DAF9_CAEEL
ID DAF9_CAEEL Reviewed; 572 AA.
AC H2KYS3; G5ECA9;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=3-ketosteroid oxygenase;
DE EC=1.14.14.- {ECO:0000269|PubMed:16529801, ECO:0000269|PubMed:22505847};
DE AltName: Full=Cytochrome P450 daf-9;
DE Short=DAF-9 {ECO:0000303|PubMed:11782415, ECO:0000303|PubMed:16529801, ECO:0000303|PubMed:22505847};
GN Name=daf-9; ORFNames=T13C5.1;
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 [MRNA] (ISOFORM B), FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11782415; DOI=10.1242/dev.129.1.221;
RA Jia K., Albert P.S., Riddle D.L.;
RT "DAF-9, a cytochrome P450 regulating C. elegans larval development and
RT adult longevity.";
RL Development 129:221-231(2002).
RN [2]
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 [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=3350212; DOI=10.1016/0012-1606(88)90138-8;
RA Albert P.S., Riddle D.L.;
RT "Mutants of Caenorhabditis elegans that form dauer-like larvae.";
RL Dev. Biol. 126:270-293(1988).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12783794; DOI=10.1242/dev.00540;
RA Ohkura K., Suzuki N., Ishihara T., Katsura I.;
RT "SDF-9, a protein tyrosine phosphatase-like molecule, regulates the
RT L3/dauer developmental decision through hormonal signaling in C. elegans.";
RL Development 130:3237-3248(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=16529801; DOI=10.1016/j.cell.2006.01.037;
RA Motola D.L., Cummins C.L., Rottiers V., Sharma K.K., Li T., Li Y.,
RA Suino-Powell K., Xu H.E., Auchus R.J., Antebi A., Mangelsdorf D.J.;
RT "Identification of ligands for DAF-12 that govern dauer formation and
RT reproduction in C. elegans.";
RL Cell 124:1209-1223(2006).
RN [6]
RP FUNCTION.
RX PubMed=18436204; DOI=10.1016/j.ydbio.2008.03.019;
RA Dixon S.J., Alexander M., Chan K.K., Roy P.J.;
RT "Insulin-like signaling negatively regulates muscle arm extension through
RT DAF-12 in Caenorhabditis elegans.";
RL Dev. Biol. 318:153-161(2008).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 [8]
RP FUNCTION.
RX PubMed=24957743; DOI=10.1007/s12263-014-0414-6;
RA Fischer M., Fitzenberger E., Kull R., Boll M., Wenzel U.;
RT "The zinc matrix metalloproteinase ZMP-2 increases survival of
RT Caenorhabditis elegans through interference with lipoprotein absorption.";
RL Genes Nutr. 9:414-414(2014).
CC -!- FUNCTION: Converts the 3-keto steroids 4-cholesten-3-one and
CC lathosterone into the carboxylic metabolites 3-keto-4-cholestenate
CC (Delta(4)-dafachronic acid, Delta(4)-DA) and 3-keto-7,(5a)-cholestenate
CC (Delta(7)-dafachronic acid, Delta(7)-DA) respectively, by catalyzing
CC successive oxidations at C-26 (PubMed:16529801, PubMed:22505847).
CC Dafachronic acids bind directly to the nuclear hormone receptor (NHR)
CC DAF-12, suppressing dauer formation and inducing reproductive growth
CC (PubMed:11782415, PubMed:12783794, PubMed:16529801, PubMed:22505847).
CC In a non-cell autonomous manner, negatively regulates body wall muscle
CC arm extensions to motor neurons probably by preventing daf-12 isoform b
CC activation (PubMed:18436204). May be involved in thermotolerance
CC (PubMed:24957743). {ECO:0000269|PubMed:11782415,
CC ECO:0000269|PubMed:12783794, ECO:0000269|PubMed:16529801,
CC ECO:0000269|PubMed:18436204, ECO:0000269|PubMed:22505847,
CC ECO:0000269|PubMed:24957743}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-cholest-7-en-3-one + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = (25S)-Delta7-dafachronate + 4 H(+) + 4 H2O +
CC 3 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:66620,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:71542, ChEBI:CHEBI:71550;
CC Evidence={ECO:0000269|PubMed:16529801, ECO:0000269|PubMed:22505847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66621;
CC Evidence={ECO:0000269|PubMed:16529801, ECO:0000269|PubMed:22505847};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholest-4-en-3-one + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = (25S)-3-oxocholest-4-en-26-oate + 4 H(+) + 4 H2O + 3
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:66624,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16175,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:71541;
CC Evidence={ECO:0000269|PubMed:16529801, ECO:0000269|PubMed:22505847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66625;
CC Evidence={ECO:0000269|PubMed:16529801, ECO:0000269|PubMed:22505847};
CC -!- PATHWAY: Steroid hormone biosynthesis; dafachronic acid biosynthesis.
