HSD17B10: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''17-β-Hydroxysteroid dehydrogenase X''' (HSD10) also known as '''3-hydroxyacyl-CoA dehydrogenase type-2''' is a mitochondrial [[enzyme]] that in humans is encoded by the ''HSD17B10'' (hydroxysteroid (17β) dehydrogenase 10) [[gene]].<ref name="pmid16899120">{{cite journal | vauthors = Marques AT, Antunes A, Fernandes PA, Ramos MJ | title = Comparative evolutionary genomics of the HADH2 gene encoding Abeta-binding alcohol dehydrogenase/17beta-hydroxysteroid dehydrogenase type 10 (ABAD/HSD10) | journal = BMC Genomics | volume = 7 | pages = 202 | date = Sep 2006 | pmid = 16899120 | pmc = 1559703 | doi = 10.1186/1471-2164-7-202 }}</ref><ref name="pmid21708223">{{cite journal | vauthors = Yang SY, He XY, Miller D | title = Hydroxysteroid (17β) dehydrogenase X in human health and disease | journal = Molecular and Cellular Endocrinology | volume = 343 | issue = 1–2 | pages = 1–6 | date = Aug 2011 | pmid = 21708223 | pmc =  | doi = 10.1016/j.mce.2011.06.011 }}</ref><ref name="pmid10329704">{{cite journal | vauthors = He XY, Merz G, Mehta P, Schulz H, Yang SY | title = Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase | journal = The Journal of Biological Chemistry | volume = 274 | issue = 21 | pages = 15014–9 | date = May 1999 | pmid = 10329704 | pmc =  | doi = 10.1074/jbc.274.21.15014 }}</ref><ref name="pmid19027726">{{cite journal | vauthors = Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U | title = The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative | journal = Chemico-Biological Interactions | volume = 178 | issue = 1–3 | pages = 94–8 | date = Mar 2009 | pmid = 19027726 | pmc = 2896744 | doi = 10.1016/j.cbi.2008.10.040 }}</ref><ref name="pmid18984158">{{cite journal | vauthors = Holzmann J, Frank P, Löffler E, Bennett KL, Gerner C, Rossmanith W | title = RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme | journal = Cell | volume = 135 | issue = 3 | pages = 462–74 | date = Oct 2008 | pmid = 18984158 | pmc =  | doi = 10.1016/j.cell.2008.09.013 }}</ref> Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined.<ref name="entrez">{{cite web | title = Entrez Gene: HSD17B10 hydroxysteroid (17-beta) dehydrogenase 10| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3028| accessdate = }}</ref> Human HSD10 [[cDNA]] was cloned from [[brain]] (NM_004493), and the resulting protein, a [[homotetramer]], was first characterized as a short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD).<ref name="pmid10600649">{{cite journal | vauthors = He XY, Yang YZ, Schulz H, Yang SY | title = Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase | journal = The Biochemical Journal | volume = 345 | pages = 139–43 | date = Jan 2000 | pmid = 10600649 | doi=10.1042/bj3450139 | issue=1 | pmc=1220740}}</ref> Active sites of this enzyme can accommodate different substrates; 17β-HSD10 is involved in the oxidation of [[isoleucine]], branched-chain [[fatty acids]], and [[xenobiotics]] as well as the metabolism of [[sex hormones]] and neuroactive [[steroids]].<ref name="pmid9338779">{{cite journal | vauthors = 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 | title = An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease | journal = Nature | volume = 389 | issue = 6652 | pages = 689–95 | date = Oct 1997 | pmid = 9338779 | pmc =  | doi = 10.1038/39522 }}</ref><ref name="pmid25007702">{{cite journal | vauthors = Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M | title = Roles of 17β-hydroxysteroid dehydrogenase type 10 in neurodegenerative disorders | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 143 | pages = 460–72 | date = Sep 2014 | pmid = 25007702 | doi = 10.1016/j.jsbmb.2014.07.001 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_HSD17B10_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1so8.
| PDB = {{PDB2|1so8}}, {{PDB2|1u7t}}, {{PDB2|2o23}}
| Name = Hydroxysteroid (17-beta) dehydrogenase 10
| HGNCid = 4800
| Symbol = HSD17B10
| AltSymbols =; 17b-HSD10; ABAD; ERAB; HADH2; HCD2; MHBD; SCHAD
| OMIM = 300256
| ECnumber = 
| Homologene = 68403
| MGIid = 1333871
| GeneAtlas_image1 = PBB_GE_HSD17B10_202282_at_tn.png
| Function = {{GNF_GO|id=GO:0003857 |text = 3-hydroxyacyl-CoA dehydrogenase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008709 |text = 7-alpha-hydroxysteroid dehydrogenase activity}} {{GNF_GO|id=GO:0016491 |text = oxidoreductase activity}} {{GNF_GO|id=GO:0047015 |text = 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}} {{GNF_GO|id=GO:0005743 |text = mitochondrial inner membrane}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}}
| Process = {{GNF_GO|id=GO:0006629 |text = lipid metabolic process}} {{GNF_GO|id=GO:0008152 |text = metabolic process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3028
    | Hs_Ensembl = ENSG00000072506
    | Hs_RefseqProtein = NP_001032900
    | Hs_RefseqmRNA = NM_001037811
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 53474931
    | Hs_GenLoc_end = 53478045
    | Hs_Uniprot = Q99714
    | Mm_EntrezGene = 15108
    | Mm_Ensembl = ENSMUSG00000025260
    | Mm_RefseqmRNA = NM_016763
    | Mm_RefseqProtein = NP_058043
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 147342597
    | Mm_GenLoc_end = 147345155
    | Mm_Uniprot = Q99N15
  }}
}}
'''Hydroxysteroid (17-beta) dehydrogenase 10''', also known as '''HSD17B10''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HSD17B10 hydroxysteroid (17-beta) dehydrogenase 10| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3028| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
17beta-hydroxysteroid dehydrogenase 10 is a member of the short-chain dehydrogenase/reductase superfamily.<ref name="pmid15860413">{{cite journal | vauthors = Yang SY, He XY, Schulz H | title = Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase | journal = Trends in Endocrinology and Metabolism | volume = 16 | issue = 4 | pages = 167–75 | year = 2005 | pmid = 15860413 | doi = 10.1016/j.tem.2005.03.006 }}</ref> This homotetrameric mitochondrial multifunctional enzyme catalyzes the [[oxidation]] of neuroactive [[steroids]] and the degradation of [[isoleucine]].<ref name="pmid19706438">{{cite journal | vauthors = Yang SY, He XY, Olpin SE, Sutton VR, McMenamin J, Philipp M, Denman RB, Malik M | title = Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 35 | pages = 14820–4 | date = Sep 2009 | pmid = 19706438 | pmc = 2728107 | doi = 10.1073/pnas.0902377106 }}</ref> This enzyme is capable of binding to other [[peptides]], such as [[estrogen receptor α]], [[amyloid-β]], and [[tRNA]] [[methyltransferase]] 10C. [[Missense mutations]] of the HSD17B10 gene result in 17β-HSD10 deficiency, an infantile [[neurodegeneration]] characterized by progressive psychomotor regression and alteration of [[mitochondria]] morphology. 17β-HSD10 exhibits only a negligible [[alcohol dehydrogenase]] activity, and is not localized in the [[endoplasmic reticulum]] or [[plasma membrane]]. Its alternate name – [[Aβ]] binding alcohol dehydrogenase (ABAD) – is a misnomer predicated on the mistaken belief that this enzyme is an alcohol dehydrogenase.<ref name="pmid25007702"/>
{{PBB_Summary
| section_title =  
| summary_text = This gene encodes 3-hydroxyacyl-CoA dehydrogenase type II, a member of the short-chain dehydrogenase/reductase superfamily. The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids, alcohols, and steroids. The protein has been implicated in the development of Alzheimer's disease, and mutations in the gene are the cause of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (MHBD). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined.<ref name="entrez">{{cite web | title = Entrez Gene: HSD17B10 hydroxysteroid (17-beta) dehydrogenase 10| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3028| accessdate = }}</ref>
}}


==References==
== Structure ==
{{reflist|2}}
 
==Further reading==
=== Gene ===
{{refbegin | 2}}
 
{{PBB_Further_reading
Human HSD17B10 gene has 6 [[exons]] resides on the [[X chromosome]] at p11.22.<ref name="entrez"/>
| citations =
 
*{{cite journal  | author=Yang SY, He XY, Schulz H |title=3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease. |journal=FEBS J. |volume=272 |issue= 19 |pages= 4874-83 |year= 2005 |pmid= 16176262 |doi= 10.1111/j.1742-4658.2005.04911.x }}
=== Protein ===
*{{cite journal | author=Yang SY, He XY, Miller D |title=HSD17B10: a gene involved in cognitive function through metabolism of isoleucine and neuroactive steroids. |journal=Mol. Genet. Metab. |volume=92 |issue= 1-2 |pages= 36-42 |year= 2007 |pmid= 17618155 |doi= 10.1016/j.ymgme.2007.06.001 }}
 
*{{cite journal  | author=Vredendaal PJ, van den Berg IE, Malingré HE, ''et al.'' |title=Human short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence. |journal=Biochem. Biophys. Res. Commun. |volume=223 |issue= 3 |pages= 718-23 |year= 1996 |pmid= 8687463 |doi= }}
The gene product is a mitochondrial protein that catalyzes the [[oxidation]] of a wide variety of [[fatty acids]] and [[steroids]], and is a subunit of mitochondrial [[ribonuclease P]], which is involved in [[tRNA]] maturation.<ref name="entrez"/> The [[molecular weight]] of 17β-HSD10 that is composed of four identical subunits is 108 kDa; each subunit consists of 261 [[amino acid]] residues.<ref name="pmid9553139">{{cite journal | vauthors = He XY, Schulz H, Yang SY | title = A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease | journal = The Journal of Biological Chemistry | volume = 273 | issue = 17 | pages = 10741–6 | date = Apr 1998 | pmid = 9553139 | doi=10.1074/jbc.273.17.10741}}</ref> Although the [[endoplasmic reticulum]] (ER)-associated [[amyloid-β]] peptide binding protein (ERAB) was reported to be associated with the ER and to consist of 262 residues with a molecular weight of 27 kDa,<ref name="pmid9338775">{{cite journal | vauthors = Beyreuther K, Masters CL | title = Alzheimer's disease. The ins and outs of amyloid-beta | journal = Nature | volume = 389 | issue = 6652 | pages = 677–8 | date = Oct 1997 | pmid = 9338775 | doi = 10.1038/39479 }}</ref> ERAB is actually identical to 17β-HSD10 that is localized in [[mitochondria]] but not ER.<ref name="pmid10329704"/>
*{{cite journal  | author=Furuta S, Kobayashi A, Miyazawa S, Hashimoto T |title=Cloning and expression of cDNA for a newly identified isozyme of bovine liver 3-hydroxyacyl-CoA dehydrogenase and its import into mitochondria. |journal=Biochim. Biophys. Acta |volume=1350 |issue= 3 |pages= 317-24 |year= 1997 |pmid= 9061028 |doi=  }}
 
*{{cite journal | author=Yan SD, Fu J, Soto C, ''et al.'' |title=An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. |journal=Nature |volume=389 |issue= 6652 |pages= 689-95 |year= 1997 |pmid= 9338779 |doi= 10.1038/39522 }}
== Clinical significance ==
*{{cite journal | author=He XY, Schulz H, Yang SY |title=A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease. |journal=J. Biol. Chem. |volume=273 |issue= 17 |pages= 10741-6 |year= 1998 |pmid= 9553139 |doi= }}
 
