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Q8IWW8 (HOT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Fe-containing alcohol dehydrogenase
Gene names
Name:ADHFE1
ORF Names:HMFT2263
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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). D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities. Ref.6

Catalytic activity

(S)-3-hydroxybutanoate + 2-oxoglutarate = acetoacetate + (R)-2-hydroxyglutarate. Ref.6

4-hydroxybutanoate + 2-oxoglutarate = succinic semialdehyde + (R)-2-hydroxyglutarate. Ref.6

Subcellular location

Mitochondrion By similarity.

Tissue specificity

Only expressed in adult liver. Ref.1

Sequence similarities

Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=0.17 mM for GHB Ref.6

KM=1.2 mM for 2-KG

KM=0.12 mM for D-2-HG

KM=0.04 mM for SSA

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 dependence:

Optimum pH is 7.5.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IWW8-1)

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: Q8IWW8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: Missing.
Isoform 3 (identifier: Q8IWW8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     299-303: RNPDD → NSTDK
     304-467: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8IWW8-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 467Hydroxyacid-oxoacid transhydrogenase, mitochondrialPRO_0000322996

Amino acid modifications

Modified residue4451N6-acetyllysine By similarity

Natural variations

Alternative sequence1 – 4848Missing in isoform 2 and isoform 4.
VSP_031984
Alternative sequence299 – 3035RNPDD → NSTDK in isoform 3 and isoform 4.
VSP_031985
Alternative sequence304 – 467164Missing in isoform 3 and isoform 4.
VSP_031986
Natural variant2421D → V in a breast cancer sample; somatic mutation. Ref.7
VAR_039470
Natural variant4491C → R. Ref.2 Ref.5
Corresponds to variant rs1060242 [ dbSNP | Ensembl ].
VAR_054015

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: C66E0EB15610A0E3

FASTA46750,308
        10         20         30         40         50         60 
MAAAARARVA YLLRQLQRAA CQCPTHSHTY SQAPGLSPSG KTTDYAFEMA VSNIRYGAAV 

        70         80         90        100        110        120 
TKEVGMDLKN MGAKNVCLMT DKNLSKLPPV QVAMDSLVKN GIPFTVYDNV RVEPTDSSFM 

       130        140        150        160        170        180 
EAIEFAQKGA FDAYVAVGGG STMDTCKAAN LYASSPHSDF LDYVSAPIGK GKPVSVPLKP 

       190        200        210        220        230        240 
LIAVPTTSGT GSETTGVAIF DYEHLKVKIG ITSRAIKPTL GLIDPLHTLH MPARVVANSG 

       250        260        270        280        290        300 
FDVLCHALES YTTLPYHLRS PCPSNPITRP AYQGSNPISD IWAIHALRIV AKYLKRAVRN 

       310        320        330        340        350        360 
PDDLEARSHM HLASAFAGIG FGNAGVHLCH GMSYPISGLV KMYKAKDYNV DHPLVPHGLS 

       370        380        390        400        410        420 
VVLTSPAVFT FTAQMFPERH LEMAEILGAD TRTARIQDAG LVLADTLRKF LFDLDVDDGL 

       430        440        450        460 
AAVGYSKADI PALVKGTLPQ ERVTKLAPCP QSEEDLAALF EASMKLY 

« Hide

Isoform 2 [UniParc].

Checksum: F1EE897BD6B3B278
Show »

FASTA41945,129
Isoform 3 [UniParc].

Checksum: B2F4BA2C5EBB4625
Show »

FASTA30332,531
Isoform 4 [UniParc].

Checksum: 7A5416F035CEB0EB
Show »

FASTA25527,353

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-242.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_653251.2. NM_144650.2.
UniGeneHs.720023.

3D structure databases

ProteinModelPortalQ8IWW8.
SMRQ8IWW8. Positions 58-463.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid126489. 2 interactions.
IntActQ8IWW8. 2 interactions.
STRING9606.ENSP00000379865.

Chemistry

ChEMBLCHEMBL4947.

PTM databases

PhosphoSiteQ8IWW8.

Polymorphism databases

DMDM74714449.

Proteomic databases

PaxDbQ8IWW8.
PRIDEQ8IWW8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379385; ENSP00000368695; ENSG00000147576. [Q8IWW8-3]
ENST00000396623; ENSP00000379865; ENSG00000147576. [Q8IWW8-1]
ENST00000415254; ENSP00000407115; ENSG00000147576. [Q8IWW8-2]
ENST00000424777; ENSP00000410883; ENSG00000147576. [Q8IWW8-3]
GeneID137872.
KEGGhsa:137872.
UCSCuc003xwb.4. human. [Q8IWW8-1]

Organism-specific databases

CTD137872.
GeneCardsGC08P067344.
HGNCHGNC:16354. ADHFE1.
HPAHPA023062.
MIM611083. gene.
neXtProtNX_Q8IWW8.
PharmGKBPA134871493.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1454.
HOGENOMHOG000243335.
HOVERGENHBG057032.
InParanoidQ8IWW8.
KOK11173.
OMARAACQCP.
PhylomeDBQ8IWW8.
TreeFamTF105710.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ8IWW8.
BgeeQ8IWW8.
CleanExHS_ADHFE1.
GenevestigatorQ8IWW8.

Family and domain databases

InterProIPR001670. ADH_Fe.
[Graphical view]
PfamPF00465. Fe-ADH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi137872.
NextBio83689.
PROQ8IWW8.
SOURCESearch...

Entry information

Entry nameHOT_HUMAN
AccessionPrimary (citable) accession number: Q8IWW8
Secondary accession number(s): B4DTJ8 expand/collapse secondary AC list , Q49A19, Q68CI7, Q6P2B6, Q96MF9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2003
Last modified: April 16, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM