ID HCD2_HUMAN Reviewed; 261 AA.
AC Q99714; Q5H927; Q6IBS9; Q8TCV9; Q96HD5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 232.
DE RecName: Full=3-hydroxyacyl-CoA dehydrogenase type-2;
DE EC=1.1.1.35 {ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:9553139};
DE AltName: Full=17-beta-estradiol 17-dehydrogenase;
DE EC=1.1.1.62 {ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011};
DE AltName: Full=2-methyl-3-hydroxybutyryl-CoA dehydrogenase {ECO:0000303|PubMed:16148061};
DE Short=MHBD {ECO:0000303|PubMed:16148061};
DE AltName: Full=3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+));
DE EC=1.1.1.239 {ECO:0000269|PubMed:12917011};
DE AltName: Full=3-hydroxy-2-methylbutyryl-CoA dehydrogenase;
DE EC=1.1.1.178 {ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:19706438, ECO:0000269|PubMed:20077426};
DE AltName: Full=3-hydroxyacyl-CoA dehydrogenase type II;
DE AltName: Full=3alpha(or 20beta)-hydroxysteroid dehydrogenase;
DE EC=1.1.1.53 {ECO:0000269|PubMed:12917011};
DE AltName: Full=7-alpha-hydroxysteroid dehydrogenase;
DE EC=1.1.1.159 {ECO:0000269|PubMed:12917011};
DE AltName: Full=Endoplasmic reticulum-associated amyloid beta-peptide-binding protein;
DE AltName: Full=Mitochondrial ribonuclease P protein 2;
DE Short=Mitochondrial RNase P protein 2;
DE AltName: Full=Short chain dehydrogenase/reductase family 5C member 1;
DE AltName: Full=Short-chain type dehydrogenase/reductase XH98G2;
DE AltName: Full=Type II HADH;
GN Name=HSD17B10; Synonyms=ERAB, HADH2, MRPP2, SCHAD, SDR5C1, XH98G2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9338779; DOI=10.1038/39522;
RA Yan S.D., Fu J., Soto C., Chen X., Zhu H., Al-Mohanna F., Collinson K.,
RA Zhu A., Stern E., Saido T., Tohyama M., Ogawa S., Roher A., Stern D.;
RT "An intracellular protein that binds amyloid-beta peptide and mediates
RT neurotoxicity in Alzheimer's disease.";
RL Nature 389:689-695(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Zhuchenko O.P., Wehnert M., Bailey J., Sun Z.S., Lee C.C.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9671743; DOI=10.1073/pnas.95.15.8709;
RA Miller A.P., Willard H.F.;
RT "Chromosomal basis of X chromosome inactivation: identification of a
RT multigene domain in Xp11.21-p11.22 that escapes X inactivation.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8709-8714(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RC TISSUE=Brain;
RX PubMed=9553139; DOI=10.1074/jbc.273.17.10741;
RA He X.Y., Schulz H., Yang S.Y.;
RT "A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an
RT amyloid beta-peptide-binding protein involved in Alzheimer's disease.";
RL J. Biol. Chem. 273:10741-10746(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 51-246.
RA Deininger M.H., Meyermann R., Schluesener H.J.;
RT "Expression, release and induction of endoplasmic reticulum-associated
RT amyloid beta-binding protein in brain disease.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=10600649; DOI=10.1042/bj3450139;
RA He X.Y., Yang Y.Z., Schulz H., Yang S.Y.;
RT "Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase
RT activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA
RT dehydrogenase.";
RL Biochem. J. 345:139-143(2000).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND PATHWAY.
RX PubMed=12917011; DOI=10.1042/bj20030877;
RA Shafqat N., Marschall H.U., Filling C., Nordling E., Wu X.Q., Bjork L.,
RA Thyberg J., Martensson E., Salim S., Jornvall H., Oppermann U.;
RT "Expanded substrate screenings of human and Drosophila type 10 17beta-
RT hydroxysteroid dehydrogenases (HSDs) reveal multiple specificities in bile
RT acid and steroid hormone metabolism: characterization of multifunctional
RT 3alpha/7alpha/7beta/17beta/20beta/21-HSD.";
RL Biochem. J. 376:49-60(2003).
RN [12]
RP INVOLVEMENT IN HSD10MD.
RX PubMed=17236142; DOI=10.1086/511527;
RA Lenski C., Kooy R.F., Reyniers E., Loessner D., Wanders R.J.A.,
RA Winnepenninckx B., Hellebrand H., Engert S., Schwartz C.E., Meindl A.,
RA Ramser J.;
RT "The reduced expression of the HADH2 protein causes X-linked mental
RT retardation, choreoathetosis, and abnormal behavior.";
RL Am. J. Hum. Genet. 80:372-377(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH KIAA0391
RP AND TRMT10C, AND SUBCELLULAR LOCATION.
RX PubMed=18984158; DOI=10.1016/j.cell.2008.09.013;
RA Holzmann J., Frank P., Loeffler E., Bennett K.L., Gerner C., Rossmanith W.;
RT "RNase P without RNA: identification and functional reconstitution of the
RT human mitochondrial tRNA processing enzyme.";
RL Cell 135:462-474(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, INTERACTION WITH TRMT10C, AND MUTAGENESIS OF SER-20 AND LYS-172.
RX PubMed=23042678; DOI=10.1093/nar/gks910;
RA Vilardo E., Nachbagauer C., Buzet A., Taschner A., Holzmann J.,
RA Rossmanith W.;
RT "A subcomplex of human mitochondrial RNase P is a bifunctional
RT methyltransferase--extensive moonlighting in mitochondrial tRNA
RT biogenesis.";
RL Nucleic Acids Res. 40:11583-11593(2012).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=24703694; DOI=10.1016/j.cmet.2014.03.013;
RA Bogenhagen D.F., Martin D.W., Koller A.;
RT "Initial steps in RNA processing and ribosome assembly occur at
RT mitochondrial DNA nucleoids.";
RL Cell Metab. 19:618-629(2014).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND VARIANTS
RP HSD10MD GLY-86; CYS-130 AND HIS-165.
RX PubMed=26338420; DOI=10.1101/gad.268482.115;
RA Boynton T.O., Shimkets L.J.;
RT "Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin
RT phospholipases.";
RL Genes Dev. 29:1903-1914(2015).
RN [19]
RP INVOLVEMENT IN HSD10MD.
RX PubMed=25575635; DOI=10.1016/j.mito.2014.12.005;
RA Chatfield K.C., Coughlin C.R. II, Friederich M.W., Gallagher R.C.,
RA Hesselberth J.R., Lovell M.A., Ofman R., Swanson M.A., Thomas J.A.,
RA Wanders R.J., Wartchow E.P., Van Hove J.L.;
RT "Mitochondrial energy failure in HSD10 disease is due to defective mtDNA
RT transcript processing.";
RL Mitochondrion 21:1-10(2015).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP FUNCTION, AND INTERACTION WITH TRMT10C.
RX PubMed=29040705; DOI=10.1093/nar/gkx902;
RA Reinhard L., Sridhara S., Haellberg B.M.;
RT "The MRPP1/MRPP2 complex is a tRNA-maturation platform in human
RT mitochondria.";
RL Nucleic Acids Res. 45:12469-12480(2017).
RN [22] {ECO:0007744|PDB:1U7T}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH NAD.
RX PubMed=15342248; DOI=10.1016/j.jmb.2004.07.071;
RA Kissinger C.R., Rejto P.A., Pelletier L.A., Thomson J.A., Showalter R.E.,
RA Abreo M.A., Agree C.S., Margosiak S., Meng J.J., Aust R.M., Vanderpool D.,
RA Li B., Tempczyk-Russell A., Villafranca J.E.;
RT "Crystal structure of human ABAD/HSD10 with a bound inhibitor: implications
RT for design of Alzheimer's disease therapeutics.";
RL J. Mol. Biol. 342:943-952(2004).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=15087549; DOI=10.1126/science.1091230;
RA Lustbader J.W., Cirilli M., Lin C., Xu H.W., Takuma K., Wang N.,
RA Caspersen C., Chen X., Pollak S., Chaney M., Trinchese F., Liu S.,
RA Gunn-Moore F., Lue L.-F., Walker D.G., Kuppusamy P., Zewier Z.L.,
RA Arancio O., Stern D., Yan S.-S., Wu H.;
RT "ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's
RT disease.";
RL Science 304:448-452(2004).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.20 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, VARIANTS HSD10MD GLY-86; CYS-130 AND HIS-165, AND CHARACTERIZATION
RP OF VARIANTS HSD10MD GLY-86; CYS-130 AND HIS-165.
RX PubMed=20077426; DOI=10.1002/emmm.200900055;
RA Rauschenberger K., Schoeler K., Sass J.O., Sauer S., Djuric Z., Rumig C.,
RA Wolf N.I., Okun J.G., Koelker S., Schwarz H., Fischer C., Grziwa B.,
RA Runz H., Nuemann A., Shafqat N., Kavanagh K.L., Haemmerling G.,
RA Wanders R.J., Shield J.P., Wendel U., Stern D., Nawroth P., Hoffmann G.F.,
RA Bartram C.R., Arnold B., Bierhaus A., Oppermann U., Steinbeisser H.,
RA Zschocke J.;
RT "A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is
RT required for mitochondrial integrity and cell survival.";
RL EMBO Mol. Med. 2:51-62(2010).
RN [25]
RP VARIANTS HSD10MD VAL-122 AND CYS-130.
RX PubMed=12696021; DOI=10.1086/375116;
RA Ofman R., Ruiter J.P.N., Feenstra M., Duran M., Poll-The B.T., Zschocke J.,
RA Ensenauer R., Lehnert W., Sass J.O., Sperl W., Wanders R.J.A.;
RT "2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by
RT mutations in the HADH2 gene.";
RL Am. J. Hum. Genet. 72:1300-1307(2003).
RN [26]
RP VARIANTS HSD10MD CYS-130 AND SER-247, AND CHARACTERIZATION OF VARIANT
RP HSD10MD SER-247.
RX PubMed=16148061; DOI=10.1203/01.pdr.0000176916.94328.cd;
RA Perez-Cerda C., Garcia-Villoria J., Ofman R., Sala P.R., Merinero B.,
RA Ramos J., Garcia-Silva M.T., Beseler B., Dalmau J., Wanders R.J.A.,
RA Ugarte M., Ribes A.;
RT "2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked
RT inborn error of isoleucine metabolism that may mimic a mitochondrial
RT disease.";
RL Pediatr. Res. 58:488-491(2005).
RN [27]
RP ERRATUM OF PUBMED:16148061.
RA Perez-Cerda C., Garcia-Villoria J., Ofman R., Sala P.R., Merinero B.,
RA Ramos J., Garcia-Silva M.T., Beseler B., Dalmau J., Wanders R.J.,
RA Ugarte M., Ribes A.;
RL Pediatr. Res. 59:162-162(2006).
