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Protein

Hydroxyacid-oxoacid transhydrogenase, mitochondrial

Gene

ADHFE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • 2-oxoglutarate metabolic process Source: Reactome
  • molecular hydrogen transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

BioCyciZFISH:HS07450-MONOMER.
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:1.1.99.24)
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

HGNCiHGNC:16354. ADHFE1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
SMRiQ8IWW8.
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

InterProiIPR001670. ADH_Fe.
[Graphical view]
PfamiPF00465. Fe-ADH. 1 hit.
[Graphical view]

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 → R.2 PublicationsCorresponds to variant rs1060242dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8IWW8.
SMRiQ8IWW8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126489. 2 interactors.
IntActiQ8IWW8. 2 interactors.
STRINGi9606.ENSP00000379865.

Chemistry databases

ChEMBLiCHEMBL4947.

PTM databases

iPTMnetiQ8IWW8.
PhosphoSitePlusiQ8IWW8.

Polymorphism and mutation databases

BioMutaiADHFE1.
DMDMi74714449.

Proteomic databases

PaxDbiQ8IWW8.
PeptideAtlasiQ8IWW8.
PRIDEiQ8IWW8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi137872.
DisGeNETi137872.
GeneCardsiADHFE1.
HGNCiHGNC:16354. ADHFE1.
HPAiHPA023062.
MIMi611083. gene.
neXtProtiNX_Q8IWW8.
OpenTargetsiENSG00000147576.
PharmGKBiPA134871493.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS07450-MONOMER.
BRENDAi1.1.99.24. 2681.
ReactomeiR-HSA-880009. Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.

Miscellaneous databases

GenomeRNAii137872.
PROiQ8IWW8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147576.
CleanExiHS_ADHFE1.
ExpressionAtlasiQ8IWW8. baseline and differential.
GenevisibleiQ8IWW8. HS.

Family and domain databases

InterProiIPR001670. ADH_Fe.
[Graphical view]
PfamiPF00465. Fe-ADH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHOT_HUMAN
AccessioniPrimary (citable) accession number: Q8IWW8
Secondary accession number(s): B4DTJ8
, Q49A19, Q68CI7, Q6P2B6, Q96MF9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 103 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.