*{{cite journal  | author=Miller AP, Willard HF |title=Chromosomal basis of X chromosome inactivation: identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 15 |pages= 8709-14 |year= 1998 |pmid= 9671743 |doi= }}
Abnormal expression, as well as [[mutations]] of the HSD17B10 gene leads to impairment of the structure, function, and dynamics of mitochondria. This may underlie the [[pathogenesis]] of the synaptic and neuronal deficiency exhibited in 17β-HSD10 related diseases, including 17β-HSD10 deficiency and [[Alzheimer's disease]] (AD).<ref name="entrez" /> Missense and silent mutations in the gene are the cause of hydroxysteroid (17β) dehydrogenase X (HSD10) deficiency, formerly MHBD deficiency, and X-linked mental retardation, choreoathetosis, and abnormal behavior (MRXS10), respectively.<ref name="pmid19706438"/><ref name="pmid22132097">{{cite journal | vauthors = Seaver LH, He XY, Abe K, Cowan T, Enns GM, Sweetman L, Philipp M, Lee S, Malik M, Yang SY | title = A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, choreoathetosis and learning disability | journal = PLOS ONE | volume = 6 | issue = 11 | pages = e27348 | date = November 2011 | pmid = 22132097 | pmc = 3222643 | doi = 10.1371/journal.pone.0027348 }}</ref><ref name="pmid17236142">{{cite journal | vauthors = Lenski C, Kooy RF, Reyniers E, Loessner D, Wanders RJ, Winnepenninckx B, Hellebrand H, Engert S, Schwartz CE, Meindl A, Ramser J | title = The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior | journal = American Journal of Human Genetics | volume = 80 | issue = 2 | pages = 372–7 | date = Feb 2007 | pmid = 17236142 | pmc = 1785340 | doi = 10.1086/511527 }}</ref> Restoration of steroid [[homeostasis]] could be achieved by the supplementation of neuroactive steroids with a proper dosing and treatment regimen or by the adjustment of 17β-HSD10 activity to protect [[neurons]].<ref name="pmid25007702"/> The discovery of this enzyme's true function has opened a new therapeutic avenue for treating AD.
*{{cite journal  | author=Sambamurti K, Lahiri DK |title=ERAB contains a putative noncleavable signal peptide. |journal=Biochem. Biophys. Res. Commun. |volume=249 |issue= 2 |pages= 546-9 |year= 1998 |pmid= 9712734 |doi= 10.1006/bbrc.1998.9178 }}
 
*{{cite journal | author=Hansis C, Jähner D, Spiess AN, ''et al.'' |title=The gene for the Alzheimer-associated beta-amyloid-binding protein (ERAB) is differentially expressed in the testicular Leydig cells of the azoospermic by w/w(v) mouse. |journal=Eur. J. Biochem. |volume=258 |issue= 1 |pages= 53-60 |year= 1998 |pmid= 9851691 |doi= }}
== Interactions ==
*{{cite journal | author=Yan SD, Shi Y, Zhu A, ''et al.'' |title=Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity. |journal=J. Biol. Chem. |volume=274 |issue= 4 |pages= 2145-56 |year= 1999 |pmid= 9890977 |doi= }}
 
*{{cite journal | author=He XY, Merz G, Mehta P, ''et al.'' |title=Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase. |journal=J. Biol. Chem. |volume=274 |issue= 21 |pages= 15014-9 |year= 1999 |pmid= 10329704 |doi= }}
HSD17B10 has been shown to [[Protein-protein interaction|interact]] with [[Amyloid precursor protein]].<ref name=pmid9338779 />
*{{cite journal | author=Oppermann UC, Salim S, Tjernberg LO, ''et al.'' |title=Binding of amyloid beta-peptide to mitochondrial hydroxyacyl-CoA dehydrogenase (ERAB): regulation of an SDR enzyme activity with implications for apoptosis in Alzheimer's disease. |journal=FEBS Lett. |volume=451 |issue= 3 |pages= 238-42 |year= 1999 |pmid= 10371197 |doi= }}
 
