ERG9_SCHPO
ID ERG9_SCHPO Reviewed; 460 AA.
AC P36596;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Squalene synthase {ECO:0000303|PubMed:8474436};
DE Short=SQS {ECO:0000303|PubMed:8474436};
DE Short=SS {ECO:0000303|PubMed:8474436};
DE EC=2.5.1.21 {ECO:0000305|PubMed:8474436};
DE AltName: Full=FPP:FPP farnesyltransferase {ECO:0000303|PubMed:8474436};
DE AltName: Full=Farnesyl-diphosphate farnesyltransferase {ECO:0000303|PubMed:8474436};
GN Name=erg9 {ECO:0000303|PubMed:8474436}; ORFNames=SPBC646.05c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND PATHWAY.
RC STRAIN=972 / ATCC 24843;
RX PubMed=8474436; DOI=10.1128/mcb.13.5.2706-2717.1993;
RA Robinson G.W., Tsay Y.H., Kienzle B.K., Smith-Monroy C.A., Bishop R.W.;
RT "Conservation between human and fungal squalene synthetases: similarities
RT in structure, function, and regulation.";
RL Mol. Cell. Biol. 13:2706-2717(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP FUNCTION.
RX PubMed=8586261; DOI=10.1111/j.1574-6968.1995.tb07929.x;
RA Harmouch N., Coulon J., Bonaly R.;
RT "Identification of 24-methylene-24,25-dihydrolanosterol as a precursor of
RT ergosterol in the yeasts Schizosaccharomyces pombe and Schizosaccharomyces
RT octosporus.";
RL FEMS Microbiol. Lett. 134:147-152(1995).
RN [4]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH POF14.
RX PubMed=17016471; DOI=10.1038/sj.emboj.7601329;
RA Tafforeau L., Le Blastier S., Bamps S., Dewez M., Vandenhaute J.,
RA Hermand D.;
RT "Repression of ergosterol level during oxidative stress by fission yeast F-
RT box protein Pof14 independently of SCF.";
RL EMBO J. 25:4547-4556(2006).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [6]
RP FUNCTION.
RX PubMed=18310029; DOI=10.1099/mic.0.2007/011155-0;
RA Iwaki T., Iefuji H., Hiraga Y., Hosomi A., Morita T., Giga-Hama Y.,
RA Takegawa K.;
RT "Multiple functions of ergosterol in the fission yeast Schizosaccharomyces
RT pombe.";
RL Microbiology 154:830-841(2008).
CC -!- FUNCTION: Squalene synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes by the late steps of the pathway
CC (PubMed:8474436). Erg9 produces squalene from 2 farnesyl pyrophosphate
CC moieties (PubMed:8474436). The third module or late pathway involves
CC the ergosterol synthesis itself through consecutive reactions that
CC mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the
CC squalene synthase erg9 catalyzes the condensation of 2 farnesyl
CC pyrophosphate moieties to form squalene, which is the precursor of all
CC steroids. Secondly, squalene is converted into lanosterol by the
CC consecutive action of the squalene epoxidase erg1 and the lanosterol
CC synthase erg7. The lanosterol 14-alpha-demethylase erg11/cyp1 catalyzes
CC C14-demethylation of lanosterol to produce 4,4'-dimethyl cholesta-
CC 8,14,24-triene-3-beta-ol. In the next steps, a complex process
CC involving various demethylation, reduction and desaturation reactions
CC catalyzed by the C-14 reductase erg24 and the C-4 demethylation complex
CC erg25-erg26-erg27 leads to the production of zymosterol. Erg28 likely
CC functions in the C-4 demethylation complex reaction by tethering erg26
CC and Erg27 to the endoplasmic reticulum or to facilitate interaction
CC between these proteins. Then, the sterol 24-C-methyltransferase erg6
CC catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of
CC zymosterol to form fecosterol. The C-8 sterol isomerase erg2 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 erg31 and erg32 then catalyze 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 (PubMed:18310029) (Probable). In the genus
CC Schizosaccharomyces, a second route exists between lanosterol and
CC fecosterol, via the methylation of lanosterol to eburicol by erg6,
CC followed by C14-demethylation by erg11/cyp1 and C4-demethylation by the
CC demethylation complex erg25-erg26-erg27 (PubMed:8586261) (Probable).
CC {ECO:0000269|PubMed:8474436, ECO:0000305|PubMed:18310029,
CC ECO:0000305|PubMed:8586261}.
