ERG1_GIBZE
ID ERG1_GIBZE Reviewed; 500 AA.
AC I1RQ76;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Squalene epoxidase ERG1 {ECO:0000303|PubMed:23442154};
DE Short=SE {ECO:0000250|UniProtKB:P32476};
DE EC=1.14.14.17 {ECO:0000250|UniProtKB:P32476};
DE AltName: Full=Ergosterol biosynthetic protein 1 {ECO:0000250|UniProtKB:P32476};
DE AltName: Full=Squalene monooxygenase ERG1 {ECO:0000250|UniProtKB:P32476};
GN Name=ERG1 {ECO:0000303|PubMed:23442154};
GN ORFNames=FG06215, FGRAMPH1_01T19781;
OS Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084
OS / PH-1) (Wheat head blight fungus) (Fusarium graminearum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=229533;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=17823352; DOI=10.1126/science.1143708;
RA Cuomo C.A., Gueldener U., Xu J.-R., Trail F., Turgeon B.G., Di Pietro A.,
RA Walton J.D., Ma L.-J., Baker S.E., Rep M., Adam G., Antoniw J., Baldwin T.,
RA Calvo S.E., Chang Y.-L., DeCaprio D., Gale L.R., Gnerre S., Goswami R.S.,
RA Hammond-Kosack K., Harris L.J., Hilburn K., Kennell J.C., Kroken S.,
RA Magnuson J.K., Mannhaupt G., Mauceli E.W., Mewes H.-W., Mitterbauer R.,
RA Muehlbauer G., Muensterkoetter M., Nelson D., O'Donnell K., Ouellet T.,
RA Qi W., Quesneville H., Roncero M.I.G., Seong K.-Y., Tetko I.V., Urban M.,
RA Waalwijk C., Ward T.J., Yao J., Birren B.W., Kistler H.C.;
RT "The Fusarium graminearum genome reveals a link between localized
RT polymorphism and pathogen specialization.";
RL Science 317:1400-1402(2007).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=26198851; DOI=10.1186/s12864-015-1756-1;
RA King R., Urban M., Hammond-Kosack M.C.U., Hassani-Pak K.,
RA Hammond-Kosack K.E.;
RT "The completed genome sequence of the pathogenic ascomycete fungus Fusarium
RT graminearum.";
RL BMC Genomics 16:544-544(2015).
RN [4]
RP FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=23442154; DOI=10.1111/nph.12193;
RA Fan J., Urban M., Parker J.E., Brewer H.C., Kelly S.L.,
RA Hammond-Kosack K.E., Fraaije B.A., Liu X., Cools H.J.;
RT "Characterization of the sterol 14alpha-demethylases of Fusarium
RT graminearum identifies a novel genus-specific CYP51 function.";
RL New Phytol. 198:821-835(2013).
CC -!- FUNCTION: Squalene epoxidase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway (By
CC similarity). ERG1 catalyzes the epoxidation of squalene into 2,3-
CC epoxysqualene (By similarity). 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. Squalene synthase is crucial for balancing the incorporation
CC of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene
CC synthesis. Secondly, squalene is converted into lanosterol by the
CC consecutive action of the squalene epoxidase ERG1 and the lanosterol
CC synthase ERG7. Then, the delta(24)-sterol C-methyltransferase ERG6
CC methylates lanosterol at C-24 to produce eburicol. Eburicol is the
CC substrate of the sterol 14-alpha demethylase encoded by CYP51A, CYP51B
CC and CYP51C, to yield 4,4,24-trimethyl ergosta-8,14,24(28)-trienol.
CC CYP51B encodes the enzyme primarily responsible for sterol 14-alpha-
CC demethylation, and plays an essential role in ascospore formation.
CC CYP51A encodes an additional sterol 14-alpha-demethylase, induced on
CC ergosterol depletion and responsible for the intrinsic variation in
CC azole sensitivity. The third CYP51 isoform, CYP51C, does not encode a
CC sterol 14-alpha-demethylase, but is required for full virulence on host
CC wheat ears. The C-14 reductase ERG24 then reduces the C14=C15 double
CC bond which leads to 4,4-dimethylfecosterol. A sequence of further
CC demethylations at C-4, involving the C-4 demethylation complex
CC containing the C-4 methylsterol oxidases ERG25, the sterol-4-alpha-
CC carboxylate 3-dehydrogenase ERG26 and the 3-keto-steroid reductase
CC ERG27, leads to the production of fecosterol via 4-methylfecosterol.