*{{cite journal | author=He XY, Yang YZ, Schulz H, Yang SY |title=Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase. |journal=Biochem. J. |volume=345 Pt 1 |issue= |pages= 139-43 |year= 2000 |pmid= 10600649 |doi= }}
== References ==
*{{cite journal | author=Yang SY, He XY |title=Role of type 10 17beta-hydroxysteroid dehydrogenase in the pathogenesis of Alzheimer's disease. |journal=Adv. Exp. Med. Biol. |volume=487 |issue=  |pages= 101-10 |year= 2001 |pmid= 11403151 |doi= }}
{{reflist|33em}}
*{{cite journal  | author=Frackowiak J, Mazur-Kolecka B, Kaczmarski W, Dickson D |title=Deposition of Alzheimer's vascular amyloid-beta is associated with decreased expression of brain L-3-hydroxyacyl-coenzyme A dehydrogenase (ERAB). |journal=Brain Res. |volume=907 |issue= 1-2 |pages= 44-53 |year= 2001 |pmid= 11430884 |doi=  }}
 
*{{cite journal | author=He XY, Merz G, Yang YZ, ''et al.'' |title=Characterization and localization of human type10 17beta-hydroxysteroid dehydrogenase. |journal=Eur. J. Biochem. |volume=268 |issue= 18 |pages= 4899-907 |year= 2001 |pmid= 11559359 |doi= }}
== Further reading ==
*{{cite journal | author=He XY, Wen GY, Merz G, ''et al.'' |title=Abundant type 10 17 beta-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model. |journal=Brain Res. Mol. Brain Res. |volume=99 |issue= 1 |pages= 46-53 |year= 2002 |pmid= 11869808 |doi= }}
{{refbegin|33em}}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Vredendaal PJ, van den Berg IE, Malingré HE, Stroobants AK, Olde Weghuis DE, Berger R | title = Human short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence | journal = Biochemical and Biophysical Research Communications | volume = 223 | issue = 3 | pages = 718–23 | date = Jun 1996 | pmid = 8687463 | doi = 10.1006/bbrc.1996.0961 }}
*{{cite journal | author=Ofman R, Ruiter JP, Feenstra M, ''et al.'' |title=2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene. |journal=Am. J. Hum. Genet. |volume=72 |issue= 5 |pages= 1300-7 |year= 2003 |pmid= 12696021 |doi= }}
* {{cite journal | vauthors = Yang SY, He XY, Schulz H | title = 3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease | journal = The FEBS Journal | volume = 272 | issue = 19 | pages = 4874–83 | date = Oct 2005 | pmid = 16176262 | doi = 10.1111/j.1742-4658.2005.04911.x }}
*{{cite journal | author=Shafqat N, Marschall HU, Filling C, ''et al.'' |title=Expanded substrate screenings of human and Drosophila type 10 17beta-hydroxysteroid dehydrogenases (HSDs) reveal multiple specificities in bile acid and steroid hormone metabolism: characterization of multifunctional 3alpha/7alpha/7beta/17beta/20beta/21-HSD. |journal=Biochem. J. |volume=376 |issue= Pt 1 |pages= 49-60 |year= 2003 |pmid= 12917011 |doi= 10.1042/BJ20030877 }}
* {{cite journal | vauthors = Yang SY, He XY, Miller D | title = HSD17B10: a gene involved in cognitive function through metabolism of isoleucine and neuroactive steroids | journal = Molecular Genetics and Metabolism | volume = 92 | issue = 1–2 | pages = 36–42 | year = 2007 | pmid = 17618155 | doi = 10.1016/j.ymgme.2007.06.001 }}
}}
* {{cite journal | vauthors = Furuta S, Kobayashi A, Miyazawa S, Hashimoto T | title = Cloning and expression of cDNA for a newly identified isozyme of bovine liver 3-hydroxyacyl-CoA dehydrogenase and its import into mitochondria | journal = Biochimica et Biophysica Acta | volume = 1350 | issue = 3 | pages = 317–24 | date = Feb 1997 | pmid = 9061028 | doi = 10.1016/s0167-4781(96)00171-6 }}
