ID HCD2_DROME Reviewed; 255 AA. AC O18404; D5A7S2; G7H840; Q059C3; Q8MRC1; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 182. DE RecName: Full=3-hydroxyacyl-CoA dehydrogenase type-2 {ECO:0000303|PubMed:9585418}; DE EC=1.1.1.35 {ECO:0000269|PubMed:12917011}; DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 10; DE Short=17-beta-HSD 10 {ECO:0000303|PubMed:12917011}; DE EC=1.1.1.51 {ECO:0000269|PubMed:12917011}; DE EC=1.1.1.62 {ECO:0000269|PubMed:12917011}; DE AltName: Full=3-hydroxyacyl-CoA dehydrogenase type II; DE AltName: Full=Hydroxysteroid dehydrogenase {ECO:0000305|PubMed:12917011}; DE EC=1.1.1.- {ECO:0000269|PubMed:12917011}; DE EC=1.1.1.53 {ECO:0000269|PubMed:12917011}; DE AltName: Full=Mitochondrial ribonuclease P protein 2; DE Short=Mitochondrial RNase P protein 2; DE AltName: Full=Scully protein {ECO:0000303|PubMed:9585418}; DE AltName: Full=Type II HADH; GN Name=scu {ECO:0000303|PubMed:27131785, GN ECO:0000312|FlyBase:FBgn0021765}; GN Synonyms=MRPP2 {ECO:0000303|PubMed:27131785}; GN ORFNames=CG7113 {ECO:0000312|FlyBase:FBgn0021765}; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL RP STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LEU-33 AND PHE-120. RC STRAIN=Canton-S; RX PubMed=9585418; DOI=10.1083/jcb.141.4.1009; RA Torroja L., Ortuno-Sahagun D., Ferrus A., Haemmerle B., Barbas J.A.; RT "Scully, an essential gene of Drosophila, is homologous to mammalian RT mitochondrial type II L-3-hydroxyacyl-CoA dehydrogenase/amyloid-beta RT peptide-binding protein."; RL J. Cell Biol. 141:1009-1018(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., RA Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [3] RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Embryo; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; RA Stapleton M., Booth B., Carlson J.W., Frise E., Sandler J., Kapadia B., RA Park S., Wan K.H., Yu C., Celniker S.E.; RL Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases. RN [6] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. 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 [7] RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=16979555; DOI=10.1016/j.cub.2006.07.062; RA Cermelli S., Guo Y., Gross S.P., Welte M.A.; RT "The lipid-droplet proteome reveals that droplets are a protein-storage RT depot."; RL Curr. Biol. 16:1783-1795(2006). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY, AND INDUCTION BY 20-HYDROXYECDYSONE. RX PubMed=17924685; DOI=10.1021/pr0705183; RA Sun Y., An S., Henrich V.C., Sun X., Song Q.; RT "Proteomic identification of PKC-mediated expression of 20E-induced protein RT in Drosophila melanogaster."; RL J. Proteome Res. 6:4478-4488(2007). RN [9] RP FUNCTION, IDENTIFICATION IN THE MITOCHONDRIAL RIBONUCLEASE P COMPLEX, RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLN-159 AND RP SER-163. RX PubMed=27131785; DOI=10.1093/nar/gkw338; RA Sen A., Karasik A., Shanmuganathan A., Mirkovic E., Koutmos M., Cox R.T.; RT "Loss of the mitochondrial protein-only ribonuclease P complex causes RT aberrant tRNA processing and lethality in Drosophila."; RL Nucleic Acids Res. 44:6409-6422(2016). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF RP GLN-159 AND SER-163. RX PubMed=34199774; DOI=10.3390/ijms22116066; RA Saoji M., Sen A., Cox R.T.; RT "Loss of Individual Mitochondrial Ribonuclease P Complex Proteins RT Differentially Affects Mitochondrial tRNA Processing In Vivo."; RL Int. J. Mol. Sci. 22:0-0(2021). RN [11] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=35663400; DOI=10.3389/fcell.2022.788516; RA Saoji M., Petersen C.E., Sen A., Tripoli B.A., Smyth J.T., Cox R.T.; RT "Reduction of Drosophila Mitochondrial RNase P in Skeletal and Heart Muscle RT Causes Muscle Degeneration, Cardiomyopathy, and Heart Arrhythmia."; RL Front. Cell Dev. Biol. 10:788516-788516(2022). CC -!