GLSK_HUMAN
ID GLSK_HUMAN Reviewed; 669 AA.
AC O94925; Q9UL05; Q9UL06; Q9UL07; Q9UN40;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Glutaminase kidney isoform, mitochondrial;
DE Short=GLS;
DE EC=3.5.1.2 {ECO:0000269|PubMed:22049910, ECO:0000269|PubMed:22538822, ECO:0000269|PubMed:24451979, ECO:0000269|PubMed:26988803, ECO:0000269|PubMed:28526749, ECO:0000269|PubMed:29317493};
DE AltName: Full=K-glutaminase;
DE AltName: Full=L-glutamine amidohydrolase;
DE Contains:
DE RecName: Full=Glutaminase kidney isoform, mitochondrial 68 kDa chain {ECO:0000250|UniProtKB:P13264};
DE Contains:
DE RecName: Full=Glutaminase kidney isoform, mitochondrial 65 kDa chain {ECO:0000250|UniProtKB:P13264};
DE Flags: Precursor;
GN Name=GLS; Synonyms=GLS1, KIAA0838;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, ALTERNATIVE
RP SPLICING, AND FUNCTION.
RC TISSUE=Placenta;
RX PubMed=11015561; DOI=10.1152/physiolgenomics.1999.1.2.51;
RA Elgadi K.M., Meguid R.A., Qian M., Souba W.W., Abcouwer S.F.;
RT "Cloning and analysis of unique human glutaminase isoforms generated by
RT tissue-specific alternative splicing.";
RL Physiol. Genomics 1:51-62(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Chavez R.A., Wang C., Cong R., Hawkinson J.E., Forsayeth J.R.;
RT "Identification and expression of human renal and hepatic glutaminase
RT isoforms.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10719215; DOI=10.1016/s0169-328x(99)00331-9;
RA Holcomb T., Taylor L., Trohkimoinen J., Curthoys N.P.;
RT "Isolation, characterization and expression of a human brain mitochondrial
RT glutaminase cDNA.";
RL Brain Res. Mol. Brain Res. 76:56-63(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 225-466.
RC TISSUE=Colon carcinoma;
RA Turner A., McGivan J.D.;
RT "Adenoma and carcinoma cell lines derived from colorectal tumours express
RT different isoforms of glutaminase.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [8]
RP INTERACTION WITH ATCAY, AND SUBCELLULAR LOCATION.
RX PubMed=16899818; DOI=10.1242/jcs.03061;
RA Buschdorf J.P., Li Chew L., Zhang B., Cao Q., Liang F.Y., Liou Y.C.,
RA Zhou Y.T., Low B.C.;
RT "Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to
RT neurite terminals and reduces glutamate levels.";
RL J. Cell Sci. 119:3337-3350(2006).
RN [9]
RP TISSUE SPECIFICITY (ISOFORM 1 AND ISOFORM 3).
RX PubMed=17940881; DOI=10.1007/s11064-007-9507-6;
RA Szeliga M., Matyja E., Obara M., Grajkowska W., Czernicki T., Albrecht J.;
RT "Relative expression of mRNAs coding for glutaminase isoforms in CNS
RT tissues and CNS tumors.";
RL Neurochem. Res. 33:808-813(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-311, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP SUBCELLULAR LOCATION.
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP FUNCTION, INVOLVEMENT IN DEE71, AND VARIANTS DEE71 81-GLN--LEU-669 DEL AND
RP LYS-272.
RX PubMed=30575854; DOI=10.1001/jamaneurol.2018.2941;
RA Rumping L., Buettner B., Maier O., Rehmann H., Lequin M., Schlump J.U.,
RA Schmitt B., Schiebergen-Bronkhorst B., Prinsen H.C.M.T., Losa M.,
RA Fingerhut R., Lemke J.R., Zwartkruis F.J.T., Houwen R.H.J., Jans J.J.M.,
RA Verhoeven-Duif N.M., van Hasselt P.M., Jamra R.;
RT "Identification of a loss-of-function mutation in the context of
RT glutaminase deficiency and neonatal epileptic encephalopathy.";
RL JAMA Neurol. 76:342-350(2019).
RN [16]
RP FUNCTION, INVOLVEMENT IN CASGID, VARIANT CASGID CYS-482, AND
RP CHARACTERIZATION OF VARIANT CASGID CYS-482.
RX PubMed=30239721; DOI=10.1093/hmg/ddy330;
RA Rumping L., Tessadori F., Pouwels P.J.W., Vringer E., Wijnen J.P.,
RA Bhogal A.A., Savelberg S.M.C., Duran K.J., Bakkers M.J.G., Ramos R.J.J.,
RA Schellekens P.A.W., Kroes H.Y., Klomp D.W.J., Black G.C.M., Taylor R.L.,
RA Bakkers J.P.W., Prinsen H.C.M.T., van der Knaap M.S., Dansen T.B.,
RA Rehmann H., Zwartkruis F.J.T., Houwen R.H.J., van Haaften G.,
RA Verhoeven-Duif N.M., Jans J.J.M., van Hasselt P.M.;
RT "GLS hyperactivity causes glutamate excess, infantile cataract and profound
RT developmental delay.";
RL Hum. Mol. Genet. 28:96-104(2019).
RN [17]
RP FUNCTION, INVOLVEMENT IN GDPAG, VARIANT GDPAG LEU-313, AND CHARACTERIZATION
RP OF VARIANT GDPAG LEU-313.
RX PubMed=30970188; DOI=10.1056/nejmoa1806627;
RA van Kuilenburg A.B.P., Tarailo-Graovac M., Richmond P.A.,
RA Droegemoeller B.I., Pouladi M.A., Leen R., Brand-Arzamendi K.,
RA Dobritzsch D., Dolzhenko E., Eberle M.A., Hayward B., Jones M.J.,
RA Karbassi F., Kobor M.S., Koster J., Kumari D., Li M., MacIsaac J.,
RA McDonald C., Meijer J., Nguyen C., Rajan-Babu I.S., Scherer S.W., Sim B.,
RA Trost B., Tseng L.A., Turkenburg M., van Vugt J.J.F.A., Veldink J.H.,
RA Walia J.S., Wang Y., van Weeghel M., Wright G.E.B., Xu X., Yuen R.K.C.,
RA Zhang J., Ross C.J., Wasserman W.W., Geraghty M.T., Santra S.,
RA Wanders R.J.A., Wen X.Y., Waterham H.R., Usdin K., van Karnebeek C.D.M.;
RT "Glutaminase deficiency caused by short tandem repeat expansion in GLS.";
RL N. Engl. J. Med. 380:1433-1441(2019).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 71-550 (ISOFORM 3) IN COMPLEXES
RP WITH GLUTAMATE AND SYNTHETIC INHIBITOR BPTES, PROTEIN SEQUENCE OF
RP N-TERMINUS, CATALYTIC ACTIVITY, MUTAGENESIS OF PHE-318; PHE-322 AND
RP TYR-394, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, IDENTIFICATION
RP BY MASS SPECTROMETRY, AND SUBUNIT.
RX PubMed=22049910; DOI=10.1021/bi201613d;
RA DeLaBarre B., Gross S., Fang C., Gao Y., Jha A., Jiang F., Song J.J.,
RA Wei W., Hurov J.B.;
RT "Full-length human glutaminase in complex with an allosteric inhibitor.";
RL Biochemistry 50:10764-10770(2011).
RN [19] {ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3VOY, ECO:0007744|PDB:3VOZ, ECO:0007744|PDB:3VP0, ECO:0007744|PDB:3VP1, ECO:0007744|PDB:3VP2, ECO:0007744|PDB:3VP3, ECO:0007744|PDB:3VP4}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 221-533 IN COMPLEXES WITH
RP GLUTAMATE AND GLUTAMINE, CATALYTIC ACTIVITY, SUBUNIT, INTERACTION WITH RAF1
RP AND MAP2K2, AND MUTAGENESIS OF LEU-321; LEU-323 AND TYR-394.
RX PubMed=22538822; DOI=10.1073/pnas.1116573109;
RA Thangavelu K., Pan C.Q., Karlberg T., Balaji G., Uttamchandani M.,
RA Suresh V., Schuler H., Low B.C., Sivaraman J.;
RT "Structural basis for the allosteric inhibitory mechanism of human kidney-
RT type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in
RT cancer cell metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7705-7710(2012).
RN [20] {ECO:0007744|PDB:4O7D}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 221-531 IN COMPLEX WITH SUBSTRATE
RP ANALOG, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP TYR-249; SER-286; LYS-289 AND TYR-466.
RX PubMed=24451979; DOI=10.1038/srep03827;
RA Thangavelu K., Chong Q.Y., Low B.C., Sivaraman J.;
RT "Structural basis for the active site inhibition mechanism of human kidney-
RT type glutaminase (KGA).";
RL Sci. Rep. 4:3827-3827(2014).
RN [21] {ECO:0007744|PDB:5FI2, ECO:0007744|PDB:5FI6, ECO:0007744|PDB:5FI7, ECO:0007744|PDB:5I94}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 72-550, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=26988803; DOI=10.1016/j.bmc.2016.03.009;
RA McDermott L.A., Iyer P., Vernetti L., Rimer S., Sun J., Boby M., Yang T.,
RA Fioravanti M., O'Neill J., Wang L., Drakes D., Katt W., Huang Q.,
RA Cerione R.;
RT "Design and evaluation of novel glutaminase inhibitors.";
RL Bioorg. Med. Chem. 24:1819-1839(2016).
RN [22] {ECO:0007744|PDB:5U0I, ECO:0007744|PDB:5U0J, ECO:0007744|PDB:5UQE}
RP X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 551-669, CATALYTIC ACTIVITY,
RP DOMAIN, AND SUBUNIT.
RX PubMed=28526749; DOI=10.1074/jbc.m117.787291;
RA Pasquali C.C., Islam Z., Adamoski D., Ferreira I.M., Righeto R.D.,
RA Bettini J., Portugal R.V., Yue W.W., Gonzalez A., Dias S.M.G.,
RA Ambrosio A.L.B.;
RT "The origin and evolution of human glutaminases and their atypical C-
RT terminal ankyrin repeats.";
RL J. Biol. Chem. 292:11572-11585(2017).
RN [23] {ECO:0007744|PDB:5WJ6}
RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 72-550, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=29317493; DOI=10.1074/jbc.m117.810101;
RA Huang Q., Stalnecker C., Zhang C., McDermott L.A., Iyer P., O'Neill J.,
RA Reimer S., Cerione R.A., Katt W.P.;
RT "Characterization of the interactions of potent allosteric inhibitors with
RT glutaminase C, a key enzyme in cancer cell glutamine metabolism.";
RL J. Biol. Chem. 293:3535-3545(2018).
CC -!- FUNCTION: Catalyzes the first reaction in the primary pathway for the
CC renal catabolism of glutamine. Plays a role in maintaining acid-base
CC homeostasis. Regulates the levels of the neurotransmitter glutamate,
CC the main excitatory neurotransmitter in the brain (PubMed:30575854,
CC PubMed:30239721, PubMed:30970188). {ECO:0000269|PubMed:30239721,
CC ECO:0000269|PubMed:30575854, ECO:0000269|PubMed:30970188}.
CC -!- FUNCTION: [Isoform 2]: Lacks catalytic activity.
CC {ECO:0000269|PubMed:11015561}.
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:22049910, ECO:0000269|PubMed:22538822,
CC ECO:0000269|PubMed:24451979, ECO:0000269|PubMed:26988803,
CC ECO:0000269|PubMed:28526749, ECO:0000269|PubMed:29317493};
CC -!- ACTIVITY REGULATION: Isoform 1 and isoform 3 are activated by
CC phosphate. Inhibited by BPTES. BPTES binds between subunits and favors
CC dissociation of the tetramer into dimers (PubMed:22049910). Inhibited
CC by 6-diazo-5-oxo-L-norleucine (DON) (PubMed:24451979). Enzyme activity
CC is stimulated by phosphorylation (PubMed:22538822).
CC {ECO:0000269|PubMed:22049910, ECO:0000269|PubMed:22538822,
CC ECO:0000269|PubMed:24451979}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.9 mM for glutamine (isoform 1) {ECO:0000269|PubMed:22049910};
CC KM=1.4 mM for glutamine (isoform 3) {ECO:0000269|PubMed:22049910};
CC -!- SUBUNIT: Homotetramer, dimer of dimers (PubMed:22538822,
CC PubMed:26988803, PubMed:28526749, PubMed:29317493). The tetramers can
CC assemble into rod-like oligomers (in vitro), but the physiological
CC significance of this is not clear (By similarity). Interacts with RAF1
CC and MAP2K2 (PubMed:22538822). Interacts with ATCAY; the interaction is
CC direct and may control GLS localization, negatively regulating its
CC activity. {ECO:0000250|UniProtKB:D3Z7P3, ECO:0000269|PubMed:16899818,
CC ECO:0000269|PubMed:22049910, ECO:0000269|PubMed:22538822,
CC ECO:0000269|PubMed:26988803, ECO:0000269|PubMed:28526749,
CC ECO:0000269|PubMed:29317493}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion
CC {ECO:0000250|UniProtKB:P13264}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:22228304}. Note=The 74-kDa cytosolic precursor is
CC translocated into the mitochondria and processed via a 72-kDa
CC intermediate to yield the mature 68- and 65-kDa subunits.
CC {ECO:0000250|UniProtKB:P13264}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion
CC {ECO:0000269|PubMed:22228304}.
CC -!- SUBCELLULAR LOCATION: [Glutaminase kidney isoform, mitochondrial 68 kDa
CC chain]: Mitochondrion matrix {ECO:0000250|UniProtKB:P13264}.
CC Note=Produced by the proteolytic processing of the 74-kDa cytosolic
CC precursor. {ECO:0000250|UniProtKB:P13264}.
CC -!- SUBCELLULAR LOCATION: [Glutaminase kidney isoform, mitochondrial 65 kDa
CC chain]: Mitochondrion matrix {ECO:0000250|UniProtKB:P13264}.
CC Note=Produced by the proteolytic processing of the 74-kDa cytosolic
CC precursor. {ECO:0000250|UniProtKB:P13264}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=KGA {ECO:0000303|PubMed:22228304,
CC ECO:0000303|PubMed:22538822, ECO:0000303|PubMed:28526749};
CC IsoId=O94925-1; Sequence=Displayed;
CC Name=2; Synonyms=GAM;
CC IsoId=O94925-2; Sequence=VSP_001765, VSP_001766;
CC Name=3; Synonyms=Glutaminase C {ECO:0000303|PubMed:22228304}, GAC
CC {ECO:0000303|PubMed:22228304, ECO:0000303|PubMed:28526749};
CC IsoId=O94925-3; Sequence=VSP_001767;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are detected in brain
CC cortex. Isoform 3 is highly expressed in astrocytoma, ganglioglioma and
CC ependymoma. Isoform 1 is highly expressed in brain and kidney, but not
CC detected in liver. Isoform 3 is highly expressed in heart and pancreas,
CC detected at lower levels in placenta, lung, pancreas and kidney, but is
CC not detected in liver. Isoform 2 is expressed in cardiac and skeletal
CC muscle. {ECO:0000269|PubMed:11015561}.
CC -!- DOMAIN: The C-terminal ANK repeats prevent the assembly of the supra-
CC tetrameric filaments. {ECO:0000269|PubMed:28526749}.
CC -!- DOMAIN: A highly mobile activation loop at the dimer-dimer interface is
CC important for enzyme activity. {ECO:0000250|UniProtKB:D3Z7P3}.
CC -!- PTM: Synthesized as a 74-kDa cytosolic precursor which is
CC proteolytically processed by the mitochondrial-processing peptidase
CC (MPP) via a 72-kDa intermediate to yield the mature mitochondrial
CC 68- and 65-kDa subunits. {ECO:0000250|UniProtKB:P13264}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 71 (DEE71)
CC [MIM:618328]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE71 is an autosomal recessive form with onset at
CC birth. Death occurs in first weeks of life.
CC {ECO:0000269|PubMed:30575854}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Infantile cataract, skin abnormalities, glutamate excess, and
CC impaired intellectual development (CASGID) [MIM:618339]: An autosomal
CC dominant disease characterized by infantile-onset cataract, erythematic
CC subcutaneous nodules, profound developmental delay, self-injurious
CC behavior, and intracerebral glutamate excess. Histopathologic analysis
CC of skin lesions show deep perivascular and periglandular
CC lymphohistiocytic infiltrates and pronounced leukocytoclasia at the
CC surface of the dermis, focal vacuolar alterations, hyperkeratosis, and
CC parakeratosis of the epidermis. {ECO:0000269|PubMed:30239721}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Global developmental delay, progressive ataxia, and elevated
CC glutamine (GDPAG) [MIM:618412]: An autosomal recessive disease
CC characterized by early-onset delay in motor skills, delayed speech,
CC progressive ataxia, and neurologic deterioration. Plasma glutamine is
CC persistently elevated by a factor of 2.5 despite normal plasma ammonia
CC levels. {ECO:0000269|PubMed:30970188}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glutaminase family. {ECO:0000305}.
CC -!- CAUTION: Isoform 3 is predicted to be expressed at very low levels due
CC to a premature stop codon in the mRNA, leading to nonsense-mediated
CC mRNA decay. Contrary to expectations, it has been shown to be well
CC expressed, and the encoded protein is detected in mitochondria
CC (PubMed:11015561, PubMed:17940881, PubMed:22228304).
CC {ECO:0000269|PubMed:11015561, ECO:0000269|PubMed:17940881,
CC ECO:0000269|PubMed:22228304, ECO:0000305|PubMed:14759258}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74861.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF158555; AAD47056.1; -; mRNA.
DR EMBL; AF097492; AAF00088.1; -; mRNA.
DR EMBL; AF097493; AAF00089.1; -; mRNA.
DR EMBL; AF097495; AAF00090.1; -; mRNA.
DR EMBL; AB020645; BAA74861.2; ALT_INIT; mRNA.
DR EMBL; AF223943; AAF33825.1; -; mRNA.
DR EMBL; AF327434; AAG47842.1; -; mRNA.
DR EMBL; BC038507; AAH38507.2; -; mRNA.
DR EMBL; AF279697; AAG17700.1; -; mRNA.
DR CCDS; CCDS2308.1; -. [O94925-1]
DR CCDS; CCDS58744.1; -. [O94925-3]
DR RefSeq; NP_001243239.1; NM_001256310.1. [O94925-3]
DR RefSeq; NP_055720.3; NM_014905.4. [O94925-1]
DR PDB; 3CZD; X-ray; 2.40 A; A=221-533.
