Hydroxyacid-oxoacid transhydrogenase, mitochondrial

Details

Name

Hydroxyacid-oxoacid transhydrogenase, mitochondrial

Synonyms

• 1.1.99.24
• ADHFe1
• Alcohol dehydrogenase iron-containing protein 1
• Fe-containing alcohol dehydrogenase
• HOT

Gene Name

ADHFE1

Organism

Humans

Amino acid sequence

>lcl|BSEQ0049427|Hydroxyacid-oxoacid transhydrogenase, mitochondrial
MAAAARARVAYLLRQLQRAACQCPTHSHTYSQAPGLSPSGKTTDYAFEMAVSNIRYGAAV
TKEVGMDLKNMGAKNVCLMTDKNLSKLPPVQVAMDSLVKNGIPFTVYDNVRVEPTDSSFM
EAIEFAQKGAFDAYVAVGGGSTMDTCKAANLYASSPHSDFLDYVSAPIGKGKPVSVPLKP
LIAVPTTSGTGSETTGVAIFDYEHLKVKIGITSRAIKPTLGLIDPLHTLHMPARVVANSG
FDVLCHALESYTTLPYHLRSPCPSNPITRPAYQGSNPISDIWAIHALRIVAKYLKRAVRN
PDDLEARSHMHLASAFAGIGFGNAGVHLCHGMSYPISGLVKMYKAKDYNVDHPLVPHGLS
VVLTSPAVFTFTAQMFPERHLEMAEILGADTRTARIQDAGLVLADTLRKFLFDLDVDDGL
AAVGYSKADIPALVKGTLPQERVTKLAPCPQSEEDLAALFEASMKLY

Number of residues

467

Molecular Weight

50307.42

Theoretical pI

Not Available

GO Classification

Functions

alcohol dehydrogenase (NAD) activity / hydroxyacid-oxoacid transhydrogenase activity / metal ion binding

Processes

2-oxoglutarate metabolic process / molecular hydrogen transport

Components

cytosol / mitochondrial matrix / mitochondrion

General Function

Metal ion binding

Specific 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.

Pfam Domain Function

• Fe-ADH (PF00465)

Transmembrane Regions

Not Available

Cellular Location

Mitochondrion

Gene sequence

>lcl|BSEQ0049428|Hydroxyacid-oxoacid transhydrogenase, mitochondrial (ADHFE1)
ATGGCCGCTGCCGCCCGAGCCCGGGTCGCGTACTTGCTGAGGCAACTGCAACGCGCAGCG
TGCCAGTGCCCAACTCATTCTCATACTTACTCCCAAGCCCCTGGACTTTCACCTTCTGGG
AAAACAACAGATTATGCCTTTGAGATGGCTGTTTCAAATATTAGATATGGAGCAGCAGTT
ACAAAGGAAGTAGGAATGGACCTAAAAAACATGGGTGCTAAAAATGTGTGCTTGATGACA
GACAAGAACCTCTCCAAGCTCCCTCCTGTGCAAGTAGCTATGGATTCCCTAGTGAAGAAT
GGCATCCCCTTTACGGTTTATGATAATGTGAGAGTGGAACCAACGGATTCAAGCTTCATG
GAAGCTATTGAGTTTGCCCAAAAGGGAGCTTTTGATGCCTATGTTGCTGTCGGTGGTGGC
TCTACCATGGACACCTGTAAGGCTGCTAATCTGTATGCATCCAGCCCTCATTCTGATTTC
CTAGATTATGTCAGTGCCCCCATTGGCAAGGGAAAGCCTGTGTCTGTGCCTCTTAAGCCT
CTGATTGCAGTGCCAACTACCTCAGGAACCGGGAGTGAAACTACTGGGGTTGCCATTTTT
GACTATGAACACTTGAAAGTAAAAATTGGCATCACTTCGAGAGCCATCAAACCCACACTG
GGACTGATTGATCCTCTGCACACCCTCCACATGCCTGCCCGAGTGGTCGCCAACAGTGGC
TTTGATGTGCTTTGCCATGCCCTGGAGTCATACACCACCCTGCCCTACCACCTGCGGAGC
CCCTGCCCTTCAAATCCCATCACACGGCCTGCGTACCAGGGCAGCAACCCAATCAGTGAC
ATTTGGGCTATCCACGCGCTGCGGATCGTGGCTAAGTATCTGAAGAGGGCTGTCAGAAAT
CCCGATGATCTTGAAGCAAGGTCTCATATGCACTTGGCAAGTGCTTTTGCTGGCATCGGC
TTTGGAAATGCTGGTGTTCATCTGTGCCATGGAATGTCTTACCCAATTTCAGGTTTAGTG
AAGATGTATAAAGCAAAGGATTACAATGTGGATCACCCACTGGTGCCCCATGGCCTTTCT
GTGGTGCTCACGTCCCCAGCGGTGTTCACTTTCACGGCCCAGATGTTTCCAGAGCGACAC
CTGGAGATGGCAGAAATACTGGGAGCCGACACCCGCACTGCCAGGATCCAAGATGCAGGG
CTGGTGTTGGCAGACACGCTCCGGAAATTCTTATTCGATCTGGATGTTGATGATGGCCTA
GCAGCTGTTGGTTACTCCAAAGCTGATATCCCCGCACTAGTGAAAGGAACGCTGCCCCAG
GAAAGGGTCACCAAGCTTGCACCCTGTCCCCAGTCAGAAGAGGATCTGGCTGCTCTGTTT
GAAGCTTCAATGAAACTGTATTAA

Chromosome Location

Not Available

Locus

Not Available

External Identifiers

Resource	Link
UniProtKB ID	Q8IWW8
UniProtKB Entry Name	HOT_HUMAN
HGNC ID	HGNC:16354

General References

1. Deng Y, Wang Z, Gu S, Ji C, Ying K, Xie Y, Mao Y: Cloning and characterization of a novel human alcohol dehydrogenase gene (ADHFe1). DNA Seq. 2002 Oct;13(5):301-6. [Article]
2. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
4. 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: 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. Oncogene. 2004 Aug 5;23(35):5901-11. [Article]
5. Struys EA, Verhoeven NM, Ten Brink HJ, Wickenhagen WV, Gibson KM, Jakobs C: Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias. J Inherit Metab Dis. 2005;28(6):921-30. [Article]
6. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
7. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB09072	Sodium oxybate	approved	no	substrate	Details