ID   DHS16_CAEEL             Reviewed;         388 AA.
AC   O16881;
DT   06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 143.
DE   RecName: Full=3beta-hydroxysteroid dehydrogenase dhs-16;
DE            EC=1.1.1.- {ECO:0000269|PubMed:22505847};
GN   Name=dhs-16; ORFNames=C10F3.2;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=22505847; DOI=10.1371/journal.pbio.1001305;
RA   Wollam J., Magner D.B., Magomedova L., Rass E., Shen Y., Rottiers V.,
RA   Habermann B., Cummins C.L., Antebi A.;
RT   "A novel 3-hydroxysteroid dehydrogenase that regulates reproductive
RT   development and longevity.";
RL   PLoS Biol. 10:E1001305-E1001305(2012).
RN   [3]
RP   FUNCTION.
RX   PubMed=22505849; DOI=10.1371/journal.pbio.1001307;
RA   Lee S.S., Schroeder F.C.;
RT   "Steroids as central regulators of organismal development and lifespan.";
RL   PLoS Biol. 10:e1001307-e1001307(2012).
CC   -!- FUNCTION: 3beta-hydroxysteroid dehydrogenase that converts 3beta-
CC       hydroxysteroids to 3-ketosteroids, an essential step in the production
CC       of dafachronic acids from cholesterol. Catalyzes the dehydrogenation of
CC       lathosterol (5alpha-cholest-7-en-3beta-ol) to lathosterone (5alpha-
CC       cholest-7-en-3-one), a step required for maximal biosynthesis of
CC       Delta(7)-dafachronic acid (PubMed:22505847). Dafachronic acids act as
CC       ligands and bind directly to the nuclear hormone receptor (NHR) daf-12,
CC       suppressing dauer formation and inducing reproductive growth, they can
CC       also regulate C.elegans lifespan (PubMed:22505847, PubMed:22505849).
CC       {ECO:0000269|PubMed:22505847, ECO:0000269|PubMed:22505849}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=lathosterol + NAD(+) = 5alpha-cholest-7-en-3-one + H(+) +
CC         NADH; Xref=Rhea:RHEA:35463, ChEBI:CHEBI:15378, ChEBI:CHEBI:17168,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:71550;
CC         Evidence={ECO:0000269|PubMed:22505847};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35464;
CC         Evidence={ECO:0000269|PubMed:22505847};
CC   -!- PATHWAY: Steroid hormone biosynthesis; dafachronic acid biosynthesis.
CC       {ECO:0000269|PubMed:22505847}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Strongly expressed in the hypodermis and posterior
CC       pharyngeal bulb and in a number of unidentified neurons of the head and
CC       tail. {ECO:0000269|PubMed:22505847}.
CC   -!- DISRUPTION PHENOTYPE: Mutants appear normal at 20 degrees Celsius but
CC       have Daf-c phenotypes (formation of dauer larvae at low population
CC       density in the presence of abundant food) at 27 degrees Celsius.
CC       {ECO:0000269|PubMed:22505847}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; FO080493; CCD64121.1; -; Genomic_DNA.
DR   PIR; T32153; T32153.
DR   RefSeq; NP_504554.1; NM_072153.6.
DR   AlphaFoldDB; O16881; -.
DR   SMR; O16881; -.
DR   STRING; 6239.C10F3.2; -.
DR   SwissLipids; SLP:000000077; -.
DR   SwissLipids; SLP:000000192; -.
DR   PaxDb; O16881; -.
DR   EnsemblMetazoa; C10F3.2.1; C10F3.2.1; WBGene00000979.
DR   GeneID; 178983; -.
DR   KEGG; cel:CELE_C10F3.2; -.
DR   UCSC; C10F3.2; c. elegans.
DR   CTD; 178983; -.
DR   WormBase; C10F3.2; CE08067; WBGene00000979; dhs-16.
DR   eggNOG; KOG1610; Eukaryota.
DR   GeneTree; ENSGT00940000165804; -.
DR   HOGENOM; CLU_010194_2_0_1; -.
DR   InParanoid; O16881; -.
DR   OMA; ANPNIGW; -.
DR   OrthoDB; 942985at2759; -.
DR   PhylomeDB; O16881; -.
DR   Reactome; R-CEL-5365859; RA biosynthesis pathway.
DR   UniPathway; UPA01020; -.
DR   PRO; PR:O16881; -.
DR   Proteomes; UP000001940; Chromosome V.
DR   Bgee; WBGene00000979; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0016229; F:steroid dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0006706; P:steroid catabolic process; IDA:UniProtKB.
DR   GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
PE   1: Evidence at protein level;
KW   Cholesterol metabolism; Lipid metabolism; Membrane; Oxidoreductase;
KW   Reference proteome; Steroid metabolism; Sterol metabolism; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..388
FT                   /note="3beta-hydroxysteroid dehydrogenase dhs-16"
FT                   /id="PRO_0000421679"
FT   TRANSMEM        2..22
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        300..320
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        346..366
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        188
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
SQ   SEQUENCE   388 AA;  44079 MW;  2C576F267167DEA5 CRC64;
     MLELIYILPL LCFVYFLFRR FVLENFYVES SGKYVMITGC DSGFGRLLAT SLLDKHVNVF
     AACFTQQGMA SLHSEWKLKK GPKGQLYTLQ LDVTSQASVD SAKSFVTKIL KEQNSKLWGL
     VNNAGIFSIH GPDDWCSVDE YASSLNVNTL GAVRMCHAFV PLIKKSRGRI VTMGSTAGRL
     HGLYVAPYVT AKFAVEAYMD CLRLEMRPFG VSVHILEPGC FKTELLNNDA QRMRIQKIWN
     SLSVETKEEY GEDYRNDFER AWEAGVNVVA NPNIGWVVDC YSHALFSWWP RLRYCPGWDA
     IFMFIPLSIF PTALQDWILA GLYKLNPGPS LTPAVLVKNK KRRSAIQWIQ FLSQIAIIPL
     LYTIFFVKNT QKQTVETSTH HHNVTVSE