ERG9_GIBZE
ID ERG9_GIBZE Reviewed; 462 AA.
AC V6RPN0;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Squalene synthase ERG9 {ECO:0000303|PubMed:22947191};
DE Short=SQS {ECO:0000250|UniProtKB:P29704};
DE Short=SS {ECO:0000250|UniProtKB:P29704};
DE EC=2.5.1.21 {ECO:0000250|UniProtKB:P29704};
DE AltName: Full=Ergosterol biosynthetic protein 9 {ECO:0000303|PubMed:22947191};
DE AltName: Full=FPP:FPP farnesyltransferase ERG9 {ECO:0000305};
DE AltName: Full=Farnesyl-diphosphate farnesyltransferase ERG9 {ECO:0000305};
GN Name=ERG9 {ECO:0000303|PubMed:22947191};
GN ORFNames=FG09381, FGRAMPH1_01T27225;
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, 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: Squalene synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway (By
CC similarity). ERG9 produces squalene from 2 farnesyl pyrophosphate
CC moieties (By similarity). The third module or late pathway involves the
CC ergosterol synthesis itself through consecutive reactions that mainly
CC occur in the endoplasmic reticulum (ER) membrane. Firstly, the squalene
CC synthase ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate
CC moieties to form squalene, which is the precursor of all steroids.
CC Squalene synthase is crucial for balancing the incorporation of
CC 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:0000250|UniProtKB:P29704,
CC ECO:0000305|PubMed:23442154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (2E,6E)-farnesyl diphosphate + H(+) + NADPH = 2 diphosphate
CC + NADP(+) + squalene; Xref=Rhea:RHEA:32295, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15440, ChEBI:CHEBI:33019, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:175763; EC=2.5.1.21;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32296;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (2E,6E)-farnesyl diphosphate + H(+) + NADH = 2 diphosphate +
CC NAD(+) + squalene; Xref=Rhea:RHEA:32299, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15440, ChEBI:CHEBI:33019, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:175763; EC=2.5.1.21;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32300;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 1/3. {ECO:0000305|PubMed:23442154}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:23442154}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P29704}; Single-pass membrane protein
CC {ECO:0000255}. Microsome {ECO:0000250|UniProtKB:P29704}.
CC -!- INDUCTION: Expression is increased in the absence of the C-24(28)
CC sterol reductase ERG4. {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 phytoene/squalene synthase family.
CC {ECO:0000305}.
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DR EMBL; HG970335; CEF84732.1; -; Genomic_DNA.
DR RefSeq; XP_011328364.1; XM_011330062.1.
DR STRING; 5518.FGSG_09381P0; -.
DR GeneID; 23556337; -.
DR KEGG; fgr:FGSG_09381; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G27225; -.
DR eggNOG; KOG1459; Eukaryota.
DR HOGENOM; CLU_031981_2_1_1; -.
DR UniPathway; UPA00767; UER00751.
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:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0051996; F:squalene synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00683; Trans_IPPS_HH; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR002060; Squ/phyt_synthse.
DR InterPro; IPR006449; Squal_synth-like.
DR InterPro; IPR019845; Squalene/phytoene_synthase_CS.
DR InterPro; IPR044844; Trans_IPPS_euk-type.
DR InterPro; IPR033904; Trans_IPPS_HH.
DR PANTHER; PTHR11626; PTHR11626; 1.
DR Pfam; PF00494; SQS_PSY; 1.
DR SFLD; SFLDG01018; Squalene/Phytoene_Synthase_Lik; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR TIGRFAMs; TIGR01559; squal_synth; 1.
DR PROSITE; PS01044; SQUALEN_PHYTOEN_SYN_1; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Microsome; Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..462
FT /note="Squalene synthase ERG9"
FT /id="PRO_0000454350"
FT TRANSMEM 406..426
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 462 AA; 53515 MW; 482F01E92B2CDDF0 CRC64;
MGYLYYLLHP YQLRSIIQWK VWHDPVHERD PSTESPELQE CFRYLNLTSR SFAAVIQELN
HELLVPITLF YLCLRGLDTI EDDMTLPLEK KIPILRNFHT TMNEDGWQFH ESQEKDKELL
EHFDVVITEL KKIKAPYHEI ITDMTRKMGN GMADYAENEE MIKNGVQTIE EYELYCHYVA
GLVGEGLTRL FVESELANPK LAERPSLTES MGQFLQKTNI IRDLHEDWQD GRRWYPKEIW
SQHVDKWEDM FNPAQQTKAI ECVSHMVLDA LKHSEECLFY MAGIKDQSVF NFVAIPEGMA
IATLELVFRN PEVLKRNVKI TKGDACKIMF ECTQNLFTVC EVFKRYTRKI AKKNDPRDPN
FLAISAQCAK IEQFIETLFP KQDPKKLTLT QAQAQNKEPT MDAGEAVVLF GVVIAALVCI
SGLMLGTAWF FGARFDHIFR EASVFLPGRE KATPMITGHE EL
