HOT_CAEEL
ID HOT_CAEEL Reviewed; 465 AA.
AC Q9U2M4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 123.
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:Y38F1A.6};
DE Flags: Precursor;
GN Name=hphd-1 {ECO:0000312|WormBase:Y38F1A.6};
GN ORFNames=Y38F1A.6 {ECO:0000312|WormBase:Y38F1A.6};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
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; AL032639; CAA21631.2; -; Genomic_DNA.
DR PIR; E88343; E88343.
DR PIR; T26686; T26686.
DR RefSeq; NP_496764.1; NM_064363.4.
DR AlphaFoldDB; Q9U2M4; -.
DR SMR; Q9U2M4; -.
DR BioGRID; 40240; 44.
DR DIP; DIP-24327N; -.
DR STRING; 6239.Y38F1A.6.1; -.
DR EPD; Q9U2M4; -.
DR PaxDb; Q9U2M4; -.
DR PeptideAtlas; Q9U2M4; -.
DR EnsemblMetazoa; Y38F1A.6.1; Y38F1A.6.1; WBGene00012608.
DR EnsemblMetazoa; Y38F1A.6.2; Y38F1A.6.2; WBGene00012608.
DR EnsemblMetazoa; Y38F1A.6.3; Y38F1A.6.3; WBGene00012608.
DR EnsemblMetazoa; Y38F1A.6.4; Y38F1A.6.4; WBGene00012608.
DR EnsemblMetazoa; Y38F1A.6.5; Y38F1A.6.5; WBGene00012608.
DR EnsemblMetazoa; Y38F1A.6.6; Y38F1A.6.6; WBGene00012608.
DR EnsemblMetazoa; Y38F1A.6.7; Y38F1A.6.7; WBGene00012608.
DR GeneID; 174942; -.
DR KEGG; cel:CELE_Y38F1A.6; -.
DR UCSC; Y38F1A.6.1; c. elegans.
DR CTD; 174942; -.
DR WormBase; Y38F1A.6; CE24222; WBGene00012608; hphd-1.
DR eggNOG; KOG3857; Eukaryota.
DR GeneTree; ENSGT00390000003849; -.
DR HOGENOM; CLU_007207_0_7_1; -.
DR InParanoid; Q9U2M4; -.
DR OMA; IRFGPGC; -.
DR OrthoDB; 776004at2759; -.
DR PhylomeDB; Q9U2M4; -.
DR Reactome; R-CEL-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR PRO; PR:Q9U2M4; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00012608; Expressed in adult organism and 4 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 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_0000324756"
SQ SEQUENCE 465 AA; 50506 MW; CB9A08D7376E2949 CRC64;
MSASLARGIL SKMGGSCCPH HAPATNPFKL AKLHGNNKST DYAFEMVCST LRFGKGVTLE
IGYDVRNLGA KKTLLITDKN VQNTIAFKNA EQALKMVNIE YEVFDDVLIE PTVNSMQKAI
AFAKSKQFDS FIAVGGGSVI DTTKAAALYA SNPEADFLDF VGPPFGKSMQ PKNPMLPLIA
VPTTAGTGSE TTAAAIMDLP EHKCKTGIRL RCIKPYLAVV DPLNVMSMPR NVAIYSGFDV
LCHALESFTA LPFDQRSPRP ENPGVRPLYQ GSNPISDVWS KEALRIIGKY FRRSIFDPTD
EEARTEMLKA SSFAGIGFGN AGVHLCHGLS YPISSQAKSC VADDYPKEKN LIPHGLSVMT
TAVADFEFTT AACPDRHLIS AQTLGADIPN NASNEYISRT LCDRLRGYMR DFGVPNGLKG
MGFEFSDIEM LTEAASHSVP NIAISPKSAD REIISTLYEK SLTVY
