mainly involved in diseases such as brain tumor and Down syndrome.

Tumor necrosis factor receptor superfamily member 12A also known as the TWEAK receptor (TWEAKR) is a protein that in humans is encoded by the TNFRSF12A gene.

CD6 is a human protein encoded by the CD6 gene.

Activating transcription factor 5, also known as ATF5, is a protein that, in humans, is encoded by the ATF5 gene.

Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule that is encoded by the myelin-related gene EMP3. EMP3 is a member of the peripheral myelin protein gene family 22-kDa (PMP22), which is mainly responsible for the formation of the sheath of compact myelin. Although the detailed functions and mechanisms of EMP3 still remain unclear, it is suggested that EMP3 is possibly epigenetically linked to certain carcinomas.

Myosin-XVIIIa is a protein that in humans is encoded by the MYO18A gene.

Transcription factor MafF is a bZip Maf transcription factor protein that in humans is encoded by the MAFF gene.

Purkinje cell protein 4 is a protein that in humans is encoded by the PCP4 gene. Also known as PEP-19, PCP4 is a 7.6 kDa protein with an IQ-motif that binds to calmodulin (CaM). PCP4 is abundant in Purkinje cells of the cerebellum, and plays an important role in synaptic plasticity.

Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the SPRED3 gene.

N-acetyltransferase 8 is a protein that in humans is encoded by the NAT8 gene.

Monocarboxylate transporter 9 is a protein that in humans is encoded by the SLC16A9 gene.

Cytochrome c oxidase subunit 5a is a protein that in humans is encoded by the COX5A gene. Cytochrome c oxidase 5A is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000135423 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000044005 - 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.
1 2 "Entrez Gene: Glutaminase 2 (liver, mitochondrial)".
↑ Liu J, Zhang C, Lin M, Zhu W, Liang Y, Hong X, Zhao Y, Young KH, Hu W, Feng Z (May 2014). "Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma". Oncotarget. 5 (9): 2635–47. doi:10.18632/oncotarget.1862. PMC 4058033 . PMID 24797434.
↑ Szeliga M, Bogacińska-Karaś M, Różycka A, Hilgier W, Marquez J, Albrecht J (Mar 2014). "Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells". Tumour Biology. 35 (3): 1855–62. doi:10.1007/s13277-013-1247-4. PMC 3967065 . PMID 24096582.

