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Q8IWW8

- HOT_HUMAN

UniProt

Q8IWW8 - HOT_HUMAN

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Protein
Hydroxyacid-oxoacid transhydrogenase, mitochondrial
Gene
ADHFE1, HMFT2263
Organism
Homo sapiens (Human)
Status
Reviewed - 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-KG
  3. KM=0.12 mM for D-2-HG
  4. KM=0.04 mM for SSA
  5. KM=0.8 mM for L-3-OHB

Vmax=16 nmol/h/mg enzyme with GHB and 2-KG as substrates

Vmax=0.5 nmol/h/mg enzyme with SSA and D-2-HG as substrates

Vmax=1.8 nmol/h/mg enzyme with L-3-OHB and 2-KG as substrates

pH dependencei

Optimum pH is 7.5.

GO - Molecular functioni

  1. hydroxyacid-oxoacid transhydrogenase activity Source: UniProtKB
  2. metal ion binding Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. 2-oxoglutarate metabolic process Source: Reactome
  2. cellular metabolic process Source: Reactome
  3. molecular hydrogen transport Source: UniProtKB
  4. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

ReactomeiREACT_25367. 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
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:16354. ADHFE1.

Subcellular locationi

Mitochondrion By similarity

GO - Cellular componenti

  1. mitochondrial matrix Source: Reactome
  2. mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134871493.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 467Hydroxyacid-oxoacid transhydrogenase, mitochondrialPRO_0000322996
Transit peptidei1 – ?Mitochondrion Reviewed prediction

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei445 – 4451N6-acetyllysine By similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ8IWW8.
PRIDEiQ8IWW8.

PTM databases

PhosphoSiteiQ8IWW8.

Expressioni

Tissue specificityi

Only expressed in adult liver.1 Publication

Gene expression databases

ArrayExpressiQ8IWW8.
BgeeiQ8IWW8.
CleanExiHS_ADHFE1.
GenevestigatoriQ8IWW8.

Organism-specific databases

HPAiHPA023062.

Interactioni

Protein-protein interaction databases

BioGridi126489. 2 interactions.
IntActiQ8IWW8. 2 interactions.
STRINGi9606.ENSP00000379865.

Structurei

3D structure databases

ProteinModelPortaliQ8IWW8.
SMRiQ8IWW8. Positions 58-463.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG1454.
HOGENOMiHOG000243335.
HOVERGENiHBG057032.
InParanoidiQ8IWW8.
KOiK11173.
OMAiRAACQCP.
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. Align

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

MAAAARARVA YLLRQLQRAA CQCPTHSHTY SQAPGLSPSG KTTDYAFEMA    50
VSNIRYGAAV TKEVGMDLKN MGAKNVCLMT DKNLSKLPPV QVAMDSLVKN 100
GIPFTVYDNV RVEPTDSSFM EAIEFAQKGA FDAYVAVGGG STMDTCKAAN 150
LYASSPHSDF LDYVSAPIGK GKPVSVPLKP LIAVPTTSGT GSETTGVAIF 200
DYEHLKVKIG ITSRAIKPTL GLIDPLHTLH MPARVVANSG FDVLCHALES 250
YTTLPYHLRS PCPSNPITRP AYQGSNPISD IWAIHALRIV AKYLKRAVRN 300
PDDLEARSHM HLASAFAGIG FGNAGVHLCH GMSYPISGLV KMYKAKDYNV 350
DHPLVPHGLS VVLTSPAVFT FTAQMFPERH LEMAEILGAD TRTARIQDAG 400
LVLADTLRKF LFDLDVDDGL AAVGYSKADI PALVKGTLPQ ERVTKLAPCP 450
QSEEDLAALF EASMKLY 467
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti242 – 2421D → V in a breast cancer sample; somatic mutation. 1 Publication
VAR_039470
Natural varianti449 – 4491C → R.2 Publications
Corresponds to variant rs1060242 [ dbSNP | Ensembl ].
VAR_054015

