DHE3_DROME
ID DHE3_DROME Reviewed; 562 AA.
AC P54385; P91624; Q8IH05; Q9VCF7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Glutamate dehydrogenase, mitochondrial;
DE Short=GDH;
DE EC=1.4.1.3;
DE Flags: Precursor;
GN Name=Gdh; Synonyms=Glud; ORFNames=CG5320;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORMS A AND C), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=10992165; DOI=10.3109/01677060009083479;
RA Papadopoulou D., Louis C.;
RT "The glutamate dehydrogenase gene of Drosophila melanogaster: molecular
RT analysis and expression.";
RL J. Neurogenet. 14:125-143(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP CHARACTERIZATION.
RX PubMed=6810872; DOI=10.1007/bf00484696;
RA Caggese C., De Pinto V., Ferrandino A.;
RT "Purification and genetic control of NAD-dependent glutamate dehydrogenase
RT from Drosophila melanogaster.";
RL Biochem. Genet. 20:449-460(1982).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH +
CC NH4(+); Xref=Rhea:RHEA:15133, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.4.1.3;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + NADPH +
CC NH4(+); Xref=Rhea:RHEA:11612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.4.1.3;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10011};
CC -!- ACTIVITY REGULATION: Subject to allosteric regulation. Activated by
CC ADP. Inhibited by GTP and ATP (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homohexamer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A; Synonyms=Long;
CC IsoId=P54385-1; Sequence=Displayed;
CC Name=C; Synonyms=Short, F;
CC IsoId=P54385-2; Sequence=VSP_001285;
CC -!- TISSUE SPECIFICITY: Expressed throughout the embryo during early stages
CC before becoming localized in mesodermal tissue by stage 8. At stage 12
CC expression is concentrated in the posterior midgut. After stage 13
CC expression it is found in the anterior and posterior midgut, the
CC hindgut, fat body, muscle, and central nervous system. In 3rd instar
CC larvae expression is found in the leg disks, the wing pouch of the wing
CC disk, the eye-antenna disk, and the developing brain medulla.
CC {ECO:0000269|PubMed:10992165}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages.
CC {ECO:0000269|PubMed:10992165}.
CC -!- MISCELLANEOUS: ADP can occupy the NADH binding site and activate the
CC enzyme. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN71256.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; Y11314; CAA72173.1; -; mRNA.
DR EMBL; Z29062; CAA82304.1; -; mRNA.
DR EMBL; AE014297; AAF56209.5; -; Genomic_DNA.
DR EMBL; AE014297; AAS65200.1; -; Genomic_DNA.
DR EMBL; AY061323; AAL28871.1; -; mRNA.
DR EMBL; BT001501; AAN71256.1; ALT_INIT; mRNA.
DR PIR; S42919; S42919.
DR RefSeq; NP_524470.4; NM_079746.6. [P54385-1]
DR RefSeq; NP_996274.1; NM_206551.3. [P54385-2]
DR AlphaFoldDB; P54385; -.
DR SMR; P54385; -.
DR BioGRID; 67768; 26.
DR IntAct; P54385; 6.
DR STRING; 7227.FBpp0088988; -.
DR PaxDb; P54385; -.
DR PRIDE; P54385; -.
DR DNASU; 42832; -.
DR EnsemblMetazoa; FBtr0089497; FBpp0088990; FBgn0001098. [P54385-2]
DR EnsemblMetazoa; FBtr0089498; FBpp0088988; FBgn0001098. [P54385-1]
DR GeneID; 42832; -.
DR KEGG; dme:Dmel_CG5320; -.
DR CTD; 42832; -.
DR FlyBase; FBgn0001098; Gdh.
DR VEuPathDB; VectorBase:FBgn0001098; -.
DR eggNOG; KOG2250; Eukaryota.
DR GeneTree; ENSGT00390000000854; -.
DR InParanoid; P54385; -.
DR PhylomeDB; P54385; -.
