ERG1_SCHPO
ID ERG1_SCHPO Reviewed; 457 AA.
AC Q9C1W3;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Squalene epoxidase erg1 {ECO:0000303|PubMed:33223513};
DE Short=SE {ECO:0000305};
DE EC=1.14.14.17 {ECO:0000305|PubMed:33223513};
DE AltName: Full=Ergosterol biosynthetic protein 1 {ECO:0000303|PubMed:33223513};
DE AltName: Full=Squalene monooxygenase erg1 {ECO:0000305};
GN Name=erg1 {ECO:0000303|PubMed:33223513}; ORFNames=SPBC713.12;
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 SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [3]
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 [4]
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 [5]
RP FUNCTION.
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).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, ACTIVITY REGULATION, AND
RP PATHWAY.
RX PubMed=33223513; DOI=10.4062/biomolther.2020.166;
RA Lee S., Nam M., Lee A.R., Lee J., Woo J., Kang N.S., Balupuri A., Lee M.,
RA Kim S.Y., Ro H., Choi Y.W., Kim D.U., Hoe K.L.;
RT "Systematic target screening revealed that tif302 could be an off-target of
RT the antifungal terbinafine in fission yeast.";
RL Biomol. Ther. 29:234-247(2021).
CC -!- FUNCTION: Squalene epoxidase; part of the third module of ergosterol
CC biosynthesis pathway that includes by the late steps of the pathway
CC (PubMed:33223513). Erg1 catalyzes the epoxidation of squalene into 2,3-
CC epoxysqualene (PubMed:33223513). The third module or late pathway
CC involves the ergosterol synthesis itself through consecutive reactions
CC that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly,
CC the squalene synthase erg9 catalyzes the condensation of 2 farnesyl
CC pyrophosphate moieties to form squalene, which is the precursor of all
CC steroids. Secondly, squalene is converted into lanosterol by the
CC consecutive action of the squalene epoxidase erg1 and the lanosterol
CC synthase erg7. The lanosterol 14-alpha-demethylase erg11/cyp1 catalyzes
CC C14-demethylation of lanosterol to produce 4,4'-dimethyl cholesta-
CC 8,14,24-triene-3-beta-ol. In the next steps, a complex process
CC involving various demethylation, reduction and desaturation reactions
CC catalyzed by the C-14 reductase erg24 and the C-4 demethylation complex
CC erg25-erg26-erg27 leads to the production of zymosterol. Erg28 likely
CC functions in the C-4 demethylation complex reaction by tethering erg26
CC and Erg27 to the endoplasmic reticulum or to facilitate interaction
CC between these proteins. Then, the sterol 24-C-methyltransferase erg6
CC catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of
CC zymosterol to form fecosterol. The C-8 sterol isomerase erg2 catalyzes
CC the reaction which results in unsaturation at C-7 in the B ring of
CC sterols and thus converts fecosterol to episterol. The sterol-C5-
CC desaturases erg31 and erg32 then catalyze the introduction of a C-5
CC double bond in the B ring to produce 5-dehydroepisterol. The C-22
CC sterol desaturase erg5 further 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. Finally, ergosta-5,7,22,24(28)-tetraen-
CC 3beta-ol is substrate of the C-24(28) sterol reductase erg4 to produce
CC ergosterol (PubMed:18310029) (Probable). In the genus
CC Schizosaccharomyces, a second route exists between lanosterol and
CC 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:0000269|PubMed:33223513, ECO:0000305|PubMed:18310029,
CC ECO:0000305|PubMed:8586261}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + squalene = (S)-
CC 2,3-epoxysqualene + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:25282, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15440, ChEBI:CHEBI:15441, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.17;
CC Evidence={ECO:0000305|PubMed:33223513};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25283;
CC Evidence={ECO:0000305|PubMed:33223513};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q14534};
CC -!- ACTIVITY REGULATION: Activity is blocked by the allylamine class
CC antifungal terbinafine. {ECO:0000269|PubMed:33223513}.
