ID   HOT_DICDI               Reviewed;         547 AA.
AC   Q54GJ7;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   24-MAY-2005, sequence version 1.
DT   25-MAY-2022, entry version 91.
DE   RecName: Full=Probable hydroxyacid-oxoacid transhydrogenase, mitochondrial;
DE            Short=HOT;
DE            EC=1.1.99.24;
DE   Flags: Precursor;
GN   Name=adhfe1; ORFNames=DDB_G0290111;
OS   Dictyostelium discoideum (Slime mold).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(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; AAFI02000153; EAL62385.1; -; Genomic_DNA.
DR   RefSeq; XP_635889.1; XM_630797.1.
DR   AlphaFoldDB; Q54GJ7; -.
DR   SMR; Q54GJ7; -.
DR   STRING; 44689.DDB0252839; -.
DR   PaxDb; Q54GJ7; -.
DR   EnsemblProtists; EAL62385; EAL62385; DDB_G0290111.
DR   GeneID; 8627488; -.
DR   KEGG; ddi:DDB_G0290111; -.
DR   dictyBase; DDB_G0290111; adhfe1.
DR   eggNOG; KOG3857; Eukaryota.
DR   HOGENOM; CLU_007207_0_7_1; -.
DR   InParanoid; Q54GJ7; -.
DR   OMA; IRFGPGC; -.
DR   PhylomeDB; Q54GJ7; -.
DR   Reactome; R-DDI-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR   PRO; PR:Q54GJ7; -.
DR   Proteomes; UP000002195; Chromosome 5.
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   3: Inferred from homology;
KW   Mitochondrion; Oxidoreductase; Reference proteome; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..547
FT                   /note="Probable hydroxyacid-oxoacid transhydrogenase,
FT                   mitochondrial"
FT                   /id="PRO_0000323002"
SQ   SEQUENCE   547 AA;  59743 MW;  B03F1DF8B3B4DFC4 CRC64;
     MTIIITKIAD KIIKSNRVKN TLQDIHIHSS NCGCHGSFKS NSVMNQTFSS FSSLTTEKNE
     QQQQQLFKQF SNSKPIPMGR KVELDTSKVI DSVYFGNTEN NNYRTNKGNT DYAFEASANN
     IRFGSGVTYE VGYDLLDMNC RNVIVFTDNN LLKLVDTDKE SAVAKCLYSL EKCGIKYTIY
     SDVSIEPTDT SFKDAISVMG KGRYDGVVAV GGGSVMDTAK AANLYNSYPP ADNDFLAYIN
     PPIGKGLLVP GPLKRPLIAI PTTCGTASET TGVCILDIKL GDGLSAKTGI ASRHLKPILG
     LVDPDNLLTL PSNVAISSGF DQLCHALESF TAIPFNQRSP RPLAPNQRPS YQGANPVSDV
     WSLRSLEMLC KNIHRFVLNP NDDYARSQMM LAASYAGLGF GNSGVHACHG MSYSISSMVK
     DYKPEGYYGL KKNLIPHGQS VILSAPAVFK FTAPSNPERH LLLAKIMGAD ISNASESDAG
     VLLSNQIVKL MKLLNVPNGL QALGYKESDI DSLVKGTLPQ HRVTKLMPKQ ATYDDLYKLF
     KDSMTIY