RN [28]
RP VARIANTS HSD10MD CYS-130; SER-210; GLN-226 AND SER-247, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=18996107; DOI=10.1016/j.clinbiochem.2008.10.006;
RA Garcia-Villoria J., Navarro-Sastre A., Fons C., Perez-Cerda C.,
RA Baldellou A., Fuentes-Castello M.A., Gonzalez I., Hernandez-Gonzalez A.,
RA Fernandez C., Campistol J., Delpiccolo C., Cortes N., Messeguer A.,
RA Briones P., Ribes A.;
RT "Study of patients and carriers with 2-methyl-3-hydroxybutyryl-CoA
RT dehydrogenase (MHBD) deficiency: difficulties in the diagnosis.";
RL Clin. Biochem. 42:27-33(2009).
RN [29]
RP VARIANTS HSD10MD CYS-130 AND GLN-249, CHARACTERIZATION OF VARIANTS HSD10MD
RP CYS-130 AND GLN-249, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND PATHWAY.
RX PubMed=19706438; DOI=10.1073/pnas.0902377106;
RA Yang S.Y., He X.Y., Olpin S.E., Sutton V.R., McMenamin J., Philipp M.,
RA Denman R.B., Malik M.;
RT "Mental retardation linked to mutations in the HSD17B10 gene interfering
RT with neurosteroid and isoleucine metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14820-14824(2009).
RN [30]
RP VARIANT HSD10MD ALA-65.
RX PubMed=22132097; DOI=10.1371/journal.pone.0027348;
RA Seaver L.H., He X.Y., Abe K., Cowan T., Enns G.M., Sweetman L., Philipp M.,
RA Lee S., Malik M., Yang S.Y.;
RT "A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory
RT epilepsy, choreoathetosis and learning disability.";
RL PLoS ONE 6:E27348-E27348(2011).
RN [31]
RP VARIANTS HSD10MD CYS-130 AND HIS-165, CHARACTERIZATION OF VARIANT HSD10MD
RP CYS-130, AND FUNCTION.
RX PubMed=24549042; DOI=10.1093/hmg/ddu072;
RA Deutschmann A.J., Amberger A., Zavadil C., Steinbeisser H., Mayr J.A.,
RA Feichtinger R.G., Oerum S., Yue W.W., Zschocke J.;
RT "Mutation or knock-down of 17beta-hydroxysteroid dehydrogenase type 10
RT cause loss of MRPP1 and impaired processing of mitochondrial heavy strand
RT transcripts.";
RL Hum. Mol. Genet. 23:3618-3628(2014).
RN [32]
RP VARIANTS HSD10MD CYS-130; SER-210; GLN-226 AND SER-247, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, MUTAGENESIS OF LYS-172, AND CHARACTERIZATION OF VARIANTS
RP HSD10MD CYS-130; SER-210; GLN-226 AND SER-247.
RX PubMed=25925575; DOI=10.1093/nar/gkv408;
RA Vilardo E., Rossmanith W.;
RT "Molecular insights into HSD10 disease: impact of SDR5C1 mutations on the
RT human mitochondrial RNase P complex.";
RL Nucleic Acids Res. 43:5112-5119(2015).
RN [33]
RP VARIANT HSD10MD GLU-212, FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH
RP TRMT10C, AND CHARACTERIZATION OF VARIANT HSD10MD GLU-212.
RX PubMed=26950678; DOI=10.1080/15476286.2016.1159381;
RA Falk M.J., Gai X., Shigematsu M., Vilardo E., Takase R., McCormick E.,
RA Christian T., Place E., Pierce E.A., Consugar M., Gamper H.B.,
RA Rossmanith W., Hou Y.M.;
RT "A novel HSD17B10 mutation impairing the activities of the mitochondrial
RT RNase P complex causes X-linked intractable epilepsy and neurodevelopmental
RT regression.";
RL RNA Biol. 13:477-485(2016).
RN [34]
RP VARIANTS HSD10MD LEU-12 AND MET-176, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND CHARACTERIZATION OF VARIANTS
RP HSD10MD LEU-12 AND MET-176.
RX PubMed=28888424; DOI=10.1016/j.bbadis.2017.09.002;
RA Oerum S., Roovers M., Leichsenring M., Acquaviva-Bourdain C., Beermann F.,
RA Gemperle-Britschgi C., Fouilhoux A., Korwitz-Reichelt A., Bailey H.J.,
RA Droogmans L., Oppermann U., Sass J.O., Yue W.W.;
RT "Novel patient missense mutations in the HSD17B10 gene affect dehydrogenase
RT and mitochondrial tRNA modification functions of the encoded protein.";
RL Biochim. Biophys. Acta 1863:3294-3302(2017).
CC -!- FUNCTION: Mitochondrial dehydrogenase involved in pathways of fatty
CC acid, branched-chain amino acid and steroid metabolism (PubMed:9553139,
CC PubMed:10600649, PubMed:12917011, PubMed:20077426, PubMed:18996107,
CC PubMed:19706438, PubMed:25925575, PubMed:26950678, PubMed:28888424).
CC Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid
CC beta-oxidation, a major degradation pathway of fatty acids. Catalyzes
CC the third step in the beta-oxidation cycle, namely the reversible
CC conversion of (S)-3-hydroxyacyl-CoA to 3-ketoacyl-CoA. Preferentially
CC accepts straight medium- and short-chain acyl-CoA substrates with
CC highest efficiency for (3S)-hydroxybutanoyl-CoA (PubMed:9553139,
CC PubMed:10600649, PubMed:12917011, PubMed:25925575, PubMed:26950678).
CC Acts as 3-hydroxy-2-methylbutyryl-CoA dehydrogenase in branched-chain
CC amino acid catabolic pathway. Catalyzes the oxidation of 3-hydroxy-2-
CC methylbutanoyl-CoA into 2-methyl-3-oxobutanoyl-CoA, a step in
CC isoleucine degradation pathway (PubMed:20077426, PubMed:18996107,
CC PubMed:19706438). Has hydroxysteroid dehydrogenase activity toward
CC steroid hormones and bile acids. Catalyzes the oxidation of 3alpha-,
CC 17beta-, 20beta- and 21-hydroxysteroids and 7alpha- and 7beta-hydroxy
CC bile acids (PubMed:10600649, PubMed:12917011). Oxidizes
CC allopregnanolone/brexanolone at the 3alpha-hydroxyl group, which is
CC known to be critical for the activation of gamma-aminobutyric acid
CC receptors (GABAARs) chloride channel (PubMed:19706438,
CC PubMed:28888424). Has phospholipase C-like activity toward cardiolipin
CC and its oxidized species. Likely oxidizes the 2'-hydroxyl in the head
CC group of cardiolipin to form a ketone intermediate that undergoes
CC nucleophilic attack by water and fragments into diacylglycerol,
CC dihydroxyacetone and orthophosphate. Has higher affinity for
CC cardiolipin with oxidized fatty acids and may degrade these species
CC during the oxidative stress response to protect cells from apoptosis
CC (PubMed:26338420). By interacting with intracellular amyloid-beta, it
CC may contribute to the neuronal dysfunction associated with Alzheimer
CC disease (AD) (PubMed:9338779). Essential for structural and functional
CC integrity of mitochondria (PubMed:20077426).
CC {ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011,
CC ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:19706438,
CC ECO:0000269|PubMed:20077426, ECO:0000269|PubMed:25925575,
CC ECO:0000269|PubMed:26338420, ECO:0000269|PubMed:26950678,
CC ECO:0000269|PubMed:28888424, ECO:0000269|PubMed:9553139}.
CC -!- FUNCTION: In addition to mitochondrial dehydrogenase activity,
CC moonlights as a component of mitochondrial ribonuclease P, a complex
CC that cleaves tRNA molecules in their 5'-ends (PubMed:18984158,
CC PubMed:24549042, PubMed:25925575, PubMed:26950678, PubMed:28888424).
CC Together with TRMT10C/MRPP1, forms a subcomplex of the mitochondrial
CC ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions
CC that are independent of the ribonuclease P activity (PubMed:23042678,
CC PubMed:29040705). The MRPP1-MRPP2 subcomplex catalyzes the formation of
CC N(1)-methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9,
CC respectively) in tRNAs; HSD17B10/MRPP2 acting as a non-catalytic
CC subunit (PubMed:23042678, PubMed:25925575, PubMed:28888424). The MRPP1-
CC MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-
CC end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-
CC MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by
CC ELAC2, retains the tRNA product after ELAC2 processing and presents the
CC nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1
CC enzyme (PubMed:29040705). Associates with mitochondrial DNA complexes
CC at the nucleoids to initiate RNA processing and ribosome assembly.
CC {ECO:0000269|PubMed:18984158, ECO:0000269|PubMed:23042678,
CC ECO:0000269|PubMed:24549042, ECO:0000269|PubMed:24703694,
CC ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26950678,
CC ECO:0000269|PubMed:28888424, ECO:0000269|PubMed:29040705}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35;
CC Evidence={ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011,
CC ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26950678,
CC ECO:0000269|PubMed:9553139};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433;
CC Evidence={ECO:0000305|PubMed:12917011};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22434;
CC Evidence={ECO:0000305|PubMed:10600649, ECO:0000305|PubMed:12917011,
CC ECO:0000305|PubMed:25925575, ECO:0000305|PubMed:26950678,
CC ECO:0000305|PubMed:9553139};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methyl-3-
CC oxobutanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:13281,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57312, ChEBI:CHEBI:57335,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.178;
CC Evidence={ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:19706438,
CC ECO:0000269|PubMed:20077426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13282;
CC Evidence={ECO:0000305|PubMed:18996107, ECO:0000305|PubMed:19706438,
CC ECO:0000305|PubMed:20077426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.239; Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53;
CC Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC Evidence={ECO:0000305|PubMed:10600649, ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholate + NAD(+) = 3alpha,12alpha-dihydroxy-7-oxo-5beta-
CC cholanate + H(+) + NADH; Xref=Rhea:RHEA:19409, ChEBI:CHEBI:11893,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.159;
CC Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19410;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:30799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286,
CC ChEBI:CHEBI:57316, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011,
CC ECO:0000269|PubMed:9553139};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30800;
CC Evidence={ECO:0000305|PubMed:12917011};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30801;
CC Evidence={ECO:0000305|PubMed:10600649, ECO:0000305|PubMed:25925575,
CC ECO:0000305|PubMed:9553139};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:31195, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62617, ChEBI:CHEBI:62619;
CC Evidence={ECO:0000269|PubMed:9553139};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31196;
CC Evidence={ECO:0000305};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31197;
CC Evidence={ECO:0000305|PubMed:9553139};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000269|PubMed:9553139};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160;
CC Evidence={ECO:0000305};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31161;
CC Evidence={ECO:0000305|PubMed:9553139};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:41992,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41993;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-pregnan-20beta-ol-3-one + NAD(+) = 5alpha-pregnane-
CC 3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:42008, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28952, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:78594; Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42009;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-pregnan-20-one + NAD(+) = 5alpha-
CC pregnane-3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:41980,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28952, ChEBI:CHEBI:50169,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:19706438, ECO:0000269|PubMed:28888424};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41981;
CC Evidence={ECO:0000305|PubMed:19706438, ECO:0000305|PubMed:28888424};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cortisone + NAD(+) = 17alpha-hydroxypregn-4-en-3,11,20-trione-
CC 21-al + H(+) + NADH; Xref=Rhea:RHEA:42016, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16962, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:78596; Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42017;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-dehydrocorticosterone + NAD(+) = H(+) + NADH + pregn-4-ene-
CC 3,11,20,21-tetraone; Xref=Rhea:RHEA:42020, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78600,
CC ChEBI:CHEBI:78601; Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42021;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cortisol + NAD(+) = 11beta,17alpha-dihydroxypregn-4-ene-
CC 3,20,21-trione + H(+) + NADH; Xref=Rhea:RHEA:42012,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17650, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78595;
CC Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42013;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + NAD(+) = 7-oxolithocholate + H(+) + NADH;
CC Xref=Rhea:RHEA:42036, ChEBI:CHEBI:15378, ChEBI:CHEBI:36234,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42037;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + ursodeoxycholate = 7-oxolithocholate + H(+) + NADH;
CC Xref=Rhea:RHEA:42028, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78604, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42029;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta,7beta-dihydroxy-5beta-cholan-24-oate + NAD(+) = 3beta-
CC hydroxy-7-oxo-5beta-cholan-24-oate + H(+) + NADH;
CC Xref=Rhea:RHEA:42024, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78602, ChEBI:CHEBI:78603;
CC Evidence={ECO:0000269|PubMed:12917011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42025;
CC Evidence={ECO:0000305|PubMed:12917011};
CC -!- ACTIVITY REGULATION: The phospholipase C-like activity toward
CC cardiolipin is inhibited by amyloid-beta peptide.
