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Protein

Hydroxyacid-oxoacid transhydrogenase, mitochondrial

Gene

ADHFE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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). D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities.1 Publication

Catalytic activityi

(S)-3-hydroxybutanoate + 2-oxoglutarate = acetoacetate + (R)-2-hydroxyglutarate.1 Publication
4-hydroxybutanoate + 2-oxoglutarate = succinic semialdehyde + (R)-2-hydroxyglutarate.1 Publication

Kineticsi

  1. KM=0.17 mM for GHB1 Publication
  2. KM=1.2 mM for 2-KG1 Publication
  3. KM=0.12 mM for D-2-HG1 Publication
  4. KM=0.04 mM for SSA1 Publication
  5. KM=0.8 mM for L-3-OHB1 Publication
  1. Vmax=16 nmol/h/mg enzyme with GHB and 2-KG as substrates1 Publication
  2. Vmax=0.5 nmol/h/mg enzyme with SSA and D-2-HG as substrates1 Publication
  3. Vmax=1.8 nmol/h/mg enzyme with L-3-OHB and 2-KG as substrates1 Publication

pH dependencei

Optimum pH is 7.5.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase

Enzyme and pathway databases

BRENDAi1.1.99.24 2681
ReactomeiR-HSA-880009 Interconversion of 2-oxoglutarate and 2-hydroxyglutarate

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxyacid-oxoacid transhydrogenase, mitochondrial (EC:1.1.99.241 Publication)
Short name:
HOT
Alternative name(s):
Alcohol dehydrogenase iron-containing protein 1
Short name:
ADHFe1
Fe-containing alcohol dehydrogenase
Gene namesi
Name:ADHFE1
ORF Names:HMFT2263
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000147576.15
HGNCiHGNC:16354 ADHFE1
MIMi611083 gene
neXtProtiNX_Q8IWW8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi137872
OpenTargetsiENSG00000147576
PharmGKBiPA134871493

Chemistry databases

ChEMBLiCHEMBL4947

Polymorphism and mutation databases

BioMutaiADHFE1
DMDMi74714449

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000322996? – 467Hydroxyacid-oxoacid transhydrogenase, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei445N6-acetyllysineBy similarity1
Modified residuei452PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ8IWW8
PeptideAtlasiQ8IWW8
PRIDEiQ8IWW8

PTM databases

iPTMnetiQ8IWW8
PhosphoSitePlusiQ8IWW8

Expressioni

Tissue specificityi

Only expressed in adult liver.1 Publication

Gene expression databases

BgeeiENSG00000147576
CleanExiHS_ADHFE1
ExpressionAtlasiQ8IWW8 baseline and differential
GenevisibleiQ8IWW8 HS

Organism-specific databases

HPAiHPA023062

Interactioni

Protein-protein interaction databases

BioGridi126489, 2 interactors
IntActiQ8IWW8, 2 interactors
STRINGi9606.ENSP00000379865

Structurei

3D structure databases

ProteinModelPortaliQ8IWW8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG3857 Eukaryota
COG1454 LUCA
GeneTreeiENSGT00390000003849
HOGENOMiHOG000243335
HOVERGENiHBG057032
InParanoidiQ8IWW8
KOiK11173
OMAiRAACQCP
OrthoDBiEOG091G064B
PhylomeDBiQ8IWW8
TreeFamiTF105710

Family and domain databases

InterProiView protein in InterPro
IPR001670 ADH_Fe/gldA
PfamiView protein in Pfam
PF00465 Fe-ADH, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IWW8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAAAARARVA YLLRQLQRAA CQCPTHSHTY SQAPGLSPSG KTTDYAFEMA
60 70 80 90 100
VSNIRYGAAV TKEVGMDLKN MGAKNVCLMT DKNLSKLPPV QVAMDSLVKN
110 120 130 140 150
GIPFTVYDNV RVEPTDSSFM EAIEFAQKGA FDAYVAVGGG STMDTCKAAN
160 170 180 190 200
LYASSPHSDF LDYVSAPIGK GKPVSVPLKP LIAVPTTSGT GSETTGVAIF
210 220 230 240 250
DYEHLKVKIG ITSRAIKPTL GLIDPLHTLH MPARVVANSG FDVLCHALES
260 270 280 290 300
YTTLPYHLRS PCPSNPITRP AYQGSNPISD IWAIHALRIV AKYLKRAVRN
310 320 330 340 350
PDDLEARSHM HLASAFAGIG FGNAGVHLCH GMSYPISGLV KMYKAKDYNV
360 370 380 390 400
DHPLVPHGLS VVLTSPAVFT FTAQMFPERH LEMAEILGAD TRTARIQDAG
410 420 430 440 450
LVLADTLRKF LFDLDVDDGL AAVGYSKADI PALVKGTLPQ ERVTKLAPCP
460
QSEEDLAALF EASMKLY
Length:467
Mass (Da):50,308
Last modified:March 1, 2003 - v1
Checksum:iC66E0EB15610A0E3
GO
Isoform 2 (identifier: Q8IWW8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: Missing.

Show »
Length:419
Mass (Da):45,129
Checksum:iF1EE897BD6B3B278
GO
Isoform 3 (identifier: Q8IWW8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     299-303: RNPDD → NSTDK
     304-467: Missing.

Note: No experimental confirmation available.
Show »
Length:303
Mass (Da):32,531
Checksum:iB2F4BA2C5EBB4625
GO
Isoform 4 (identifier: Q8IWW8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: Missing.
     299-303: RNPDD → NSTDK
     304-467: Missing.

Note: No experimental confirmation available.
Show »
Length:255
Mass (Da):27,353
Checksum:i7A5416F035CEB0EB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_039470242D → V in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_054015449C → R2 PublicationsCorresponds to variant dbSNP:rs1060242Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0319841 – 48Missing in isoform 2 and isoform 4. 3 PublicationsAdd BLAST48
Alternative sequenceiVSP_031985299 – 303RNPDD → NSTDK in isoform 3 and isoform 4. 2 Publications5
Alternative sequenceiVSP_031986304 – 467Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST164

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY033237 mRNA Translation: AAK44223.1
AK056992 mRNA Translation: BAB71335.1
AK300243 mRNA Translation: BAG62010.1
CH471068 Genomic DNA Translation: EAW86902.1
CH471068 Genomic DNA Translation: EAW86903.1
CH471068 Genomic DNA Translation: EAW86907.1
BC064634 mRNA Translation: AAH64634.1
AB075879 mRNA Translation: BAD38661.1
CCDSiCCDS6190.2 [Q8IWW8-1]
RefSeqiNP_653251.2, NM_144650.2 [Q8IWW8-1]
UniGeneiHs.720023

Genome annotation databases

EnsembliENST00000396623; ENSP00000379865; ENSG00000147576 [Q8IWW8-1]
ENST00000415254; ENSP00000407115; ENSG00000147576 [Q8IWW8-2]
ENST00000424777; ENSP00000410883; ENSG00000147576 [Q8IWW8-3]
GeneIDi137872
KEGGihsa:137872
UCSCiuc003xwb.5 human [Q8IWW8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHOT_HUMAN
AccessioniPrimary (citable) accession number: Q8IWW8
Secondary accession number(s): B4DTJ8
, Q49A19, Q68CI7, Q6P2B6, Q96MF9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2003
Last modified: March 28, 2018
This is version 108 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health