CC {ECO:0000269|PubMed:16529801, ECO:0000269|PubMed:22505847}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Note=Localizes to dendrite-like structure in
CC XXXL/R cells. {ECO:0000269|PubMed:12783794}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=H2KYS3-1; Sequence=Displayed;
CC Name=b;
CC IsoId=H2KYS3-2; Sequence=VSP_045859;
CC -!- TISSUE SPECIFICITY: Expressed in the 2 embryonic head hypodermal cells
CC XXXL/R. {ECO:0000269|PubMed:12783794}.
CC -!- DISRUPTION PHENOTYPE: The daf-9 mutant is dauer-like in head shape,
CC cuticle, and deirid ultrastructure, intermediate in amphid and inner
CC labial neuron morphology, and nondauer or abnormal in the intestine
CC (PubMed:3350212). Also, the daf-9 mutant exhibits abnormal reproductive
CC development, molting defects and increased adult longevity
CC (PubMed:11782415). {ECO:0000269|PubMed:11782415,
CC ECO:0000269|PubMed:3350212}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF407572; AAL65132.1; -; mRNA.
DR EMBL; FO080546; CCD64552.1; -; Genomic_DNA.
DR EMBL; FO080546; CCD64553.1; -; Genomic_DNA.
DR RefSeq; NP_001024903.1; NM_001029732.1. [H2KYS3-2]
DR RefSeq; NP_741807.2; NM_171699.4. [H2KYS3-1]
DR AlphaFoldDB; H2KYS3; -.
DR SMR; H2KYS3; -.
DR BioGRID; 45821; 4.
DR STRING; 6239.T13C5.1a; -.
DR SwissLipids; SLP:000000035; -.
DR EPD; H2KYS3; -.
DR PaxDb; H2KYS3; -.
DR PRIDE; H2KYS3; -.
DR EnsemblMetazoa; T13C5.1a.1; T13C5.1a.1; WBGene00000905. [H2KYS3-1]
DR EnsemblMetazoa; T13C5.1b.1; T13C5.1b.1; WBGene00000905. [H2KYS3-2]
DR GeneID; 180889; -.
DR KEGG; cel:CELE_T13C5.1; -.
DR CTD; 180889; -.
DR WormBase; T13C5.1a; CE27206; WBGene00000905; daf-9. [H2KYS3-1]
DR WormBase; T13C5.1b; CE30451; WBGene00000905; daf-9. [H2KYS3-2]
DR eggNOG; KOG0156; Eukaryota.
DR InParanoid; H2KYS3; -.
DR OMA; CIRWRIV; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; H2KYS3; -.
DR Reactome; R-CEL-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-CEL-211916; Vitamins.
DR Reactome; R-CEL-211958; Miscellaneous substrates.
DR Reactome; R-CEL-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR UniPathway; UPA01020; -.
DR PRO; PR:H2KYS3; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000905; Expressed in larva and 1 other tissue.
DR ExpressionAtlas; H2KYS3; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
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:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IBA:GO_Central.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; IMP:WormBase.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0040024; P:dauer larval development; IMP:WormBase.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0030334; P:regulation of cell migration; IMP:WormBase.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cholesterol metabolism; Heme; Iron; Lipid metabolism;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..572
FT /note="3-ketosteroid oxygenase"
FT /id="PRO_0000421678"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..36
FT /note="MHLENRVLSSVLDYASKFYKRMSSLVFFSANSIQVQ -> MPLVIGRFSSLS
FT CERASIWCN (in isoform b)"
FT /evidence="ECO:0000303|PubMed:11782415"
FT /id="VSP_045859"
SQ SEQUENCE 572 AA; 66598 MW; BD0A0B845E550487 CRC64;
MHLENRVLSS VLDYASKFYK RMSSLVFFSA NSIQVQMNIS QSSWIKCRDW MAFALSHHII
MGIYLLILRN FLPQVVPDFE WQHYFMRVFI VHIIYIIISY FIRITRYPPG PPPMAVFGNS
PFVNILTPEQ TFLEYREIYG PIFTLHLSQP TIILAEYKTI QEALVKNGQQ TSGRSSAESF
VLFTGDRLNG DGVILAMRQK WKDMRHEISR FMNKWYGAPM DELVLHHTRC LEQELAKIAE
TKSLIDLRDP LAGAIANVIQ QITIGRNYMY QDQEFQTQLR DINAVVKEIM TAEVFFVNCY
PWLRYLPEGI LRKWTNYKRS GFRLQQWFRT ILEEHHVNRH QGDFMSHMID LQESKQEQFR
DLSIILTCGD MWTGGMETTV TTLRWGIIYL LNNPEVQAKC QMEILDVFGN DIPDMGKMNQ
TPYVRATLSE IQRLANVLPW AIPHKTIEEC NIGGYDIPVN TEIIPALGAV LFDPNVFESP
KQFKPERFLD EEGKYRVMEE FRPFGLGPRV CLGERIARTE LYLIFASLLQ NFRFYLNRGD
PIPVAERVIG GITAPPKPYA TRVEYLGNRL IN
