ERG7_GIBZE
ID ERG7_GIBZE Reviewed; 766 AA.
AC A0A0E0SP71;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2016, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Lanosterol synthase ERG7 {ECO:0000303|PubMed:22947191};
DE EC=5.4.99.7 {ECO:0000250|UniProtKB:P38604};
DE AltName: Full=Ergosterol biosynthetic protein 7 {ECO:0000250|UniProtKB:P38604};
DE AltName: Full=Lanosterol cyclase ERG7 {ECO:0000303|PubMed:22947191};
DE AltName: Full=Oxidosqualene--lanosterol cyclase ERG7 {ECO:0000250|UniProtKB:P38604};
DE Short=OSC {ECO:0000250|UniProtKB:P38604};
GN Name=ERG7 {ECO:0000303|PubMed:22947191};
GN ORFNames=FG05950, FGRAMPH1_01T19145;
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 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 [5]
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: Lanosterol synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway (By
CC similarity). ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to
CC lanosterol, a reaction that forms the sterol core (By similarity). The
CC third module or late pathway involves the ergosterol synthesis itself
CC through consecutive reactions that mainly occur in the endoplasmic
CC reticulum (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes
CC the 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:P38604, ECO:0000305|PubMed:23442154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3-epoxysqualene = lanosterol; Xref=Rhea:RHEA:14621,
CC ChEBI:CHEBI:15441, ChEBI:CHEBI:16521; EC=5.4.99.7;
CC Evidence={ECO:0000250|UniProtKB:P38604};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14622;
CC Evidence={ECO:0000250|UniProtKB:P38604};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 3/3. {ECO:0000305|PubMed:23442154}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:23442154}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000250|UniProtKB:P38604}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P38604};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P38604}.
CC Note=Predominantly in lipid particles. {ECO:0000250|UniProtKB:P38604}.
CC -!- INDUCTION: Expression is increased in the absence of the C-24(28)
CC sterol reductase ERG4 (PubMed:22947191). Expression is also
CC significantly higher when CYP51A is deleted or in the CYP51B/CYP51C
CC double deletant (PubMed:23442154). {ECO:0000269|PubMed:22947191,
CC 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 terpene cyclase/mutase family.
CC {ECO:0000305}.
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DR EMBL; HG970334; CEF88234.1; -; Genomic_DNA.
DR STRING; 5518.FGSG_05950P0; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G19145; -.
DR eggNOG; KOG0497; Eukaryota.
DR UniPathway; UPA00767; UER00753.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000070720; Chromosome 3.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0016866; F:intramolecular transferase activity; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016104; P:triterpenoid biosynthetic process; IEA:InterPro.
DR CDD; cd02892; SQCY_1; 1.
DR InterPro; IPR032696; SQ_cyclase_C.
DR InterPro; IPR032697; SQ_cyclase_N.
DR InterPro; IPR018333; Squalene_cyclase.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR PANTHER; PTHR11764; PTHR11764; 1.
DR Pfam; PF13243; SQHop_cyclase_C; 1.
DR Pfam; PF13249; SQHop_cyclase_N; 1.
DR SFLD; SFLDG01016; Prenyltransferase_Like_2; 1.
DR SUPFAM; SSF48239; SSF48239; 2.
DR TIGRFAMs; TIGR01787; squalene_cyclas; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Isomerase; Lipid biosynthesis; Lipid droplet;
KW Lipid metabolism; Membrane; Reference proteome; Repeat;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism.
FT CHAIN 1..766
FT /note="Lanosterol synthase ERG7"
FT /id="PRO_0000454352"
FT REPEAT 148..190
FT /note="PFTB 1"
FT /evidence="ECO:0000255"
FT REPEAT 586..626
FT /note="PFTB 2"
FT /evidence="ECO:0000255"
FT REPEAT 635..676
FT /note="PFTB 3"
FT /evidence="ECO:0000255"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 482
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P48449"
SQ SEQUENCE 766 AA; 87750 MW; 1B8FD4DD15264E13 CRC64;
MVANSTGRDA SALKSRKRAA DSESEPLLKQ GQPFPKQPRI GSELDKTRWR LKDDDSRHTW
HYLEDDDAAK EWPQSYAEKW YLNQSLDLPD LPSPDSPLAA ATNGLDFFEK LQLPSGHWGC
EYGGPMFLLP SVVITWYVTR TPISPSKATA IYNYISARAH PEDGGWGLHI EGESSVFGTL
MNYVALRLVG VEADDPVLVK ARGTLHKMGG ALYAPHWAKF WMGVLGVMDW DVVNPVPPEI
WLLPDWVPFA PWRWWIHIRM VFLPMGWLYS KRWSCEETDV IRSLRKEVFI EDYAKIKWTS
HRNDIGVVDN YHPKSWLLNT ANWLIVNIWN PYLRPNVLKE KAEAWSSKQV DMEDANTDYA
CLAPVNATMN TVMCYARDGP DNYGVQRHIE RLEEFLWVKD EGMLVNGTNG VQCWDTAFLI
QAVFEAGLHK DEKWKPMLMK SLQYLERQQI REDCVDQDVC YRQPRKGGWP FSNKDQGYGV
SDCISEAMKA IILLQKVGGL PEVLEERRLF DAVDTLLLYQ NSNGGMSSYE KRRGGEWLEM
LNAAEVFGRI MIEYDYPECT TACVTALSLF NKYWPDYRTK EVKTLIRTAA EWIKSNQRPD
GGWYGSWGIC FTYAGMFALE SMKHIGQTYA TGENSRRGCD FLISKQRADG GWSESYKACE
TMEYVEHPSG SLVVQTAWAL IGLMEADYPH VEPLKRGIQL IMDRQQPNGE WLQEAIEGVF
NKSCMISYPN YKFTFTIKAL GMFAKRFPEE KLVPSWALQG NGIEKS