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:0000305|PubMed:8474436};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32296;
CC Evidence={ECO:0000305|PubMed:8474436};
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:0000305|PubMed:8474436};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32300;
CC Evidence={ECO:0000305|PubMed:8474436};
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:0000269|PubMed:8474436}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000269|PubMed:8474436}.
CC -!- SUBUNIT: Interacts with pof14. {ECO:0000269|PubMed:17016471}.
CC -!- INTERACTION:
CC P36596; Q10223: pof14; NbExp=5; IntAct=EBI-1794119, EBI-1793014;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16823372, ECO:0000269|PubMed:17016471}; Single-pass
CC membrane protein {ECO:0000269|PubMed:16823372,
CC ECO:0000269|PubMed:17016471}.
CC -!- MISCELLANEOUS: In Aspergillus, 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 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. In the genus
CC Schizosaccharomyces, 2 routes exist from lanosterol to erposterol: the
CC classical one via zymosterol and the second one via the formation of
CC eburicol followed by demethylation. {ECO:0000269|PubMed:8586261}.
CC -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC {ECO:0000305}.
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DR EMBL; L06071; AAA35343.1; -; mRNA.
DR EMBL; CU329671; CAA22809.1; -; Genomic_DNA.
DR PIR; B48057; B48057.
DR PIR; T40581; T40581.
DR RefSeq; NP_595363.1; NM_001021271.2.
DR AlphaFoldDB; P36596; -.
DR SMR; P36596; -.
DR BioGRID; 277625; 6.
DR IntAct; P36596; 3.
DR MINT; P36596; -.
DR STRING; 4896.SPBC646.05c.1; -.
DR iPTMnet; P36596; -.
DR MaxQB; P36596; -.
DR PaxDb; P36596; -.
DR PRIDE; P36596; -.
DR EnsemblFungi; SPBC646.05c.1; SPBC646.05c.1:pep; SPBC646.05c.
DR GeneID; 2541110; -.
DR KEGG; spo:SPBC646.05c; -.
DR PomBase; SPBC646.05c; erg9.
DR VEuPathDB; FungiDB:SPBC646.05c; -.
DR eggNOG; KOG1459; Eukaryota.
DR HOGENOM; CLU_031981_2_1_1; -.
DR InParanoid; P36596; -.
DR OMA; RFWPKEI; -.
DR PhylomeDB; P36596; -.
DR Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00767; UER00751.
DR UniPathway; UPA00768; -.
DR PRO; PR:P36596; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005783; C:endoplasmic reticulum; IGI:PomBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:PomBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042175; C:nuclear outer membrane-endoplasmic reticulum membrane network; IDA:PomBase.
DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IGI:PomBase.
DR GO; GO:0051996; F:squalene synthase activity; ISS:PomBase.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IGI:PomBase.
DR GO; GO:0045338; P:farnesyl diphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
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 1: Evidence at protein level;
KW Endoplasmic reticulum; Isoprene biosynthesis; Lipid biosynthesis;
KW Lipid metabolism; Magnesium; Membrane; Multifunctional enzyme; NADP;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..460
FT /note="Squalene synthase"
FT /id="PRO_0000067451"
FT TRANSMEM 425..445
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 460 AA; 53321 MW; BAEE7F24B6CE5D25 CRC64;
MSLANRIEEI RCLCQYKLWN DLPSYGEDEN VPQNIRRCYQ LLDMTSRSFA VVIKELPNGI
REAVMIFYLV LRGLDTVEDD MTLPLDKKLP ILRDFYKTIE VEGWTFNESG PNEKDRQLLV
EFDVVIKEYL NLSEGYRNVI SNITKEMGDG MAYYASLAEK NDGFSVETIE DFNKYCHYVA
GLVGIGLSRL FAQSKLEDPD LAHSQAISNS LGLFLQKVNI IRDYREDFDD NRHFWPREIW
SKYTSSFGDL CLPDNSEKAL ECLSDMTANA LTHATDALVY LSQLKTQEIF NFCAIPQVMA
IATLAAVFRN PDVFQTNVKI RKGQAVQIIL HSVNLKNVCD LFLRYTRDIH YKNTPKDPNF
LKISIECGKI EQVSESLFPR RFREMYEKAY VSKLSEQKKG NGTQKAILND EQKELYRKDL
QKLGISILFV FFIILVCLAV IFYVFNIRIH WSDFKELNLF
