GLS2

glutaminase 2 (liver, mitochondrial)
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4BQM
Identifiers
Aliases	GLS2, GA, GLS, LGA, hLGA
External IDs	MGI: 2143539 HomoloGene: 40861 GeneCards: 27165
Gene ontology Molecular function • hydrolase activity • protein binding • glutaminase activity Cellular component • mitochondrial matrix • mitochondrion • presynapse Biological process • regulation of apoptotic process • glutamate secretion • cellular amino acid metabolic process • transcription initiation from RNA polymerase II promoter • glutamine metabolic process • cellular amino acid biosynthetic process • glutamate biosynthetic process • gene expression • cellular nitrogen compound metabolic process • neurotransmitter secretion • small molecule metabolic process • glutamine catabolic process • reactive oxygen species metabolic process • positive regulation of protein targeting to mitochondrion • synaptic transmission Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	27165	216456
Ensembl	ENSG00000135423	ENSMUSG00000044005
UniProt	Q9UI32	Q571F8
RefSeq (mRNA)	XM_005268797 NM_001280796 NM_001280797 NM_001280798 NM_013267 NM_138566	NM_001033264 NM_001285777 NM_001285779 XM_006513572 XM_011243423
RefSeq (protein)	NP_001267727.1 NP_037399.2	NP_001028436.2
Location (UCSC)	Chr 12: 56.47 – 56.49 Mb	Chr 10: 128.19 – 128.21 Mb
PubMed search
Wikidata

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Glutaminase 2 (liver, mitochondrial) is a protein that in humans is encoded by the GLS2 gene.^[1]

Structure

The GLS2 gene is on the 12th chromosome in humans, with its specific location being 12q13.3. It contains 19 exons.^[1]

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.^[2] Additionally, silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells.^[3]

References

1. "Entrez Gene: Glutaminase 2 (liver, mitochondrial)".
2. 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. PMID 24797434.
3. 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. PMID 24096582.

Further reading

• 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. doi:10.1038/nature10354. 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 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. doi:10.1073/pnas.1001006107. 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. 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.
• 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. 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.
• 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. PMID 15496140.

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