DR PDB; 3UNW; X-ray; 2.56 A; A/B/C/D=71-597.
DR PDB; 3UO9; X-ray; 2.30 A; A/B/C/D=71-597.
DR PDB; 3VOY; X-ray; 2.20 A; A=221-533.
DR PDB; 3VOZ; X-ray; 2.40 A; A=221-533.
DR PDB; 3VP0; X-ray; 2.40 A; A=221-533.
DR PDB; 3VP1; X-ray; 2.30 A; A=221-533.
DR PDB; 3VP2; X-ray; 2.70 A; A=221-533.
DR PDB; 3VP3; X-ray; 2.70 A; A=221-533.
DR PDB; 3VP4; X-ray; 2.45 A; A=221-533.
DR PDB; 4O7D; X-ray; 2.30 A; A=221-531.
DR PDB; 5D3O; X-ray; 2.79 A; A/B=72-597.
DR PDB; 5FI2; X-ray; 2.50 A; A/B/C/D=72-597.
DR PDB; 5FI6; X-ray; 2.52 A; A/B/C/D=72-597.
DR PDB; 5FI7; X-ray; 2.50 A; A/B/C/D=72-597.
DR PDB; 5HL1; X-ray; 2.40 A; A/B/C/D=72-597.
DR PDB; 5I94; X-ray; 2.98 A; A/B/C/D=72-597.
DR PDB; 5JYO; X-ray; 2.10 A; A/B/C/D/E/F/G/H=221-533.
DR PDB; 5JYP; X-ray; 2.74 A; A=221-533.
DR PDB; 5U0I; X-ray; 1.42 A; A/B=551-669.
DR PDB; 5U0J; X-ray; 1.72 A; A/B/C/D=551-669.
DR PDB; 5UQE; X-ray; 3.60 A; A/B/C/D/F=137-656.
DR PDB; 5WJ6; X-ray; 2.44 A; A/B/C/D=72-550.
DR PDB; 6LOX; X-ray; 3.20 A; A/B/C/D=71-600.
DR PDB; 6UJG; X-ray; 3.00 A; A/B/C/D/E/F/G/H=72-550.
DR PDB; 6UJM; X-ray; 2.50 A; A/B/C/D=72-550.
DR PDB; 6UK6; X-ray; 2.90 A; A/B/C/D=72-550.
DR PDB; 6UKB; X-ray; 3.00 A; A/B/C/D=72-550.
DR PDB; 6UL9; X-ray; 2.50 A; A/B/C/D=72-550.
DR PDB; 6ULA; X-ray; 2.95 A; A/B/C/D/E/F/G/H=72-550.
DR PDB; 6ULJ; X-ray; 2.69 A; A/B/C/D=72-550.
DR PDB; 6UMC; X-ray; 2.75 A; A/B/C/D=72-550.
DR PDB; 6UMD; X-ray; 2.70 A; A/B/C/D=72-550.
DR PDB; 6UME; X-ray; 2.90 A; A/B/C/D=72-550.
DR PDB; 6UMF; X-ray; 2.68 A; A/B/C/D=72-550.
DR PDB; 7SBM; X-ray; 2.80 A; A/B/C/D=72-550.
DR PDB; 7SBN; X-ray; 2.14 A; A/B/C/D=72-550.
DR PDBsum; 3CZD; -.
DR PDBsum; 3UNW; -.
DR PDBsum; 3UO9; -.
DR PDBsum; 3VOY; -.
DR PDBsum; 3VOZ; -.
DR PDBsum; 3VP0; -.
DR PDBsum; 3VP1; -.
DR PDBsum; 3VP2; -.
DR PDBsum; 3VP3; -.
DR PDBsum; 3VP4; -.
DR PDBsum; 4O7D; -.
DR PDBsum; 5D3O; -.
DR PDBsum; 5FI2; -.
DR PDBsum; 5FI6; -.
DR PDBsum; 5FI7; -.
DR PDBsum; 5HL1; -.
DR PDBsum; 5I94; -.
DR PDBsum; 5JYO; -.
DR PDBsum; 5JYP; -.
DR PDBsum; 5U0I; -.
DR PDBsum; 5U0J; -.
DR PDBsum; 5UQE; -.
DR PDBsum; 5WJ6; -.
DR PDBsum; 6LOX; -.
DR PDBsum; 6UJG; -.
DR PDBsum; 6UJM; -.
DR PDBsum; 6UK6; -.
DR PDBsum; 6UKB; -.
DR PDBsum; 6UL9; -.
DR PDBsum; 6ULA; -.
DR PDBsum; 6ULJ; -.
DR PDBsum; 6UMC; -.
DR PDBsum; 6UMD; -.
DR PDBsum; 6UME; -.
DR PDBsum; 6UMF; -.
