ERG3_CANAL
ID ERG3_CANAL Reviewed; 386 AA.
AC Q59VG6;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Delta(7)-sterol 5(6)-desaturase ERG3 {ECO:0000305};
DE EC=1.14.19.20 {ECO:0000305|PubMed:10433965};
DE AltName: Full=C-5 sterol desaturase ERG3 {ECO:0000303|PubMed:10433965};
DE AltName: Full=Ergosterol Delta(5,6) desaturase erg3 {ECO:0000305};
DE AltName: Full=Ergosterol biosynthesis protein 3 {ECO:0000303|PubMed:10433965};
DE AltName: Full=Sterol-C5-desaturase ERG3 {ECO:0000303|PubMed:10433965};
GN Name=ERG3 {ECO:0000303|PubMed:10433965}; OrderedLocusNames=orf19.767;
GN ORFNames=CAALFM_C104770CA;
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 FUNCTION, AND AZOLE-RESISTANCE.
RX PubMed=9000517; DOI=10.1016/s0014-5793(96)01360-9;
RA Kelly S.L., Lamb D.C., Kelly D.E., Manning N.J., Loeffler J., Hebart H.,
RA Schumacher U., Einsele H.;
RT "Resistance to fluconazole and cross-resistance to amphotericin B in
RT Candida albicans from AIDS patients caused by defective sterol delta5,6-
RT desaturation.";
RL FEBS Lett. 400:80-82(1997).
RN [5]
RP FUNCTION.
RX PubMed=10433965; DOI=10.1016/s0378-1119(99)00263-2;
RA Miyazaki Y., Geber A., Miyazaki H., Falconer D., Parkinson T.,
RA Hitchcock C., Grimberg B., Nyswaner K., Bennett J.E.;
RT "Cloning, sequencing, expression and allelic sequence diversity of ERG3 (C-
RT 5 sterol desaturase gene) in Candida albicans.";
RL Gene 236:43-51(1999).
RN [6]
RP FUNCTION, VARIANTS GLU-97; GLY-147; PRO-193; ALA-237; ASN-243; ALA-330;
RP VAL-351 AND THR-353, AND AZOLE-RESISTANCE.
RX PubMed=20733039; DOI=10.1128/aac.00348-10;
RA Martel C.M., Parker J.E., Bader O., Weig M., Gross U., Warrilow A.G.,
RA Rolley N., Kelly D.E., Kelly S.L.;
RT "Identification and characterization of four azole-resistant erg3 mutants
RT of Candida albicans.";
RL Antimicrob. Agents Chemother. 54:4527-4533(2010).
RN [7]
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: C-5 sterol desaturase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathwa
CC (PubMed:9000517, PubMed:10433965, PubMed:20733039). ERG3 catalyzes the
CC introduction of a C-5 double bond in the B ring to produce 5-
CC dehydroepisterol (PubMed:10433965). The third module or late pathway
CC involves the ergosterol synthesis itself through consecutive reactions
CC that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly,
CC the squalene synthase ERG9 catalyzes the condensation of 2 farnesyl
CC pyrophosphate moieties to form squalene, which is the precursor of all
CC steroids. Squalene synthase is crucial for balancing the incorporation
CC of 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:10433965,
CC ECO:0000269|PubMed:20733039, ECO:0000269|PubMed:9000517, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a Delta(7)-sterol + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = a
CC Delta(5),Delta(7)-sterol + 2 Fe(III)-[cytochrome b5] + 2 H2O;
CC Xref=Rhea:RHEA:54320, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:138130,
CC ChEBI:CHEBI:138131; EC=1.14.19.20;
CC Evidence={ECO:0000305|PubMed:10433965};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54321;
CC Evidence={ECO:0000305|PubMed:10433965};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P53045};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis; ergosterol from
CC zymosterol: step 3/5. {ECO:0000305|PubMed:10433965}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is repressed during spider biofilm formation
CC (PubMed:22265407). {ECO:0000269|PubMed:22265407}.
