ERG3_YEAST
ID ERG3_YEAST Reviewed; 365 AA.
AC P32353; D6VY58;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Delta(7)-sterol 5(6)-desaturase ERG3 {ECO:0000303|PubMed:1864507};
DE EC=1.14.19.20 {ECO:0000269|PubMed:1864507};
DE AltName: Full=C-5 sterol desaturase ERG3 {ECO:0000303|PubMed:1864507};
DE AltName: Full=Ergosterol Delta(5,6) desaturase ERG3 {ECO:0000303|PubMed:1864507};
DE AltName: Full=Ergosterol biosynthetic protein 3 {ECO:0000303|PubMed:1864507};
DE AltName: Full=Sterol-C5-desaturase {ECO:0000303|PubMed:1864507};
GN Name=ERG3 {ECO:0000303|PubMed:1864507}; Synonyms=PSO6, SYR1;
GN OrderedLocusNames=YLR056W; ORFNames=L2150;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=1864507; DOI=10.1016/0378-1119(91)90535-j;
RA Arthington B.A., Bennett L.G., Skatrud P.L., Guynn C.J., Barbuch R.J.,
RA Ulbright C.E., Bard M.;
RT "Cloning, disruption and sequence of the gene encoding yeast C-5 sterol
RT desaturase.";
RL Gene 102:39-44(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Renauld G., Lacroute F., Cassart J.-P., Vandenhaute J., Delcour J.;
RL Submitted (MAR-1992) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8180700; DOI=10.1099/13500872-140-2-353;
RA Taguchi N., Takano Y., Julmanop C., Wang Y., Stock S., Takemoto J.Y.,
RA Miyakawa T.;
RT "Identification and analysis of the Saccharomyces cerevisiae SYR1 gene
RT reveals that ergosterol is involved in the action of syringomycin.";
RL Microbiology 140:353-359(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [7]
RP INDUCTION.
RX PubMed=8772195; DOI=10.1016/0014-5793(96)00807-1;
RA Arthington-Skaggs B.A., Crowell D.N., Yang H., Sturley S.L., Bard M.;
RT "Positive and negative regulation of a sterol biosynthetic gene (ERG3) in
RT the post-squalene portion of the yeast ergosterol pathway.";
RL FEBS Lett. 392:161-165(1996).
RN [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-324 AND LYS-344, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=SUB592;
RX PubMed=12872131; DOI=10.1038/nbt849;
RA Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G.,
RA Roelofs J., Finley D., Gygi S.P.;
RT "A proteomics approach to understanding protein ubiquitination.";
RL Nat. Biotechnol. 21:921-926(2003).
RN [10]
RP FUNCTION, AND INTERACTION WITH ERG28.
RX PubMed=15995173; DOI=10.1194/jlr.m500153-jlr200;
RA Mo C., Bard M.;
RT "Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex.";
RL J. Lipid Res. 46:1991-1998(2005).
RN [11]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [12]
RP REVIEW ON ERGOSTEROL BIOSYNTHESIS.
RX PubMed=32679672; DOI=10.3390/genes11070795;
RA Jorda T., Puig S.;
RT "Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae.";
RL Genes (Basel) 11:0-0(2020).
CC -!- FUNCTION: C-5 sterol desaturase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway
CC (PubMed:1864507). ERG3 catalyzes the introduction of a C-5 double bond
CC in the B ring to produce 5-dehydroepisterol (PubMed:1864507). The third
CC module or late pathway involves the ergosterol synthesis itself through
CC consecutive reactions that mainly occur in the endoplasmic reticulum
CC (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes the
CC condensation of 2 farnesyl pyrophosphate moieties to form squalene,
CC which is the precursor of all steroids. Squalene synthase is crucial
CC for balancing the incorporation of farnesyl diphosphate (FPP) into
CC sterol and nonsterol isoprene synthesis. Secondly, the squalene
CC epoxidase ERG1 catalyzes the stereospecific oxidation of squalene to
CC (S)-2,3-epoxysqualene, which is considered to be a rate-limiting enzyme
CC in steroid biosynthesis. Then, the lanosterol synthase ERG7 catalyzes
CC the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that
CC forms the sterol core. In the next steps, lanosterol is transformed to
CC zymosterol through a complex process involving various demethylation,
CC reduction and desaturation reactions. The lanosterol 14-alpha-
CC demethylase ERG11 (also known as CYP51) catalyzes C14-demethylation of
CC lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol,
CC which is critical for ergosterol biosynthesis. The C-14 reductase ERG24
CC reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-8,14,24-
CC trienol to produce 4,4-dimethyl-cholesta-8,24-dienol. 4,4-dimethyl-
CC cholesta-8,24-dienol is substrate of the C-4 demethylation complex
CC ERG25-ERG26-ERG27 in which ERG25 catalyzes the three-step
CC monooxygenation required for the demethylation of 4,4-dimethyl and
CC 4alpha-methylsterols, ERG26 catalyzes the oxidative decarboxylation
CC that results in a reduction of the 3-beta-hydroxy group at the C-3
CC carbon to an oxo group, and ERG27 is responsible for the reduction of
CC the keto group on the C-3. ERG28 has a role as a scaffold to help
CC anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and ERG29
CC regulates the activity of the iron-containing C4-methylsterol oxidase
CC ERG25. 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-desaturase ERG3 then
CC catalyzes the introduction of a C-5 double bond in the B ring to
CC 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:32679672).