* {{cite journal | vauthors = He XY, Schulz H, Yang SY | title = A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease | journal = The Journal of Biological Chemistry | volume = 273 | issue = 17 | pages = 10741–6 | date = Apr 1998 | pmid = 9553139 | doi = 10.1074/jbc.273.17.10741 }}
* {{cite journal | vauthors = Miller AP, Willard HF | title = Chromosomal basis of X chromosome inactivation: identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 15 | pages = 8709–14 | date = Jul 1998 | pmid = 9671743 | pmc = 21141 | doi = 10.1073/pnas.95.15.8709 }}
* {{cite journal | vauthors = Hansis C, Jähner D, Spiess AN, Boettcher K, Ivell R | title = The gene for the Alzheimer-associated beta-amyloid-binding protein (ERAB) is differentially expressed in the testicular Leydig cells of the azoospermic by w/w(v) mouse | journal = European Journal of Biochemistry / FEBS | volume = 258 | issue = 1 | pages = 53–60 | date = Nov 1998 | pmid = 9851691 | doi = 10.1046/j.1432-1327.1998.2580053.x }}
* {{cite journal | vauthors = Oppermann UC, Salim S, Tjernberg LO, Terenius L, Jörnvall H | title = Binding of amyloid beta-peptide to mitochondrial hydroxyacyl-CoA dehydrogenase (ERAB): regulation of an SDR enzyme activity with implications for apoptosis in Alzheimer's disease | journal = FEBS Letters | volume = 451 | issue = 3 | pages = 238–42 | date = May 1999 | pmid = 10371197 | doi = 10.1016/S0014-5793(99)00586-4 }}
* {{cite journal | vauthors = He XY, Yang YZ, Schulz H, Yang SY | title = Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase | journal = The Biochemical Journal | volume = 345 | issue = 1 | pages = 139–43 | date = Jan 2000 | pmid = 10600649 | pmc = 1220740 | doi = 10.1042/bj3450139 }}
* {{Cite book | vauthors = Yang SY, He XY | title = Role of type 10 17beta-hydroxysteroid dehydrogenase in the pathogenesis of Alzheimer's disease | journal = Advances in Experimental Medicine and Biology | volume = 487 | issue = | pages = 101–10 | year = 2001 | pmid = 11403151 | doi = 10.1007/978-1-4615-1249-3_8 | isbn = 978-1-4613-5461-1 }}
* {{cite journal | vauthors = Frackowiak J, Mazur-Kolecka B, Kaczmarski W, Dickson D | title = Deposition of Alzheimer's vascular amyloid-beta is associated with decreased expression of brain L-3-hydroxyacyl-coenzyme A dehydrogenase (ERAB) | journal = Brain Research | volume = 907 | issue = 1–2 | pages = 44–53 | date = Jul 2001 | pmid = 11430884 | doi = 10.1016/S0006-8993(01)02497-0 }}
* {{cite journal | vauthors = He XY, Merz G, Yang YZ, Mehta P, Schulz H, Yang SY | title = Characterization and localization of human type10 17beta-hydroxysteroid dehydrogenase | journal = European Journal of Biochemistry / FEBS | volume = 268 | issue = 18 | pages = 4899–907 | date = Sep 2001 | pmid = 11559359 | doi = 10.1046/j.0014-2956.2001.02421.2421.x }}
* {{cite journal | vauthors = He XY, Wen GY, Merz G, Lin D, Yang YZ, Mehta P, Schulz H, Yang SY | title = Abundant type 10 17 beta-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model | journal = Brain Research. Molecular Brain Research | volume = 99 | issue = 1 | pages = 46–53 | date = Feb 2002 | pmid = 11869808 | doi = 10.1016/S0169-328X(02)00102-X }}
* {{cite journal | vauthors = Ofman R, Ruiter JP, Feenstra M, Duran M, Poll-The BT, Zschocke J, Ensenauer R, Lehnert W, Sass JO, Sperl W, Wanders RJ | title = 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene | journal = American Journal of Human Genetics | volume = 72 | issue = 5 | pages = 1300–7 | date = May 2003 | pmid = 12696021 | pmc = 1180283 | doi = 10.1086/375116 }}
{{refend}}
{{refend}}


