Reviewed, UniProtKB/Swiss-Prot Q4QQW3 (HOT_RAT)

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
      Short name=ADHFe1

Gene names

Name:

Adhfe1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein 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.2.
Tissue specificity	Expressed in kidney and liver. Ref.2
Sequence similarities	Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.
Biophysicochemical properties	Kinetic parameters: KM=0.3 mM for GHB KM=0.4 mM for D-2-HG KM=0.018 mM for 2-KG KM=0.005 mM for SSA KM=3 mM for L-3-OHB

Ontologies

Keywords
Cellular component	Mitochondrion
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 Inferred from sequence or structural similarity. 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 467		Hydroxyacid-oxoacid transhydrogenase, mitochondrial		PRO_0000322999

Sequences

	Sequence		Length	Mass (Da)
	Q4QQW3-1 [UniParc]. Last modified July 19, 2005. Version 1. Checksum: 97F4EB2243EBE7DB	FASTA	467	50,226
	10 20 30 40 50 60 MAAAARARVT HLLRHLQSTA CQCPTHSHTY SQVPGLSPSG KTTDYAFEMA VSNIRYGAGV 70 80 90 100 110 120 TKEVGMDLQN MGAKNVCLMT DKNLSQLPPV QIVMDSLSKN GISFQVYDNV RVEPTDGSFM 130 140 150 160 170 180 DAIEFAKKGA FDAYVAVGGG STMDTCKAAN LYACSPHSEF LDYVNAPIGK GKPVTVPLKP 190 200 210 220 230 240 LIAVPTTSGT GSETTGVAIF DYEHLKVKTG IASRAIKPTL GLVDPLHTLH MPCQVVANSG 250 260 270 280 290 300 FDVLCHALES YTAIPYSMRS PCPSNPIQRP AYQGSNPISD IWAVHALRIV AKYLKRAVRN 310 320 330 340 350 360 PDDLEARSSM HLASAFAGIG FGNAGVHLCH GMSYPISGLV KTYKAKEYNV DHPLVPHGLS 370 380 390 400 410 420 VVLTSPAVFT FTAQMFPERH LETAEILGAN IRTAKIQDAG PVLADALRKF LFDLNVDDGL 430 440 450 460 AALGYSKDDI PSLVKGTLPQ ERVTKLAPRA QSEEDLSALF EASMKLY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Liver.
[2]	"Isolation and characterization of a hydroxyacid-oxoacid transhydrogenase from rat kidney mitochondria." Kaufman E.E., Nelson T., Fales H.M., Levin D.M. J. Biol. Chem. 263:16872-16879(1988) [PubMed: 3182820] [Abstract] Cited for: SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC097945 mRNA. Translation: AAH97945.1.
IPI	IPI00358481.
RefSeq	NP_001020594.1.
UniGene	Rn.17173
3D structure databases
SMR	Q4QQW3. Positions 46-465.
ModBase	Search...
Protein-protein interaction databases
STRING	Q4QQW3.
Genome annotation databases
Ensembl	ENSRNOT00000009462; ENSRNOP00000009462; ENSRNOG00000007069; Rattus norvegicus. [Genome view]
GeneID	362474.
KEGG	rno:362474.
UCSC	NM_001025423. rat.
Organism-specific databases
CTD	362474.
RGD	1308863. Adhfe1.
Phylogenomic databases
eggNOG	roNOG10256.
HOVERGEN	Q4QQW3.
InParanoid	Q4QQW3.
Enzyme and pathway databases
BRENDA	1.1.99.24. 248.
Gene expression databases
ArrayExpress	Q4QQW3.
Genevestigator	Q4QQW3.
Family and domain databases
InterPro	IPR001670. ADH_Fe. [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	680067.

Entry information

Entry name

HOT_RAT

Accession

Primary (citable) accession number: Q4QQW3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	July 19, 2005
Last modified:	February 9, 2010
This is version 35 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)