ID ERG5_SCHPO Reviewed; 543 AA.
AC O13820;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 3.
DT 27-MAR-2024, entry version 154.
DE RecName: Full=C-22 sterol desaturase ERG5 {ECO:0000303|PubMed:18310029};
DE EC=1.14.19.41 {ECO:0000305|PubMed:18310029};
DE AltName: Full=Cytochrome P450 61 {ECO:0000250|UniProtKB:P54781};
DE AltName: Full=Ergosterol biosynthetic protein 5 {ECO:0000303|PubMed:18310029};
GN Name=erg5 {ECO:0000303|PubMed:18310029};
GN Synonyms=cyp61 {ECO:0000250|UniProtKB:P54781}; ORFNames=SPAC19A8.04;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP REVISION OF GENE MODEL.
RX PubMed=21511999; DOI=10.1126/science.1203357;
RA Rhind N., Chen Z., Yassour M., Thompson D.A., Haas B.J., Habib N.,
RA Wapinski I., Roy S., Lin M.F., Heiman D.I., Young S.K., Furuya K., Guo Y.,
RA Pidoux A., Chen H.M., Robbertse B., Goldberg J.M., Aoki K., Bayne E.H.,
RA Berlin A.M., Desjardins C.A., Dobbs E., Dukaj L., Fan L., FitzGerald M.G.,
RA French C., Gujja S., Hansen K., Keifenheim D., Levin J.Z., Mosher R.A.,
RA Mueller C.A., Pfiffner J., Priest M., Russ C., Smialowska A., Swoboda P.,
RA Sykes S.M., Vaughn M., Vengrova S., Yoder R., Zeng Q., Allshire R.,
RA Baulcombe D., Birren B.W., Brown W., Ekwall K., Kellis M., Leatherwood J.,
RA Levin H., Margalit H., Martienssen R., Nieduszynski C.A., Spatafora J.W.,
RA Friedman N., Dalgaard J.Z., Baumann P., Niki H., Regev A., Nusbaum C.;
RT "Comparative functional genomics of the fission yeasts.";
RL Science 332:930-936(2011).
RN [3]
RP FUNCTION.
RC STRAIN=972 / ATCC 24843;
RX PubMed=8474436; DOI=10.1128/mcb.13.5.2706-2717.1993;
RA Robinson G.W., Tsay Y.H., Kienzle B.K., Smith-Monroy C.A., Bishop R.W.;
RT "Conservation between human and fungal squalene synthetases: similarities
RT in structure, function, and regulation.";
RL Mol. Cell. Biol. 13:2706-2717(1993).
RN [4]
RP FUNCTION.
RX PubMed=8586261; DOI=10.1111/j.1574-6968.1995.tb07929.x;
RA Harmouch N., Coulon J., Bonaly R.;
RT "Identification of 24-methylene-24,25-dihydrolanosterol as a precursor of
RT ergosterol in the yeasts Schizosaccharomyces pombe and Schizosaccharomyces
RT octosporus.";
RL FEMS Microbiol. Lett. 134:147-152(1995).
RN [5]
RP INDUCTION.
RX PubMed=16537923; DOI=10.1128/mcb.26.7.2817-2831.2006;
RA Todd B.L., Stewart E.V., Burg J.S., Hughes A.L., Espenshade P.J.;
RT "Sterol regulatory element binding protein is a principal regulator of
RT anaerobic gene expression in fission yeast.";
RL Mol. Cell. Biol. 26:2817-2831(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH DAP1.
RX PubMed=17276356; DOI=10.1016/j.cmet.2006.12.009;
RA Hughes A.L., Powell D.W., Bard M., Eckstein J., Barbuch R., Link A.J.,
RA Espenshade P.J.;
RT "Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes.";
RL Cell Metab. 5:143-149(2007).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=18310029; DOI=10.1099/mic.0.2007/011155-0;
RA Iwaki T., Iefuji H., Hiraga Y., Hosomi A., Morita T., Giga-Hama Y.,
RA Takegawa K.;
RT "Multiple functions of ergosterol in the fission yeast Schizosaccharomyces
RT pombe.";
RL Microbiology 154:830-841(2008).
