HSD3B_CAEEL
ID HSD3B_CAEEL Reviewed; 462 AA.
AC Q9XWF0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase 1;
DE Short=HSD-1 {ECO:0000303|PubMed:18495818, ECO:0000303|PubMed:24411940};
DE EC=1.1.1.145 {ECO:0000305|PubMed:18495818};
DE EC=5.3.3.1 {ECO:0000305|PubMed:18495818};
DE AltName: Full=3beta_HSD domain-containing protein 1;
GN Name=hsd-1 {ECO:0000312|EMBL:CAA21722.1, ECO:0000312|WormBase:Y6B3B.11};
GN ORFNames=Y6B3B.11 {ECO:0000312|WormBase:Y6B3B.11};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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=18495818; DOI=10.1242/dev.016972;
RA Patel D.S., Fang L.L., Svy D.K., Ruvkun G., Li W.;
RT "Genetic identification of HSD-1, a conserved steroidogenic enzyme that
RT directs larval development in Caenorhabditis elegans.";
RL Development 135:2239-2249(2008).
RN [3]
RP FUNCTION, AND PATHWAY.
RX PubMed=20178781; DOI=10.1016/j.ydbio.2010.02.022;
RA Dumas K.J., Guo C., Wang X., Burkhart K.B., Adams E.J., Alam H., Hu P.J.;
RT "Functional divergence of dafachronic acid pathways in the control of C.
RT elegans development and lifespan.";
RL Dev. Biol. 340:605-612(2010).
RN [4]
RP FUNCTION, AND PATHWAY.
RX PubMed=24411940; DOI=10.1016/j.cmet.2013.11.024;
RA Mahanti P., Bose N., Bethke A., Judkins J.C., Wollam J., Dumas K.J.,
RA Zimmerman A.M., Campbell S.L., Hu P.J., Antebi A., Schroeder F.C.;
RT "Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear
RT hormone receptor, regulating C. elegans development and lifespan.";
RL Cell Metab. 19:73-83(2014).
CC -!- FUNCTION: Hydroxysteroid dehydrogenase involved in the biosynthesis of
CC dafrachonic acids (PubMed:18495818, PubMed:20178781, PubMed:24411940).
CC Catalyzes the dehydrogenation of cholesterol or its derivatives and the
CC isomerization of the double carbon bond on the sterol ring. Modifies
CC sterols into a Delta(4)-3-keto-sterols such as cholest-4-en-3-one,
CC precursor of Delta(4)-dafachronic acid (PubMed:18495818). Contributes
CC to the production of Delta(7)-dafachronic acid in the XXX cells
CC (PubMed:24411940). Dafachronic acids act as ligands and bind directly
CC to the nuclear hormone receptor (NHR) daf-12 suppressing dauer
CC formation and inducing reproductive growth (PubMed:18495818,
CC PubMed:24411940). Acts in parallel to AKT-1 to promote reproductive
CC development via DAF-16/FoxO and DAF-12 (PubMed:20178781).
CC {ECO:0000269|PubMed:18495818, ECO:0000269|PubMed:20178781,
CC ECO:0000269|PubMed:24411940, ECO:0000303|PubMed:18495818}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-
CC steroid + H(+) + NADH; Xref=Rhea:RHEA:24076, ChEBI:CHEBI:1722,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:47907, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.145;
CC Evidence={ECO:0000305|PubMed:18495818};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24077;
CC Evidence={ECO:0000305|PubMed:18495818};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + NAD(+) = cholest-5-en-3-one + H(+) + NADH;
CC Xref=Rhea:RHEA:35459, ChEBI:CHEBI:15378, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:63906;
CC Evidence={ECO:0000303|PubMed:18495818};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35460;
CC Evidence={ECO:0000303|PubMed:18495818};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid;
CC Xref=Rhea:RHEA:14709, ChEBI:CHEBI:47907, ChEBI:CHEBI:47909;
CC EC=5.3.3.1; Evidence={ECO:0000305|PubMed:18495818};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14710;
CC Evidence={ECO:0000305|PubMed:18495818};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholest-5-en-3-one = cholest-4-en-3-one; Xref=Rhea:RHEA:32187,
CC ChEBI:CHEBI:16175, ChEBI:CHEBI:63906; EC=5.3.3.1;
CC Evidence={ECO:0000303|PubMed:18495818};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32188;
CC Evidence={ECO:0000303|PubMed:18495818};
CC -!- PATHWAY: Steroid hormone biosynthesis; dafachronic acid biosynthesis.
