HOT_RAT
ID HOT_RAT Reviewed; 467 AA.
AC Q4QQW3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 93.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=3182820; DOI=10.1016/s0021-9258(18)37472-6;
RA Kaufman E.E., Nelson T., Fales H.M., Levin D.M.;
RT "Isolation and characterization of a hydroxyacid-oxoacid transhydrogenase
RT from rat kidney mitochondria.";
RL J. Biol. Chem. 263:16872-16879(1988).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 mM for GHB {ECO:0000269|PubMed:3182820};
CC KM=0.4 mM for D-2-HG {ECO:0000269|PubMed:3182820};
CC KM=0.018 mM for 2-KG {ECO:0000269|PubMed:3182820};
CC KM=0.005 mM for SSA {ECO:0000269|PubMed:3182820};
CC KM=3 mM for L-3-OHB {ECO:0000269|PubMed:3182820};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:3182820}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney and liver.
CC {ECO:0000269|PubMed:3182820}.
CC -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC family. Hydroxyacid-oxoacid transhydrogenase subfamily. {ECO:0000305}.
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DR EMBL; BC097945; AAH97945.1; -; mRNA.
DR RefSeq; NP_001020594.1; NM_001025423.1.
DR AlphaFoldDB; Q4QQW3; -.
DR SMR; Q4QQW3; -.
DR IntAct; Q4QQW3; 1.
DR STRING; 10116.ENSRNOP00000009462; -.
DR iPTMnet; Q4QQW3; -.
DR PhosphoSitePlus; Q4QQW3; -.
DR PaxDb; Q4QQW3; -.
DR PRIDE; Q4QQW3; -.
DR GeneID; 362474; -.
DR KEGG; rno:362474; -.
DR UCSC; RGD:1308863; rat.
DR CTD; 137872; -.
DR RGD; 1308863; Adhfe1.
DR VEuPathDB; HostDB:ENSRNOG00000007069; -.
DR eggNOG; KOG3857; Eukaryota.
DR HOGENOM; CLU_007207_0_7_1; -.
DR InParanoid; Q4QQW3; -.
DR OMA; IRFGPGC; -.
DR OrthoDB; 776004at2759; -.
DR PhylomeDB; Q4QQW3; -.
DR TreeFam; TF105710; -.
DR Reactome; R-RNO-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR SABIO-RK; Q4QQW3; -.
DR PRO; PR:Q4QQW3; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000007069; Expressed in liver and 18 other tissues.
DR Genevisible; Q4QQW3; RN.
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 1: Evidence at protein 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 ?..467
FT /note="Hydroxyacid-oxoacid transhydrogenase, mitochondrial"
FT /id="PRO_0000322999"
FT MOD_RES 445
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R0N6"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 467 AA; 50226 MW; 97F4EB2243EBE7DB CRC64;
MAAAARARVT HLLRHLQSTA CQCPTHSHTY SQVPGLSPSG KTTDYAFEMA VSNIRYGAGV
TKEVGMDLQN MGAKNVCLMT DKNLSQLPPV QIVMDSLSKN GISFQVYDNV RVEPTDGSFM
DAIEFAKKGA FDAYVAVGGG STMDTCKAAN LYACSPHSEF LDYVNAPIGK GKPVTVPLKP
LIAVPTTSGT GSETTGVAIF DYEHLKVKTG IASRAIKPTL GLVDPLHTLH MPCQVVANSG
FDVLCHALES YTAIPYSMRS PCPSNPIQRP AYQGSNPISD IWAVHALRIV AKYLKRAVRN
PDDLEARSSM HLASAFAGIG FGNAGVHLCH GMSYPISGLV KTYKAKEYNV DHPLVPHGLS
VVLTSPAVFT FTAQMFPERH LETAEILGAN IRTAKIQDAG PVLADALRKF LFDLNVDDGL
AALGYSKDDI PSLVKGTLPQ ERVTKLAPRA QSEEDLSALF EASMKLY