CC -!- FUNCTION: C-22 sterol desaturase; part of the third module of
CC ergosterol biosynthesis pathway that includes by the late steps of the
CC pathway (PubMed:18310029). Erg5 converts 5-dehydroepisterol into
CC ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double
CC bond in the sterol side chain (By similarity). The third module or late
CC pathway involves the ergosterol synthesis itself through consecutive
CC reactions that mainly occur in the endoplasmic reticulum (ER) membrane.
CC Firstly, the squalene synthase erg9 catalyzes the condensation of 2
CC farnesyl pyrophosphate moieties to form squalene, which is the
CC precursor of all steroids. Secondly, squalene is converted into
CC lanosterol by the consecutive action of the squalene epoxidase erg1 and
CC the lanosterol synthase erg7. The lanosterol 14-alpha-demethylase
CC erg11/cyp1 catalyzes C14-demethylation of lanosterol to produce 4,4'-
CC dimethyl cholesta-8,14,24-triene-3-beta-ol. In the next steps, a
CC complex process involving various demethylation, reduction and
CC desaturation reactions catalyzed by the C-14 reductase erg24 and the C-
CC 4 demethylation complex erg25-erg26-erg27 leads to the production of
CC zymosterol. Erg28 likely functions in the C-4 demethylation complex
CC reaction by tethering erg26 and Erg27 to the endoplasmic reticulum or
CC to facilitate interaction between these proteins. Then, the sterol 24-
CC C-methyltransferase erg6 catalyzes the methyl transfer from S-adenosyl-
CC methionine to the C-24 of zymosterol to form fecosterol. The C-8 sterol
CC isomerase erg2 catalyzes the reaction which results in unsaturation at
CC C-7 in the B ring of sterols and thus converts fecosterol to episterol.
CC The sterol-C5-desaturases erg31 and erg32 then catalyze the
CC introduction of a C-5 double bond in the B ring to produce 5-
CC dehydroepisterol. The C-22 sterol desaturase erg5 further converts 5-
CC dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming
CC the C-22(23) double bond in the sterol side chain. Finally, ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28) sterol
CC reductase erg4 to produce ergosterol (PubMed:18310029) (Probable). In
CC the genus Schizosaccharomyces, a second route exists between lanosterol
CC and fecosterol, via the methylation of lanosterol to eburicol by erg6,
CC followed by C14-demethylation by erg11/cyp1 and C4-demethylation by the
CC demethylation complex erg25-erg26-erg27 (PubMed:8586261) (Probable).
CC {ECO:0000250|UniProtKB:P54781, ECO:0000269|PubMed:18310029,
CC ECO:0000305|PubMed:18310029, ECO:0000305|PubMed:8586261}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-dehydroepisterol + H(+) + NADPH + O2 = ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol + 2 H2O + NADP(+);
CC Xref=Rhea:RHEA:33467, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:18249, ChEBI:CHEBI:52972,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.19.41;
CC Evidence={ECO:0000305|PubMed:18310029};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33468;
CC Evidence={ECO:0000305|PubMed:18310029};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000269|PubMed:18310029}.
CC -!- SUBUNIT: Interacts with dap1. {ECO:0000269|PubMed:17276356}.
CC -!- INDUCTION: Up-regulated by sre1 in response to absence of oxygen.
CC {ECO:0000269|PubMed:16537923}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ergosterol
CC (PubMed:18310029). Leads to susceptibility to cycloheximide and to
CC staurosporine, but does not affect tolerance to nystatin and to
CC amphotericin B (PubMed:18310029). {ECO:0000269|PubMed:18310029}.
