HOT_DROME
ID HOT_DROME Reviewed; 464 AA.
AC Q9W265; Q8SX03; Q95S86;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Probable hydroxyacid-oxoacid transhydrogenase, mitochondrial;
DE Short=HOT;
DE EC=1.1.99.24;
DE Flags: Precursor;
GN Name=T3dh; ORFNames=CG3425;
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 [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 [2]
RP GENOME REANNOTATION.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo, and Ovary;
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).
CC -!- FUNCTION: Catalyzes the cofactor-independent reversible oxidation of
CC gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to
CC reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG).
CC L-3-hydroxybutyrate (L-3-OHB) is also a substrate for HOT when using 2-
CC KG as hydrogen acceptor, resulting in the formation of D-2-HG (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-3-hydroxybutanoate + 2-oxoglutarate = (R)-2-
CC hydroxyglutarate + acetoacetate; Xref=Rhea:RHEA:23048,
CC ChEBI:CHEBI:11047, ChEBI:CHEBI:13705, ChEBI:CHEBI:15801,
CC ChEBI:CHEBI:16810; EC=1.1.99.24;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 4-hydroxybutanoate = (R)-2-hydroxyglutarate +
CC succinate semialdehyde; Xref=Rhea:RHEA:24734, ChEBI:CHEBI:15801,
CC ChEBI:CHEBI:16724, ChEBI:CHEBI:16810, ChEBI:CHEBI:57706;
CC EC=1.1.99.24;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC family. Hydroxyacid-oxoacid transhydrogenase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL28462.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAF46832.1; -; Genomic_DNA.
DR EMBL; AY060914; AAL28462.1; ALT_INIT; mRNA.
DR EMBL; AY094924; AAM11277.1; -; mRNA.
DR RefSeq; NP_477209.2; NM_057861.3.
DR AlphaFoldDB; Q9W265; -.
DR SMR; Q9W265; -.
DR STRING; 7227.FBpp0071759; -.
DR PaxDb; Q9W265; -.
DR PRIDE; Q9W265; -.
DR DNASU; 37551; -.
DR EnsemblMetazoa; FBtr0071848; FBpp0071759; FBgn0017482.
DR GeneID; 37551; -.
DR KEGG; dme:Dmel_CG3425; -.
DR CTD; 37551; -.
DR FlyBase; FBgn0017482; T3dh.
DR VEuPathDB; VectorBase:FBgn0017482; -.
DR eggNOG; KOG3857; Eukaryota.
DR GeneTree; ENSGT00390000003849; -.
DR HOGENOM; CLU_007207_0_7_1; -.
DR InParanoid; Q9W265; -.
DR OMA; IRFGPGC; -.
DR OrthoDB; 776004at2759; -.
DR PhylomeDB; Q9W265; -.
DR Reactome; R-DME-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR BioGRID-ORCS; 37551; 0 hits in 1 CRISPR screen.
DR ChiTaRS; T3dh; fly.
DR GenomeRNAi; 37551; -.
DR PRO; PR:Q9W265; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0017482; Expressed in adult Malpighian tubule (Drosophila) and 13 other tissues.
DR ExpressionAtlas; Q9W265; baseline and differential.
DR Genevisible; Q9W265; DM.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0047988; F:hydroxyacid-oxoacid transhydrogenase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0006539; P:glutamate catabolic process via 2-oxoglutarate; ISS:UniProtKB.
DR CDD; cd08190; HOT; 1.
DR InterPro; IPR001670; ADH_Fe/GldA.
DR InterPro; IPR039697; Alcohol_dehydrogenase_Fe.
DR InterPro; IPR042157; HOT.
DR PANTHER; PTHR11496; PTHR11496; 1.
DR Pfam; PF00465; Fe-ADH; 1.
PE 2: Evidence at transcript level;
KW Mitochondrion; Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..464
FT /note="Probable hydroxyacid-oxoacid transhydrogenase,
FT mitochondrial"
FT /id="PRO_0000323005"
FT CONFLICT 108
FT /note="R -> L (in Ref. 3; AAM11277)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 50018 MW; 2351EA6F02E957CD CRC64;
MSRKNVLGLI NTIVANSCKC PAHSHNYGSA APTASQTGRM EYAFEMSAST VRFGPGVSAE
VGADLRNLGA RKVCLVTDKN VVQLPSVKVA LDSLARNGIN YEVYDETRVE PTDGSMWHAV
EFARGKEFDA FLAIGGGSAM DTAKAANLFS SDANAEFLDY VNCPIGRGKE ISVKLKPLIA
MPTTSGTGSE TTGVAIFDYK KLHAKTGISS KFLKPTLAVI DPLHTLSQPQ RVMAFAGFDV
FCHALESFTA VDYRERGLAP SDPSLRPTYQ GRNPVSDVWA RFALETIRKN FVNAIYQPDN
LEARSQMHLA STMAGVGFGN AGVHLCHGLS YPISGNVRDY KPKGYSADHA LIPHGLSVVI
SAPAVFEFTA PACPDRHLEA AQLLGAEVRG VEKADAGRLL ADTVRGFMQR AGIENGLREL
GFSSSDIPAL VEGTLPQERI TKLAPRAQTQ ENLSQLFEKS MEVY
