You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP00379
Secondary Accession Numbers
  • 5616
  • HMDBP03243
  • HMDBP05449
Name 3-hydroxyacyl-CoA dehydrogenase type-2
Synonyms
  1. 17-beta-HSD 10
  2. 17-beta-hydroxysteroid dehydrogenase 10
  3. 3-hydroxy-2-methylbutyryl-CoA dehydrogenase
  4. 3-hydroxyacyl-CoA dehydrogenase type II
  5. Endoplasmic reticulum-associated amyloid beta-peptide-binding protein
  6. Mitochondrial RNase P protein 2
  7. Mitochondrial ribonuclease P protein 2
  8. Short-chain type dehydrogenase/reductase XH98G2
  9. Type II HADH
Gene Name HSD17B10
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Functions in mitochondrial tRNA maturation. Part of mitochondrial ribonuclease P, an enzyme composed of MRPP1/TRMT10C, MRPP2/HSD17B10 and MRPP3/KIAA0391, which cleaves tRNA molecules in their 5'-ends. By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD).
Pathways
  • 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
  • 3-hydroxyisobutyric acid dehydrogenase deficiency
  • 3-hydroxyisobutyric aciduria
  • 3-Methylcrotonyl Coa Carboxylase Deficiency Type I
  • 3-Methylglutaconic Aciduria Type I
  • 3-Methylglutaconic Aciduria Type III
  • 3-Methylglutaconic Aciduria Type IV
  • Alzheimer's disease
  • Beta-Ketothiolase Deficiency
  • Fatty Acid Elongation In Mitochondria
  • Isobutyryl-coa dehydrogenase deficiency
  • Isovaleric acidemia
  • Isovaleric Aciduria
  • Long-chain-3-hydroxyacyl-coa dehydrogenase deficiency (LCHAD)
  • Maple Syrup Urine Disease
  • Methylmalonate Semialdehyde Dehydrogenase Deficiency
  • Methylmalonic Aciduria
  • Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids
  • Propionic Acidemia
  • Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (SCHAD)
  • Valine, Leucine and Isoleucine Degradation
  • Valine, leucine and isoleucine degradation
  • Valproic Acid Metabolism Pathway
Reactions
(S)-3-hydroxyacyl-CoA + NAD → 3-oxoacyl-CoA + NADH details
2-Methyl-3-hydroxybutyryl-CoA + NAD → 2-Methylacetoacetyl-CoA + NADH details
2-Methyl-3-hydroxybutyryl-CoA + NAD → 2-Methylacetoacetyl-CoA + NADH + Hydrogen Ion details
GO Classification
Biological Process
branched-chain amino acid catabolic process
cellular nitrogen compound metabolic process
Leydig cell differentiation
cell aging
tRNA processing
protein homotetramerization
lipid metabolic process
Cellular Component
mitochondrial matrix
endoplasmic reticulum
plasma membrane
mitochondrial inner membrane
Function
binding
catalytic activity
oxidoreductase activity
Molecular Function
NAD binding
beta-amyloid binding
3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity
acetoacetyl-CoA reductase activity
cholate 7-alpha-dehydrogenase activity
estradiol 17-beta-dehydrogenase activity
steroid binding
3-hydroxyacyl-CoA dehydrogenase activity
Process
metabolic process
physiological process
metabolism
oxidation reduction
Cellular Location
  1. Mitochondrion
  2. Secreted
Gene Properties
Chromosome Location X
Locus Xp11.2
SNPs HSD17B10
Gene Sequence
>786 bp
ATGGCAGCAGCGTGTCGGAGCGTGAAGGGCCTGGTGGCGGTAATAACCGGAGGAGCCTCG
GGCCTGGGCCTGGCCACGGCGGAGCGACTTGTGGGGCAGGGAGCCTCTGCTGTGCTTCTG
GACCTGCCCAACTCGGGTGGGGAGGCCCAAGCCAAGAAGTTAGGAAACAACTGCGTTTTC
GCCCCAGCCGACGTGACCTCTGAGAAGGATGTGCAAACAGCTCTGGCTCTAGCAAAAGGA
AAGTTTGGCCGTGTGGATGTAGCTGTCAACTGTGCAGGCATCGCGGTGGCTAGCAAGACG
TACAACTTAAAGAAGGGCCAGACCCATACCTTGGAAGACTTCCAGCGAGTTCTTGATGTG
AATCTCATGGGCACCTTCAATGTGATCCGCCTGGTGGCTGGTGAGATGGGCCAGAATGAA
CCAGACCAGGGAGGCCAACGTGGGGTCATCATCAACACTGCCAGTGTGGCTGCCTTCGAG
GGTCAGGTTGGACAAGCTGCATACTCTGCTTCCAAGGGGGGAATAGTGGGCATGACACTG
CCCATTGCTCGGGATCTGGCTCCCATAGGTATCCGGGTGATGACCATTGCCCCAGGTCTG
TTTGGCACCCCACTGCTGACCAGCCTCCCAGAGAAAGTGTGCAACTTCTTGGCCAGCCAA