- FUNCTION: Mitochondrial dehydrogenase involved in pathways of fatty CC acid, and steroid metabolism (PubMed:12917011). Versatile enzyme CC presenting two types of activity; L-3-hydroxyacyl-CoA dehydrogenase CC ((3S)-3-hydroxyacyl-CoA dehydrogenase) activity and hydroxysteroid CC dehydrogenase (HSD) activity with a wide substrate spectrum. As a (3S)- CC 3-hydroxyacyl-CoA dehydrogenase, it functions in the third step of the CC fatty acid beta-oxidation pathway, a major metabolic process in which CC fatty acids are oxidized to provide a significant source of energy, CC while also generating acyl-CoA metabolites used by many metabolic CC routes (PubMed:12917011) (Probable). As a HSD, it functions in the CC degradation pathways of glucocorticoids and sex steroids and CC epimerization of bile acids; catalyzes the beta-oxidation at position CC 17 of androgens and estrogens, has 3-alpha-hydroxysteroid dehydrogenase CC activity with androsterone, and carries out oxidative conversions of 7- CC beta-hydroxylated bile acids like ursodeoxycholate or CC isoursodeoxycholate (also known as 3-beta,7-beta-dihydroxy-5-beta- CC cholan-24-oate or 7-beta-hydroxyisolithocholate, respectively). Also CC exhibits 20-beta-OH and 21-OH dehydrogenase activities with C21 CC steroids (PubMed:12917011). Essential for structural and functional CC integrity of mitochondria (PubMed:27131785, PubMed:34199774, CC PubMed:35663400). Required for cell survival during embryonic CC development (PubMed:9585418). May play a role in germline formation CC (PubMed:9585418, PubMed:12917011). {ECO:0000269|PubMed:12917011, CC ECO:0000269|PubMed:27131785, ECO:0000269|PubMed:34199774, CC ECO:0000269|PubMed:35663400, ECO:0000269|PubMed:9585418, CC ECO:0000305|PubMed:9585418}. 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:27131785, CC PubMed:34199774, PubMed:35663400). Essential for the structural and CC functional integrity of mitochondria (PubMed:27131785, PubMed:34199774, CC PubMed:35663400). Function is essential for pupal development CC (PubMed:27131785, PubMed:34199774). {ECO:0000269|PubMed:27131785, CC ECO:0000269|PubMed:34199774, ECO:0000269|PubMed:35663400}. 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:12917011}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433; CC Evidence={ECO:0000269|PubMed:12917011}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22434; CC Evidence={ECO:0000269|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:12917011}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30800; CC Evidence={ECO:0000269|PubMed:12917011}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30801; CC Evidence={ECO:0000269|PubMed:12917011}; 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; EC=1.1.1.51; CC Evidence={ECO:0000269|PubMed:12917011}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930; CC Evidence={ECO:0000269|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:0000269|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:12917011}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613; CC Evidence={ECO:0000269|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:0000269|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:0000269|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:0000269|PubMed:12917011}; 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:0000269|PubMed:12917011}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cortisol + NAD(+) = 11beta,17alpha-dihydroxypregn-4- CC ene-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:0000269|PubMed:12917011}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5alpha-pregnan-20beta-ol-3-one + NAD(+) = 5alpha- CC pregnane-3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:42008, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28952, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78594; CC Evidence={ECO:0000269|PubMed:12917011}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42009; CC Evidence={ECO:0000269|PubMed:12917011}; 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:0000269|PubMed:12917011}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=33.7 uM for acetoacetyl-CoA (in the presence of 0.2 mM NADH, at pH CC 6.4 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; CC KM=101 uM for (3S)-3-hydroxybutanoyl-CoA (beta-hydroxybutyryl-CoA) CC (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12917011}; CC KM=37.3 uM for androsterone (in the presence of 1 mM NAD, at pH 9.3 CC and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; CC KM=12.3 uM for 17beta-hydroxy-5alpha-androstan-3-one CC (5-alpha-dihydrotestosterone) (in the presence of 0.2 mM NADH, at pH CC 6.4 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; CC KM=11.1 uM for 17-beta-estradiol (in the presence of 1 mM NAD, at pH CC 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; CC KM=9 uM for 5alpha-pregnan-20beta-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=3 uM for 