{{protein-stub}}
{{PDB Gallery|geneid=3028}}
{{WikiDoc Sources}}

Latest revision as of 22:35, 5 September 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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RefSeq (protein)

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17-β-Hydroxysteroid dehydrogenase X (HSD10) also known as 3-hydroxyacyl-CoA dehydrogenase type-2 is a mitochondrial enzyme that in humans is encoded by the HSD17B10 (hydroxysteroid (17β) dehydrogenase 10) gene.[1][2][3][4][5] Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined.[6] Human HSD10 cDNA was cloned from brain (NM_004493), and the resulting protein, a homotetramer, was first characterized as a short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD).[7] Active sites of this enzyme can accommodate different substrates; 17β-HSD10 is involved in the oxidation of isoleucine, branched-chain fatty acids, and xenobiotics as well as the metabolism of sex hormones and neuroactive steroids.[8][9]

Function

17beta-hydroxysteroid dehydrogenase 10 is a member of the short-chain dehydrogenase/reductase superfamily.[10] This homotetrameric mitochondrial multifunctional enzyme catalyzes the oxidation of neuroactive steroids and the degradation of isoleucine.[11] This enzyme is capable of binding to other peptides, such as estrogen receptor α, amyloid-β, and tRNA methyltransferase 10C. Missense mutations of the HSD17B10 gene result in 17β-HSD10 deficiency, an infantile neurodegeneration characterized by progressive psychomotor regression and alteration of mitochondria morphology. 17β-HSD10 exhibits only a negligible alcohol dehydrogenase activity, and is not localized in the endoplasmic reticulum or plasma membrane. Its alternate name – Aβ binding alcohol dehydrogenase (ABAD) – is a misnomer predicated on the mistaken belief that this enzyme is an alcohol dehydrogenase.[9]

Structure

Gene

Human HSD17B10 gene has 6 exons resides on the X chromosome at p11.22.[6]

Protein

The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids, and is a subunit of mitochondrial ribonuclease P, which is involved in tRNA maturation.[6] The molecular weight of 17β-HSD10 that is composed of four identical subunits is 108 kDa; each subunit consists of 261 amino acid residues.[12] Although the endoplasmic reticulum (ER)-associated amyloid-β peptide binding protein (ERAB) was reported to be associated with the ER and to consist of 262 residues with a molecular weight of 27 kDa,[13] ERAB is actually identical to 17β-HSD10 that is localized in mitochondria but not ER.[3]

Clinical significance

Abnormal expression, as well as mutations of the HSD17B10 gene leads to impairment of the structure, function, and dynamics of mitochondria. This may underlie the pathogenesis of the synaptic and neuronal deficiency exhibited in 17β-HSD10 related diseases, including 17β-HSD10 deficiency and Alzheimer's disease (AD).[6] Missense and silent mutations in the gene are the cause of hydroxysteroid (17β) dehydrogenase X (HSD10) deficiency, formerly MHBD deficiency, and X-linked mental retardation, choreoathetosis, and abnormal behavior (MRXS10), respectively.[11][14][15] Restoration of steroid homeostasis could be achieved by the supplementation of neuroactive steroids with a proper dosing and treatment regimen or by the adjustment of 17β-HSD10 activity to protect neurons.[9] The discovery of this enzyme's true function has opened a new therapeutic avenue for treating AD.

