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]
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. PMC3772747. PMID24144296.
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. PMID17669570. S2CID22744937.
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. PMC3605033. PMID22286219.
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. PMID22888977. S2CID205624752.