CC {ECO:0000269|PubMed:26338420}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25.7 uM for acetoacetyl-CoA (in the presence of 0.2 mM NADH, at pH
CC 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=85.2 uM for beta-hydroxybutyryl-CoA (in the presence of 1 mM NAD,
CC at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=41 uM for androsterone (in the presence of 1 mM NAD, at pH 9.3 and
CC 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=5 uM for 5-alpha-pregnan-20-beta-ol-3-one (in the presence of 1 mM
CC NAD, at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=219 uM for isoursodeoxycholic acid (in the presence of 1 mM NAD,
CC at pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=36.4 uM for chenodeoxycholic acid (in the presence of 1 mM NAD, at
CC pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=1.7 uM for dehydrocorticosterone (in the presence of 1 mM NAD, at
CC pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=30.6 uM for NADH (in the presence of acetoacetyl-CoA, at pH 7.0
CC and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=42.3 uM for NAD (in the presence of beta-hydroxybutyryl-CoA, at pH
CC 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011};
CC KM=69 uM for DL-3-hydroxybutyryl-CoA {ECO:0000269|PubMed:28888424};
CC KM=7.7 uM for 3alpha-hydroxy-5alpha-pregnan-20-one/allopregnanolone
CC {ECO:0000269|PubMed:28888424};
CC KM=30 uM for 3alpha-hydroxy-5alpha-pregnan-20-one/allopregnanolone
CC {ECO:0000269|PubMed:19706438};
CC KM=140 uM for tetramyristoyl cardiolipin
CC {ECO:0000269|PubMed:26338420};
CC KM=148 uM for tetralinoleoyl cardiolipin
CC {ECO:0000269|PubMed:26338420};
CC KM=40 uM for oxidized tetralinoleoyl cardiolipin
CC {ECO:0000269|PubMed:26338420};
CC KM=7.1 uM for (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA
CC {ECO:0000269|PubMed:19706438};
CC Vmax=14.8 umol/min/mg enzyme toward (2S,3S)-3-hydroxy-2-
CC methylbutanoyl-CoA {ECO:0000269|PubMed:19706438};
CC Vmax=150 umol/min/mg enzyme 3alpha-hydroxy-5alpha-pregnan-20-
CC one/allopregnanolone {ECO:0000269|PubMed:19706438};
CC Note=kcat is 458 min(-1) for DL-3-hydroxybutyryl-CoA
CC (PubMed:28888424). kcat is 706 min(-1) for allopregnanolone
CC (PubMed:28888424). {ECO:0000269|PubMed:28888424};
CC pH dependence:
CC Optimum pH is 9.3 for the dehydrogenase reaction at 25 degrees
CC Celsius, and 7.0 for the reductase reaction at 25 degrees Celsius.
CC {ECO:0000269|PubMed:12917011};
CC -!- PATHWAY: Amino-acid degradation; L-isoleucine degradation.
CC {ECO:0000269|PubMed:19706438}.
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:10600649, ECO:0000269|PubMed:12917011,
CC ECO:0000269|PubMed:9553139}.
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:10600649,
CC ECO:0000269|PubMed:12917011}.
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000269|PubMed:12917011}.
CC -!- SUBUNIT: Homotetramer (PubMed:15342248, PubMed:20077426,
CC PubMed:25925575). Component of mitochondrial ribonuclease P, a complex
CC composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3
CC (PubMed:18984158, PubMed:25925575, PubMed:26950678, PubMed:28888424).
CC Interacts with TRMT10C/MRPP1; forming the MRPP1-MRPP2 subcomplex of the
CC mitochondrial ribonuclease P complex (PubMed:23042678,
CC PubMed:29040705). {ECO:0000269|PubMed:15342248,
CC ECO:0000269|PubMed:18984158, ECO:0000269|PubMed:20077426,
CC ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25925575,
CC ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:28888424,
CC ECO:0000269|PubMed:29040705}.
CC -!- INTERACTION:
CC Q99714; P05067: APP; NbExp=7; IntAct=EBI-79964, EBI-77613;
CC Q99714; PRO_0000000092 [P05067]: APP; NbExp=2; IntAct=EBI-79964, EBI-821758;
CC Q99714; P13639: EEF2; NbExp=3; IntAct=EBI-79964, EBI-352560;
CC Q99714; Q12931: TRAP1; NbExp=3; IntAct=EBI-79964, EBI-1055869;
CC Q99714; Q7L0Y3: TRMT10C; NbExp=22; IntAct=EBI-79964, EBI-2107046;
CC Q99714-2; P05067: APP; NbExp=3; IntAct=EBI-25939412, EBI-77613;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:12917011,
CC ECO:0000269|PubMed:18984158}. Mitochondrion matrix, mitochondrion
CC nucleoid {ECO:0000269|PubMed:24703694}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99714-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99714-2; Sequence=VSP_007830;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in normal tissues but is
CC overexpressed in neurons affected in AD. {ECO:0000269|PubMed:9338779}.
