ID   HOT_BOVIN               Reviewed;         466 AA.
AC   A6QP15;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   21-AUG-2007, sequence version 1.
DT   03-AUG-2022, entry version 74.
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   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Brain cortex;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JUL-2007) 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   -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC       family. Hydroxyacid-oxoacid transhydrogenase subfamily. {ECO:0000305}.
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DR   EMBL; BC149097; AAI49098.1; -; mRNA.
DR   RefSeq; NP_001095357.1; NM_001101887.1.
DR   AlphaFoldDB; A6QP15; -.
DR   SMR; A6QP15; -.
DR   STRING; 9913.ENSBTAP00000005874; -.
DR   PaxDb; A6QP15; -.
DR   PeptideAtlas; A6QP15; -.
DR   Ensembl; ENSBTAT00000005874; ENSBTAP00000005874; ENSBTAG00000004476.
DR   GeneID; 507711; -.
DR   KEGG; bta:507711; -.
DR   CTD; 137872; -.
DR   VEuPathDB; HostDB:ENSBTAG00000004476; -.
DR   VGNC; VGNC:25674; ADHFE1.
DR   eggNOG; KOG3857; Eukaryota.
DR   GeneTree; ENSGT00390000003849; -.
DR   InParanoid; A6QP15; -.
DR   OMA; IRFGPGC; -.
DR   OrthoDB; 776004at2759; -.
DR   Proteomes; UP000009136; Chromosome 14.
DR   Bgee; ENSBTAG00000004476; Expressed in liver and 105 other tissues.
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   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; Lipid metabolism; Mitochondrion; Oxidoreductase;
KW   Phosphoprotein; Reference proteome; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..466
FT                   /note="Hydroxyacid-oxoacid transhydrogenase, mitochondrial"
FT                   /id="PRO_0000322995"
FT   MOD_RES         444
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R0N6"
FT   MOD_RES         451
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R0N6"
SQ   SEQUENCE   466 AA;  50343 MW;  EB601252CBE6DA6E CRC64;
     MAAARSRVVH LLRLLQRAAC QCPSHSHTYS QAPGLSPSGK TTDYAFEMAV STIRYGAGVT
     KEVGMDLQSM GAKNVCLMTD KNLSQLPPVQ TVMDSLVKNG INFKVYDHVR VEPTDTSFME
     AIEFAKKGAF DAFLAVGGGS TIDTCKAANL YSSSPDSDFL DYVNAPIGKG KPVTVPLKPL
     IAVPTTSGTG SETTGVAIFD YEHLKVKTGI ASRAIKPTLG LIDPLHTLHM PERVVANSGF
     DVLCHALESY TALPYHMRSP CPSSPITRPA YQGSNPISDI WAVHALRIVA KYLKRAIRNP
     DDLEARSNMH LASAFAGIGF GNAGVHLCHG MSYPISGLVK TYKAKDYNVD HPLVPHGLSV
     VLTSPAVFTF TSQMFPERHL EVAEILGADT RTARRPDAGP VLADTLRKFL FDLDVDDGLA
     AIGYSKADIP ELVKGTLPQE RVTKLAPRPQ SEEDLSALFE ASMKLY