CC {ECO:0000269|PubMed:1864507, ECO:0000303|PubMed:32679672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=episterol + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = 5-
CC dehydroepisterol + 2 Fe(III)-[cytochrome b5] + 2 H2O;
CC Xref=Rhea:RHEA:46560, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:23929, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:52972; EC=1.14.19.20;
CC Evidence={ECO:0000269|PubMed:1864507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46561;
CC Evidence={ECO:0000269|PubMed:1864507};
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:0000269|PubMed:1864507}.
CC -!- SUBUNIT: Interacts with ERG28. {ECO:0000269|PubMed:15995173}.
CC -!- INTERACTION:
CC P32353; P53045: ERG25; NbExp=3; IntAct=EBI-6554, EBI-6506;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: The ERG3 promoter contains 2 upstream activation sequences,
CC UAS1 and UAS2 (PubMed:8772195). UAS1 regulates gene expression but does
CC not affect sterol regulation (PubMed:8772195). UAS2 is required for
CC sterol regulation (PubMed:8772195). The absence of sterol
CC esterification leads to a decrease of ERG3 expression (PubMed:8772195).
CC {ECO:0000269|PubMed:8772195}.
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: Present with 36200 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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DR EMBL; M62623; AAA34594.1; -; Genomic_DNA.
DR EMBL; S46162; AAB39844.1; -; Genomic_DNA.
DR EMBL; M64989; AAA34595.1; -; Genomic_DNA.
DR EMBL; D14299; BAA20292.1; -; Genomic_DNA.
DR EMBL; X94607; CAA64303.1; -; Genomic_DNA.
DR EMBL; Z73228; CAA97586.1; -; Genomic_DNA.
DR EMBL; AY692996; AAT93015.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09374.1; -; Genomic_DNA.
DR PIR; JQ1146; JQ1146.
DR RefSeq; NP_013157.1; NM_001181943.1.
DR AlphaFoldDB; P32353; -.
DR SMR; P32353; -.
DR BioGRID; 31331; 1133.
DR DIP; DIP-4136N; -.
DR IntAct; P32353; 12.
DR MINT; P32353; -.
DR STRING; 4932.YLR056W; -.
DR iPTMnet; P32353; -.
DR MaxQB; P32353; -.
DR PaxDb; P32353; -.
DR PRIDE; P32353; -.
DR EnsemblFungi; YLR056W_mRNA; YLR056W; YLR056W.
DR GeneID; 850745; -.
DR KEGG; sce:YLR056W; -.
DR SGD; S000004046; ERG3.
DR VEuPathDB; FungiDB:YLR056W; -.
DR eggNOG; KOG0872; Eukaryota.
DR GeneTree; ENSGT00550000075101; -.
DR HOGENOM; CLU_047036_3_0_1; -.
DR InParanoid; P32353; -.
DR OMA; IFPLQKM; -.
DR BioCyc; MetaCyc:YLR056W-MON; -.
DR BioCyc; YEAST:YLR056W-MON; -.
DR Reactome; R-SCE-6807047; Cholesterol biosynthesis via desmosterol.
DR Reactome; R-SCE-6807062; Cholesterol biosynthesis via lathosterol.
DR SABIO-RK; P32353; -.
DR UniPathway; UPA00768; UER00762.
DR PRO; PR:P32353; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P32353; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:SGD.
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:0000248; F:C-5 sterol desaturase activity; IDA:SGD.
DR GO; GO:0050046; F:delta7-sterol 5(6)-desaturase activity; IEA:UniProtKB-EC.
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:SGD.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR006694; Fatty_acid_hydroxylase.
DR Pfam; PF04116; FA_hydroxylase; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Iron; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..365
FT /note="Delta(7)-sterol 5(6)-desaturase ERG3"
FT /id="PRO_0000117027"
FT TOPO_DOM 1..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 114..140
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..365
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 187..311
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT MOTIF 200..204
FT /note="Histidine box-1"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT MOTIF 213..217
FT /note="Histidine box-2"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT MOTIF 288..292
FT /note="Histidine box-3"
FT /evidence="ECO:0000250|UniProtKB:P53045"
FT CROSSLNK 324
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT CROSSLNK 344
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
SQ SEQUENCE 365 AA; 42730 MW; 7F441DA6927A711C CRC64;
MDLVLEVADH YVLDDLYAKV LPASLAANIP VKWQKLLGLN SGFSNSTILQ ETLNSKNAVK
ECRRFYGQVP FLFDMSTTSF ASLLPRSSIL REFLSLWVIV TIFGLLLYLF TASLSYVFVF
DKSIFNHPRY LKNQMAMEIK LAVSAIPWMS MLTVPWFVME LNGHSKLYMK IDYENHGVRK
LIIEYFTFIF FTDCGVYLAH RWLHWPRVYR ALHKPHHKWL VCTPFASHSF HPVDGFLQSI
SYHIYPLILP LHKVSYLILF TFVNFWTVMI HDGQYLSNNP AVNGTACHTV HHLYFNYNYG
QFTTLWDRLG GSYRRPDDSL FDPKLRDAKE TWDAQVKEVE HFIKEVEGDD NDRIYENDPN
TKKNN