Interactions

HSD17B10 has been shown to interact with Amyloid precursor protein.[8]

References

  1. ↑ Marques AT, Antunes A, Fernandes PA, Ramos MJ (Sep 2006). "Comparative evolutionary genomics of the HADH2 gene encoding Abeta-binding alcohol dehydrogenase/17beta-hydroxysteroid dehydrogenase type 10 (ABAD/HSD10)". BMC Genomics. 7: 202. doi:10.1186/1471-2164-7-202. PMC 1559703. PMID 16899120.
  2. ↑ Yang SY, He XY, Miller D (Aug 2011). "Hydroxysteroid (17β) dehydrogenase X in human health and disease". Molecular and Cellular Endocrinology. 343 (1–2): 1–6. doi:10.1016/j.mce.2011.06.011. PMID 21708223.
  3. ↑ 3.0 3.1 He XY, Merz G, Mehta P, Schulz H, Yang SY (May 1999). "Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase". The Journal of Biological Chemistry. 274 (21): 15014–9. doi:10.1074/jbc.274.21.15014. PMID 10329704.
  4. ↑ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Mar 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1–3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  5. ↑ Holzmann J, Frank P, Löffler E, Bennett KL, Gerner C, Rossmanith W (Oct 2008). "RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme". Cell. 135 (3): 462–74. doi:10.1016/j.cell.2008.09.013. PMID 18984158.
  6. ↑ 6.0 6.1 6.2 6.3 "Entrez Gene: HSD17B10 hydroxysteroid (17-beta) dehydrogenase 10".
  7. ↑ He XY, Yang YZ, Schulz H, Yang SY (Jan 2000). "Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase". The Biochemical Journal. 345 (1): 139–43. doi:10.1042/bj3450139. PMC 1220740. PMID 10600649.
  8. ↑ 8.0 8.1 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 (Oct 1997). "An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease". Nature. 389 (6652): 689–95. doi:10.1038/39522. PMID 9338779.
  9. ↑ 9.0 9.1 9.2 Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (Sep 2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in neurodegenerative disorders". The Journal of Steroid Biochemistry and Molecular Biology. 143: 460–72. doi:10.1016/j.jsbmb.2014.07.001. PMID 25007702.
  10. ↑ Yang SY, He XY, Schulz H (2005). "Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase". Trends in Endocrinology and Metabolism. 16 (4): 167–75. doi:10.1016/j.tem.2005.03.006. PMID 15860413.
  11. ↑ 11.0 11.1 Yang SY, He XY, Olpin SE, Sutton VR, McMenamin J, Philipp M, Denman RB, Malik M (Sep 2009). "Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism". Proceedings of the National Academy of Sciences of the United States of America. 106 (35): 14820–4. doi:10.1073/pnas.0902377106. PMC 2728107. PMID 19706438.
  12. ↑ He XY, Schulz H, Yang SY (Apr 1998). "A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease". The Journal of Biological Chemistry. 273 (17): 10741–6. doi:10.1074/jbc.273.17.10741. PMID 9553139.
  13. ↑ Beyreuther K, Masters CL (Oct 1997). "Alzheimer's disease. The ins and outs of amyloid-beta". Nature. 389 (6652): 677–8. doi:10.1038/39479. PMID 9338775.
  14. ↑ Seaver LH, He XY, Abe K, Cowan T, Enns GM, Sweetman L, Philipp M, Lee S, Malik M, Yang SY (November 2011). "A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, choreoathetosis and learning disability". PLOS ONE. 6 (11): e27348. doi:10.1371/journal.pone.0027348. PMC 3222643. PMID 22132097.
  15. ↑ Lenski C, Kooy RF, Reyniers E, Loessner D, Wanders RJ, Winnepenninckx B, Hellebrand H, Engert S, Schwartz CE, Meindl A, Ramser J (Feb 2007). "The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior". American Journal of Human Genetics. 80 (2): 372–7. doi:10.1086/511527. PMC 1785340. PMID 17236142.

Further reading

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