DR PDBsum; 7SBM; -.
DR PDBsum; 7SBN; -.
DR AlphaFoldDB; O94925; -.
DR SMR; O94925; -.
DR BioGRID; 109006; 193.
DR DIP; DIP-50591N; -.
DR IntAct; O94925; 56.
DR MINT; O94925; -.
DR STRING; 9606.ENSP00000317379; -.
DR BindingDB; O94925; -.
DR ChEMBL; CHEMBL2146302; -.
DR DrugBank; DB13155; Esculin.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB00130; L-Glutamine.
DR GuidetoPHARMACOLOGY; 2891; -.
DR GlyConnect; 2043; 3 N-Linked glycans (1 site).
DR GlyGen; O94925; 2 sites, 6 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; O94925; -.
DR PhosphoSitePlus; O94925; -.
DR SwissPalm; O94925; -.
DR BioMuta; GLS; -.
DR CPTAC; CPTAC-516; -.
DR CPTAC; CPTAC-517; -.
DR EPD; O94925; -.
DR jPOST; O94925; -.
DR MassIVE; O94925; -.
DR MaxQB; O94925; -.
DR PaxDb; O94925; -.
DR PeptideAtlas; O94925; -.
DR PRIDE; O94925; -.
DR ProteomicsDB; 50560; -. [O94925-1]
DR ProteomicsDB; 50561; -. [O94925-2]
DR ProteomicsDB; 50562; -. [O94925-3]
DR TopDownProteomics; O94925-2; -. [O94925-2]
DR Antibodypedia; 34041; 460 antibodies from 33 providers.
DR DNASU; 2744; -.
DR Ensembl; ENST00000320717.8; ENSP00000317379.3; ENSG00000115419.13. [O94925-1]
DR Ensembl; ENST00000338435.8; ENSP00000340689.4; ENSG00000115419.13. [O94925-3]
DR GeneID; 2744; -.
DR KEGG; hsa:2744; -.
DR MANE-Select; ENST00000320717.8; ENSP00000317379.3; NM_014905.5; NP_055720.3.
DR UCSC; uc002use.4; human. [O94925-1]
DR CTD; 2744; -.
DR DisGeNET; 2744; -.
DR GeneCards; GLS; -.
DR HGNC; HGNC:4331; GLS.
DR HPA; ENSG00000115419; Tissue enhanced (kidney).
DR MalaCards; GLS; -.
DR MIM; 138280; gene.
DR MIM; 618328; phenotype.
DR MIM; 618339; phenotype.
DR MIM; 618412; phenotype.
DR neXtProt; NX_O94925; -.
DR OpenTargets; ENSG00000115419; -.
DR Orphanet; 557064; Neonatal epileptic encephalopathy due to glutaminase deficiency.
DR Orphanet; 557056; Spastic ataxia-dysarthria due to glutaminase deficiency.
DR PharmGKB; PA28734; -.
DR VEuPathDB; HostDB:ENSG00000115419; -.
DR eggNOG; KOG0506; Eukaryota.
DR GeneTree; ENSGT00390000010463; -.
DR HOGENOM; CLU_016439_1_0_1; -.
DR InParanoid; O94925; -.
DR OMA; QCCSMEA; -.
DR OrthoDB; 349094at2759; -.
DR PhylomeDB; O94925; -.
DR TreeFam; TF313359; -.
DR BRENDA; 3.5.1.2; 2681.
DR PathwayCommons; O94925; -.
DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-8964539; Glutamate and glutamine metabolism.
DR SABIO-RK; O94925; -.
DR SignaLink; O94925; -.
DR SIGNOR; O94925; -.
DR BioGRID-ORCS; 2744; 36 hits in 1075 CRISPR screens.
DR ChiTaRS; GLS; human.
DR EvolutionaryTrace; O94925; -.
DR GenomeRNAi; 2744; -.
DR Pharos; O94925; Tchem.
DR PRO; PR:O94925; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O94925; protein.
DR Bgee; ENSG00000115419; Expressed in middle temporal gyrus and 201 other tissues.
DR ExpressionAtlas; O94925; baseline and differential.
DR Genevisible; O94925; HS.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004359; F:glutaminase activity; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0006537; P:glutamate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0090461; P:glutamate homeostasis; IMP:UniProtKB.
DR GO; GO:0006543; P:glutamine catabolic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; IEA:Ensembl.
DR GO; GO:0001967; P:suckling behavior; IEA:Ensembl.
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 3D-structure; Acetylation; Alternative splicing; ANK repeat; Cataract;
KW Cytoplasm; Direct protein sequencing; Disease variant; Epilepsy; Hydrolase;
KW Mitochondrion; Phosphoprotein; Reference proteome; Repeat; Transit peptide.
