ERG9_ASPFU
ID ERG9_ASPFU Reviewed; 471 AA.
AC Q4WAG4;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Squalene synthase erg9 {ECO:0000303|PubMed:16110826};
DE Short=SQS {ECO:0000303|PubMed:16110826};
DE Short=SS {ECO:0000303|PubMed:16110826};
DE EC=2.5.1.21 {ECO:0000250|UniProtKB:P29704};
DE AltName: Full=Ergosterol biosynthesis protein 9 {ECO:0000303|PubMed:16110826};
DE AltName: Full=FPP:FPP farnesyltransferase erg9 {ECO:0000305};
DE AltName: Full=Farnesyl-diphosphate farnesyltransferase erg9 {ECO:0000305};
GN Name=erg9 {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_7G01220;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP IDENTIFICATION, FUNCTION, AND PATHWAY.
RX PubMed=16110826; DOI=10.1080/13693780400029114;
RA Ferreira M.E., Colombo A.L., Paulsen I., Ren Q., Wortman J., Huang J.,
RA Goldman M.H., Goldman G.H.;
RT "The ergosterol biosynthesis pathway, transporter genes, and azole
RT resistance in Aspergillus fumigatus.";
RL Med. Mycol. 43:S313-S319(2005).
RN [3]
RP FUNCTION.
RX PubMed=18191972; DOI=10.1016/j.steroids.2007.11.005;
RA Alcazar-Fuoli L., Mellado E., Garcia-Effron G., Lopez J.F., Grimalt J.O.,
RA Cuenca-Estrella J.M., Rodriguez-Tudela J.L.;
RT "Ergosterol biosynthesis pathway in Aspergillus fumigatus.";
RL Steroids 73:339-347(2008).
CC -!- FUNCTION: Squalene synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway
CC (PubMed:16110826) (Probable). Erg9 produces squalene from 2 farnesyl
CC pyrophosphate moieties (By similarity). The third module or late
CC pathway involves the ergosterol synthesis itself through consecutive
CC reactions that mainly occur in the endoplasmic reticulum (ER) membrane.
CC Firstly, the squalene synthase erg9 catalyzes the condensation of 2
CC farnesyl pyrophosphate moieties to form squalene, which is the
CC precursor of all steroids. Squalene synthase is crucial for balancing
CC the incorporation of farnesyl diphosphate (FPP) into sterol and
CC nonsterol isoprene synthesis. Secondly, squalene is converted into
CC lanosterol by the consecutive action of the squalene epoxidase erg1 and
CC the lanosterol synthase erg7. Then, the delta(24)-sterol C-
CC methyltransferase erg6 methylates lanosterol at C-24 to produce
CC eburicol. Eburicol is the substrate of the sterol 14-alpha demethylase
CC encoded by cyp51A and cyp51B, to yield 4,4,24-trimethyl ergosta-
CC 8,14,24(28)-trienol. The C-14 reductase erg24 then reduces the C14=C15
CC double bond which leads to 4,4-dimethylfecosterol. A sequence of
CC further demethylations at C-4, involving the C-4 demethylation complex
CC containing the C-4 methylsterol oxidases erg25A or erg25B, the sterol-
CC 4-alpha-carboxylate 3-dehydrogenase erg26 and the 3-keto-steroid
CC reductase erg27, leads to the production of fecosterol via 4-
CC methylfecosterol. The C-8 sterol isomerase erg2 then catalyzes the
CC reaction which results in unsaturation at C-7 in the B ring of sterols
CC and thus converts fecosterol to episterol. The sterol-C5-desaturase
CC erg3B then catalyzes the introduction of a C-5 double bond in the B
CC ring to produce 5-dehydroepisterol. The 2 other sterol-C5-desaturases,
CC erg3A and erg3C, seem to be less important in ergosterol biosynthesis.
CC The C-22 sterol desaturase erg5 further converts 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 reductases erg4A
CC and erg4B to produce ergosterol. Possible alternative sterol
CC biosynthetic pathways might exist from fecosterol to ergosterol,
CC depending on the activities of the erg3 isoforms (PubMed:16110826,
CC PubMed:18191972) (Probable). {ECO:0000250|UniProtKB:P29704,
CC ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:18191972}.
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 -!- 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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000305|PubMed:16110826}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P29704}; Single-pass membrane protein
CC {ECO:0000255}. Microsome {ECO:0000250|UniProtKB:P29704}.
CC -!- MISCELLANEOUS: In Aspergillus, the biosynthesis pathway of the sterol
CC precursors leading to the prevalent sterol ergosterol differs from
CC yeast. The ring system 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 Aspergillus,
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:0000305|PubMed:18191972}.
CC -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000015; EAL84772.1; -; Genomic_DNA.
DR RefSeq; XP_746810.1; XM_741717.1.
DR STRING; 746128.CADAFUBP00008534; -.
DR EnsemblFungi; EAL84772; EAL84772; AFUA_7G01220.
DR GeneID; 3504159; -.
DR KEGG; afm:AFUA_7G01220; -.
DR VEuPathDB; FungiDB:Afu7g01220; -.
DR eggNOG; KOG1459; Eukaryota.
DR HOGENOM; CLU_031981_2_1_1; -.
DR InParanoid; Q4WAG4; -.
DR OMA; RFWPKEI; -.
DR OrthoDB; 563702at2759; -.
DR UniPathway; UPA00768; -.
DR Proteomes; UP000002530; Chromosome 7.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IBA:GO_Central.
DR GO; GO:0051996; F:squalene synthase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0045338; P:farnesyl diphosphate metabolic process; IBA:GO_Central.
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.
DR PROSITE; PS01045; SQUALEN_PHYTOEN_SYN_2; 1.
PE 3: Inferred from homology;
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..471
FT /note="Squalene synthase erg9"
FT /id="PRO_0000454116"
FT TRANSMEM 420..440
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 471 AA; 54723 MW; 0321510C180BDAFF CRC64;
MGVAANAFYY IFHPSELRSI LQWKIWHNPV HERDESNESE TAKTCFKFLD LTSRSFSAVI
KELHPELLLP MCIFYLTLRG LDTIEDDTSI PLETKEPLLR GFKDVLEQDG WNFTGNRPEE
KDRELLVQFH NVITEFKRLK PAYKAVIKDI TEKMGNGMAD YCRKAALDDA SVKTVEEYDL
YCWYVAGLVG EGSTRLFVEA EFGNPALLKR TELYKSMGLF LQKTNIIRDV REDFDDGRQF
WPKEIWSKHV TNFEDLFKPE NREAALNCSS EMVLNALRHA EECLFYLAGL REQSVFNFCA
IPQSMAIATL SLCFRNPAIF ERNIKIKKGE ACQLMMESTQ NLRILYEAFR RYAREIHKKN
TPKDPNFLEI GIACAKIEKF IETIFPSQSA EEANRRVLGQ KSEAEQEKAR LEAETRKDVL
FMMALMGVIV VFVSIVMIGF AWYFGARFDL AWQELRKGNF RPPKHLRDRE L
