ID   HOT_PONAB               Reviewed;         467 AA.
AC   Q5RF11; Q5R5E1; Q5RA35;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   25-MAY-2022, entry version 71.
DE   RecName: Full=Hydroxyacid-oxoacid transhydrogenase, mitochondrial;
DE            Short=HOT;
DE            EC=1.1.99.24;
DE   AltName: Full=Alcohol dehydrogenase iron-containing protein 1;
DE            Short=ADHFe1;
DE   Flags: Precursor;
GN   Name=ADHFE1;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q5RF11-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5RF11-2; Sequence=VSP_031988;
CC   -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC       family. Hydroxyacid-oxoacid transhydrogenase subfamily. {ECO:0000305}.
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DR   EMBL; CR857350; CAH89646.1; -; mRNA.
DR   EMBL; CR859187; CAH91375.1; -; mRNA.
DR   EMBL; CR860920; CAH93025.1; -; mRNA.
DR   RefSeq; NP_001127410.1; NM_001133938.1.
DR   RefSeq; NP_001128888.1; NM_001135416.1.
DR   AlphaFoldDB; Q5RF11; -.
DR   SMR; Q5RF11; -.
DR   STRING; 9601.ENSPPYP00000020906; -.
DR   GeneID; 100174480; -.
DR   GeneID; 100189822; -.
DR   KEGG; pon:100189822; -.
DR   CTD; 137872; -.
DR   eggNOG; KOG3857; Eukaryota.
DR   InParanoid; Q5RF11; -.
DR   OrthoDB; 776004at2759; -.
DR   Proteomes; UP000001595; Unplaced.
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   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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   Acetylation; Alternative splicing; Lipid metabolism; Mitochondrion;
KW   Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..467
FT                   /note="Hydroxyacid-oxoacid transhydrogenase, mitochondrial"
FT                   /id="PRO_0000322998"
FT   MOD_RES         445
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R0N6"
FT   MOD_RES         452
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R0N6"
FT   VAR_SEQ         1..48
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_031988"
FT   CONFLICT        60
FT                   /note="V -> A (in Ref. 1; CAH91375)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        147
FT                   /note="M -> K (in Ref. 1; CAH93025/CAH91375)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        163
FT                   /note="Y -> H (in Ref. 1; CAH93025)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        254
FT                   /note="L -> P (in Ref. 1; CAH91375)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   467 AA;  50260 MW;  CFC3D34BF6F65B6C CRC64;
     MAAASRARVA YLLRQLQRAA CQCPTHSHTY SQAPGLSPSG KTTDYAFEMA VSNIRYGAGV
     TKEVGMDLQN MGAKNVCLMT DKNLSKLPPV QVAMDSLVKN GIPFTVYDNV RVEPTDASFM
     EAIEFAQKGA FDAYVAVGGG STMDTCMAAN LYASSPHSDF LDYVSAPIGK GKPVSVPLKP
     LIAVPTTSGT GSETTGVAIF DYEHLKVKIG IASRAIKPTL GLIDPLHTLH MPARVVANSG
     FDVLCHALES YTTLPYHLRS PCPSNPITRP AYQGSNPISD IWAIHALRIV AKYLKRAVRN
     PDDLEARSHM HLASAFAGIG FGNAGVHLCH GMSYPISGLV KTYKAKDYNV DHPLVPHGLS
     VVLTSPAVFT FTAQMFPERH LETAEILGAD TRTARIQDAG LVLADTLRKF LFDLDVDDGL
     AAVGYSKADI PALVKGTLPQ ERVTKLAPRP QSEEDLAALF EASMKLY