CC -!- DISEASE: HSD10 mitochondrial disease (HSD10MD) [MIM:300438]: An X-
CC linked multisystemic disorder with highly variable severity. Age at
CC onset ranges from the neonatal period to early childhood. Features
CC include progressive neurodegeneration, psychomotor retardation, loss of
CC mental and motor skills, seizures, cardiomyopathy, and visual and
CC hearing impairment. Some patients manifest lactic acidosis and
CC metabolic acidosis. {ECO:0000269|PubMed:12696021,
CC ECO:0000269|PubMed:16148061, ECO:0000269|PubMed:17236142,
CC ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:19706438,
CC ECO:0000269|PubMed:20077426, ECO:0000269|PubMed:22132097,
CC ECO:0000269|PubMed:24549042, ECO:0000269|PubMed:25575635,
CC ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26338420,
CC ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:28888424}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; U96132; AAC51812.1; -; mRNA.
DR EMBL; U73514; AAB68958.1; -; mRNA.
DR EMBL; AF069134; AAC39900.1; -; mRNA.
DR EMBL; AF035555; AAC15902.1; -; mRNA.
DR EMBL; AF037438; AAC16419.1; -; Genomic_DNA.
DR EMBL; CR456723; CAG33004.1; -; mRNA.
DR EMBL; Z97054; CAI42652.1; -; Genomic_DNA.
DR EMBL; Z97054; CAI42653.1; -; Genomic_DNA.
DR EMBL; CH471154; EAW93157.1; -; Genomic_DNA.
DR EMBL; CH471154; EAW93158.1; -; Genomic_DNA.
DR EMBL; BC000372; AAH00372.1; -; mRNA.
DR EMBL; BC008708; AAH08708.1; -; mRNA.
DR EMBL; AY092415; AAM18189.1; -; mRNA.
DR CCDS; CCDS14354.1; -. [Q99714-1]
DR CCDS; CCDS35300.1; -. [Q99714-2]
DR RefSeq; NP_001032900.1; NM_001037811.2. [Q99714-2]
DR RefSeq; NP_004484.1; NM_004493.2. [Q99714-1]
DR PDB; 1SO8; X-ray; 2.30 A; A=1-261.
DR PDB; 1U7T; X-ray; 2.00 A; A/B/C/D=1-261.
DR PDB; 2O23; X-ray; 1.20 A; A/B=1-261.
DR PDB; 7ONU; EM; 3.00 A; A/B/C/D=1-261.
DR PDBsum; 1SO8; -.
DR PDBsum; 1U7T; -.
DR PDBsum; 2O23; -.
DR PDBsum; 7ONU; -.
DR AlphaFoldDB; Q99714; -.
DR EMDB; EMD-13002; -.
DR SMR; Q99714; -.
DR BioGRID; 109278; 540.
DR ComplexPortal; CPX-6155; Mitochondrial ribonuclease P complex.
DR ComplexPortal; CPX-6161; Mitochondrial tRNA:m(1)R9 methyltransferase complex.
DR CORUM; Q99714; -.
DR IntAct; Q99714; 214.
DR MINT; Q99714; -.
DR STRING; 9606.ENSP00000168216; -.
DR BindingDB; Q99714; -.
DR ChEMBL; CHEMBL4159; -.
DR DrugBank; DB02820; 1-Azepan-1-Yl-2-Phenyl-2-(4-Thioxo-1,4-Dihydro-Pyrazolo[3,4-D]Pyrimidin-5-Yl)Ethanone Adduct.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB09568; Omega-3-carboxylic acids.
DR SwissLipids; SLP:000000787; -.
DR GlyGen; Q99714; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q99714; -.
DR MetOSite; Q99714; -.
DR PhosphoSitePlus; Q99714; -.
DR SwissPalm; Q99714; -.
DR BioMuta; HSD17B10; -.
DR DMDM; 2492759; -.
DR REPRODUCTION-2DPAGE; IPI00017726; -.
DR REPRODUCTION-2DPAGE; Q99714; -.
DR UCD-2DPAGE; Q99714; -.
DR CPTAC; CPTAC-522; -.
DR CPTAC; CPTAC-523; -.
DR EPD; Q99714; -.
DR jPOST; Q99714; -.
DR MassIVE; Q99714; -.
DR MaxQB; Q99714; -.
DR PaxDb; 9606-ENSP00000168216; -.
DR PeptideAtlas; Q99714; -.
DR ProteomicsDB; 78427; -. [Q99714-1]
DR ProteomicsDB; 78428; -. [Q99714-2]
DR Pumba; Q99714; -.
DR TopDownProteomics; Q99714-1; -. [Q99714-1]
DR TopDownProteomics; Q99714-2; -. [Q99714-2]
DR Antibodypedia; 357; 622 antibodies from 42 providers.
DR DNASU; 3028; -.
DR Ensembl; ENST00000168216.11; ENSP00000168216.6; ENSG00000072506.14. [Q99714-1]
DR Ensembl; ENST00000375304.9; ENSP00000364453.5; ENSG00000072506.14. [Q99714-2]
DR GeneID; 3028; -.
DR KEGG; hsa:3028; -.
DR MANE-Select; ENST00000168216.11; ENSP00000168216.6; NM_004493.3; NP_004484.1.
