ERG5A_GIBZE
ID ERG5A_GIBZE Reviewed; 536 AA.
AC I1RE80;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=C-22 sterol desaturase ERG5A {ECO:0000303|PubMed:24785759};
DE EC=1.14.19.41 {ECO:0000305|PubMed:23442154};
DE AltName: Full=Ergosterol biosynthetic protein 5A {ECO:0000303|PubMed:24785759};
GN Name=ERG5A {ECO:0000303|PubMed:24785759};
GN ORFNames=FG01959, FGRAMPH1_01T04729;
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, DISRUPTION PHENOTYPE, 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).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=24785759; DOI=10.1016/j.fgb.2014.04.010;
RA Yun Y., Yin D., Dawood D.H., Liu X., Chen Y., Ma Z.;
RT "Functional characterization of FgERG3 and FgERG5 associated with
RT ergosterol biosynthesis, vegetative differentiation and virulence of
RT Fusarium graminearum.";
RL Fungal Genet. Biol. 68:60-70(2014).
CC -!- FUNCTION: C-22 sterol desaturase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (By similarity). ERG5A and ERG5B 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 (By similarity). The third module
CC or 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:P54781, ECO:0000305|PubMed:23442154}.
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:23442154};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33468;
CC Evidence={ECO:0000305|PubMed:23442154};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:23442154}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Leads to a severe decrease in conidiation and
CC virulence when ERG5B is also deleted (PubMed:23442154). The absence of
CC both ERG5A and ERG5B seems not to affect the ergosterol production
CC (PubMed:24785759). {ECO:0000269|PubMed:23442154,
CC ECO:0000269|PubMed:24785759}.
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 cytochrome P450 family. {ECO:0000305}.
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DR EMBL; HG970332; CEF74171.1; -; Genomic_DNA.
DR RefSeq; XP_011317815.1; XM_011319513.1.
DR STRING; 5518.FGSG_01959P0; -.
DR GeneID; 23549366; -.
DR KEGG; fgr:FGSG_01959; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G04729; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_023517_0_0_1; -.
DR InParanoid; I1RE80; -.
DR UniPathway; UPA00768; -.
DR PHI-base; PHI:3037; -.
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:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..536
FT /note="C-22 sterol desaturase ERG5A"
FT /id="PRO_0000454353"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 481
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|UniProtKB:P04798"
SQ SEQUENCE 536 AA; 60505 MW; 5D0ECF58300C2A4E CRC64;
MEAVNSTTSG FSSVLAGTKY ANVNIPPQID YVIEAVSNAG VWTWVFTLVA LCIAYDQIAY
IVRKGPIVGP AMKIPFIGPF LDSMDPRFDG YHAKWSSGPL SCVSIFHKFV VIASTRDMAR
KVFNSPAYVK PTVVDVAPKL LGHDNWVFLD GKAHVDFRKG LNGLFTRKAL ELYLPGQEEA
YNTYFKHFLK MTKDAGGKPV PFMHEFREVM CAVSCRTFVG HYISDEAVTK IAEDYYLITA
ALELVNLPVI LPYTKSWYGK KAADMVLAEF SKCAAKSKVR MAAGGEVTCI MDAWILSMIQ
SERWRKAEEK GEPHNVEKPS PLLRMFNDYE ISQTIFTFLF ASQDATSSAA TWLFQVTAQR
PDVLDRVREE NIKIRNGDPN APLTMDQLES LTYTRAVVRE LLRWRPPVIM VPYVTKKAFP
LTDDYTVPKG SMLIPTTFMA LHDPEVYDNP SHFDPERYYS GDAEEKGSKN YLVFGTGPHY
CLGQVYAQLN LALMIGKASV MLDWKHHATP KSEEIKVFAT IFPMDDCPLT FEERKW
