GLSL_MOUSE
ID GLSL_MOUSE Reviewed; 602 AA.
AC Q571F8; B2RUF2; Q3TMJ6;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Glutaminase liver isoform, mitochondrial;
DE Short=GLS;
DE EC=3.5.1.2 {ECO:0000269|PubMed:22228304};
DE AltName: Full=L-glutaminase;
DE AltName: Full=L-glutamine amidohydrolase;
DE Short=LGA {ECO:0000303|PubMed:23935106};
DE Flags: Precursor;
GN Name=Gls2; Synonyms=Kiaa4146;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-253, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-279; LYS-284 AND LYS-329, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [7]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=22228304; DOI=10.1073/pnas.1112495109;
RA Cassago A., Ferreira A.P., Ferreira I.M., Fornezari C., Gomes E.R.,
RA Greene K.S., Pereira H.M., Garratt R.C., Dias S.M., Ambrosio A.L.;
RT "Mitochondrial localization and structure-based phosphate activation
RT mechanism of glutaminase C with implications for cancer metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:1092-1097(2012).
RN [8]
RP SUBUNIT.
RX PubMed=23935106; DOI=10.1074/jbc.m113.501346;
RA Ferreira A.P., Cassago A., Goncalves Kde A., Dias M.M., Adamoski D.,
RA Ascencao C.F., Honorato R.V., de Oliveira J.F., Ferreira I.M.,
RA Fornezari C., Bettini J., Oliveira P.S., Paes Leme A.F., Portugal R.V.,
RA Ambrosio A.L., Dias S.M.;
RT "Active glutaminase C self-assembles into a supratetrameric oligomer that
RT can be disrupted by an allosteric inhibitor.";
RL J. Biol. Chem. 288:28009-28020(2013).
CC -!- FUNCTION: Plays an important role in the regulation of glutamine
CC catabolism. Promotes mitochondrial respiration and increases ATP
CC generation in cells by catalyzing the synthesis of glutamate and alpha-
CC ketoglutarate. Increases cellular anti-oxidant function via NADH and
CC glutathione production. May play a role in preventing tumor
CC proliferation. {ECO:0000250|UniProtKB:Q9UI32}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamine = L-glutamate + NH4(+);
CC Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; EC=3.5.1.2;
CC Evidence={ECO:0000269|PubMed:22228304};
CC -!- ACTIVITY REGULATION: Enzyme activity is not stimulated by phosphate.
CC Phosphate increases kcat, but decreases substrate affinity, resulting
CC in unchanged enzyme activity. {ECO:0000269|PubMed:22228304}.
CC -!- SUBUNIT: Homotetramer, dimer of dimers (By similarity). Does not
CC assemble into higher oligomers (PubMed:23935106). Interacts with the
CC PDZ domain of the syntrophin SNTA1. Interacts with the PDZ domain of
CC TAX1BP3 (By similarity). {ECO:0000250|UniProtKB:Q9UI32,
CC ECO:0000269|PubMed:23935106}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9UI32}.
CC -!- SIMILARITY: Belongs to the glutaminase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD90156.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK220231; BAD90156.1; ALT_INIT; mRNA.
DR EMBL; AK165896; BAE38445.1; -; mRNA.
DR EMBL; BC141115; AAI41116.1; -; mRNA.
DR CCDS; CCDS24263.1; -.
DR RefSeq; NP_001028436.2; NM_001033264.3.
DR AlphaFoldDB; Q571F8; -.
DR SMR; Q571F8; -.
DR BioGRID; 229751; 1.
DR STRING; 10090.ENSMUSP00000047376; -.
DR BindingDB; Q571F8; -.
DR ChEMBL; CHEMBL2176860; -.
DR iPTMnet; Q571F8; -.
DR PhosphoSitePlus; Q571F8; -.
DR SwissPalm; Q571F8; -.
DR EPD; Q571F8; -.
DR jPOST; Q571F8; -.
DR MaxQB; Q571F8; -.
DR PaxDb; Q571F8; -.
DR PeptideAtlas; Q571F8; -.
DR PRIDE; Q571F8; -.
DR ProteomicsDB; 271397; -.
DR Antibodypedia; 28236; 310 antibodies from 30 providers.
DR DNASU; 216456; -.
DR Ensembl; ENSMUST00000044776; ENSMUSP00000047376; ENSMUSG00000044005.
