NVD_DROME
ID NVD_DROME Reviewed; 429 AA.
AC Q1JUZ1; Q5BIG3;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Cholesterol 7-desaturase nvd;
DE EC=1.14.19.21 {ECO:0000269|PubMed:21632547};
DE AltName: Full=Neverland {ECO:0000303|PubMed:16763204, ECO:0000303|PubMed:21632547};
DE Short=Nvd_Dm {ECO:0000303|PubMed:16763204, ECO:0000303|PubMed:21632547};
DE AltName: Full=Rieske-domain protein Neverland {ECO:0000312|EMBL:BAE94193.1};
GN Name=nvd {ECO:0000303|PubMed:16763204, ECO:0000312|FlyBase:FBgn0287185};
GN ORFNames=CG40050 {ECO:0000312|FlyBase:FBgn0287185};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, PATHWAY, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=Oregon-R {ECO:0000312|EMBL:BAE94193.1};
RX PubMed=16763204; DOI=10.1242/dev.02428;
RA Yoshiyama T., Namiki T., Mita K., Kataoka H., Niwa R.;
RT "Neverland is an evolutionally conserved Rieske-domain protein that is
RT essential for ecdysone synthesis and insect growth.";
RL Development 133:2565-2574(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAX33409.1};
RA Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA Park S., Wan K., Yu C., Rubin G.M., Celniker S.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 (PubMed:21632547). Essential
CC regulator of steroid biosynthesis, as this reaction is the first step
CC in the synthesis of the steroid hormone Delta(7)-dafachronic acid
CC (PubMed:21632547, PubMed:16763204). Required for insect molting,
CC metamorphosis and body growth throughout development via the regulation
CC of ecdysteroid biosynthesis in the prothoracic gland (PubMed:16763204).
CC {ECO:0000269|PubMed:16763204, ECO:0000269|PubMed:21632547}.
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:21632547};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45025;
CC Evidence={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:21632547};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51645;
CC Evidence={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:0000305|PubMed:16763204, ECO:0000305|PubMed:21632547}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the prothoracic gland
CC and weakly in brain and malpighian tubules.
CC {ECO:0000269|PubMed:16763204}.
CC -!- DISRUPTION PHENOTYPE: RNAi animals show apparent growth arrest in body
CC size compared with control animal, also loss of nvd-Dm function
CC prevents larval growth prior to the initiation of the molting process.
CC {ECO:0000269|PubMed:16763204}.
CC -!- MISCELLANEOUS: Nvd_Dm plays a pivotal role in larval development in
CC Drosophila. On this basis of the prolonged first instar larval
CC phenotype, the gene was named 'neverland', which is the fictional
CC island featured in J. M. Barrie's play Peter Pan, where children cease
CC to age. {ECO:0000303|PubMed:16763204}.
CC -!- SIMILARITY: Belongs to the cholesterol 7-desaturase family.
CC {ECO:0000305}.
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; AB232987; BAE94193.1; -; mRNA.
DR EMBL; AE014296; ABW08586.1; -; Genomic_DNA.
DR EMBL; BT021261; AAX33409.1; -; mRNA.
DR RefSeq; NP_001097670.1; NM_001104200.3.
DR AlphaFoldDB; Q1JUZ1; -.
DR SMR; Q1JUZ1; -.
DR STRING; 7227.FBpp0112384; -.
DR SwissLipids; SLP:000000089; -.
DR PaxDb; Q1JUZ1; -.
DR EnsemblMetazoa; FBtr0113473; FBpp0112384; FBgn0287185.
DR GeneID; 5740633; -.
DR KEGG; dme:Dmel_CG40050; -.
DR UCSC; CG40050-RA; d. melanogaster.
DR CTD; 5740633; -.
DR FlyBase; FBgn0287185; nvd.
DR VEuPathDB; VectorBase:FBgn0287185; -.
DR eggNOG; ENOG502QS20; Eukaryota.
DR GeneTree; ENSGT00390000016856; -.
DR HOGENOM; CLU_037178_0_0_1; -.
DR InParanoid; Q1JUZ1; -.
DR OMA; AVYQMRR; -.
DR OrthoDB; 1199207at2759; -.
DR PhylomeDB; Q1JUZ1; -.
DR BioCyc; MetaCyc:MON-18094; -.
DR UniPathway; UPA01020; -.
DR BioGRID-ORCS; 5740633; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 5740633; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR ExpressionAtlas; Q1JUZ1; baseline and differential.
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:0102294; F:cholesterol dehydrogenase activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0045456; P:ecdysteroid biosynthetic process; IMP:FlyBase.
DR GO; GO:0002168; P:instar larval development; IMP:FlyBase.
DR GO; GO:0007552; P:metamorphosis; IMP:FlyBase.
DR GO; GO:0035264; P:multicellular organism growth; IMP:FlyBase.
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; Oxidoreductase; Reference proteome;
KW Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..429
FT /note="Cholesterol 7-desaturase nvd"
FT /id="PRO_0000452609"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 98..201
FT /note="Rieske"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 138
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 140
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 158
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 161
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT CONFLICT 17
FT /note="K -> R (in Ref. 4; AAX33409)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="P -> T (in Ref. 4; AAX33409)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 429 AA; 50106 MW; CA4D2F0D1F8191CC CRC64;
MTSYSLFWMS LLKNNWKPIS NDFVICLWTL AVTFIRIYWI FFVPLEWKKD LDNEKWSFLR
KTENVVCYNH KRDTINRLRK LKIQKIIELP PPYPNGWYGI LKSSQLKAGE ATCVSCLGED
LVIFRSKKDI VFILDAYCPH LGANLGIGGS VADDCVICPF HQWKFRGTDG LCINIPYSTS
VPKGSKLKKW ISQEVDGFIF IWYHAEQTEL PWDLPVPMGE IDDTFVYHGH NEFYINCHIQ
EIPENGADIA HFNAIHKKNF INGSWAQKKR LFGLGSHHWK ARWSPFTGKL KYLAEVNLSH
TFKLFGKFGC FRMEVSGKQI GPSIVCLEVN SYTFGKIKVF QYITPIEPML QKVVHEFYGP
RWIAPLMKIF IYGESLMFER DIKIWNHKVF NRNPILAKED ASIKKFRLWF SQFYSSNSKI
YSEATNIGW
