ID   GLSL_RAT                Reviewed;         602 AA.
AC   P28492; Q3MHS6; Q5FVU0; Q64606;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2005, sequence version 3.
DT   24-JAN-2024, entry version 170.
DE   RecName: Full=Glutaminase liver isoform, mitochondrial;
DE            Short=GLS;
DE            EC=3.5.1.2 {ECO:0000250|UniProtKB:Q571F8};
DE   AltName: Full=L-glutaminase;
DE   AltName: Full=L-glutamine amidohydrolase;
DE   Flags: Precursor;
GN   Name=Gls2; Synonyms=Ga;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE [GENOMIC
RP   DNA] OF 68-94.
RC   TISSUE=Liver;
RX   PubMed=9164856; DOI=10.1042/bj3240193;
RA   Chung-Bok M.I., Vincent N., Jhala U., Watford M.;
RT   "Rat hepatic glutaminase: identification of the full coding sequence and
RT   characterization of a functional promoter.";
RL   Biochem. J. 324:193-200(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
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   [3]
RP   PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 147-602.
RC   TISSUE=Liver;
RX   PubMed=2191954; DOI=10.1016/s0021-9258(18)86993-9;
RA   Smith E.M., Watford M.;
RT   "Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence
RT   similarity to kidney-type glutaminase.";
RL   J. Biol. Chem. 265:10631-10636(1990).
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:0000250|UniProtKB:Q571F8};
CC   -!- SUBUNIT: Homotetramer, dimer of dimers (By similarity). Does not
CC       assemble into higher oligomers (By similarity). Interacts with the PDZ
CC       domain of the syntrophin SNTA1. Interacts with the PDZ domain of
CC       TAX1BP3 (By similarity). {ECO:0000250|UniProtKB:Q571F8,
CC       ECO:0000250|UniProtKB:Q9UI32}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9UI32}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P28492-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P28492-2; Sequence=VSP_015534;
CC   -!- TISSUE SPECIFICITY: Liver specific.
CC   -!- SIMILARITY: Belongs to the glutaminase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH89776.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; J05499; AAC37707.1; -; mRNA.
DR   EMBL; L76175; AAC37708.1; -; Genomic_DNA.
DR   EMBL; BC089776; AAH89776.1; ALT_INIT; mRNA.
DR   EMBL; BC104712; AAI04713.1; -; mRNA.
DR   PIR; A35444; A35444.
DR   RefSeq; NP_001257715.1; NM_001270786.1. [P28492-1]
DR   RefSeq; NP_001257716.1; NM_001270787.1.
DR   RefSeq; NP_620259.2; NM_138904.2. [P28492-2]
DR   AlphaFoldDB; P28492; -.
DR   SMR; P28492; -.
DR   BioGRID; 251392; 2.
DR   IntAct; P28492; 1.
DR   MINT; P28492; -.
DR   STRING; 10116.ENSRNOP00000018737; -.
DR   PhosphoSitePlus; P28492; -.
DR   PaxDb; 10116-ENSRNOP00000018737; -.
DR   GeneID; 192268; -.
DR   KEGG; rno:192268; -.
DR   UCSC; RGD:620359; rat. [P28492-1]
DR   AGR; RGD:620359; -.
DR   CTD; 27165; -.
DR   RGD; 620359; Gls2.
DR   eggNOG; KOG0506; Eukaryota.
DR   HOGENOM; CLU_016439_1_0_1; -.
DR   InParanoid; P28492; -.
DR   OrthoDB; 537490at2759; -.
DR   PhylomeDB; P28492; -.
DR   TreeFam; TF313359; -.
DR   BioCyc; MetaCyc:MONOMER-13074; -.
DR   Reactome; R-RNO-210500; Glutamate Neurotransmitter Release Cycle.
DR   Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-RNO-8964539; Glutamate and glutamine metabolism.
DR   SABIO-RK; P28492; -.
DR   PRO; PR:P28492; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:RGD.
DR   GO; GO:0005739; C:mitochondrion; ISO:RGD.
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:RGD.
DR   GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR   Gene3D; 1.10.238.210; -; 1.
DR   Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR   Gene3D; 3.40.710.10; DD-peptidase/beta-lactamase superfamily; 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   NCBIfam; TIGR03814; Gln_ase; 1.
DR   PANTHER; PTHR12544; GLUTAMINASE; 1.
DR   PANTHER; PTHR12544:SF33; GLUTAMINASE LIVER ISOFORM, MITOCHONDRIAL; 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; Ankyrin repeat; 1.
DR   SUPFAM; SSF56601; beta-lactamase/transpeptidase-like; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 1.
DR   Genevisible; P28492; RN.
PE   2: Evidence at transcript level;
KW   Acetylation; Alternative splicing; ANK repeat; Hydrolase; Mitochondrion;
KW   Reference proteome; 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_0000011627"
FT   REPEAT          518..551
FT                   /note="ANK 1"
FT   REPEAT          552..585
FT                   /note="ANK 2"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          46..67
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..15
FT                   /note="Polar residues"
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:0000250|UniProtKB:Q571F8"
FT   MOD_RES         279
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q571F8"
FT   MOD_RES         284
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q571F8"
FT   MOD_RES         329
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q571F8"
FT   VAR_SEQ         1..67
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9164856"
FT                   /id="VSP_015534"
FT   CONFLICT        76
FT                   /note="L -> V (in Ref. 1; AAC37708)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        336..337
FT                   /note="KG -> NP (in Ref. 1)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   602 AA;  66248 MW;  F4AE3BD30626A00F CRC64;
     MRSMRALQNA LSRAGSHGQR GGWGHPSRGP LLGGGVRYYF GEAAAQGRGT PHSHQPQHSD
     HDASNSGMLP RLGDLLFYTI AEGQERIPIH KFTTALKATG LQTSDPRLQD CMSKMQRMVQ
     ESSSGGLLDR ELFQKCVSSN IVLLTQAFRK KFVIPDFEEF TGHVDRIFED AKELTGGKVA
     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 LGNSHRGISF CQKLVSLFNF HNYDNLRHCA RKLDPRREGG
     EVRNKTVVNL LFAAYSGDVS ALRRFALSAV DMEQKDYDSR TALHVAAAEG HIDVVKFLIE
     ACKVNPFVKD RWGNIPLDDA VQFNHLEVVK LLQDYHDSYM LSETQAEVAA ETLSKENLES
     MV
//