DR GeneID; 216456; -.
DR KEGG; mmu:216456; -.
DR UCSC; uc007hlo.2; mouse.
DR CTD; 27165; -.
DR MGI; MGI:2143539; Gls2.
DR VEuPathDB; HostDB:ENSMUSG00000044005; -.
DR eggNOG; KOG0506; Eukaryota.
DR GeneTree; ENSGT00390000010463; -.
DR HOGENOM; CLU_016439_1_0_1; -.
DR InParanoid; Q571F8; -.
DR OMA; MAGNEFM; -.
DR OrthoDB; 349094at2759; -.
DR PhylomeDB; Q571F8; -.
DR TreeFam; TF313359; -.
DR Reactome; R-MMU-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-8964539; Glutamate and glutamine metabolism.
DR BioGRID-ORCS; 216456; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Gls2; mouse.
DR PRO; PR:Q571F8; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q571F8; protein.
DR Bgee; ENSMUSG00000044005; Expressed in left lobe of liver and 124 other tissues.
DR ExpressionAtlas; Q571F8; baseline and differential.
DR Genevisible; Q571F8; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004359; F:glutaminase activity; IBA:GO_Central.
DR GO; GO:0006537; P:glutamate biosynthetic process; IBA:GO_Central.
DR GO; GO:0006543; P:glutamine catabolic process; IBA:GO_Central.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.40.710.10; -; 1.
DR HAMAP; MF_00313; Glutaminase; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR InterPro; IPR015868; Glutaminase.
DR InterPro; IPR041541; Glutaminase_EF-hand.
DR PANTHER; PTHR12544; PTHR12544; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF17959; EF-hand_14; 1.
DR Pfam; PF04960; Glutaminase; 1.
DR SMART; SM00248; ANK; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
DR TIGRFAMs; TIGR03814; Gln_ase; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW Acetylation; ANK repeat; Hydrolase; Mitochondrion; Reference proteome;
KW Repeat; Transit peptide.
FT TRANSIT 1..14
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 15..602
FT /note="Glutaminase liver isoform, mitochondrial"
FT /id="PRO_0000011626"
FT REPEAT 518..551
FT /note="ANK 1"
FT REPEAT 552..585
FT /note="ANK 2"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 45..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94925"
FT BINDING 268
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94925"
FT BINDING 314
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94925"
FT BINDING 321
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94925"
FT BINDING 347
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94925"
FT BINDING 399
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94925"
FT BINDING 417
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94925"
FT MOD_RES 253
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 279
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 284
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 329
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 312
FT /note="Q -> K (in Ref. 2; BAE38445)"
FT /evidence="ECO:0000305"
FT CONFLICT 584
FT /note="T -> S (in Ref. 3; AAI41116)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 602 AA; 66366 MW; BA07D22ADB082F76 CRC64;
MRSMRALQNA LSRAGSHGRR GGWGHPSRGP LLGRGVRYYL GEAAAQGRGT PHSHQPQHSD
HDASHSGMLP RLGDLLFYTI AEGQERIPIH KFTTALKATG LQTSDPRLQD CMSKMQRMVQ
ESSSGGLLDR ELFQKCVSSN IVLLTQAFRK KFVIPDFEEF TGHVDRIFED AKEPTGGKVA
AYIPHLAKSN PDLWGVSLCT VDGQRHSVGH TKIPFCLQSC VKPLTYAISV STLGTDYVHK
FVGKEPSGLR YNKLSLNEEG IPHNPMVNAG AIVVSSLIKM DCNKAEKFDF VLQYLNKMAG
NEFMGFSNAT FQSEKETGDR NYAIGYYLKE KKCFPKGVDM MAALDLYFQL CSVEVTCESG
SVMAATLANG GICPITGESV LSAEAVRNTL SLMHSCGMYD FSGQFAFHVG LPAKSAVSGA
ILLVVPNVMG MMCLSPPLDK LGNSQRGINF CQKLVSLFNF HNYDNLRHCA RKLDPRREGG
EVRNKTVVNL LFAAYSGDVS ALRRFALSAM DMEQKDYDSR TALHVAAAEG HIEVVKFLIE
ACKVNPFVKD RWGNIPLDDA VQFNHLEVVK LLQDYHDSYL LSETQAEAAA ETLSKENLES
MV
