HOT_MOUSE
ID HOT_MOUSE Reviewed; 465 AA.
AC Q8R0N6; Q78SV3; Q8BYP0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 130.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus, and Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [3]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=17559793; DOI=10.1016/j.abb.2007.04.018;
RA Kim J.Y., Tillison K.S., Zhou S., Lee J.H., Smas C.M.;
RT "Differentiation-dependent expression of Adhfe1 in adipogenesis.";
RL Arch. Biochem. Biophys. 464:100-111(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-443, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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:0000269|PubMed:17559793}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8R0N6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R0N6-2; Sequence=VSP_031987;
CC -!- TISSUE SPECIFICITY: Expressed in white and brown adipose tissues,
CC liver, and kidney. Expression is differentiation-dependent during in
CC vitro brown and white adipogenesis. {ECO:0000269|PubMed:17559793}.
CC -!- INDUCTION: Down-regulated of 40% in white adipose tissue of ob/ob obese
CC mice. {ECO:0000269|PubMed:17559793}.
CC -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC family. Hydroxyacid-oxoacid transhydrogenase subfamily. {ECO:0000305}.
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DR EMBL; AK038853; BAC30151.1; -; mRNA.
DR EMBL; AK050178; BAC34108.1; -; mRNA.
DR EMBL; BC026584; AAH26584.2; -; mRNA.
DR CCDS; CCDS14812.1; -. [Q8R0N6-1]
DR RefSeq; NP_780445.1; NM_175236.4. [Q8R0N6-1]
DR RefSeq; XP_006495649.1; XM_006495586.2. [Q8R0N6-2]
DR RefSeq; XP_017168188.1; XM_017312699.1.
DR AlphaFoldDB; Q8R0N6; -.
DR SMR; Q8R0N6; -.
DR BioGRID; 218012; 2.
DR IntAct; Q8R0N6; 1.
DR STRING; 10090.ENSMUSP00000116627; -.
DR iPTMnet; Q8R0N6; -.
DR PhosphoSitePlus; Q8R0N6; -.
DR SwissPalm; Q8R0N6; -.
DR jPOST; Q8R0N6; -.
DR MaxQB; Q8R0N6; -.
DR PaxDb; Q8R0N6; -.
DR PeptideAtlas; Q8R0N6; -.
DR PRIDE; Q8R0N6; -.
DR ProteomicsDB; 273131; -. [Q8R0N6-1]
DR ProteomicsDB; 273132; -. [Q8R0N6-2]
DR DNASU; 76187; -.
DR Ensembl; ENSMUST00000144177; ENSMUSP00000116627; ENSMUSG00000025911. [Q8R0N6-1]
DR GeneID; 76187; -.
DR KEGG; mmu:76187; -.
DR UCSC; uc007agl.2; mouse. [Q8R0N6-1]
DR CTD; 137872; -.
DR MGI; MGI:1923437; Adhfe1.
DR VEuPathDB; HostDB:ENSMUSG00000025911; -.
DR eggNOG; KOG3857; Eukaryota.
DR GeneTree; ENSGT00390000003849; -.
DR InParanoid; Q8R0N6; -.
DR OMA; IRFGPGC; -.
DR OrthoDB; 776004at2759; -.
DR PhylomeDB; Q8R0N6; -.
DR TreeFam; TF105710; -.
DR Reactome; R-MMU-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR SABIO-RK; Q8R0N6; -.
DR BioGRID-ORCS; 76187; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Adhfe1; mouse.
DR PRO; PR:Q8R0N6; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8R0N6; protein.
DR Bgee; ENSMUSG00000025911; Expressed in right kidney and 101 other tissues.
DR ExpressionAtlas; Q8R0N6; baseline and differential.
DR Genevisible; Q8R0N6; MM.
DR GO; GO:0005739; C:mitochondrion; IDA: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; Alternative splicing; Lipid metabolism; Mitochondrion;
KW Oxidoreductase; Phosphoprotein; 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_0000322997"
FT MOD_RES 443
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..46
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031987"
SQ SEQUENCE 465 AA; 49937 MW; CD1463685F788C2A CRC64;
MAAAARARVT HLLRHLQSTA CQCPTHSHTY SQAPGPSGKT ADYAFEMAVS NIRYGAGVTK
EVGMDLQNMG AKNVCLMTDK NLSQLPPVQI VMDSLSKNGI SFQVYDDVRV EPTDGSFMDA
IEFAKKGAFD AYVAVGGGST MDTCKAANLY ASSPHSEFLD YVNAPIGKGK PVTVPLKPLI
AVPTTSGTGS ETTGVAIFDY EHLKVKTGIA SRAIKPTLGL VDPLHTLHMP CQVVANSGFD
VLCHALESYT AIPYSMRSPC PSNPIQRPAY QGSNPISDIW AVHALQIVAK YLKRAVRNPD
DLEARSKMHL ASAFAGIGFG NAGVHLCHGM SYPISGLVKT YKAKEYNVDH PLVPHGLSVV
LTSPAVFTFT AQMFPERHLE TAGILGANIR TARIQDAGLV LADALRKFLF DLNVDDGLAA
LGYSKDDIPS LVKGTLPQER VTKLAPRAQS EEDLSALFEA SMKLY