GTGCCCTTCCCTAGCCGACTGGGTGACCCTGCTGAGTATGCTCACCTCGTACAGGCCATC
ATCGAGAACCCATTCCTCAATGGAGAGGTCATCCGGCTGGATGGGGCCATTCGTATGCAG
CCTTGA
Protein Properties
Number of Residues 261
Molecular Weight 25983.695
Theoretical pI 7.211
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>3-hydroxyacyl-CoA dehydrogenase type-2
MAAACRSVKGLVAVITGGASGLGLATAERLVGQGASAVLLDLPNSGGEAQAKKLGNNCVF
APADVTSEKDVQTALALAKGKFGRVDVAVNCAGIAVASKTYNLKKGQTHTLEDFQRVLDV
NLMGTFNVIRLVAGEMGQNEPDQGGQRGVIINTASVAAFEGQVGQAAYSASKGGIVGMTL
PIARDLAPIGIRVMTIAPGLFGTPLLTSLPEKVCNFLASQVPFPSRLGDPAEYAHLVQAI
IENPFLNGEVIRLDGAIRMQP
GenBank ID Protein 57210025
UniProtKB/Swiss-Prot ID Q99714
UniProtKB/Swiss-Prot Entry Name HCD2_HUMAN
PDB IDs
GenBank Gene ID U96132
GeneCard ID HSD17B10
GenAtlas ID HSD17B10
HGNC ID HGNC:4800
References
General References
  1. 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. [PubMed:15489334 ]
  2. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  3. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR: The DNA sequence of the human X chromosome. Nature. 2005 Mar 17;434(7031):325-37. [PubMed:15772651 ]
  4. Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama M, Ogawa S, Roher A, Stern D: An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. Nature. 1997 Oct 16;389(6652):689-95. [PubMed:9338779 ]
  5. Miller AP, Willard HF: Chromosomal basis of X chromosome inactivation: identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8709-14. [PubMed:9671743 ]
  6. He XY, Schulz H, Yang SY: A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease. J Biol Chem. 1998 Apr 24;273(17):10741-6. [PubMed:9553139 ]
  7. Lenski C, Kooy RF, Reyniers E, Loessner D, Wanders RJ, Winnepenninckx B, Hellebrand H, Engert S, Schwartz CE, Meindl A, Ramser J: The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior. Am J Hum Genet. 2007 Feb;80(2):372-7. Epub 2006 Dec 28. [PubMed:17236142 ]
  8. Froyen G, Corbett M, Vandewalle J, Jarvela I, Lawrence O, Meldrum C, Bauters M, Govaerts K, Vandeleur L, Van Esch H, Chelly J, Sanlaville D, van Bokhoven H, Ropers HH, Laumonnier F, Ranieri E, Schwartz CE, Abidi F, Tarpey PS, Futreal PA, Whibley A, Raymond FL, Stratton MR, Fryns JP, Scott R, Peippo M, Sipponen M, Partington M, Mowat D, Field M, Hackett A, Marynen P, Turner G, Gecz J: Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. Am J Hum Genet. 2008 Feb;82(2):432-43. doi: 10.1016/j.ajhg.2007.11.002. Epub 2008 Jan 24. [PubMed:18252223 ]
  9. Holzmann J, Frank P, Loffler E, Bennett KL, Gerner C, Rossmanith W: RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell. 2008 Oct 31;135(3):462-74. doi: 10.1016/j.cell.2008.09.013. [PubMed:18984158 ]
  10. Kissinger CR, Rejto PA, Pelletier LA, Thomson JA, Showalter RE, Abreo MA, Agree CS, Margosiak S, Meng JJ, Aust RM, Vanderpool D, Li B, Tempczyk-Russell A, Villafranca JE: Crystal structure of human ABAD/HSD10 with a bound inhibitor: implications for design of Alzheimer's disease therapeutics. J Mol Biol. 2004 Sep 17;342(3):943-52. [PubMed:15342248 ]
  11. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H: ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science. 2004 Apr 16;304(5669):448-52. [PubMed:15087549 ]
  12. Ofman R, Ruiter JP, Feenstra M, Duran M, Poll-The BT, Zschocke J, Ensenauer R, Lehnert W, Sass JO, Sperl W, Wanders RJ: 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene. Am J Hum Genet. 2003 May;72(5):1300-7. Epub 2003 Apr 14. [PubMed:12696021 ]
  13. Perez-Cerda C, Garcia-Villoria J, Ofman R, Sala PR, Merinero B, Ramos J, Garcia-Silva MT, Beseler B, Dalmau J, Wanders RJ, Ugarte M, Ribes A: 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease. Pediatr Res. 2005 Sep;58(3):488-91. [PubMed:16148061 ]