DR UCSC; uc004dsl.2; human. [Q99714-1]
DR AGR; HGNC:4800; -.
DR CTD; 3028; -.
DR DisGeNET; 3028; -.
DR GeneCards; HSD17B10; -.
DR HGNC; HGNC:4800; HSD17B10.
DR HPA; ENSG00000072506; Low tissue specificity.
DR MalaCards; HSD17B10; -.
DR MIM; 300256; gene.
DR MIM; 300438; phenotype.
DR neXtProt; NX_Q99714; -.
DR OpenTargets; ENSG00000072506; -.
DR Orphanet; 85295; HSD10 disease, atypical type.
DR Orphanet; 391428; HSD10 disease, infantile type.
DR Orphanet; 391457; HSD10 disease, neonatal type.
DR PharmGKB; PA162391638; -.
DR VEuPathDB; HostDB:ENSG00000072506; -.
DR eggNOG; KOG1199; Eukaryota.
DR GeneTree; ENSGT00940000155170; -.
DR HOGENOM; CLU_010194_42_0_1; -.
DR InParanoid; Q99714; -.
DR OMA; QGIRVCT; -.
DR OrthoDB; 149879at2759; -.
DR PhylomeDB; Q99714; -.
DR TreeFam; TF354307; -.
DR BioCyc; MetaCyc:HS01071-MONOMER; -.
DR BRENDA; 1.1.1.135; 2681.
DR BRENDA; 1.1.1.178; 2681.
DR BRENDA; 1.1.1.35; 2681.
DR BRENDA; 1.1.1.62; 2681.
DR PathwayCommons; Q99714; -.
DR Reactome; R-HSA-6785470; tRNA processing in the mitochondrion.
DR Reactome; R-HSA-6787450; tRNA modification in the mitochondrion.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR Reactome; R-HSA-8868766; rRNA processing in the mitochondrion.
DR SABIO-RK; Q99714; -.
DR SignaLink; Q99714; -.
DR SIGNOR; Q99714; -.
DR UniPathway; UPA00221; -.
DR UniPathway; UPA00364; -.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 3028; 179 hits in 813 CRISPR screens.
DR ChiTaRS; HSD17B10; human.
DR EvolutionaryTrace; Q99714; -.
DR GeneWiki; HSD17B10; -.
DR GenomeRNAi; 3028; -.
DR Pharos; Q99714; Tchem.
DR PRO; PR:Q99714; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q99714; Protein.
DR Bgee; ENSG00000072506; Expressed in right lobe of liver and 111 other cell types or tissues.
DR ExpressionAtlas; Q99714; baseline and differential.
DR Genevisible; Q99714; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:UniProtKB.
DR GO; GO:0030678; C:mitochondrial ribonuclease P complex; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:CAFA.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0043527; C:tRNA methyltransferase complex; IPI:ComplexPortal.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0047015; F:3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0106281; F:chenodeoxycholate 7-alpha-dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0008709; F:cholate 7-alpha-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; IBA:GO_Central.
DR GO; GO:0106282; F:isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB.
DR GO; GO:0106283; F:ursodeoxycholate 7-beta-dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0008209; P:androgen metabolic process; IDA:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0062173; P:brexanolone metabolic process; IDA:UniProtKB.
DR GO; GO:0008207; P:C21-steroid hormone metabolic process; IDA:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0006550; P:isoleucine catabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:1990180; P:mitochondrial tRNA 3'-end processing; IDA:UniProtKB.
DR GO; GO:0097745; P:mitochondrial tRNA 5'-end processing; IDA:UniProtKB.
DR GO; GO:0070901; P:mitochondrial tRNA methylation; IDA:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR CDD; cd05371; HSD10-like_SDR_c; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43658:SF8; 3-HYDROXYACYL-COA DEHYDROGENASE TYPE-2; 1.
DR PANTHER; PTHR43658; SHORT-CHAIN DEHYDROGENASE/REDUCTASE; 1.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Disease variant;
KW Fatty acid metabolism; Intellectual disability; Lipid metabolism;
KW Mitochondrion; Mitochondrion nucleoid; NAD; Neurodegeneration;
KW Oxidoreductase; Reference proteome; Steroid metabolism; tRNA processing.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..261
FT /note="3-hydroxyacyl-CoA dehydrogenase type-2"
FT /id="PRO_0000054810"
FT ACT_SITE 168
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:15087549"
FT BINDING 20
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 22
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 64
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 65
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 91
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 155
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15087549"
FT BINDING 168
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 172
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 201
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT BINDING 203
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15342248,
FT ECO:0007744|PDB:1U7T"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:25944712"
FT MOD_RES 53
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08756"
FT MOD_RES 53
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08756"
FT MOD_RES 69
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08756"
FT MOD_RES 99
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08756"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08756"
FT MOD_RES 212
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08756"
FT MOD_RES 212
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08756"
FT VAR_SEQ 191..199
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007830"
FT VARIANT 12
