ERG7_SCHPO
ID ERG7_SCHPO Reviewed; 721 AA.
AC Q10231;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Lanosterol synthase erg7 {ECO:0000303|PubMed:8604986};
DE EC=5.4.99.7 {ECO:0000305|PubMed:8604986};
DE AltName: Full=2,3-epoxysqualene--lanosterol cyclase erg7 {ECO:0000305};
DE AltName: Full=Ergosterol biosynthetic protein 7 {ECO:0000303|PubMed:8604986};
DE AltName: Full=Oxidosqualene--lanosterol cyclase erg7 {ECO:0000305};
GN Name=erg7 {ECO:0000303|PubMed:8604986}; ORFNames=SPAC13G7.01c, SPAC4G9.21c;
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.
RX PubMed=8604986; DOI=10.1006/bbrc.1996.0232;
RA Corey E.J., Matsuda S.P.T., Baker C.H., Ting A.Y., Cheng H.;
RT "Molecular cloning of a Schizosaccharomyces pombe cDNA encoding lanosterol
RT synthase and investigation of conserved tryptophan residues.";
RL Biochem. Biophys. Res. Commun. 219:327-331(1996).
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 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: Lanosterol synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes by the late steps of the pathway
CC (PubMed:8604986). Erg7 catalyzes the cyclization of (S)-2,3
CC oxidosqualene to lanosterol, a reaction that forms the sterol core (By
CC similarity). The third module or late pathway involves the ergosterol
CC synthesis itself through consecutive reactions that mainly occur in the
CC endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase
CC erg9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to
CC form squalene, which is the precursor of all steroids. Secondly,
CC squalene is converted into lanosterol by the consecutive action of the
CC squalene epoxidase erg1 and the lanosterol synthase erg7. The
CC lanosterol 14-alpha-demethylase erg11/cyp1 catalyzes C14-demethylation
CC of lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-
CC ol. In the next steps, a complex process involving various
CC demethylation, reduction and desaturation reactions catalyzed by the C-
CC 14 reductase erg24 and the C-4 demethylation complex erg25-erg26-erg27
CC leads to the production of zymosterol. Erg28 likely functions in the C-
CC 4 demethylation complex reaction by tethering erg26 and Erg27 to the
CC endoplasmic reticulum or to facilitate interaction between these
CC proteins. Then, the sterol 24-C-methyltransferase erg6 catalyzes the
CC methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to
CC form fecosterol. The C-8 sterol isomerase erg2 catalyzes the reaction
CC which results in unsaturation at C-7 in the B ring of sterols and thus
CC converts fecosterol to episterol. The sterol-C5-desaturases erg31 and
CC erg32 then catalyze the introduction of a C-5 double bond in the B ring
CC to produce 5-dehydroepisterol. The C-22 sterol desaturase erg5 further
CC converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC by forming the C-22(23) double bond in the sterol side chain. Finally,
CC ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28)
CC sterol reductase erg4 to produce ergosterol (PubMed:18310029)
CC (Probable). In the genus Schizosaccharomyces, a second route exists
CC between lanosterol and fecosterol, via the methylation of lanosterol to
CC eburicol by erg6, followed by C14-demethylation by erg11/cyp1 and C4-
CC demethylation by the demethylation complex erg25-erg26-erg27
CC (PubMed:8586261) (Probable). {ECO:0000250|UniProtKB:P38604,
CC ECO:0000269|PubMed:8604986, ECO:0000305|PubMed:18310029,
CC ECO:0000305|PubMed:8586261}.
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:0000305|PubMed:8604986};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14622;
CC Evidence={ECO:0000305|PubMed:8604986};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 3/3. {ECO:0000269|PubMed:8604986}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000269|PubMed:8604986}.
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 -!- 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 terpene cyclase/mutase family.
CC {ECO:0000305}.
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DR EMBL; U41368; AAA92502.1; -; mRNA.
DR EMBL; CU329670; CAA93571.1; -; Genomic_DNA.
DR PIR; JC4643; JC4643.
DR RefSeq; NP_593702.2; NM_001019134.2.
DR AlphaFoldDB; Q10231; -.
DR SMR; Q10231; -.
DR STRING; 4896.SPAC13G7.01c.1; -.
DR MaxQB; Q10231; -.
DR PaxDb; Q10231; -.
DR PRIDE; Q10231; -.
DR EnsemblFungi; SPAC13G7.01c.1; SPAC13G7.01c.1:pep; SPAC13G7.01c.
DR GeneID; 2542882; -.
DR KEGG; spo:SPAC13G7.01c; -.
DR PomBase; SPAC13G7.01c; erg7.
DR VEuPathDB; FungiDB:SPAC13G7.01c; -.
DR eggNOG; KOG0497; Eukaryota.
DR HOGENOM; CLU_009074_2_1_1; -.
DR InParanoid; Q10231; -.
DR OMA; CWARQTI; -.
DR PhylomeDB; Q10231; -.
DR Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00767; UER00753.
DR UniPathway; UPA00768; -.
DR PRO; PR:Q10231; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:PomBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; IBA:GO_Central.
DR GO; GO:0000250; F:lanosterol synthase activity; ISO:PomBase.
DR GO; GO:0006696; P:ergosterol biosynthetic process; ISO:PomBase.
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; IPR002365; Terpene_synthase_CS.
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.
DR PROSITE; PS01074; TERPENE_SYNTHASES; 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.
FT CHAIN 1..721
FT /note="Lanosterol synthase erg7"
FT /id="PRO_0000072656"
FT REPEAT 121..162
FT /note="PFTB 1"
FT REPEAT 555..595
FT /note="PFTB 2"
FT REPEAT 604..645
FT /note="PFTB 3"
FT REPEAT 662..703
FT /note="PFTB 4"
FT ACT_SITE 451
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P48449"
SQ SEQUENCE 721 AA; 82819 MW; 445B67F4BF7BFBA3 CRC64;
MEACRVRPEL SKTVEQIDKS LWRLNIDSAG GETWEYVTKE EAEKRPLTIA EKYFLGFDLD
LPKRPPAKTP LESAEYGYEF FRRLQLPDGH WASPYEGPMF LICGAVFAFY ISQTPFPKGW
APEIIQYLIN HTNDDGGWGI HTEGVSTVFG TSMNYVVLRI LGMDAGHPVA TRARNRLHEL
GGAIGCPHWG KFWLATLNCY DWDGVNPIPP ELWLLPDWIP FHPGKWWCHV RLVYLPMGYM
YGERLKCPKD SLIMQLRKEL YVENYDSINF ADHRNTISDV DLYFPHTQIL DRLNWILEKY
FTYLRPSWLK KLGTRRAYEL IKIEDQNTDY SCIGPVNAAM NTVCVYFHEG PSSKAFQKHI
QRLHDFMWVQ PEGMLMRGTN GLQVWETSFT LQALVESGLY EKEAFKPDIA KALEFLDRQQ
IRTQYEGSGY RYNSLGAWPF SNITQGYTVS DTTSEALRAV LLVQSLPDFE KLVDIPRLRL
SVDVILGMQN ENLGFASYEP ARTGEWMELL NPAEVFGNIM VEYSYPECTT SVILALRAFT
KYDPGYRRDE IENTIENALE YVVKMQRPDG SWYGSWAICF TYAAMFATGS LASAGRYYEN
CPVQKKACEF LLSKQRPDGG WSESYMACVT GVYTETESSL VTQTGWALDA LINAKYPDRK
PIEKGIKFLM ASQKSDGSWQ QKSMEGIFNK NVAIAYPNYK LYFSIYTLGK FAKQYGNYLT
I