CC {ECO:0000269|PubMed:18495818, ECO:0000269|PubMed:20178781,
CC ECO:0000269|PubMed:24411940}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed exclusively in the neuron-like XXX(L/R)
CC cells through all four larval stages and becomes fainter in adults.
CC {ECO:0000269|PubMed:18495818}.
CC -!- DISRUPTION PHENOTYPE: Mutants are hypersensitive to pheromone induction
CC and form dauers more readily than the wild-type.
CC {ECO:0000269|PubMed:18495818}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
CC -!- CAUTION: Although thought to contribute to D(4)-dafrachronic acid
CC biosynthesis, the latter may not be present at physiologically relevant
CC concentrations in C.elegans and comparative metabolomics would indicate
CC 7-dehydrogenase activity and participation in D(7)-dafrachronic acid
CC biosynthesis instead. {ECO:0000269|PubMed:24411940}.
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; BX284601; CAA21722.1; -; Genomic_DNA.
DR PIR; T27323; T27323.
DR RefSeq; NP_493402.1; NM_061001.1.
DR AlphaFoldDB; Q9XWF0; -.
DR STRING; 6239.Y6B3B.11; -.
DR SwissLipids; SLP:000000034; -.
DR PaxDb; Q9XWF0; -.
DR EnsemblMetazoa; Y6B3B.11.1; Y6B3B.11.1; WBGene00012394.
DR GeneID; 189371; -.
DR KEGG; cel:CELE_Y6B3B.11; -.
DR UCSC; Y6B3B.11; c. elegans.
DR CTD; 189371; -.
DR WormBase; Y6B3B.11; CE20185; WBGene00012394; hsd-1.
DR eggNOG; KOG1430; Eukaryota.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; Q9XWF0; -.
DR OMA; ACMDINA; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; Q9XWF0; -.
DR UniPathway; UPA01020; -.
DR Proteomes; UP000001940; Chromosome I.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IMP:WormBase.
DR GO; GO:0102294; F:cholesterol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0004769; F:steroid delta-isomerase activity; IEA:UniProtKB-EC.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0016126; P:sterol biosynthetic process; IMP:WormBase.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Isomerase; Lipid metabolism; Membrane; NAD;
KW Oxidoreductase; Reference proteome; Steroid metabolism; Sterol metabolism;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..462
FT /note="3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)
FT isomerase 1"
FT /id="PRO_0000452999"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 224
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 51..56
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 220
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 224
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
SQ SEQUENCE 462 AA; 52607 MW; 9622E27F41B14DA3 CRC64;
MSIKRLSMRL KKGIHRSWNR MTSLEAGLEE EKEIKIVEEP EPRPWKVLIT GGAGHLAENL
VAKLEEMTRD SIRPKIREML EKEMPAVIST KVDKEVEKRL PMYIQIVLVD VLEPRGRVLK
HHVAFVKCSF DDECTMKTAL EQVDTVYHLA AVGMTGQYAR DRKACMDINA VGTMNLLIWA
RNSGVQRFIY TSSVGVVFSG EPMYNATEEV GYPDDFYNYY CESKAHAERI VQKASGHRMR
TTVLRFNGIY GPGEKRVTER VVKFMLTGMW IATCKPNGVE AQTQLSSVAN CIQGLVKAEL
ALRWSDTPHG QIYNIMDKTP VGTFSFWTPL NIALGFSSSM ITVPATPIRL FAYLSQIIAD
RMRIDPIVSV LEVDLLLVNN TFNIEKAERD LGYEPSVSAI PEIIEHYLHR LPPDVVRPKG
RSDFYVKVAV LVLGTILIFV AVFSFTFWMY LIFQRLSRWN PF