3beta,7beta-dihydroxy-5beta-cholan-24-oate (also known as CC isoursodeoxycholate or 7beta-hydroxyisolithocholate) (in the presence CC of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12917011}; CC KM=32.5 uM for NADH (in the presence of acetoacetyl-CoA, at pH 7.0 CC and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; CC KM=64.4 uM for NAD (in the presence of (3S)-3-hydroxybutanoyl-CoA, at CC pH 9.3 and 25 degrees Celsius) {ECO:0000269|PubMed:12917011}; CC KM=124 uM for NAD (in the presence of aldosterone, at pH 9.3 and 25 CC degrees Celsius) {ECO:0000269|PubMed:12917011}; CC pH dependence: CC Optimum pH is 9.3 for the dehydrogenase reaction, and 6.4 for the CC reductase reaction. {ECO:0000269|PubMed:12917011}; CC -!- SUBUNIT: Component of mitochondrial ribonuclease P, a complex composed CC of rswl/MRPP1, scu/MRPP2 and mldr/MRPP3. {ECO:0000269|PubMed:27131785, CC ECO:0000269|PubMed:34199774}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:27131785, CC ECO:0000269|PubMed:34199774}. Note=Localizes to the lipid droplet CC fraction in early embryos (PubMed:16979555). CC {ECO:0000269|PubMed:16979555}. CC -!- TISSUE SPECIFICITY: Found in many tissues including CNS, imaginal disks CC and salivary glands. Highest expression in both embryonic gonadal CC primordia and mature ovaries and testes. {ECO:0000269|PubMed:9585418}. CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryonic development. In CC adults, expression is higher in females than in males. CC {ECO:0000269|PubMed:9585418}. CC -!- INDUCTION: By 20-hydroxyecdysone. {ECO:0000269|PubMed:17924685}. CC -!- DISRUPTION PHENOTYPE: Embryonic and pupal lethal (PubMed:9585418, CC PubMed:34199774). Pupation is developmentally delayed and pupae fail to CC enclose into adults (PubMed:34199774). Males, before the onset of CC lethality, have small testes and degenerating spermatocytes with a CC large accumulation of small fat-containing vesicles in the cytoplasm CC and almost no mitochondria (PubMed:9585418). Photoreceptors fail to CC differentiate normally, are unable to form proper rhabdomeres and CC contain smaller mitochondria with swollen crestae (PubMed:9585418). CC Larvae display reduced ATP and mitochondrial morphological defects, CC that are indicative of mitochondrial dysfunction (PubMed:34199774). CC RNAi-mediated knockdown is pupal lethal, with the majority of pupae CC undergoing pupation but then all fail to enclose into adults CC (PubMed:27131785). Larvae also display reduced levels of ATP CC (PubMed:27131785). Conditional RNAi-mediated knockdown in different CC tissues, produce various phenotypes that result from adherent, CC dysfunctional mitochondria (PubMed:27131785, PubMed:35663400). RNAi- CC mediated knockdown in skeletal muscle is pharate pupal lethal CC (PubMed:35663400). Reduces sarcomere size, and affects myofibril CC organization and structure, resulting in abnormal wing posture CC (PubMed:35663400). Cardiac-specific RNAi-mediated knockdown reduces CC lifespan and results in adult wing defects (PubMed:35663400). Adult CC hearts display impaired contractility but heart rhythm is not affected CC (PubMed:35663400). RNAi-mediated knockdown in dopaminergic neurons has CC no effect on climbing ability (PubMed:27131785). CC {ECO:0000269|PubMed:27131785, ECO:0000269|PubMed:34199774, CC ECO:0000269|PubMed:35663400, ECO:0000269|PubMed:9585418}. CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=ADE60673.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AET07646.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AFH07442.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y15102; CAA75377.1; -; mRNA. DR EMBL; AE014298; AAF48797.1; -; Genomic_DNA. DR EMBL; AE014298; AFH07442.1; ALT_INIT; Genomic_DNA. DR EMBL; AY121672; AAM51999.1; -; mRNA. DR EMBL; BT029045; ABJ16978.1; -; mRNA. DR EMBL; BT122199; ADE60673.1; ALT_INIT; mRNA. DR EMBL; BT132763; AET07646.1; ALT_INIT; mRNA. DR RefSeq; NP_523396.1; NM_078672.5. DR AlphaFoldDB; O18404; -. DR SMR; O18404; -. DR BioGRID; 59109; 78. DR ComplexPortal; CPX-2632; Mitochondrial ribonuclease P complex. DR DIP; DIP-17092N; -. DR IntAct; O18404; 6. DR STRING; 7227.FBpp0074285; -. DR SwissLipids; SLP:000000795; -. DR PaxDb; 7227-FBpp0074285; -. DR DNASU; 32789; -. DR EnsemblMetazoa; FBtr0074511; FBpp0074285; FBgn0021765. DR GeneID; 32789; -. DR KEGG; dme:Dmel_CG7113; -. DR AGR; FB:FBgn0021765; -. DR