ERG4_GIBZE
ID ERG4_GIBZE Reviewed; 596 AA.
AC I1RZZ3;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Delta(24(24(1)))-sterol reductase {ECO:0000303|PubMed:22947191};
DE EC=1.3.1.71 {ECO:0000305|PubMed:22947191};
DE AltName: Full=C-24(28) sterol reductase {ECO:0000303|PubMed:22947191};
DE AltName: Full=Sterol Delta(24(28))-reductase {ECO:0000303|PubMed:22947191};
GN Name=ERG4 {ECO:0000303|PubMed:22947191}; ORFNames=FGRAMPH1_01T07045;
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, AND DISRUPTION PHENOTYPE.
RX PubMed=22947191; DOI=10.1111/j.1364-3703.2012.00829.x;
RA Liu X., Jiang J., Yin Y., Ma Z.;
RT "Involvement of FgERG4 in ergosterol biosynthesis, vegetative
RT differentiation and virulence in Fusarium graminearum.";
RL Mol. Plant Pathol. 14:71-83(2013).
RN [5]
RP FUNCTION, 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: Delta(24(24(1)))-sterol reductase; part of the third module
CC of ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:22947191). ERG4 catalyzes the last step of ergosterol
CC biosynthesis by converting ergosta-5,7,22,24(28)-tetraen-3beta-ol into
CC ergosterol (PubMed:22947191). The third module or late pathway involves
CC the ergosterol synthesis itself through consecutive reactions that
CC mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the
CC 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:0000269|PubMed:22947191,
CC ECO:0000305|PubMed:23442154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ergosterol + NADP(+) = ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC + H(+) + NADPH; Xref=Rhea:RHEA:18501, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16933, ChEBI:CHEBI:18249, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.3.1.71;
CC Evidence={ECO:0000305|PubMed:22947191};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18503;
CC Evidence={ECO:0000305|PubMed:22947191};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:22947191}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ergosterol and leads
CC to the accumulation of sterol intermediates (PubMed:22947191). Leads to
CC reduced deoxynivalenol (DON) production (PubMed:22947191). Results in
CC reduced mycelial growth as well as less conidia (PubMed:22947191).
CC Leads to decreased virulence (PubMed:22947191). Exhibits a
CC significantly increased sensitivity to the divalent cations Cu(2+),
CC Mg(2+) and Ca(2+), as well as to the trivalent cations Fe(3+) and
CC Al(3+) (PubMed:22947191). Shows increased resistance to cell wall-
CC degrading enzymes and significantly increases sensitivity to osmotic
CC stress mediated by NaCl and D-sorbitol, and to oxidative stress
CC generated by H(2)O(2) and paraquat (PubMed:22947191). Decreases
CC tolerance to sterol biosynthesis inhibitors, including triadimefon and
CC tebuconazole (targeting sterol 14-alpha-demethylase), the amine
CC fungicides tridemorph, fenpropidin and spiroxamine (targeting sterol C-
CC 14 reductase or sterol delta-7,8-isomerase) and the polyene fungicides
CC nystatin and amphotericin B (binding to ergosterol) (PubMed:22947191).
CC Does not affect the sensitivity to the dicarboximide fungicide
CC iprodione (PubMed:22947191). Finally, ERG4 deletion leads to increased
CC expression of the ergosterol biosynthesis genes CYP51A, CYP51B, CYP51C,
CC ERG2, ERG6A, ERG6B, ERG7, ERG24A and ERG24B (PubMed:22947191).
CC {ECO:0000269|PubMed:22947191}.
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 ERG4/ERG24 family. {ECO:0000305}.
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DR EMBL; HG970332; SCB64533.1; -; Genomic_DNA.
DR RefSeq; XP_011318924.1; XM_011320622.1.
DR STRING; 5518.FGSG_10003P0; -.
DR GeneID; 23556926; -.
DR KEGG; fgr:FGSG_10003; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G07045; -.
DR eggNOG; KOG1435; Eukaryota.
DR HOGENOM; CLU_015631_3_0_1; -.
DR InParanoid; I1RZZ3; -.
DR UniPathway; UPA00768; -.
DR PHI-base; PHI:2728; -.
DR Proteomes; UP000070720; Chromosome 1.
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:0016628; F:oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Virulence.
FT CHAIN 1..596
FT /note="Delta(24(24(1)))-sterol reductase"
FT /id="PRO_0000454358"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 419..439
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 454..474
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 535..557
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..77
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..122
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 477
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 481
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 516
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 528..529
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 568
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 572..576
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 583
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
SQ SEQUENCE 596 AA; 68354 MW; FD1F4099A15F926F CRC64;
MSSRYSLRQT PRKKELFEGM VETPIRRSRS ARRQTSQPLS DVETDSTVEI LPQPTEVLPQ
PTRRRTARFK EELDSDTDSD NMGAVNRAAN GKTNGHANGN GNGYTNGHGN GNGHATNGHA
TSNGAAPIQA VIEKTKGVSH DPHVVDGWRP GQDPKVDYSG EVEFGGSFGT AAMMTLFPVL
MWYMWIGATY YDGKFPSRTE GQSWSEFGAH LANLVYTGAF PRLQVWAWYW SYLIVEGAFY
CLLPGVWGYG KPLPHEGGKQ LPYYCNAYWS LYTTLACLAG LHYSGIWPLY TAVDEFGPLL
SVAILSGFLV SIVAYFSALW RGKQHRMTGY PIYDFFMGAE LNPRMFGILD FKMFFEVRMP
WYILLILSLG TAARQHEQYG YVSGEVWFLV MAHFLYANAC AKGEELIITT WDMYYEKWGF
MLIFWNLAGV PLSYCHCTIY LANHHPDVYR WNRGILAAMF VGYLFWYWVW DSCNSQKNRF
RAMEKGKLVL RNTFPQVPWQ TIHNPKTIVS PQGTILVDGW YGLARKIHYT ADVWFAVSWG
LITGFESPFP WFYPVFFCCM IAHRAARDIH RCRRKYGDAW LEYERRVPYL FIPYVI