Suhre K, Shin SY, Petersen AK, Mohney RP, Meredith D, Wägele B, Altmaier E, Deloukas P, Erdmann J, Grundberg E, Hammond CJ, de Angelis MH, Kastenmüller G, Köttgen A, Kronenberg F, Mangino M, Meisinger C, Meitinger T, Mewes HW, Milburn MV, Prehn C, Raffler J, Ried JS, Römisch-Margl W, Samani NJ, Small KS, Wichmann HE, Zhai G, Illig T, Spector TD, Adamski J, Soranzo N, Gieger C (Sep 2011). "Human metabolic individuality in biomedical and pharmaceutical research". Nature. 477 (7362): 54–60. Bibcode:2011Natur.477...54S. doi:10.1038/nature10354. PMC 3832838 . PMID 21886157.
Xiang L, Xie G, Liu C, Zhou J, Chen J, Yu S, Li J, Pang X, Shi H, Liang H (Dec 2013). "Knock-down of glutaminase 2 expression decreases glutathione, NADH, and sensitizes cervical cancer to ionizing radiation". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1833 (12): 2996–3005. doi: 10.1016/j.bbamcr.2013.08.003 . PMID 23954443.
Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z (Apr 2010). "Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function". Proceedings of the National Academy of Sciences of the United States of America. 107 (16): 7455–60. Bibcode:2010PNAS..107.7455H. doi: 10.1073/pnas.1001006107 . PMC 2867677 . PMID 20378837.
Olalla L, Gutiérrez A, Campos JA, Khan ZU, Alonso FJ, Segura JA, Márquez J, Aledo JC (Oct 2002). "Nuclear localization of L-type glutaminase in mammalian brain". The Journal of Biological Chemistry. 277 (41): 38939–44. doi: 10.1074/jbc.C200373200 . PMID 12163477.
Cheng CY, Schache M, Ikram MK, Young TL, Guggenheim JA, Vitart V, MacGregor S, Verhoeven VJ, Barathi VA, Liao J, Hysi PG, Bailey-Wilson JE, St Pourcain B, Kemp JP, McMahon G, Timpson NJ, Evans DM, Montgomery GW, Mishra A, Wang YX, Wang JJ, Rochtchina E, Polasek O, Wright AF, Amin N, van Leeuwen EM, Wilson JF, Pennell CE, van Duijn CM, de Jong PT, Vingerling JR, Zhou X, Chen P, Li R, Tay WT, Zheng Y, Chew M, Burdon KP, Craig JE, Iyengar SK, Igo RP, Lass JH, Chew EY, Haller T, Mihailov E, Metspalu A, Wedenoja J, Simpson CL, Wojciechowski R, Höhn R, Mirshahi A, Zeller T, Pfeiffer N, Lackner KJ, Bettecken T, Meitinger T, Oexle K, Pirastu M, Portas L, Nag A, Williams KM, Yonova-Doing E, Klein R, Klein BE, Hosseini SM, Paterson AD, Makela KM, Lehtimaki T, Kahonen M, Raitakari O, Yoshimura N, Matsuda F, Chen LJ, Pang CP, Yip SP, Yap MK, Meguro A, Mizuki N, Inoko H, Foster PJ, Zhao JH, Vithana E, Tai ES, Fan Q, Xu L, Campbell H, Fleck B, Rudan I, Aung T, Hofman A, Uitterlinden AG, Bencic G, Khor CC, Forward H, Pärssinen O, Mitchell P, Rivadeneira F, Hewitt AW, Williams C, Oostra BA, Teo YY, Hammond CJ, Stambolian D, Mackey DA, Klaver CC, Wong TY, Saw SM, Baird PN (Aug 2013). "Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error". American Journal of Human Genetics. 93 (2): 264–77. doi:10.1016/j.ajhg.2013.06.016. PMC 3772747 . PMID 24144296.
Maeshima H, Ohnuma T, Sakai Y, Shibata N, Baba H, Ihara H, Higashi M, Ohkubo T, Nozawa E, Abe S, Ichikawa A, Nakano Y, Utsumi Y, Suzuki T, Arai H (Oct 2007). "Increased plasma glutamate by antipsychotic medication and its relationship to glutaminase 1 and 2 genotypes in schizophrenia -- Juntendo University Schizophrenia Projects (JUSP)". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 31 (7): 1410–8. doi:10.1016/j.pnpbp.2007.06.009. PMID 17669570. S2CID 22744937.
Kettunen J, Tukiainen T, Sarin AP, Ortega-Alonso A, Tikkanen E, Lyytikäinen LP, Kangas AJ, Soininen P, Würtz P, Silander K, Dick DM, Rose RJ, Savolainen MJ, Viikari J, Kähönen M, Lehtimäki T, Pietiläinen KH, Inouye M, McCarthy MI, Jula A, Eriksson J, Raitakari OT, Salomaa V, Kaprio J, Järvelin MR, Peltonen L, Perola M, Freimer NB, Ala-Korpela M, Palotie A, Ripatti S (Mar 2012). "Genome-wide association study identifies multiple loci influencing human serum metabolite levels". Nature Genetics. 44 (3): 269–76. doi:10.1038/ng.1073. PMC 3605033 . PMID 22286219.
Szeliga M, Zgrzywa A, Obara-Michlewska M, Albrecht J (Nov 2012). "Transfection of a human glioblastoma cell line with liver-type glutaminase (LGA) down-regulates the expression of DNA-repair gene MGMT and sensitizes the cells to alkylating agents". Journal of Neurochemistry. 123 (3): 428–36. doi:10.1111/j.1471-4159.2012.07917.x. PMID 22888977. S2CID 205624752.
Pérez-Gómez C, Campos-Sandoval JA, Alonso FJ, Segura JA, Manzanares E, Ruiz-Sánchez P, González ME, Márquez J, Matés JM (Mar 2005). "Co-expression of glutaminase K and L isoenzymes in human tumour cells". The Biochemical Journal. 386 (Pt 3): 535–42. doi:10.1042/BJ20040996. PMC 1134872 . PMID 15496140.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on human chromosome 12 is a stub. You can help Wikipedia by expanding it.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000135423 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000044005 - 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] 1 2 "Entrez Gene: Glutaminase 2 (liver, mitochondrial)".

[6] Liu J, Zhang C, Lin M, Zhu W, Liang Y, Hong X, Zhao Y, Young KH, Hu W, Feng Z (May 2014). "Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma". Oncotarget. 5 (9): 2635–47. doi:10.18632/oncotarget.1862. PMC 4058033 . PMID 24797434.

[7] Szeliga M, Bogacińska-Karaś M, Różycka A, Hilgier W, Marquez J, Albrecht J (Mar 2014). "Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells". Tumour Biology. 35 (3): 1855–62. doi:10.1007/s13277-013-1247-4. PMC 3967065 . PMID 24096582.

[1]

[2]

[3]

[4]

[5]

[6]

[7]