CTD; 32789; -. DR FlyBase; FBgn0021765; scu. DR VEuPathDB; VectorBase:FBgn0021765; -. DR eggNOG; KOG1199; Eukaryota. DR GeneTree; ENSGT00940000155170; -. DR HOGENOM; CLU_010194_42_0_1; -. DR InParanoid; O18404; -. DR OMA; QGIRVCT; -. DR OrthoDB; 149879at2759; -. DR PhylomeDB; O18404; -. DR Reactome; R-DME-70895; Branched-chain amino acid catabolism. DR SignaLink; O18404; -. DR BioGRID-ORCS; 32789; 0 hits in 1 CRISPR screen. DR ChiTaRS; scu; fly. DR GenomeRNAi; 32789; -. DR PRO; PR:O18404; -. DR Proteomes; UP000000803; Chromosome X. DR Bgee; FBgn0021765; Expressed in seminal fluid secreting gland and 19 other cell types or tissues. DR ExpressionAtlas; O18404; baseline and differential. DR GO; GO:0030678; C:mitochondrial ribonuclease P complex; IDA:FlyBase. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0047015; F:3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0047022; F:7-beta-hydroxysteroid dehydrogenase (NADP+) activity; IDA:FlyBase. DR GO; GO:0018454; F:acetoacetyl-CoA reductase activity; IDA:FlyBase. DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; IDA:FlyBase. DR GO; GO:0106282; F:isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity; IEA:RHEA. DR GO; GO:0016229; F:steroid dehydrogenase activity; IDA:FlyBase. DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IDA:FlyBase. DR GO; GO:0106283; F:ursodeoxycholate 7-beta-dehydrogenase (NAD+) activity; IEA:RHEA. DR GO; GO:0006637; P:acyl-CoA metabolic process; IDA:FlyBase. DR GO; GO:0008209; P:androgen metabolic process; IDA:FlyBase. DR GO; GO:0008205; P:ecdysone metabolic process; IDA:FlyBase. DR GO; GO:0008210; P:estrogen metabolic process; IDA:FlyBase. DR GO; GO:0006631; P:fatty acid metabolic process; IDA:FlyBase. DR GO; GO:0090646; P:mitochondrial tRNA processing; IMP:FlyBase. DR GO; GO:0008202; P:steroid metabolic process; IDA:FlyBase. 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 SMART; SM00822; PKS_KR; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00061; ADH_SHORT; 1. DR Genevisible; O18404; DM. PE 1: Evidence at protein level; KW Mitochondrion; NAD; Oxidoreductase; Reference proteome; tRNA processing. FT CHAIN 1..255 FT /note="3-hydroxyacyl-CoA dehydrogenase type-2" FT /id="PRO_0000054813" FT ACT_SITE 162 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001" FT BINDING 14 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 16 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 35 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 58 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 59 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 85 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 149 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 162 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 166 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 195 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 197 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT MUTAGEN 33 FT /note="L->Q: Lethal allele." FT /evidence="ECO:0000269|PubMed:9585418" FT MUTAGEN 120 FT /note="F->I: Lethal allele." FT /evidence="ECO:0000269|PubMed:9585418" FT MUTAGEN 159 FT /note="Missing: Pupal lethal; pupation is developmentally FT delayed and pupae fail to enclose into adults. Larvae also FT display reduced levels of ATP, abnormal neuroblast FT mitochondrial morphology, and the accumulation of FT unprocessed mitochondrial tRNAs transcripts for tRNA(Ile), FT tRNA(Gly), tRNA(Val) and tRNA(Leu) (CUN)." FT /evidence="ECO:0000269|PubMed:27131785, FT ECO:0000269|PubMed:34199774" FT MUTAGEN 163 FT /note="S->F: Pupal lethal; pupation is developmentally FT delayed and pupae fail to enclose into adults. Larvae also FT display reduced levels of ATP, abnormal neuroblast FT mitochondrial morphology, and the accumulation of FT unprocessed mitochondrial tRNAs transcripts for tRNA(Ile), FT tRNA(Gly), tRNA(Val) and tRNA(Leu) (CUN)." FT /evidence="ECO:0000269|PubMed:27131785, FT ECO:0000269|PubMed:34199774" FT CONFLICT 134 FT /note="E -> K (in Ref. 4; AAM51999)" FT /evidence="ECO:0000305" SQ SEQUENCE 255 AA; 26905 MW; F58690643FA0FD03 CRC64; MIKNAVSLVT GGASGLGRAT AERLAKQGAS VILADLPSSK GNEVAKELGD KVVFVPVDVT SEKDVSAALQ TAKDKFGRLD LTVNCAGTAT AVKTFNFNKN VAHRLEDFQR VININTVGTF NVIRLSAGLM GANEPNQDGQ RGVIVNTASV AAFDGQIGQA AYSASKAAVV GMTLPIARDL STQGIRICTI APGLFNTPML AALPEKVRTF LAKSIPFPQR LGEPSEYAHL VQAIYENPLL NGEVIRIDGA LRMMP //