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4848Missing in isoform 2 and isoform 4.
VSP_031984Add
BLAST
Alternative sequencei299 – 3035RNPDD → NSTDK in isoform 3 and isoform 4.
VSP_031985
Alternative sequencei304 – 467164Missing in isoform 3 and isoform 4.
VSP_031986Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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

EnsembliENST00000379385; ENSP00000368695; ENSG00000147576. [Q8IWW8-3]
ENST00000396623; ENSP00000379865; ENSG00000147576. [Q8IWW8-1]
ENST00000415254; ENSP00000407115; ENSG00000147576. [Q8IWW8-2]
ENST00000424777; ENSP00000410883; ENSG00000147576. [Q8IWW8-3]
GeneIDi137872.
KEGGihsa:137872.
UCSCiuc003xwb.4. human. [Q8IWW8-1]

Polymorphism databases

DMDMi74714449.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS6190.2. [Q8IWW8-1 ]
RefSeqi NP_653251.2. NM_144650.2. [Q8IWW8-1 ]
UniGenei Hs.720023.

3D structure databases

ProteinModelPortali Q8IWW8.
SMRi Q8IWW8. Positions 58-463.
ModBasei Search...

Protein-protein interaction databases

BioGridi 126489. 2 interactions.
IntActi Q8IWW8. 2 interactions.
STRINGi 9606.ENSP00000379865.

Chemistry

ChEMBLi CHEMBL4947.

PTM databases

PhosphoSitei Q8IWW8.

Polymorphism databases

DMDMi 74714449.

Proteomic databases

PaxDbi Q8IWW8.
PRIDEi Q8IWW8.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000379385 ; ENSP00000368695 ; ENSG00000147576 . [Q8IWW8-3 ]
ENST00000396623 ; ENSP00000379865 ; ENSG00000147576 . [Q8IWW8-1 ]
ENST00000415254 ; ENSP00000407115 ; ENSG00000147576 . [Q8IWW8-2 ]
ENST00000424777 ; ENSP00000410883 ; ENSG00000147576 . [Q8IWW8-3 ]
GeneIDi 137872.
KEGGi hsa:137872.
UCSCi uc003xwb.4. human. [Q8IWW8-1 ]

Organism-specific databases

CTDi 137872.
GeneCardsi GC08P067344.
HGNCi HGNC:16354. ADHFE1.
HPAi HPA023062.
MIMi 611083. gene.
neXtProti NX_Q8IWW8.
PharmGKBi PA134871493.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1454.
HOGENOMi HOG000243335.
HOVERGENi HBG057032.
InParanoidi Q8IWW8.
KOi K11173.
OMAi RAACQCP.
PhylomeDBi Q8IWW8.
TreeFami TF105710.

Enzyme and pathway databases

Reactomei REACT_25367. Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.

Miscellaneous databases

GenomeRNAii 137872.
NextBioi 83689.
PROi Q8IWW8.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8IWW8.
Bgeei Q8IWW8.
CleanExi HS_ADHFE1.
Genevestigatori Q8IWW8.

Family and domain databases

InterProi IPR001670. ADH_Fe.
[Graphical view ]
Pfami PF00465. Fe-ADH. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of a novel human alcohol dehydrogenase gene (ADHFe1)."
    Deng Y., Wang Z., Gu S., Ji C., Ying K., Xie Y., Mao Y.
    DNA Seq. 13:301-306(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
    Tissue: Fetal brain.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANT ARG-449.
    Tissue: Placenta and Skeletal muscle.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
    Tissue: Pancreas.
  5. "Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas."
    Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S., Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S., Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.
    Oncogene 23:5901-5911(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 415-467, VARIANT ARG-449.
    Tissue: Hepatoblastoma.
  6. "Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias."
    Struys E.A., Verhoeven N.M., Ten Brink H.J., Wickenhagen W.V., Gibson K.M., Jakobs C.
    J. Inherit. Metab. Dis. 28:921-930(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBSTRATE SPECIFICITY, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
  7. Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-242.

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: September 3, 2014
This is version 83 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

External Data

Dasty 3

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