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding. {ECO:0000250|UniProtKB:P53045}.
CC -!- MISCELLANEOUS: Defects in C-5 sterol desaturation results in antibiotic
CC and azole resistance of Candida albicans during infection, particularly
CC in AIDS patients. {ECO:0000269|PubMed:20733039,
CC ECO:0000269|PubMed:9000517}.
CC -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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DR EMBL; CP017623; AOW26151.1; -; Genomic_DNA.
DR RefSeq; XP_713577.1; XM_708484.2.
DR AlphaFoldDB; Q59VG6; -.
DR STRING; 237561.Q59VG6; -.
DR PRIDE; Q59VG6; -.
DR EnsemblFungi; KHC83255; KHC83255; W5Q_00467.
DR EnsemblFungi; KHC89648; KHC89648; I503_00470.
DR GeneID; 3644776; -.
DR KEGG; cal:CAALFM_C104770CA; -.
DR CGD; CAL0000190948; ERG3.
DR VEuPathDB; FungiDB:C1_04770C_A; -.
DR eggNOG; KOG0872; Eukaryota.
DR HOGENOM; CLU_047036_3_0_1; -.
DR InParanoid; Q59VG6; -.
DR OMA; IFPLQKM; -.
DR OrthoDB; 1249774at2759; -.
DR BRENDA; 1.14.19.20; 1096.
DR UniPathway; UPA00768; UER00762.
DR PHI-base; PHI:8029; -.
DR PHI-base; PHI:8122; -.
DR Proteomes; UP000000559; Chromosome 1.
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:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0000248; F:C-5 sterol desaturase activity; IMP:CGD.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:CGD.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0044182; P:filamentous growth of a population of unicellular organisms; IMP:CGD.
DR GO; GO:0036180; P:filamentous growth of a population of unicellular organisms in response to biotic stimulus; IMP:CGD.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR006694; Fatty_acid_hydroxylase.
DR Pfam; PF04116; FA_hydroxylase; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..386
FT /note="Delta(7)-sterol 5(6)-desaturase ERG3"
FT /id="PRO_0000454172"
FT TRANSMEM 120..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 214..337
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT MOTIF 226..230
FT /note="Histidine box-1"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT MOTIF 239..243
FT /note="Histidine box-2"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT MOTIF 314..318
FT /note="Histidine box-3"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT VARIANT 97
FT /note="K -> E (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
FT VARIANT 147
FT /note="D -> G (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
FT VARIANT 193
FT /note="L -> P (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
FT VARIANT 237
FT /note="V -> A (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
FT VARIANT 243
FT /note="H -> N (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
FT VARIANT 330
FT /note="T -> A (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
FT VARIANT 351
FT /note="A -> V (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
FT VARIANT 353
FT /note="A -> T (in strain: azole-resistant isolates)"
FT /evidence="ECO:0000269|PubMed:20733039"
SQ SEQUENCE 386 AA; 45419 MW; E5CF1DA5EAFCF83B CRC64;
MDIVLEICDY YLFDKVYADV FPKDGAVHEF LKPAIQSFSQ IDFPSLPNLD SFDTNSTLIS
SNNFNISNVN PATIPSYLFS KIASYQDKSE IYGLAPKFFP ATDFINTSFL ARSNIFRETL
SLFIITTIFG WLLYFIVAYL SYVFVFDKKI FNHPRYLKNQ MSLEIKRATT AIPVMVLLTI
PFFLLELNGY SFLYLDINEC TGGYKAILWQ IPKFILFTDC GIYFLHRWLH WPSVYKVLHK
PHHKWIVCTP FASHAFHPVD GFFQSLPYHL YPLLFPLHKV LYLFLFTFVN FWTVMIHDGS
YWSNDPVVNG TACHTVHHLY FNYNYGQFTT LWDRLGNSYR RPDDSLFVKD AKAEEEKKIW
KEQTRKMEEI RGEVEGKVDD REYVEQ
