Reviewed, UniProtKB/Swiss-Prot Q8R0N6 (HOT_MOUSE)

Names and origin

Protein names

Recommended name:
    Hydroxyacid-oxoacid transhydrogenase, mitochondrial
      Short name=HOT
    EC=1.1.99.24
Alternative name(s):
    Alcohol dehydrogenase iron-containing protein 1

Gene names

Name:

Adhfe1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). L-3-hydroxybutyrate (L-3-OHB) is also a substrate for HOT when using 2-KG as hydrogen acceptor, resulting in the formation of D-2-HG By similarity.
Catalytic activity	(S)-3-hydroxybutanoate + 2-oxoglutarate = acetoacetate + (R)-2-hydroxyglutarate. 2-oxoglutaric acid + 4-hydroxybutanoic acid = (R)-2-hydroxyglutaric acid + succinic semialdehyde.
Subcellular location	Mitochondrion. Ref.3
Tissue specificity	Expressed in white and brown adipose tissues, liver, and kidney. Expression is differentiation-dependent during in vitro brown and white adipogenesis. Ref.3
Induction	Down-regulated of 40% in white adipose tissue of ob/ob obese mice. Ref.3
Sequence similarities	Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Molecular function	Oxidoreductase
Gene Ontology (GO)
Biological process	molecular hydrogen transport Inferred from sequence or structural similarity. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrion Ref.3 Inferred from direct assay. Source: UniProtKB
Molecular function	hydroxyacid-oxoacid transhydrogenase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8R0N6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8R0N6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 465		Hydroxyacid-oxoacid transhydrogenase, mitochondrial		PRO_0000322997
Natural variations
	Alternative sequence	1 – 46	46	Missing in isoform 2.		VSP_031987

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 2. Checksum: CD1463685F788C2A	FASTA	465	49,937
	10 20 30 40 50 60 MAAAARARVT HLLRHLQSTA CQCPTHSHTY SQAPGPSGKT ADYAFEMAVS NIRYGAGVTK 70 80 90 100 110 120 EVGMDLQNMG AKNVCLMTDK NLSQLPPVQI VMDSLSKNGI SFQVYDDVRV EPTDGSFMDA 130 140 150 160 170 180 IEFAKKGAFD AYVAVGGGST MDTCKAANLY ASSPHSEFLD YVNAPIGKGK PVTVPLKPLI 190 200 210 220 230 240 AVPTTSGTGS ETTGVAIFDY EHLKVKTGIA SRAIKPTLGL VDPLHTLHMP CQVVANSGFD 250 260 270 280 290 300 VLCHALESYT AIPYSMRSPC PSNPIQRPAY QGSNPISDIW AVHALQIVAK YLKRAVRNPD 310 320 330 340 350 360 DLEARSKMHL ASAFAGIGFG NAGVHLCHGM SYPISGLVKT YKAKEYNVDH PLVPHGLSVV 370 380 390 400 410 420 LTSPAVFTFT AQMFPERHLE TAGILGANIR TARIQDAGLV LADALRKFLF DLNVDDGLAA 430 440 450 460 LGYSKDDIPS LVKGTLPQER VTKLAPRAQS EEDLSALFEA SMKLY
	Isoform 2. Checksum: 510F18E8678AB656	FASTA	419	45,015
	10 20 30 40 50 60 MAVSNIRYGA GVTKEVGMDL QNMGAKNVCL MTDKNLSQLP PVQIVMDSLS KNGISFQVYD 70 80 90 100 110 120 DVRVEPTDGS FMDAIEFAKK GAFDAYVAVG GGSTMDTCKA ANLYASSPHS EFLDYVNAPI 130 140 150 160 170 180 GKGKPVTVPL KPLIAVPTTS GTGSETTGVA IFDYEHLKVK TGIASRAIKP TLGLVDPLHT 190 200 210 220 230 240 LHMPCQVVAN SGFDVLCHAL ESYTAIPYSM RSPCPSNPIQ RPAYQGSNPI SDIWAVHALQ 250 260 270 280 290 300 IVAKYLKRAV RNPDDLEARS KMHLASAFAG IGFGNAGVHL CHGMSYPISG LVKTYKAKEY 310 320 330 340 350 360 NVDHPLVPHG LSVVLTSPAV FTFTAQMFPE RHLETAGILG ANIRTARIQD AGLVLADALR 370 380 390 400 410 KFLFDLNVDD GLAALGYSKD DIPSLVKGTL PQERVTKLAP RAQSEEDLSA LFEASMKLY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Hypothalamus and Liver.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N. Tissue: Kidney.
[3]	"Differentiation-dependent expression of Adhfe1 in adipogenesis." Kim J.Y., Tillison K.S., Zhou S., Lee J.H., Smas C.M. Arch. Biochem. Biophys. 464:100-111(2007) [PubMed: 17559793] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK038853 mRNA. Translation: BAC30151.1. AK050178 mRNA. Translation: BAC34108.1. BC026584 mRNA. Translation: AAH26584.2.
IPI	IPI00227186. IPI00889240.
RefSeq	NP_780445.1.
UniGene	Mm.28514
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000025911. Mus musculus. [Contig view]
GeneID	76187.
KEGG	mmu:76187.
Organism-specific databases
MGI	MGI:1923437. Adhfe1.
Phylogenomic databases
HOGENOM	Q8R0N6.
HOVERGEN	Q8R0N6.
OMA	Q8R0N6. YSKADIP.
Enzyme and pathway databases
BRENDA	1.1.99.24. 244.
Gene expression databases
ArrayExpress	Q8R0N6.
Bgee	Q8R0N6.
CleanEx	MM_ADHFE1.
Family and domain databases
InterPro	IPR001670. ADH_Fe. IPR018211. ADH_Fe_CS. [Graphical view]
Pfam	PF00465. Fe-ADH. 1 hit. [Graphical view]
PROSITE	PS00913. ADH_IRON_1. False negative. PS00060. ADH_IRON_2. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	344737.
SOURCE	Search...

Entry information

Entry name

HOT_MOUSE

Accession

Primary (citable) accession number: Q8R0N6
Secondary accession number(s): Q78SV3, Q8BYP0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	July 5, 2004
Last modified:	June 16, 2009
This is version 48 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)