ID   HOT_CAEBR               Reviewed;         465 AA.
AC   A8WTJ7;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-JAN-2008, sequence version 1.
DT   03-AUG-2022, entry version 66.
DE   RecName: Full=Hydroxyacid-oxoacid transhydrogenase, mitochondrial {ECO:0000250|UniProtKB:Q8IWW8};
DE            Short=HOT;
DE            EC=1.1.99.24 {ECO:0000250|UniProtKB:Q8IWW8};
DE   AltName: Full=3-Hydroxypropionate-oxoacid transhydrogenase {ECO:0000312|WormBase:CBG02769};
DE   Flags: Precursor;
GN   Name=hphd-1 {ECO:0000312|WormBase:CBG02769};
GN   ORFNames=CBG02769 {ECO:0000312|WormBase:CBG02769};
OS   Caenorhabditis briggsae.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6238;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AF16;
RX   PubMed=14624247; DOI=10.1371/journal.pbio.0000045;
RA   Stein L.D., Bao Z., Blasiar D., Blumenthal T., Brent M.R., Chen N.,
RA   Chinwalla A., Clarke L., Clee C., Coghlan A., Coulson A., D'Eustachio P.,
RA   Fitch D.H.A., Fulton L.A., Fulton R.E., Griffiths-Jones S., Harris T.W.,
RA   Hillier L.W., Kamath R., Kuwabara P.E., Mardis E.R., Marra M.A.,
RA   Miner T.L., Minx P., Mullikin J.C., Plumb R.W., Rogers J., Schein J.E.,
RA   Sohrmann M., Spieth J., Stajich J.E., Wei C., Willey D., Wilson R.K.,
RA   Durbin R.M., Waterston R.H.;
RT   "The genome sequence of Caenorhabditis briggsae: a platform for comparative
RT   genomics.";
RL   PLoS Biol. 1:166-192(2003).
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.
CC       {ECO:0000250|UniProtKB:Q8IWW8}.
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         Evidence={ECO:0000250|UniProtKB:Q8IWW8};
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; Evidence={ECO:0000250|UniProtKB:Q8IWW8};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q8R0N6}.
CC   -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC       family. Hydroxyacid-oxoacid transhydrogenase subfamily. {ECO:0000305}.
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DR   EMBL; HE601438; CAP23809.1; -; Genomic_DNA.
DR   RefSeq; XP_002631017.1; XM_002630971.1.
DR   AlphaFoldDB; A8WTJ7; -.
DR   SMR; A8WTJ7; -.
DR   STRING; 6238.CBG02769; -.
DR   PRIDE; A8WTJ7; -.
DR   EnsemblMetazoa; CBG02769.1; CBG02769.1; WBGene00025759.
DR   GeneID; 8572531; -.
DR   KEGG; cbr:CBG_02769; -.
DR   CTD; 8572531; -.
DR   WormBase; CBG02769; CBP00579; WBGene00025759; Cbr-hphd-1.
DR   eggNOG; KOG3857; Eukaryota.
DR   HOGENOM; CLU_007207_0_7_1; -.
DR   InParanoid; A8WTJ7; -.
DR   OMA; IRFGPGC; -.
DR   OrthoDB; 776004at2759; -.
DR   Proteomes; UP000008549; Chromosome II.
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; IPR018211; ADH_Fe_CS.
DR   InterPro; IPR039697; Alcohol_dehydrogenase_Fe.
DR   InterPro; IPR042157; HOT.
DR   PANTHER; PTHR11496; PTHR11496; 1.
DR   Pfam; PF00465; Fe-ADH; 1.
DR   PROSITE; PS00913; ADH_IRON_1; 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           ?..465
FT                   /note="Hydroxyacid-oxoacid transhydrogenase, mitochondrial"
FT                   /id="PRO_0000324755"
SQ   SEQUENCE   465 AA;  50702 MW;  3B9DA79103CD2DE6 CRC64;
     MSASLARGML HKMGGSCCPH HAPTTNPFRM AKLHGNNKST DYAFEMVCST LRFGKGVTLE
     IGYDVRNLGA KKTLLITDKN VQNTIAFKNA EQALKMVNIE YEIFDDVLIE PSEKSMQKAI
     AFAKSKPFDS FIAVGGGSVI DTTKAAALYA SNPEADFLDF VGPPFGKSLQ PKNPMLPLIA
     VPTTAGTGSE TTAAAIMDLP EHKCKTGIRL RCIKPYLAVV DPLNVMSMPR NVAIYSGFDV
     LCHALESYTA LPYDQRSPRP ARPEVRPVYQ GSNPISDVWS REALRIIGQY FRRSVFDPSD
     EEARTEMLKA SSFAGIGFGN AGVHLCHGLS YPISSQAKGC VAHDYPQDKN LIPHGLSVMT
     TAVADFEFTT AACPDRHLVA AQTLGADIPN NADNEYISRT LCDQLRGFMK DFGVPNGLKG
     MGFEYSDIDH LTEAASHSVP NIVISPKSTD RDIISKLYEK SLTVY