CC -!- MISCELLANEOUS: In Aspergillus, the biosynthesis pathway of the sterol
CC precursors leading to the prevalent sterol ergosterol differs from
CC yeast. The ringsystem of lanosterol in S.cerevisiae is firstly
CC demethylised in three enzymatic steps leading to the intermediate
CC zymosterol and secondly a methyl group is added to zymosterol by the
CC sterol 24-C-methyltransferase to form fecosterol. In Aspergillus,
CC lanosterol is firstly transmethylated by the sterol 24-C-
CC methyltransferase leading to the intermediate eburicol and secondly
CC demethylated in three steps to form fecosterol. In the genus
CC Schizosaccharomyces, 2 routes exist from lanosterol to erposterol: the
CC classical one via zymosterol and the second one via the formation of
CC eburicol followed by demethylation. {ECO:0000269|PubMed:8586261}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255}.
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DR EMBL; CU329670; CAB11640.3; -; Genomic_DNA.
DR PIR; T37957; T37957.
DR RefSeq; NP_593788.2; NM_001019217.2.
DR AlphaFoldDB; O13820; -.
DR SMR; O13820; -.
DR BioGRID; 278930; 176.
DR STRING; 284812.O13820; -.
DR iPTMnet; O13820; -.
DR MaxQB; O13820; -.
DR PaxDb; 4896-SPAC19A8-04-1; -.
DR EnsemblFungi; SPAC19A8.04.1; SPAC19A8.04.1:pep; SPAC19A8.04.
DR GeneID; 2542469; -.
DR KEGG; spo:SPAC19A8.04; -.
DR PomBase; SPAC19A8.04; erg5.
DR VEuPathDB; FungiDB:SPAC19A8.04; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_023517_0_0_1; -.
DR InParanoid; O13820; -.
DR OMA; IMDAWIL; -.
DR UniPathway; UPA00768; -.
DR PRO; PR:O13820; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:PomBase.
DR GO; GO:0000249; F:C-22 sterol desaturase activity; ISO:PomBase.
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; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:PomBase.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR CDD; cd11082; CYP61_CYP710; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24286:SF228; C-22 STEROL DESATURASE ERG5; 1.
DR PANTHER; PTHR24286; CYTOCHROME P450 26; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Lipid biosynthesis; Lipid metabolism; Metal-binding;
KW Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism;
KW Stress response.
FT CHAIN 1..543
FT /note="C-22 sterol desaturase ERG5"
FT /id="PRO_0000334491"
FT BINDING 461
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"
SQ SEQUENCE 543 AA; 62271 MW; C0ED03E73532A4AA CRC64;
MEMNQTETLI PAARNVIRVL GYEIEYSKWT ICFALLAVCI AYDQISYQMQ KGHIPGPRFK
IPFMGSFLDS MKPTFEKYNA KWQTGPLSCV SVFHKFVVIA SERDLARKIL NSPSYVQPCV
VDAGKKILKH TNWVFLDGRD HIEYRKGLNG LFTTRALASY LPAQEAVYNK YFKEFLAHSK
DDYAQYMIPF RDINVATSCR TFCGYYISDD AIKHIADEYW KITAAMELVN FPIVLPFTKV
WYGIQSRKVV MRYFMKAAAE SRKNMEAGNA PACMMEEWIH EMIETRKYKS ENKEGAEKPS
VLIREFSDEE ISLTFLSFLF ASQDATSSAM TWLFQLLADH PDVLQKVREE QLRIRKGDID
VPLSLDLMEK MTYTRAVVKE CLRLRPPVLM VPYRVKKAFP ITPDYTVPKD AMVIPTLYGA
LHDSKVYPEP ETFNPDRWAP NGLAEQSPKN WMVFGNGPHV CLGQRYAVNH LIACIGKASI
MLDWKHKRTP DSDTQMIFAT TFPQDMCYLK FSPFDASTVD WKNSKEAFSN EAVSAATVET
ESA
//
