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O18404 (HCD2_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
3-hydroxyacyl-CoA dehydrogenase type-2

EC=1.1.1.35
Alternative name(s):
17-beta-hydroxysteroid dehydrogenase 10
Short name=17-beta-HSD 10
EC=1.1.1.51
3-hydroxy-2-methylbutyryl-CoA dehydrogenase
EC=1.1.1.178
3-hydroxyacyl-CoA dehydrogenase type II
Mitochondrial ribonuclease P protein 2
Short name=Mitochondrial RNase P protein 2
Scully protein
Type II HADH
Gene names
Name:scu
ORF Names:CG7113
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length255 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function in mitochondrial tRNA maturation. Catalyzes the beta-oxidation at position 17 of androgens and estrogens, and has 3-alpha-hydroxysteroid dehydrogenase activity with androsterone. Catalyzes the third step in the beta-oxidation of fatty acids. Carries out oxidative conversions of 7-beta-hydroxylated bile acids. Also exhibits 20-beta-OH and 21-OH dehydrogenase activities with C21 steroids. Required for cell survival during embryonic development. May play a role in germline formation. Ref.1 Ref.6

Catalytic activity

(S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH. Ref.6

(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD+ = 2-methylacetoacetyl-CoA + NADH. Ref.6

Testosterone + NAD(P)+ = androst-4-ene-3,17-dione + NAD(P)H. Ref.6

Subunit structure

Multimer Potential.

Subcellular location

Mitochondrion By similarity. Note: Localizes to the lipid droplet fraction in early embryos. Ref.7

Tissue specificity

Found in many tissues including CNS, imaginal disks and salivary glands. Highest expression in both embryonic gonadal primordia and mature ovaries and testes. Ref.1

Developmental stage

Expressed throughout embryonic development. In adults, expression is higher in females than in males. Ref.1

Induction

By 20-hydroxyecdysone. Ref.8

Disruption phenotype

Embryonic and pupal lethal. Male mutants show small testes and degenerating spermatocytes with a large accumulation of small fat-containing vesicles in the cytoplasm and almost no mitochondria. Null mutant photoreceptors fail to differentiate normally, are unable to form proper rhabdomeres and present smaller mitochondria with fewer, but swollen crestae, than wild-type cells. Ref.1

Sequence similarities

Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Biophysicochemical properties

Kinetic parameters:

KM=33.7 µM for acetoacetyl-CoA (in the presence of 0.2 mM NADH, at pH 6.4 and 25 degrees Celsius) Ref.6

KM=101 µM for beta-hydroxybutyryl-CoA (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius)

KM=37.3 µM for androsterone (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius)

KM=12.3 µM for 5-alpha-dihydrotestosterone (in the presence of 0.2 mM NADH, at pH 6.4 and 25 degrees Celsius)

KM=11.1 µM for 17-beta-estradiol (in the presence of 0.2 mM NADH, at pH 9.3 and 25 degrees Celsius)

KM=9 µM for 5-alpha-pregnan-20-beta-ol-3-one (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius)

KM=3 µM for isoursodeoxycholic acid (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius)

KM=32.5 µM for NADH (in the presence of acetoacetyl-CoA, at pH 7.0 and 25 degrees Celsius)

KM=64.4 µM for NAD (in the presence of beta-hydroxybutyryl-CoA, at pH 9.3 and 25 degrees Celsius)

KM=124 µM for NAD (in the presence of aldosterone, at pH 9.3 and 25 degrees Celsius)

pH dependence:

Optimum pH is 9.3 for the dehydrogenase reaction, and 6.4 for the reductase reaction.

Sequence caution

The sequence AET07646.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processtRNA processing
   Cellular componentMitochondrion
   LigandNAD
   Molecular functionOxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacyl-CoA metabolic process

Inferred from direct assay Ref.6. Source: FlyBase

androgen metabolic process

Inferred from direct assay Ref.6. Source: FlyBase

ecdysone metabolic process

Inferred from direct assay Ref.6. Source: FlyBase

estrogen metabolic process

Inferred from direct assay Ref.6. Source: FlyBase

fatty acid metabolic process

Inferred from direct assay Ref.6. Source: FlyBase

steroid metabolic process

Inferred from direct assay Ref.6. Source: FlyBase

tRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Non-traceable author statement Ref.6. Source: FlyBase

lipid particle

Inferred from direct assay PubMed 16543254Ref.7. Source: FlyBase

microtubule associated complex

Inferred from direct assay PubMed 18433294. Source: FlyBase

mitochondrion

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_function3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

