ERG9_CANAL
ID ERG9_CANAL Reviewed; 448 AA.
AC A0A1D8PI71;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 25-MAY-2022, entry version 20.
DE RecName: Full=Squalene synthase ERG9 {ECO:0000303|PubMed:14653518};
DE Short=SQS {ECO:0000305};
DE Short=SS {ECO:0000305};
DE EC=2.5.1.21 {ECO:0000250|UniProtKB:P29704};
DE AltName: Full=Ergosterol biosynthesis protein 9 {ECO:0000303|PubMed:14653518};
DE AltName: Full=FPP:FPP farnesyltransferase ERG9 {ECO:0000305};
DE AltName: Full=Farnesyl-diphosphate farnesyltransferase ERG9 {ECO:0000305};
GN Name=ERG9 {ECO:0000303|PubMed:14653518}; OrderedLocusNames=orf19.3616;
GN ORFNames=CAALFM_C208610WA;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP INDUCTION.
RX PubMed=14653518; DOI=10.1080/1369378031000137233;
RA Song J.L., Lyons C.N., Holleman S., Oliver B.G., White T.C.;
RT "Antifungal activity of fluconazole in combination with lovastatin and
RT their effects on gene expression in the ergosterol and prenylation pathways
RT in Candida albicans.";
RL Med. Mycol. 41:417-425(2003).
RN [5]
RP INDUCTION.
RX PubMed=22265407; DOI=10.1016/j.cell.2011.10.048;
RA Nobile C.J., Fox E.P., Nett J.E., Sorrells T.R., Mitrovich Q.M.,
RA Hernday A.D., Tuch B.B., Andes D.R., Johnson A.D.;
RT "A recently evolved transcriptional network controls biofilm development in
RT Candida albicans.";
RL Cell 148:126-138(2012).
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, the squalene epoxidase ERG1 catalyzes the
CC stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, which is
CC considered to be a rate-limiting enzyme in steroid biosynthesis. Then,
CC the lanosterol synthase ERG7 catalyzes the cyclization of (S)-2,3
CC oxidosqualene to lanosterol, a reaction that forms the sterol core. In
CC the next steps, lanosterol is transformed to zymosterol through a
CC complex process involving various demethylation, reduction and
CC desaturation reactions. The lanosterol 14-alpha-demethylase ERG11 (also
CC known as CYP51) catalyzes C14-demethylation of lanosterol to produce
CC 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol, which is critical for
CC ergosterol biosynthesis. The C-14 reductase ERG24 reduces the C14=C15
CC double bond of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4-
CC dimethyl-cholesta-8,24-dienol. 4,4-dimethyl-cholesta-8,24-dienol is
CC substrate of the C-4 demethylation complex ERG25-ERG26-ERG27 in which
CC ERG25 catalyzes the three-step monooxygenation required for the
CC demethylation of 4,4-dimethyl and 4alpha-methylsterols, ERG26 catalyzes
CC the oxidative decarboxylation that results in a reduction of the 3-
CC beta-hydroxy group at the C-3 carbon to an oxo group, and ERG27 is
CC responsible for the reduction of the keto group on the C-3. ERG28 has a
CC role as a scaffold to help anchor ERG25, ERG26 and ERG27 to the
CC endoplasmic reticulum and ERG29 regulates the activity of the iron-
CC containing C4-methylsterol oxidase ERG25. Then, the sterol 24-C-
CC methyltransferase ERG6 catalyzes the methyl transfer from S-adenosyl-
CC methionine to the C-24 of zymosterol to form fecosterol. The C-8 sterol
CC isomerase ERG2 catalyzes the reaction which results in unsaturation at
CC C-7 in the B ring of sterols and thus converts fecosterol to episterol.
CC The sterol-C5-desaturase ERG3 then catalyzes the introduction of a C-5
CC double bond in the B ring to produce 5-dehydroepisterol. The C-22
CC sterol desaturase ERG5 further converts 5-dehydroepisterol into
CC ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double
CC bond in the sterol side chain. Finally, ergosta-5,7,22,24(28)-tetraen-
CC 3beta-ol is substrate of the C-24(28) sterol reductase ERG4 to produce
CC ergosterol (Probable). {ECO:0000250|UniProtKB:P29704, ECO:0000305}.
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:0000250|UniProtKB:P29704}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}. Microsome
CC {ECO:0000250|UniProtKB:P29704}.
CC -!- INDUCTION: Expression is induced by lovastatin and fluconazole and is
CC repressed by amphotericin B and caspofungin (PubMed:14653518).
CC Expression is repressed during spider biofilm formation
CC (PubMed:22265407). {ECO:0000269|PubMed:14653518,
CC ECO:0000269|PubMed:22265407}.
CC -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC {ECO:0000305}.
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DR EMBL; CP017624; AOW27849.1; -; Genomic_DNA.
DR RefSeq; XP_714460.2; XM_709367.2.
DR AlphaFoldDB; A0A1D8PI71; -.
DR SMR; A0A1D8PI71; -.
DR STRING; 237561.A0A1D8PI71; -.
DR GeneID; 3643913; -.
DR KEGG; cal:CAALFM_C208610WA; -.
DR CGD; CAL0000181444; ERG9.
DR VEuPathDB; FungiDB:C2_08610W_A; -.
DR eggNOG; KOG1459; Eukaryota.
DR OMA; RFWPKEI; -.
DR OrthoDB; 563702at2759; -.
DR UniPathway; UPA00767; UER00751.
DR Proteomes; UP000000559; Chromosome 2.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:CGD.
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:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; ISS:CGD.
DR GO; GO:0051996; F:squalene synthase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; ISS:CGD.
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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW Membrane; Microsome; NADP; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..448
FT /note="Squalene synthase ERG9"
FT /id="PRO_0000454171"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 448 AA; 51230 MW; F9321421BA563311 CRC64;
MGKFLQLLSH PIELKAVIQL FGFRQPLHPG KRDVNDKELV RCYELLNLTS RSFAAVIEEL
HPELRDAVMI FYLVLRALDT IEDDMTIKSS IKIPLLREFD TKLNTKNWTF DGNGPNEKDR
TVLVEFDKIL NVYHRLKPQY QDIIKSITFK MGNGMADYIL DEEFNVNGVA TVEDYNLYCH
YVAGLVGEGL TNLFVLANFG DKTLTENNFA KADSMGLFLQ KTNIIRDYHE DLQDGRSFWP
REIWSKYTEN LQDFHKVKTP AKEFAGVSCI NELVLNALGH VTDCLDYLSL VKDPSSFSFC
AIPQVMAVAT LAEVYNNPKV LHGVVKIRKG TTCRLILESR TLPGVVKIFK EYIQVINHKS
SVRDPNYLKI GIKCGEIEQY CEMIYPNKQA LPPSMKSLPE NKFTKIVASR ESIDLSVQRR
IEQENFNCNV VLFGIGALIL SLIYFVLY
