ID   HOT_DROPS               Reviewed;         464 AA.
AC   Q28XT3;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   20-JAN-2009, sequence version 2.
DT   03-AUG-2022, entry version 71.
DE   RecName: Full=Probable hydroxyacid-oxoacid transhydrogenase, mitochondrial;
DE            Short=HOT;
DE            EC=1.1.99.24;
DE   Flags: Precursor;
GN   ORFNames=GA17444;
OS   Drosophila pseudoobscura pseudoobscura (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=46245;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MV2-25 / Tucson 14011-0121.94;
RX   PubMed=15632085; DOI=10.1101/gr.3059305;
RA   Richards S., Liu Y., Bettencourt B.R., Hradecky P., Letovsky S.,
RA   Nielsen R., Thornton K., Hubisz M.J., Chen R., Meisel R.P., Couronne O.,
RA   Hua S., Smith M.A., Zhang P., Liu J., Bussemaker H.J., van Batenburg M.F.,
RA   Howells S.L., Scherer S.E., Sodergren E., Matthews B.B., Crosby M.A.,
RA   Schroeder A.J., Ortiz-Barrientos D., Rives C.M., Metzker M.L., Muzny D.M.,
RA   Scott G., Steffen D., Wheeler D.A., Worley K.C., Havlak P., Durbin K.J.,
RA   Egan A., Gill R., Hume J., Morgan M.B., Miner G., Hamilton C., Huang Y.,
RA   Waldron L., Verduzco D., Clerc-Blankenburg K.P., Dubchak I., Noor M.A.F.,
RA   Anderson W., White K.P., Clark A.G., Schaeffer S.W., Gelbart W.M.,
RA   Weinstock G.M., Gibbs R.A.;
RT   "Comparative genome sequencing of Drosophila pseudoobscura: chromosomal,
RT   gene, and cis-element evolution.";
RL   Genome Res. 15:1-18(2005).
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}.
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DR   EMBL; CM000071; EAL26233.2; -; Genomic_DNA.
DR   RefSeq; XP_001361654.2; XM_001361617.3.
DR   AlphaFoldDB; Q28XT3; -.
DR   SMR; Q28XT3; -.
DR   STRING; 7237.FBpp0278465; -.
DR   EnsemblMetazoa; FBtr0280027; FBpp0278465; FBgn0077457.
DR   GeneID; 4805213; -.
DR   KEGG; dpo:Dpse_GA17444; -.
DR   eggNOG; KOG3857; Eukaryota.
DR   HOGENOM; CLU_007207_0_7_1; -.
DR   InParanoid; Q28XT3; -.
DR   OMA; IRFGPGC; -.
DR   Proteomes; UP000001819; Chromosome 3.
DR   Bgee; FBgn0077457; Expressed in insect adult head and 2 other tissues.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IEA:InterPro.
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   3: Inferred from homology;
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_0000323006"
SQ   SEQUENCE   464 AA;  50033 MW;  4769F346C24C90B1 CRC64;
     MSRKNVLNLI NTIVANSCKC PAHSHNYGSA APTGVQTGQK EYAFEMSAST VRFGPGVSVE
     VGADLRNLGA KKVCLVTDRN VAKLPSVKVA LDSLARHGIN YEVYDETRVE PTDASLWHAA
     DYARQNEFDA FLAIGGGSVM DTAKAANLFS SDREAEFLDY VNCPIGKGKE ISVKLKPLIA
     MPTTSGTGSE TTGVAIFDYK RLHAKTGISS KYLKPTLAII DPLHTLSQPE RVMAFAGFDV
     FCHALESFTA VDYRERGPAP SDPSLRPTYQ GRNPISDVWA RFALETIRKN FINAIYEPGN
     LEARSQMHLA STMAGVGFGN AGVHLCHGLS YPISGNVRNY KPAGYTADHA LIPHGLSVVI
     SAPAVFEFTA PACPDRHLEA AKLLGAKVDG VRASDAGRLL ADTVRGFMQR AGIENGLREL
     GFSSSDVPNL VDGTLPQERI TKLAPRAQTQ ENLAQLFENS MVAY