FT /note="V -> L (in HSD10MD; decreased dehydrogenase
FT activity; decreased tRNA methylation; decreased
FT mitochondrial tRNA 5'-end processing)"
FT /evidence="ECO:0000269|PubMed:28888424"
FT /id="VAR_080049"
FT VARIANT 65
FT /note="V -> A (in HSD10MD; uncertain significance;
FT dbSNP:rs104886492)"
FT /evidence="ECO:0000269|PubMed:22132097"
FT /id="VAR_078863"
FT VARIANT 86
FT /note="D -> G (in HSD10MD; decreased 3-hydroxy-2-
FT methylbutyryl-CoA dehydrogenase activity; no effect on
FT NAD(+) binding; complete loss of phospholipase C-like
FT activity toward cardiolipin; dbSNP:rs587777651)"
FT /evidence="ECO:0000269|PubMed:20077426,
FT ECO:0000269|PubMed:26338420"
FT /id="VAR_078864"
FT VARIANT 122
FT /note="L -> V (in HSD10MD; dbSNP:rs28935476)"
FT /evidence="ECO:0000269|PubMed:12696021"
FT /id="VAR_015987"
FT VARIANT 130
FT /note="R -> C (in HSD10MD; decreased stability; decreased
FT 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity;
FT decreased mitochondrial tRNA 5'-end processing; decreased
FT tRNA methylation; does not affect homotetramerization;
FT complete loss of phospholipase C-like activity toward
FT cardiolipin; dbSNP:rs28935475)"
FT /evidence="ECO:0000269|PubMed:12696021,
FT ECO:0000269|PubMed:16148061, ECO:0000269|PubMed:18996107,
FT ECO:0000269|PubMed:19706438, ECO:0000269|PubMed:20077426,
FT ECO:0000269|PubMed:24549042, ECO:0000269|PubMed:25925575,
FT ECO:0000269|PubMed:26338420"
FT /id="VAR_015988"
FT VARIANT 165
FT /note="Q -> H (in HSD10MD; loss of 3-hydroxy-2-
FT methylbutyryl-CoA dehydrogenase activity; does not bind
FT NAD(+); complete loss of phospholipase C-like activity
FT toward cardiolipin)"
FT /evidence="ECO:0000269|PubMed:20077426,
FT ECO:0000269|PubMed:24549042, ECO:0000269|PubMed:26338420"
FT /id="VAR_078865"
FT VARIANT 176
FT /note="V -> M (in HSD10MD; decreased dehydrogenase
FT activity; strongly decreased tRNA methylation; strongly
FT decreased mitochondrial tRNA 5'-end processing)"
FT /evidence="ECO:0000269|PubMed:28888424"
FT /id="VAR_080050"
FT VARIANT 210
FT /note="P -> S (in HSD10MD; decreased 3-hydroxyacyl-CoA
FT dehydrogenase activity; decreased mitochondrial tRNA 5'-end
FT processing; decreased tRNA methylation; does not affect
FT homotetramerization)"
FT /evidence="ECO:0000269|PubMed:18996107,
FT ECO:0000269|PubMed:25925575"
FT /id="VAR_080051"
FT VARIANT 212
FT /note="K -> E (in HSD10MD; 4-fold decrease of 3-
FT hydroxyacyl-CoA dehydrogenase activity; decreased
FT interaction with TRMT10C; decreased function in
FT mitochondrial tRNA methylation; decreased function in
FT mitochondrial tRNA processing; dbSNP:rs886041974)"
FT /evidence="ECO:0000269|PubMed:26950678"
FT /id="VAR_078866"
FT VARIANT 226
FT /note="R -> Q (in HSD10MD; strongly decreased 3-
FT hydroxyacyl-CoA dehydrogenase activity; abolished
FT mitochondrial tRNA 5'-end processing; abolished tRNA
FT methylation; impaired homotetramerization;
FT dbSNP:rs1556894502)"
FT /evidence="ECO:0000269|PubMed:18996107,
FT ECO:0000269|PubMed:25925575"
FT /id="VAR_080052"
FT VARIANT 247
FT /note="N -> S (in HSD10MD; strongly decreased 3-
FT hydroxyacyl-CoA dehydrogenase activity; abolished
FT mitochondrial tRNA 5'-end processing; abolished tRNA
FT methylation; impaired homotetramerization;
FT dbSNP:rs122461163)"
FT /evidence="ECO:0000269|PubMed:16148061,
FT ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:25925575"
FT /id="VAR_032093"
FT VARIANT 249
FT /note="E -> Q (in HSD10MD; decreased 3-hydroxy-2-
FT methylbutyryl-CoA dehydrogenase activity;
FT dbSNP:rs62626305)"
FT /evidence="ECO:0000269|PubMed:19706438"
FT /id="VAR_078867"
FT MUTAGEN 20
FT /note="S->F: Decreased dehydrogenase activity. Does not
FT affect mitochondrial tRNA 5'-end processing. Does not
FT affect tRNA methylation."
FT /evidence="ECO:0000269|PubMed:23042678,
FT ECO:0000269|PubMed:25925575"
FT MUTAGEN 172
FT /note="K->A: Abolishes dehydrogenase activity. Does not
FT affect mitochondrial tRNA 5'-end processing. Does not
FT affect tRNA methylation. Does not affect
FT homotetramerization."
FT /evidence="ECO:0000269|PubMed:23042678,
FT ECO:0000269|PubMed:25925575"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:2O23"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 21..32
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 47..54
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 68..82
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:2O23"
FT TURN 103..106
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 111..121
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 123..136
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 166..186
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 204..208
FT /evidence="ECO:0007829|PDB:1U7T"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:2O23"
FT HELIX 230..242
FT /evidence="ECO:0007829|PDB:2O23"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:2O23"
SQ SEQUENCE 261 AA; 26923 MW; 9E74F242E3E6FEF1 CRC64;
MAAACRSVKG LVAVITGGAS GLGLATAERL VGQGASAVLL DLPNSGGEAQ AKKLGNNCVF
APADVTSEKD VQTALALAKG KFGRVDVAVN CAGIAVASKT YNLKKGQTHT LEDFQRVLDV
NLMGTFNVIR LVAGEMGQNE PDQGGQRGVI INTASVAAFE GQVGQAAYSA SKGGIVGMTL
PIARDLAPIG IRVMTIAPGL FGTPLLTSLP EKVCNFLASQ VPFPSRLGDP AEYAHLVQAI
IENPFLNGEV IRLDGAIRMQ P
//