DR Reactome; R-DME-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-DME-8964539; Glutamate and glutamine metabolism.
DR BioGRID-ORCS; 42832; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Gdh; fly.
DR GenomeRNAi; 42832; -.
DR PRO; PR:P54385; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0001098; Expressed in adult hindgut (Drosophila) and 61 other tissues.
DR ExpressionAtlas; P54385; baseline and differential.
DR Genevisible; P54385; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; HDA:FlyBase.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004352; F:glutamate dehydrogenase (NAD+) activity; IDA:FlyBase.
DR GO; GO:0004354; F:glutamate dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0004353; F:glutamate dehydrogenase [NAD(P)+] activity; IDA:FlyBase.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IDA:FlyBase.
DR GO; GO:0006538; P:glutamate catabolic process; IBA:GO_Central.
DR GO; GO:0006536; P:glutamate metabolic process; IDA:FlyBase.
DR GO; GO:0006116; P:NADH oxidation; IDA:FlyBase.
DR CDD; cd01076; NAD_bind_1_Glu_DH; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR006095; Glu/Leu/Phe/Val_DH.
DR InterPro; IPR033524; Glu/Leu/Phe/Val_DH_AS.
DR InterPro; IPR006096; Glu/Leu/Phe/Val_DH_C.
DR InterPro; IPR006097; Glu/Leu/Phe/Val_DH_dimer_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR033922; NAD_bind_Glu_DH.
DR Pfam; PF00208; ELFV_dehydrog; 1.
DR Pfam; PF02812; ELFV_dehydrog_N; 1.
DR PRINTS; PR00082; GLFDHDRGNASE.
DR SMART; SM00839; ELFV_dehydrog; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00074; GLFV_DEHYDROGENASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; GTP-binding; Mitochondrion; NAD;
KW Nucleotide-binding; Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..53
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 54..562
FT /note="Glutamate dehydrogenase, mitochondrial"
FT /id="PRO_0000007214"
FT ACT_SITE 174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10011"
FT BINDING 132..134
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 138
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 162
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 243
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 257
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 261
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 310
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 313
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 430
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 436
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 442
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250"
FT BINDING 521
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250"
FT VAR_SEQ 460..472
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_001285"
FT CONFLICT 6..180
FT /note="Missing (in Ref. 4; AAN71256)"
FT /evidence="ECO:0000305"
FT CONFLICT 11..15
FT /note="GARRQ -> APAAR (in Ref. 1; CAA72173)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 562 AA; 62536 MW; 687A183D3BC0211F CRC64;
MYHLKSLARQ GARRQQELAT LAKALPTAVM QSSRGYATEH QIPDRLKDVP TAKDPRFFDM
VEYFFHRGCQ IAEESLVDDM KGKLTRDEKK QKVKGILMLM QPCDHIIEIA FPLRRDAGNY
EMITGYRAQH STHKTPTKGG IRFSLDVSRD EVKALSALMT FKCACVDVPF GGAKAGLKIN
PKEYSEHELE KITRRFTLEL AKKGFIGPGV DVPAPDMGTG EREMSWIADT YAKTIGHLDI
NAHACVTGKP INQGGIHGRV SATGRGVFHG LENFINEANY MSQIGTTPGW GGKTFIVQGF
GNVGLHTTRY LTRAGATCIG VIEHDGTLYN PEGIDPKLLE DYKNEHGTIV GYQNAKPYEG
ENLMFEKCDI FIPAAVEKVI TSENANRIQA KIIAEAANGP TTPAADKILI DRNILVIPDL
YINAGGVTVS FFEWLKNLNH VSYGRLTFKY ERESNYHLLA SVQQSIERII NDESVQESLE
RRFGRVGGRI PVTPSESFQK RISGASEKDI VHSGLDYTME RSARAIMKTA MKYNLGLDLR
TAAYVNSIEK IFTTYRDAGL AF