3-hydroxyacyl-CoA dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

7-beta-hydroxysteroid dehydrogenase (NADP+) activity

Inferred from direct assay Ref.6. Source: FlyBase

acetoacetyl-CoA reductase activity

Inferred from direct assay Ref.6. Source: FlyBase

estradiol 17-beta-dehydrogenase activity

Inferred from direct assay Ref.6. Source: FlyBase

steroid dehydrogenase activity

Inferred from direct assay Ref.6. Source: FlyBase

testosterone dehydrogenase (NAD+) activity

Inferred from direct assay Ref.6. Source: FlyBase

testosterone dehydrogenase [NAD(P)] activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 2552553-hydroxyacyl-CoA dehydrogenase type-2
PRO_0000054813

Regions

Nucleotide binding6 – 3126NAD By similarity

Sites

Active site1621Proton acceptor By similarity
Binding site1491Substrate By similarity

Experimental info

Mutagenesis331L → Q: Lethal allele. Ref.1
Mutagenesis1201F → I: Lethal allele. Ref.1
Sequence conflict1341E → K in AAM51999. Ref.4

Sequences

Sequence LengthMass (Da)Tools
O18404 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: F58690643FA0FD03

FASTA25526,905
        10         20         30         40         50         60 
MIKNAVSLVT GGASGLGRAT AERLAKQGAS VILADLPSSK GNEVAKELGD KVVFVPVDVT 

        70         80         90        100        110        120 
SEKDVSAALQ TAKDKFGRLD LTVNCAGTAT AVKTFNFNKN VAHRLEDFQR VININTVGTF 

       130        140        150        160        170        180 
NVIRLSAGLM GANEPNQDGQ RGVIVNTASV AAFDGQIGQA AYSASKAAVV GMTLPIARDL 

       190        200        210        220        230        240 
STQGIRICTI APGLFNTPML AALPEKVRTF LAKSIPFPQR LGEPSEYAHL VQAIYENPLL 

       250 
NGEVIRIDGA LRMMP 

« Hide

References

« Hide 'large scale' references
[1]"Scully, an essential gene of Drosophila, is homologous to mammalian mitochondrial type II L-3-hydroxyacyl-CoA dehydrogenase/amyloid-beta peptide-binding protein."
Torroja L., Ortuno-Sahagun D., Ferrus A., Haemmerle B., Barbas J.A.
J. Cell Biol. 141:1009-1018(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF LEU-33 AND PHE-120.
Strain: Canton-S.
[2]"The genome sequence of Drosophila melanogaster."
Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. expand/collapse author list , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Berkeley.
[3]"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review."
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. expand/collapse author list , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: Berkeley.
[4]"A Drosophila full-length cDNA resource."
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E.
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Berkeley.
Tissue: Embryo.
[5]Stapleton M., Booth B., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C., Celniker S.E.
Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Berkeley.
[6]"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."
Shafqat N., Marschall H.U., Filling C., Nordling E., Wu X.Q., Bjork L., Thyberg J., Martensson E., Salim S., Jornvall H., Oppermann U.
Biochem. J. 376:49-60(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[7]"The lipid-droplet proteome reveals that droplets are a protein-storage depot."
Cermelli S., Guo Y., Gross S.P., Welte M.A.
Curr. Biol. 16:1783-1795(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[8]"Proteomic identification of PKC-mediated expression of 20E-induced protein in Drosophila melanogaster."
Sun Y., An S., Henrich V.C., Sun X., Song Q.
J. Proteome Res. 6:4478-4488(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INDUCTION BY 20-HYDROXYECDYSONE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y15102 mRNA. Translation: CAA75377.1.
AE014298 Genomic DNA. Translation: AAF48797.1.
AY121672 mRNA. Translation: AAM51999.1.
BT029045 mRNA. Translation: ABJ16978.1.
BT132763 mRNA. Translation: AET07646.1. Different initiation.
RefSeqNP_523396.1. NM_078672.4.
UniGeneDm.7957.

3D structure databases

ProteinModelPortalO18404.
SMRO18404. Positions 2-255.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid59109. 74 interactions.
DIPDIP-17092N.
IntActO18404. 2 interactions.
MINTMINT-289527.

Proteomic databases

PaxDbO18404.
PRIDEO18404.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaFBtr0074511; FBpp0074285; FBgn0021765.
GeneID32789.
KEGGdme:Dmel_CG7113.

Organism-specific databases

CTD32789.
FlyBaseFBgn0021765. scu.

Phylogenomic databases

eggNOGCOG1028.
GeneTreeENSGT00710000106273.
InParanoidO18404.
KOK08683.
OMALMGANEP.
OrthoDBEOG7JT6X7.
PhylomeDBO18404.

Gene expression databases

BgeeO18404.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]
PfamPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSPR00081. GDHRDH.
PR00080. SDRFAMILY.
PROSITEPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSscu. drosophila.
GenomeRNAi32789.
NextBio780387.
PROO18404.

Entry information

Entry nameHCD2_DROME
AccessionPrimary (citable) accession number: O18404
Secondary accession number(s): G7H840, Q059C3, Q8MRC1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase