ER24A_GIBZE
ID ER24A_GIBZE Reviewed; 485 AA.
AC I1RR90; A0A098DNK6;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Delta(14)-sterol reductase ERG24A {ECO:0000303|PubMed:21436218};
DE EC=1.3.1.70 {ECO:0000305|PubMed:23442154};
DE AltName: Full=C-14 sterol reductase ERG24A {ECO:0000303|PubMed:21436218};
DE AltName: Full=Ergosterol biosynthetic protein 24A {ECO:0000303|PubMed:21436218};
DE AltName: Full=Sterol C14-reductase ERG24A {ECO:0000305};
GN Name=ERG24A {ECO:0000303|PubMed:21436218};
GN ORFNames=FG06606, FGRAMPH1_01T22691;
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=21436218; DOI=10.1099/mic.0.045690-0;
RA Liu X., Fu J., Yun Y., Yin Y., Ma Z.;
RT "A sterol C-14 reductase encoded by FgERG24B is responsible for the
RT intrinsic resistance of Fusarium graminearum to amine fungicides.";
RL Microbiology 157:1665-1675(2011).
RN [5]
RP INDUCTION.
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 [6]
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(14)-sterol reductase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:21436218). Catalyzes the reduction of the C14=C15
CC double bond within 4,4,24-trimethyl ergosta-8,14,24(28)-trienolto
CC produce 4,4-dimethylfecosterol (By similarity). The third module or
CC late pathway involves the ergosterol synthesis itself through
CC consecutive reactions that mainly occur in the endoplasmic reticulum
CC (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes the
CC condensation of 2 farnesyl pyrophosphate moieties to form squalene,
CC which is the precursor of all steroids. Squalene synthase is crucial
CC for balancing the incorporation of farnesyl diphosphate (FPP) into
CC sterol and nonsterol isoprene synthesis. Secondly, squalene is
CC converted into lanosterol by the consecutive action of the squalene
CC epoxidase ERG1 and the lanosterol synthase ERG7. Then, the delta(24)-
CC sterol C-methyltransferase ERG6 methylates lanosterol at C-24 to
CC produce eburicol. Eburicol is the substrate of the sterol 14-alpha
CC demethylase encoded by CYP51A, CYP51B and CYP51C, to yield 4,4,24-
CC trimethyl ergosta-8,14,24(28)-trienol. CYP51B encodes the enzyme
CC primarily responsible for sterol 14-alpha-demethylation, and plays an
CC essential role in ascospore formation. CYP51A encodes an additional
CC sterol 14-alpha-demethylase, induced on ergosterol depletion and
CC responsible for the intrinsic variation in azole sensitivity. The third
CC CYP51 isoform, CYP51C, does not encode a sterol 14-alpha-demethylase,
CC but is required for full virulence on host wheat ears. The C-14
CC reductase ERG24 then reduces the C14=C15 double bond which leads to
CC 4,4-dimethylfecosterol. A sequence of further demethylations at C-4,
CC involving the C-4 demethylation complex containing the C-4 methylsterol
CC oxidases ERG25, the sterol-4-alpha-carboxylate 3-dehydrogenase ERG26
CC and the 3-keto-steroid reductase ERG27, leads to the production of
CC fecosterol via 4-methylfecosterol. ERG28 has a role as a scaffold to
CC help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum. The C-
CC 8 sterol isomerase ERG2 then catalyzes the reaction which results in
CC unsaturation at C-7 in the B ring of sterols and thus converts
CC fecosterol to episterol. The sterol-C5-desaturases ERG3A and ERG3BB
CC then catalyze the introduction of a C-5 double bond in the B ring to
CC produce 5-dehydroepisterol. The C-22 sterol desaturases ERG5A and ERG5B
CC further convert 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-
CC 3beta-ol by forming the C-22(23) double bond in the sterol side chain.
CC Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-
CC 24(28) sterol reductase ERG4 to produce ergosterol (Probable).
CC {ECO:0000250|UniProtKB:Q4WKA5, ECO:0000269|PubMed:21436218,
CC ECO:0000305|PubMed:23442154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + H(+) + NADPH;
CC Xref=Rhea:RHEA:18561, ChEBI:CHEBI:15378, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.70;
CC Evidence={ECO:0000305|PubMed:23442154};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:23442154}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is increased in the absence of the C-24(28)
CC sterol reductase ERG4. {ECO:0000269|PubMed:22947191}.
CC -!- DISRUPTION PHENOTYPE: In contrast to the disruption of ERG24B, does not
CC affect sensitivity to amine fungicides. {ECO:0000269|PubMed:21436218}.
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; HG970335; CEF82929.1; -; Genomic_DNA.
DR RefSeq; XP_011326222.1; XM_011327920.1.
DR STRING; 5518.FGSG_06606P0; -.
DR GeneID; 23553730; -.
DR KEGG; fgr:FGSG_06606; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G22691; -.
DR eggNOG; KOG1435; Eukaryota.
DR HOGENOM; CLU_015631_0_3_1; -.
DR InParanoid; I1RR90; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000070720; Chromosome 4.
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.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..485
FT /note="Delta(14)-sterol reductase ERG24A"
FT /id="PRO_0000454359"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..279
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..305
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..451
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 485 AA; 54819 MW; 76E57F8E7C18AF7F CRC64;
MAVKPKQPPA QEQHGYEFFG PPGAFAISFF LPVLVYVFNF VCNDISGCPA PSLLQPKTFS
LDALKQEVGW PHNGVAGLVS WNGTLAVIGY NVLSLILYRV LPAIEVEGTQ LSSGGRLKYR
FNTLYSSTFT LAVLAAGTIA QGAEFPVWTF MSENFIQILS ANIIYSYLVS TFVYVRSFSV
KHGNKENREL AAGGHSGNIL YDWFIGRELN PRIEIPLIGE VDIKEFLELR PGMMGWIIMN
CSWCAQQYRN YGFVTDSSIL ITAVQALYVF DSWWNEPAIL TTMDITTDGF GMMLAFGDIV
WVPYVYSLQT RYLSVHPVSL GPLGLAAMLG LIGLGFYIFR SANNEKNRFR TNPNDPRVSH
LKYIQTKTGS KLLTTGWWGM SRHINYLGDW IQSWPYCLPT GLAGYQIMSA GANIEGAYVM
HDGREVVQGE AQGWGMLITY FYILYFGILL IHRERRDDEK CHRKYGKDWE EYRKIVRSRI
VPGLY