FT TRANSIT 1..54
FT /note="Mitochondrion"
FT /evidence="ECO:0000305"
FT CHAIN 55..669
FT /note="Glutaminase kidney isoform, mitochondrial 68 kDa
FT chain"
FT /id="PRO_0000011622"
FT CHAIN 73..669
FT /note="Glutaminase kidney isoform, mitochondrial 65 kDa
FT chain"
FT /evidence="ECO:0000250|UniProtKB:P13264"
FT /id="PRO_0000447412"
FT REPEAT 585..614
FT /note="ANK 1"
FT REPEAT 619..648
FT /note="ANK 2"
FT REGION 68..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..322
FT /note="Highly mobile activation loop"
FT /evidence="ECO:0000250|UniProtKB:D3Z7P3"
FT REGION 647..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 286
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22049910,
FT ECO:0000269|PubMed:22538822, ECO:0000305|PubMed:24451979,
FT ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3UNW,
FT ECO:0007744|PDB:3VP0, ECO:0007744|PDB:3VP1"
FT BINDING 335
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22049910,
FT ECO:0000269|PubMed:22538822, ECO:0000305|PubMed:24451979,
FT ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3UNW,
FT ECO:0007744|PDB:3VP0, ECO:0007744|PDB:3VP1"
FT BINDING 381
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22049910,
FT ECO:0000269|PubMed:22538822, ECO:0000305|PubMed:24451979,
FT ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3UNW,
FT ECO:0007744|PDB:3VP0, ECO:0007744|PDB:3VP1"
FT BINDING 388
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22049910,
FT ECO:0000269|PubMed:22538822, ECO:0000305|PubMed:24451979,
FT ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3UNW,
FT ECO:0007744|PDB:3VP1"
FT BINDING 414
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22049910,
FT ECO:0000269|PubMed:22538822, ECO:0000305|PubMed:24451979,
FT ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3UNW,
FT ECO:0007744|PDB:3VP0, ECO:0007744|PDB:3VP1"
FT BINDING 466
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22049910,
FT ECO:0000269|PubMed:22538822, ECO:0000305|PubMed:24451979,
FT ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3UNW,
FT ECO:0007744|PDB:3VP0, ECO:0007744|PDB:3VP1"
FT BINDING 484
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22049910,
FT ECO:0000269|PubMed:22538822, ECO:0000305|PubMed:24451979,
FT ECO:0007744|PDB:3CZD, ECO:0007744|PDB:3UNW,
FT ECO:0007744|PDB:3VP0, ECO:0007744|PDB:3VP1"
FT SITE 72..73
FT /note="Cleavage; by MPP"
FT /evidence="ECO:0000250|UniProtKB:P13264"
FT MOD_RES 130
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:D3Z7P3"
FT MOD_RES 164
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:D3Z7P3"
FT MOD_RES 311
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 652
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13264"
FT VAR_SEQ 162..169
FT /note="ALKSTGLR -> VSFYIFLS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001765"
FT VAR_SEQ 170..669
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001766"
FT VAR_SEQ 551..669
FT /note="VKSVINLLFAAYTGDVSALRRFALSAMDMEQRDYDSRTALHVAAAEGHVEVV
FT KFLLEACKVNPFPKDRWNNTPMDEALHFGHHDVFKILQEYQVQYTPQGDSDNGKENQTV
FT HKNLDGLL -> HSFGPLDYESLQQELALKETVWKKVSPESNEDISTTVVYRMESLGEK
FT S (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11015561"
FT /id="VSP_001767"
FT VARIANT 81..669
FT /note="Missing (in DEE71)"
FT /evidence="ECO:0000269|PubMed:30575854"
FT /id="VAR_081971"
FT VARIANT 254
FT /note="A -> P (in dbSNP:rs16833035)"
FT /id="VAR_049188"
FT VARIANT 272
FT /note="R -> K (in DEE71; dbSNP:rs1558972120)"
FT /evidence="ECO:0000269|PubMed:30575854"
FT /id="VAR_081972"
FT VARIANT 313
FT /note="P -> L (in GDPAG; loss of enzyme activity;
FT dbSNP:rs1558973667)"
FT /evidence="ECO:0000269|PubMed:30970188"
FT /id="VAR_081973"
FT VARIANT 482
FT /note="S -> C (in CASGID; increased enzyme activity;
FT dbSNP:rs1558986214)"
FT /evidence="ECO:0000269|PubMed:30239721"
FT /id="VAR_081974"
FT MUTAGEN 249
FT /note="Y->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:24451979"
FT MUTAGEN 286
FT /note="S->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:24451979"
FT MUTAGEN 289
FT /note="K->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:24451979"
FT MUTAGEN 318
FT /note="F->Y: No effect on catalytic activity. Loss of
FT inhibition by BPTES; when associated with S-322."
