DAF36_CAEEL
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 03-AUG-2022, entry version 139.
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; -.
DR SwissLipids; SLP:000000036; -.
DR SwissLipids; SLP:000000191; -.
DR EPD; Q17938; -.
DR PaxDb; Q17938; -.
DR PeptideAtlas; Q17938; -.
DR PRIDE; 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 CTD; 179422; -.
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; 1199207at2759; -.
DR PhylomeDB; Q17938; -.
DR BioCyc; MetaCyc:MON-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 tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 Gene3D; 2.102.10.10; -; 1.
DR InterPro; IPR045605; KshA-like_C.
DR InterPro; IPR017941; Rieske_2Fe-2S.
DR InterPro; IPR036922; Rieske_2Fe-2S_sf.
DR Pfam; PF19298; KshA_C; 1.
DR Pfam; PF00355; Rieske; 1.
DR SUPFAM; SSF50022; SSF50022; 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