CYP51_DANRE
ID CYP51_DANRE Reviewed; 499 AA.
AC Q1JPY5; Q6RIA7;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Lanosterol 14-alpha demethylase {ECO:0000305};
DE Short=LDM {ECO:0000305};
DE EC=1.14.14.154 {ECO:0000269|PubMed:24361620};
DE AltName: Full=Cytochrome P450 family member 51 {ECO:0000303|PubMed:24361620};
DE Short=CYP51 {ECO:0000303|PubMed:24361620};
DE AltName: Full=Sterol 14-alpha demethylase {ECO:0000303|PubMed:24361620};
GN Name=cyp51 {ECO:0000303|PubMed:24361620,
GN ECO:0000312|ZFIN:ZDB-GENE-040625-2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AAI16553.1};
RN [1] {ECO:0000312|EMBL:AAR89625.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24361620; DOI=10.1016/j.bbagen.2013.12.009;
RA Morrison A.M., Goldstone J.V., Lamb D.C., Kubota A., Lemaire B.,
RA Stegeman J.J.;
RT "Identification, modeling and ligand affinity of early deuterostome CYP51s,
RT and functional characterization of recombinant zebrafish sterol 14alpha-
RT demethylase.";
RL Biochim. Biophys. Acta 1840:1825-1836(2014).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3] {ECO:0000312|EMBL:AAI16553.1, ECO:0000312|EMBL:AAI64033.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye {ECO:0000312|EMBL:AAI16553.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes C14-demethylation of lanosterol; it transforms
CC lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
CC {ECO:0000269|PubMed:24361620}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4
CC H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154;
CC Evidence={ECO:0000269|PubMed:24361620};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q16850};
CC -!- ACTIVITY REGULATION: Inhibited by ketoconazole. May also be inhibited
CC to a lesser extent by propiconazole. {ECO:0000269|PubMed:24361620}.
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 1/6. {ECO:0000305|PubMed:24361620}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q64654}; Single-pass membrane protein
CC {ECO:0000255}. Membrane {ECO:0000305|PubMed:24361620}; Single-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in intestine. Moderately
CC expressed in liver, with higher levels in females compared to males.
CC Also detected at low levels in brain, eye, kidney and testis.
CC {ECO:0000269|PubMed:24361620}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|RuleBase:RU000461, ECO:0000305}.
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DR EMBL; AY496939; AAR89625.1; -; mRNA.
DR EMBL; CU638710; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC116552; AAI16553.1; -; mRNA.
DR EMBL; BC164033; AAI64033.1; -; mRNA.
DR RefSeq; NP_001001730.2; NM_001001730.2.
DR AlphaFoldDB; Q1JPY5; -.
DR SMR; Q1JPY5; -.
DR STRING; 7955.ENSDARP00000062550; -.
DR PaxDb; Q1JPY5; -.
DR Ensembl; ENSDART00000062551; ENSDARP00000062550; ENSDARG00000042641.
DR GeneID; 414331; -.
DR KEGG; dre:414331; -.
DR CTD; 13121; -.
DR ZFIN; ZDB-GENE-040625-2; cyp51.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00930000151026; -.
DR HOGENOM; CLU_001570_15_0_1; -.
DR InParanoid; Q1JPY5; -.
DR OMA; AWTLIEL; -.
DR OrthoDB; 572303at2759; -.
DR PhylomeDB; Q1JPY5; -.
DR TreeFam; TF105091; -.
DR Reactome; R-DRE-191273; Cholesterol biosynthesis.
DR Reactome; R-DRE-211976; Endogenous sterols.
DR UniPathway; UPA00770; UER00754.
DR PRO; PR:Q1JPY5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000042641; Expressed in zone of skin and 28 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008398; F:sterol 14-demethylase activity; IDA:ZFIN.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0001878; P:response to yeast; IDA:ZFIN.
DR GO; GO:0016125; P:sterol 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; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW Monooxygenase; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..499
FT /note="Lanosterol 14-alpha demethylase"
FT /id="PRO_0000439597"
FT TRANSMEM 13..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 441
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q16850"
FT CONFLICT 37
FT /note="F -> I (in Ref. 1; AAR89625)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="T -> A (in Ref. 1; AAR89625)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 57001 MW; 857A748791360CF2 CRC64;
MTILEVGSQL IESAVLQMSL TSVLLTASVF TLTLGYFSKL LFTQHSSEHT KYPPHIPSSL
PFLGQAVAFG RSPIEFLEKA YEQYGPVVSF TMVGKTFTYL LGSDAAALMF NSKNEDLNAE
DVYARLTTPV FGKGVAYDVP NPLFLEQKKM LKTGLNIAQF KQHVEIIEEE TKDYFRRWGE
SGERNLFDAL SELIILTASR CLHGCEIRSL LDERVAQLYA DLDGGFTHAA WLLPGWLPLP
SFRRRDRAHL EIKKIFYNVI KKRREDTEKH DDILQTLIDA TYKDGRPLSD DEIAGMLIGL
LLAGQHTSST TSAWMGFFLA RDRALQERCY SEQKSVCGEE LPPLHYDQLK DLSLLDRCLK
ETLRLRPPIM TMMRMAKTPQ KVGEYTIPPG HQVCVSPTVN HRLQDTWAER LDFDPDRYLH
DNPAAGEKFA YIPFGAGRHR CIGENFAYVQ IKTIWSTLLR MFDFELVDGH FPPVNYTTMI
HTPHNPIIRY TRRNTQPQQ