CC ERG28 has a role as a scaffold to help anchor ERG25, ERG26 and ERG27 to
CC the endoplasmic reticulum. The C-8 sterol isomerase ERG2 then 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 ERG3A and ERG3BB then catalyze the introduction of a C-5
CC double bond in the B ring to produce 5-dehydroepisterol. The C-22
CC sterol desaturases ERG5A and ERG5B further convert 5-dehydroepisterol
CC into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23)
CC double bond in the sterol side chain. Finally, ergosta-5,7,22,24(28)-
CC tetraen-3beta-ol is substrate of the C-24(28) sterol reductase ERG4 to
CC produce ergosterol (Probable). {ECO:0000250|UniProtKB:P32476,
CC ECO:0000305|PubMed:23442154}.
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:0000250|UniProtKB:P32476};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25283;
CC Evidence={ECO:0000250|UniProtKB:P32476};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000305|PubMed:23442154};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 2/3. {ECO:0000305|PubMed:23442154}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:23442154}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P32476}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P32476}; Multi-pass membrane protein
CC {ECO:0000255}. Lipid droplet {ECO:0000250|UniProtKB:P32476}.
CC -!- INDUCTION: Expression is significantly lower when CYP51A or CYP51C are
CC deleted. {ECO:0000269|PubMed:23442154}.
CC -!- MISCELLANEOUS: In Fusarium, 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 Fusarium,
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.
CC {ECO:0000269|PubMed:23442154}.
CC -!- SIMILARITY: Belongs to the squalene monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; HG970334; CEF87525.1; -; Genomic_DNA.
DR RefSeq; XP_011324860.1; XM_011326558.1.
DR STRING; 5518.FGSG_06215P0; -.
DR GeneID; 23553352; -.
DR KEGG; fgr:FGSG_06215; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G19781; -.
DR eggNOG; KOG1298; Eukaryota.
DR HOGENOM; CLU_026390_0_0_1; -.
DR InParanoid; I1RQ76; -.
DR UniPathway; UPA00767; UER00752.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000070720; Chromosome 3.
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:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004506; F:squalene monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR006076; FAD-dep_OxRdtase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR013698; Squalene_epoxidase.
DR InterPro; IPR040125; Squalene_monox.
DR PANTHER; PTHR10835; PTHR10835; 1.
DR Pfam; PF01266; DAO; 1.
DR Pfam; PF08491; SE; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Lipid biosynthesis;
KW Lipid droplet; Lipid metabolism; Membrane; Microsome; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..500
FT /note="Squalene epoxidase ERG1"
FT /id="PRO_0000454351"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 474..494
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 30..31
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 50..51
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 58
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 145
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 332
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT BINDING 345
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
FT SITE 92
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q14534"
SQ SEQUENCE 500 AA; 55157 MW; 6F423D232384C81C CRC64;
MASILTTTEA QTRRREQYHE ADVVVVGAGV FGCTMAFALA NQGRSVLLLE RWLKEPDRIV
GELLQPGGVA SLQKLGLGHC VEGIDAKPCY GYTIFYHGEK VLVPYPGIDD EGSPTHAWGG
HSTGDRSTRP SGCSFHHGRF INKLRESCIA HKNITVVETE VVKTLRGEVS DQILGVESRT
MNKETGKKEQ DYYFGQLTII ADGYDSKWRQ EVLKTKPKVC SKFYALELID CDLPQPGHGH
VIIGNAFPIL LYQIGTHETR ALIDVPQGIP EASPENGGVR GYIRNFVLPA LPPSIRPSAE
KALEDGKIPR SMPNSWLPPT KQRANGAILL GDAMNMRHPL TGGGMTVAFN DVVILSELLH
PDKVGDLGDS KLINNALEEL YWRRKPLTGI INVLAQALYS LFAANDRQLR ALQYGCFTYF
KNGDTDGPVA LLAGILQRPF ILAYHFFSVA FLAIWLNACS VVGCGILGIF KFPLAIIDAV
LILWKACIVF IPIMWRESFQ