FT /evidence="ECO:0000269|PubMed:22049910"
FT MUTAGEN 321
FT /note="L->A: Decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:22538822"
FT MUTAGEN 322
FT /note="F->S: No effect on catalytic activity. Loss of
FT inhibition by BPTES; when associated with Y-318."
FT /evidence="ECO:0000269|PubMed:22049910"
FT MUTAGEN 323
FT /note="L->A: Decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:22538822"
FT MUTAGEN 394
FT /note="Y->A: Decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:22538822"
FT MUTAGEN 394
FT /note="Y->L: No effect on catalytic activity. Loss of
FT inhibition by BPTES."
FT /evidence="ECO:0000269|PubMed:22049910"
FT MUTAGEN 466
FT /note="Y->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:24451979"
FT CONFLICT 6
FT /note="G -> S (in Ref. 1; AAF00090)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="E -> D (in Ref. 1; AAF00090)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="F -> L (in Ref. 4; AAG47842)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="V -> A (in Ref. 1; AAD47056)"
FT /evidence="ECO:0000305"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:3UO9"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:3UO9"
FT HELIX 156..165
FT /evidence="ECO:0007829|PDB:3UO9"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:3UO9"
FT HELIX 176..188
FT /evidence="ECO:0007829|PDB:3UO9"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:6UK6"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:5WJ6"
FT HELIX 197..204
FT /evidence="ECO:0007829|PDB:3UO9"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:3UO9"
FT HELIX 208..216
FT /evidence="ECO:0007829|PDB:3UO9"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:3UO9"
FT HELIX 224..239
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 272..277
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 288..300
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 302..305
FT /evidence="ECO:0007829|PDB:5JYO"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:3VOY"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:5WJ6"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:6UMF"
FT HELIX 335..344
FT /evidence="ECO:0007829|PDB:5JYO"
FT TURN 345..348
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 351..365
FT /evidence="ECO:0007829|PDB:5JYO"
FT TURN 366..368
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 375..384
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 386..397
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 407..418
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 420..422
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 424..435
FT /evidence="ECO:0007829|PDB:5JYO"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:5JYO"
FT TURN 441..443
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 450..463
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 469..475
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 486..492
FT /evidence="ECO:0007829|PDB:5JYO"
FT TURN 493..495
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 496..501
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:5JYO"
FT HELIX 512..525
FT /evidence="ECO:0007829|PDB:5JYO"
FT STRAND 533..535
FT /evidence="ECO:0007829|PDB:6LOX"
FT HELIX 554..563
FT /evidence="ECO:0007829|PDB:5U0I"
FT HELIX 566..574
FT /evidence="ECO:0007829|PDB:5U0I"
FT HELIX 589..596
FT /evidence="ECO:0007829|PDB:5U0I"
FT HELIX 599..607
FT /evidence="ECO:0007829|PDB:5U0I"
FT HELIX 623..629
FT /evidence="ECO:0007829|PDB:5U0I"
FT HELIX 633..640
FT /evidence="ECO:0007829|PDB:5U0I"
SQ SEQUENCE 669 AA; 73461 MW; 4E5E63505E84E0B7 CRC64;
MMRLRGSGML RDLLLRSPAG VSATLRRAQP LVTLCRRPRG GGRPAAGPAA AARLHPWWGG
GGWPAEPLAR GLSSSPSEIL QELGKGSTHP QPGVSPPAAP AAPGPKDGPG ETDAFGNSEG
KELVASGENK IKQGLLPSLE DLLFYTIAEG QEKIPVHKFI TALKSTGLRT SDPRLKECMD
MLRLTLQTTS DGVMLDKDLF KKCVQSNIVL LTQAFRRKFV IPDFMSFTSH IDELYESAKK
QSGGKVADYI PQLAKFSPDL WGVSVCTVDG QRHSTGDTKV PFCLQSCVKP LKYAIAVNDL
GTEYVHRYVG KEPSGLRFNK LFLNEDDKPH NPMVNAGAIV VTSLIKQGVN NAEKFDYVMQ
FLNKMAGNEY VGFSNATFQS ERESGDRNFA IGYYLKEKKC FPEGTDMVGI LDFYFQLCSI
EVTCESASVM AATLANGGFC PITGERVLSP EAVRNTLSLM HSCGMYDFSG QFAFHVGLPA
KSGVAGGILL VVPNVMGMMC WSPPLDKMGN SVKGIHFCHD LVSLCNFHNY DNLRHFAKKL
DPRREGGDQR VKSVINLLFA AYTGDVSALR RFALSAMDME QRDYDSRTAL HVAAAEGHVE
VVKFLLEACK VNPFPKDRWN NTPMDEALHF GHHDVFKILQ EYQVQYTPQG DSDNGKENQT
VHKNLDGLL
