ERG7_CANAL
ID ERG7_CANAL Reviewed; 728 AA.
AC Q04782; A0A1D8PGL9; Q5AM05;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Lanosterol synthase {ECO:0000305};
DE EC=5.4.99.7 {ECO:0000269|PubMed:2185141};
DE AltName: Full=2,3-epoxysqualene--lanosterol cyclase {ECO:0000305};
DE AltName: Full=Ergosterol biosynthesis protein 7 {ECO:0000303|PubMed:8486282};
DE AltName: Full=Oxidosqualene--lanosterol cyclase {ECO:0000303|PubMed:2185141};
DE Short=OSC {ECO:0000303|PubMed:2185141};
GN Name=ERG7 {ECO:0000303|PubMed:8486282}; OrderedLocusNames=CAALFM_C202460WA;
GN ORFNames=CaO19.1570;
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 [GENOMIC DNA], AND FUNCTION.
RX PubMed=8486282; DOI=10.1016/0378-1119(93)90631-c;
RA Roessner C.A., Min C., Hardin S.H., Harris-Haller L.W., McCollum J.C.,
RA Scott A.I.;
RT "Sequence of the Candida albicans erg7 gene.";
RL Gene 127:149-150(1993).
RN [2]
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 [3]
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 [4]
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=2185141; DOI=10.1016/0378-1119(90)90299-7;
RA Kelly R., Miller S.M., Lai M.H., Kirsch D.R.;
RT "Cloning and characterization of the 2,3-oxidosqualene cyclase-coding gene
RT of Candida albicans.";
RL Gene 87:177-183(1990).
RN [6]
RP INDUCTION.
RX PubMed=15473366; DOI=10.1080/13693780410001712016;
RA Pierson C.A., Eckstein J., Barbuch R., Bard M.;
RT "Ergosterol gene expression in wild-type and ergosterol-deficient mutants
RT of Candida albicans.";
RL Med. Mycol. 42:385-389(2004).
RN [7]
RP INDUCTION.
RX PubMed=15820985; DOI=10.1093/jac/dki088;
RA Copping V.M.S., Barelle C.J., Hube B., Gow N.A.R., Brown A.J.P., Odds F.C.;
RT "Exposure of Candida albicans to antifungal agents affects expression of
RT SAP2 and SAP9 secreted proteinase genes.";
RL J. Antimicrob. Chemother. 55:645-654(2005).
CC -!- FUNCTION: Lanosterol synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway
CC (PubMed:8486282, PubMed:2185141). ERG7 catalyzes the cyclization of
CC (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol
CC core (PubMed:2185141). 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:0000269|PubMed:2185141,
CC ECO:0000269|PubMed:8486282, ECO:0000305}.
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:0000269|PubMed:2185141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14622;
CC Evidence={ECO:0000269|PubMed:2185141};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 3/3. {ECO:0000269|PubMed:2185141}.
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 -!- INDUCTION: Expression is induced in the presence of fluconazole
CC (PubMed:15820985). Expression is up-regulated when ERG6, CYP51/ERG11 or
CC ERG24 are deleted (PubMed:15473366). {ECO:0000269|PubMed:15473366,
CC ECO:0000269|PubMed:15820985}.
CC -!- SIMILARITY: Belongs to the terpene cyclase/mutase family.
CC {ECO:0000305}.
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DR EMBL; L04305; AAA34342.1; -; Genomic_DNA.
DR EMBL; CP017624; AOW27286.1; -; Genomic_DNA.
DR PIR; JN0664; JN0664.
DR RefSeq; XP_722612.2; XM_717519.2.
DR AlphaFoldDB; Q04782; -.
DR SMR; Q04782; -.
DR BioGRID; 1218855; 1.
DR STRING; 237561.Q04782; -.
DR ChEMBL; CHEMBL1075056; -.
DR DrugBank; DB00239; Oxiconazole.
DR GeneID; 3635761; -.
DR KEGG; cal:CAALFM_C202460WA; -.
DR CGD; CAL0000184383; ERG7.
DR VEuPathDB; FungiDB:C2_02460W_A; -.
DR eggNOG; KOG0497; Eukaryota.
DR HOGENOM; CLU_009074_2_1_1; -.
DR InParanoid; Q04782; -.
DR OrthoDB; 365003at2759; -.
DR UniPathway; UPA00767; UER00753.
DR PRO; PR:Q04782; -.
DR Proteomes; UP000000559; Chromosome 2.
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; IGI:CGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IGI:CGD.
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 1: Evidence at protein level;
KW Endoplasmic reticulum; Isomerase; Lipid biosynthesis; Lipid droplet;
KW Lipid metabolism; Membrane; Reference proteome; Repeat;
KW Steroid biosynthesis.
FT CHAIN 1..728
FT /note="Lanosterol synthase"
FT /id="PRO_0000072654"
FT REPEAT 117..159
FT /note="PFTB 1"
FT /evidence="ECO:0000255"
FT REPEAT 561..602
FT /note="PFTB 2"
FT /evidence="ECO:0000255"
FT REPEAT 611..657
FT /note="PFTB 3"
FT /evidence="ECO:0000255"
FT ACT_SITE 450
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT CONFLICT 66..67
FT /note="PD -> SG (in Ref. 1; AAA34342)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 728 AA; 83783 MW; 1449ACB621540255 CRC64;
MYYSEEIGLP KTDISRWRLR SDALGRETWH YLSQSECESE PQSTFVQWLL ESPDFPSPPS
SDIHTPDEAA RKGADFLKLL QLDNGIFPCQ YKGPMFMTIG YVTANYYSKT EIPEPYRVEM
IRYIVNTAHP VDGGWGLHSV DKSTCFGTTM NYVCLRLLGM EKDHPVLVKA RKTLHRLGGA
IKNPHWGKAW LSILNLYEWE GVNPAPPELW RLPYWLPIHP AKWWVHTRAI YLPLGYTSAN
RVQCELDPLL KEIRNEIYVP SQLPYESIKF GNQRNNVCGV DLYYPHTKIL DFANSILSKW
EAVRPKWLLN WVNKKVYDLI VKEYQNTEYL CIAPVSFAFN MVVTCHYEGS ESENFKKLQN
RMNDVLFHGP QGMTVMGTNG VQVWDAAFMV QYFFMTGLVD DPKYHDMIRK SYLFLVRSQF
TENCVDGSFR DRRKGAWPFS TKEQGYTVSD CTAEAMKAII MVRNHASFAD IRDEIKDENL
FDAVEVLLQI QNVGEWEYGS FSTYEGIKAP LLLEKLNPAE VFNNIMVEYP YVECTDSSVL
GLTYFAKYYP DYKPELIQKT ISSAIQYILD SQDNIDGSWY GCWGICYTYA SMFALEALHT
VGLDYESSSA VKKGCDFLIS KQLPDGGWSE SMKGCETHSY VNGENSLVVQ SAWALIGLIL
GNYPDEEPIK RGIQFLMKRQ LPTGEWKYED IEGVFNHSCA IEYPSYRFLF PIKALGLYKN
KYGDKVLV
