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Q8IWW8

- HOT_HUMAN

UniProt

Q8IWW8 - HOT_HUMAN

Protein

Hydroxyacid-oxoacid transhydrogenase, mitochondrial

Gene

ADHFE1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 84 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    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

    Vmax=16 nmol/h/mg enzyme with GHB and 2-KG as substrates1 Publication

    Vmax=0.5 nmol/h/mg enzyme with SSA and D-2-HG as substrates1 Publication

    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

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

    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

    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

    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 – ?MitochondrionSequence Analysis

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei445 – 4451N6-acetyllysineBy 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.
    ModBaseiSearch...
    MobiDBiSearch...

    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. 3 PublicationsVSP_031984Add
    BLAST
    Alternative sequencei299 – 3035RNPDD → NSTDK in isoform 3 and isoform 4. 2 PublicationsVSP_031985
    Alternative sequencei304 – 467164Missing in isoform 3 and isoform 4. 2 PublicationsVSP_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

    EnsembliENST00000396623; 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...
    MobiDBi 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 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

    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: October 1, 2014
    This is version 84 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