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 2/3. {ECO:0000269|PubMed:33223513}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000269|PubMed:33223513}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P32476}; Multi-pass membrane protein
CC {ECO:0000305}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16823372}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16823372}. Vacuole membrane
CC {ECO:0000269|PubMed:16823372}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16823372}.
CC -!- INDUCTION: Expression is anaerobically up-regulated via the sterol
CC regulatory element binding protein sre1 (PubMed:16537923). Expression
CC is reduced in cells deleted for the translation-related genes tif302,
CC rpl2501, and rpl31, rps2402, rps2801, rps1002, rps1601, rps1802,
CC rps1901, and rpl1602; or the transcription-related genes spt7, spt20
CC and elp2. {ECO:0000269|PubMed:16537923, ECO:0000269|PubMed:33223513}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of squalene.
CC {ECO:0000269|PubMed:33223513}.
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 squalene monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; CU329671; CAC22613.1; -; Genomic_DNA.
DR RefSeq; NP_595351.1; NM_001021259.2.
DR AlphaFoldDB; Q9C1W3; -.
DR SMR; Q9C1W3; -.
DR BioGRID; 277621; 3.
DR STRING; 4896.SPBC713.12.1; -.
DR iPTMnet; Q9C1W3; -.
DR MaxQB; Q9C1W3; -.
DR PaxDb; Q9C1W3; -.
DR PRIDE; Q9C1W3; -.
DR EnsemblFungi; SPBC713.12.1; SPBC713.12.1:pep; SPBC713.12.
DR GeneID; 2541106; -.
DR KEGG; spo:SPBC713.12; -.
DR PomBase; SPBC713.12; erg1.
DR VEuPathDB; FungiDB:SPBC713.12; -.
DR eggNOG; KOG1298; Eukaryota.
DR HOGENOM; CLU_026390_0_0_1; -.
DR InParanoid; Q9C1W3; -.
DR OMA; KSKFWGL; -.
DR PhylomeDB; Q9C1W3; -.
DR Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00767; UER00752.
DR UniPathway; UPA00768; -.
DR PRO; PR:Q9C1W3; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005737; C:cytoplasm; HDA:PomBase.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:PomBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:PomBase.
DR GO; GO:0000329; C:fungal-type vacuole membrane; HDA:PomBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004506; F:squalene monooxygenase activity; ISS:PomBase.
DR GO; GO:0006696; P:ergosterol biosynthetic process; ISS:PomBase.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR013698; Squalene_epoxidase.
DR InterPro; IPR040125; Squalene_monox.
DR PANTHER; PTHR10835; PTHR10835; 1.
DR Pfam; PF08491; SE; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix;
KW Vacuole.
FT CHAIN 1..457
FT /note="Squalene epoxidase erg1"
FT /id="PRO_0000209850"
FT TRANSMEM 347..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 433..453
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 15..16
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 35..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 43
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 114
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 130
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 293
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 306
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT SITE 77
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
SQ SEQUENCE 457 AA; 50339 MW; 67D1B26BBD8CA527 CRC64;
MATQDADIII IGAGITGCAL GAALGRQGRK VLVLERDMSE PDRIVGELLQ PGGIEALEKI
GIADAVEGID GQWTSGYQIF YGDSNVSVPY PSKPNGGAYQ GIGFHYGRFV MNLRKALTST
PNVTVTEATV NELLRDETGE VITGVVTSSK KSESPVEYKA PLTIVCDGCF SKFRKAFIDH
PIQVTDHFLG LILTNPDYIA PGRGHVILSK VAPMVLYPIS STEARILINY PGKNLPPMET
LKKYVLESCV PNMPEKLRPS LKAAVYNDRL RSMPNQFLPP TVNRTKGMIL VGDSNNMRHP
LTGGGMTVCF HDAYLLSRFI SPSAVPDLLD YERILNQMNK FHWKRKGYSF VINVLSIALY
KLFTPKNRYM KALESGCIDY FKRGGNCVEG PIRLLGGLDH SPSHLIGHFY AVCLYGIYQY
VLSGPALLMP VRIIESLLIF LQASLVIIPY ILSEMSS
