ID   DAF36_CAEEL             Reviewed;         428 AA.
AC   Q17938;
DT   06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 2.
DT   27-MAR-2024, entry version 147.
DE   RecName: Full=Cholesterol 7-desaturase {ECO:0000303|PubMed:21749634};
DE            EC=1.14.19.21 {ECO:0000269|PubMed:16563875, ECO:0000269|PubMed:21632547, ECO:0000269|PubMed:21749634};
DE   AltName: Full=Cholesterol desaturase daf-36;
DE   AltName: Full=Rieske oxygenase DAF-36/Neverland {ECO:0000303|PubMed:21632547};
DE            Short=DAF-36/NVD {ECO:0000303|PubMed:21632547};
GN   Name=daf-36; ORFNames=C12D8.5;
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, AND TISSUE SPECIFICITY.
RX   PubMed=16563875; DOI=10.1016/j.devcel.2006.02.008;
RA   Rottiers V., Motola D.L., Gerisch B., Cummins C.L., Nishiwaki K.,
RA   Mangelsdorf D.J., Antebi A.;
RT   "Hormonal control of C. elegans dauer formation and life span by a Rieske-
RT   like oxygenase.";
RL   Dev. Cell 10:473-482(2006).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=21749634; DOI=10.1111/j.1474-9726.2011.00733.x;
RA   Wollam J., Magomedova L., Magner D.B., Shen Y., Rottiers V., Motola D.L.,
RA   Mangelsdorf D.J., Cummins C.L., Antebi A.;
RT   "The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in
RT   steroidogenic pathways governing longevity.";
RL   Aging Cell 10:879-884(2011).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF CYS-122 AND
RP   ASP-234.
RX   PubMed=21632547; DOI=10.1074/jbc.m111.244384;
RA   Yoshiyama-Yanagawa T., Enya S., Shimada-Niwa Y., Yaguchi S., Haramoto Y.,
RA   Matsuya T., Shiomi K., Sasakura Y., Takahashi S., Asashima M., Kataoka H.,
RA   Niwa R.;
RT   "The conserved Rieske oxygenase DAF-36/Neverland is a novel cholesterol-
RT   metabolizing enzyme.";
RL   J. Biol. Chem. 286:25756-25762(2011).
CC   -!- FUNCTION: Catalyzes the production of 7-dehydrocholesterol (7-DHC or
CC       cholesta-5,7-dien-3beta-ol) by inserting a double bond (desaturating)
CC       at the C7-C8 single bond of cholesterol. This reaction is the first
CC       step in the synthesis of the steroid hormone Delta(7)-dafachronic acid
CC       (one of the principal steroid hormones in nematodes). Dafachronic acids
CC       bind directly to the nuclear hormone receptor (NHR) daf-12, suppressing
CC       dauer formation and inducing reproductive growth.
CC       {ECO:0000269|PubMed:16563875, ECO:0000269|PubMed:21632547,
CC       ECO:0000269|PubMed:21749634}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cholesterol + H(+) + NADPH + O2 = 7-dehydrocholesterol + 2 H2O
CC         + NADP(+); Xref=Rhea:RHEA:45024, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113,
CC         ChEBI:CHEBI:17759, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         EC=1.14.19.21; Evidence={ECO:0000269|PubMed:16563875,
CC         ECO:0000269|PubMed:21632547, ECO:0000269|PubMed:21749634};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45025;
CC         Evidence={ECO:0000269|PubMed:16563875, ECO:0000269|PubMed:21749634,
CC         ECO:0000305|PubMed:21632547};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cholesterol + H(+) + NADH + O2 = 7-dehydrocholesterol + 2 H2O
CC         + NAD(+); Xref=Rhea:RHEA:51644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16113, ChEBI:CHEBI:17759,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.14.19.21;
CC         Evidence={ECO:0000269|PubMed:16563875, ECO:0000269|PubMed:21632547,
CC         ECO:0000269|PubMed:21749634};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51645;
CC         Evidence={ECO:0000269|PubMed:16563875, ECO:0000269|PubMed:21749634,
CC         ECO:0000305|PubMed:21632547};
CC   -!- COFACTOR:
CC       Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00628};
CC       Note=Binds 1 [2Fe-2S] cluster per subunit. {ECO:0000255|PROSITE-
CC       ProRule:PRU00628};
CC   -!- PATHWAY: Steroid hormone biosynthesis; dafachronic acid biosynthesis.
CC       {ECO:0000269|PubMed:16563875, ECO:0000269|PubMed:21749634,
CC       ECO:0000305|PubMed:21632547}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in intestine at all postembryonic stages,
CC       including dauer. Expression is reduced in daf-2 mutants.
CC       {ECO:0000269|PubMed:16563875}.
CC   -!- SIMILARITY: Belongs to the cholesterol 7-desaturase family.
CC       {ECO:0000305}.
