ERG26_GIBZE
ID ERG26_GIBZE Reviewed; 303 AA.
AC I1S4E7; A0A098D107;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase ERG26, decarboxylating {ECO:0000250|UniProtKB:P53199};
DE EC=1.1.1.- {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=C-3 sterol dehydrogenase ERG26 {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=C-4 decarboxylase ERG26 {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=Ergosterol biosynthetic protein 26 {ECO:0000303|PubMed:23442154};
GN Name=ERG26 {ECO:0000303|PubMed:23442154}; ORFNames=FGRAMPH1_01T00597;
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 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: Sterol-4-alpha-carboxylate 3-dehydrogenase; part of the third
CC module of ergosterol biosynthesis pathway that includes the late steps
CC of the pathway (By similarity). ERG26 is a catalytic component of the
CC C-4 demethylation complex that catalyzes the conversion of 4,4-
CC dimethylfecosterol into fecosterol via 4-methylfecosterol (By
CC similarity). The third module or late pathway involves the ergosterol
CC synthesis itself through consecutive reactions that mainly occur in the
CC endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase
CC ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to
CC form squalene, which is the precursor of all steroids. Squalene
CC synthase is crucial for balancing the incorporation of farnesyl
CC diphosphate (FPP) into sterol and nonsterol isoprene synthesis.
CC Secondly, squalene is converted into lanosterol by the consecutive
CC action of the squalene epoxidase ERG1 and the lanosterol synthase ERG7.
CC Then, the delta(24)-sterol C-methyltransferase ERG6 methylates
CC lanosterol at C-24 to produce eburicol. Eburicol is the substrate of
CC the sterol 14-alpha demethylase encoded by CYP51A, CYP51B and CYP51C,
CC to yield 4,4,24-trimethyl ergosta-8,14,24(28)-trienol. CYP51B encodes
CC the enzyme primarily responsible for sterol 14-alpha-demethylation, and
CC plays an essential role in ascospore formation. CYP51A encodes an
CC additional sterol 14-alpha-demethylase, induced on ergosterol depletion
CC and responsible for the intrinsic variation in azole sensitivity. The
CC third CYP51 isoform, CYP51C, does not encode a sterol 14-alpha-
CC demethylase, but is required for full virulence on host wheat ears. The
CC C-14 reductase ERG24 then reduces the C14=C15 double bond which leads
CC to 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:P53199, ECO:0000305|PubMed:23442154}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:23442154}.
CC -!- SUBUNIT: Heterotetramer of ERG25, ERG26, ERG27 and ERG28 (By
CC similarity). ERG28 acts as a scaffold to tether ERG27 and other 4,4-
CC demethylation-related enzymes, forming a demethylation enzyme complex,
CC in the endoplasmic reticulum (By similarity).
CC {ECO:0000250|UniProtKB:P53199}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P53199}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P53199}.
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 3-beta-HSD family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; HG970332; CEF72100.1; -; Genomic_DNA.
DR RefSeq; XP_011315848.1; XM_011317546.1.
DR STRING; 5518.FGSG_11714P0; -.
DR GeneID; 23558533; -.
DR KEGG; fgr:FGSG_11714; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G00597; -.
DR eggNOG; KOG1430; Eukaryota.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; I1S4E7; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000070720; Chromosome 1.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane; NAD;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis.
FT CHAIN 1..303
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase ERG26,
FT decarboxylating"
FT /id="PRO_0000454364"
FT REGION 77..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 106
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 8..9
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 30..32
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 71
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 102
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A0A059TC02"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 106
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 128..131
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
SQ SEQUENCE 303 AA; 34289 MW; A8C88BAC11EAEEAC CRC64;
MPKLQLRSLA SQDKIEEIFE RFKPHAVIHT ASPSYMDTKK TLMSKNVDGT KALLEAARTC
SDTKAFVFTS SDEAIMPTQE PTSEENAHRY DENNAPNAPN TYALSKALAK RLVIAANSEE
LYTSVIRIPG IYGKYDDNFI PQLVSSMREK EHKMQVGNNT KVFEFLYVNK AAEAHIMAMK
ALLNPSTRDQ VGGEDFFISD GKPQGLFDFC RRIYAAAGSP VRPEEVTSIP LSVMQTMAST
MEWVYWVFTL GTVQPSLRRI SMDHLDTGCC WSLDKARRIL GYEPVQDQDK VIERTMDWTM
KTF