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DR   EMBL; Z73969; CAA98235.2; -; Genomic_DNA.
DR   PIR; T19219; T19219.
DR   RefSeq; NP_505629.2; NM_073228.4.
DR   AlphaFoldDB; Q17938; -.
DR   SMR; Q17938; -.
DR   STRING; 6239.C12D8.5.1; -.
DR   SwissLipids; SLP:000000036; -.
DR   SwissLipids; SLP:000000191; -.
DR   EPD; Q17938; -.
DR   PaxDb; 6239-C12D8-5; -.
DR   PeptideAtlas; Q17938; -.
DR   EnsemblMetazoa; C12D8.5.1; C12D8.5.1; WBGene00007536.
DR   GeneID; 179422; -.
DR   KEGG; cel:CELE_C12D8.5; -.
DR   UCSC; C12D8.5; c. elegans.
DR   AGR; WB:WBGene00007536; -.
DR   WormBase; C12D8.5; CE34156; WBGene00007536; daf-36.
DR   eggNOG; ENOG502QS20; Eukaryota.
DR   GeneTree; ENSGT00390000016856; -.
DR   HOGENOM; CLU_037178_0_0_1; -.
DR   InParanoid; Q17938; -.
DR   OMA; AVYQMRR; -.
DR   OrthoDB; 294884at2759; -.
DR   PhylomeDB; Q17938; -.
DR   BioCyc; MetaCyc:MONOMER-18486; -.
DR   BRENDA; 1.14.19.21; 1045.
DR   BRENDA; 1.3.1.21; 1045.
DR   UniPathway; UPA01020; -.
DR   PRO; PR:Q17938; -.
DR   Proteomes; UP000001940; Chromosome V.
DR   Bgee; WBGene00007536; Expressed in adult organism and 3 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR   CDD; cd03469; Rieske_RO_Alpha_N; 1.
DR   Gene3D; 2.102.10.10; Rieske [2Fe-2S] iron-sulphur domain; 1.
DR   InterPro; IPR045605; KshA-like_C.
DR   InterPro; IPR017941; Rieske_2Fe-2S.
DR   InterPro; IPR036922; Rieske_2Fe-2S_sf.
DR   PANTHER; PTHR21266:SF60; CHOLESTEROL 7-DESATURASE; 1.
DR   PANTHER; PTHR21266; IRON-SULFUR DOMAIN CONTAINING PROTEIN; 1.
DR   Pfam; PF19298; KshA_C; 1.
DR   Pfam; PF00355; Rieske; 1.
DR   SUPFAM; SSF55961; Bet v1-like; 1.
DR   SUPFAM; SSF50022; ISP domain; 1.
DR   PROSITE; PS51296; RIESKE; 1.
PE   1: Evidence at protein level;
KW   2Fe-2S; Cholesterol metabolism; Iron; Iron-sulfur; Lipid metabolism;
KW   Membrane; Metal-binding; NADP; Oxidoreductase; Reference proteome;
KW   Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix.
FT   CHAIN           1..428
FT                   /note="Cholesterol 7-desaturase"
FT                   /id="PRO_0000421680"
FT   TRANSMEM        6..26
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          81..187
FT                   /note="Rieske"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT   BINDING         122
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /evidence="ECO:0000305"
FT   BINDING         124
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT   BINDING         143
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT   BINDING         146
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT   MUTAGEN         122
FT                   /note="C->A: Abrogates cholesterol dehydrogenase activity."
FT                   /evidence="ECO:0000269|PubMed:21632547"
FT   MUTAGEN         234
FT                   /note="D->A: Abrogates cholesterol dehydrogenase activity."
FT                   /evidence="ECO:0000269|PubMed:21632547"
SQ   SEQUENCE   428 AA;  49550 MW;  93F0293DF344CBBA CRC64;
     MLLEQIWGFL TAHPISVVTT ILIVYLIHIT LKPLNRVRRL GDVGLFFGKP ELKGFYRERQ
     LERLKLLRRV GDMPPVFPNG WYCVCESEKL ANNQIMEITV LGQFLSLIRS ESGAVYITDS
     YCPHIGANFN IGGRVVRDNC IQCPFHGWIF SAETGKCVEV PYDEGRIPEQ AKVTTWPCIE
     RNNNIYLWYH CDGAEPEWEI PEITEITDGF WHLGGRTEHE VMCHIQEIPE NGADIAHLNY
     LHKSAPPVTK GSDIIKTDLS DPQPAVQHVW DGKWEVKSEE DRHCGVMHLN QFMTFWGYKV
     PLTSSKLVAE QHGPGIVHML FDFGIWGKGV VFQTVTPEEA LLQRVRFRIF SNIPWFFVKF
     FMTVEAMQFE RDVFIWSNKK YIKSPLLVKN DGPIQKHRRW FSQFYTENSP KMLKDGSLSN
     QAKSIFDW
//