ERG27_YEAST
ID ERG27_YEAST Reviewed; 347 AA.
AC Q12452; D6VYA1;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=3-keto-steroid reductase ERG27 {ECO:0000303|PubMed:10535978};
DE EC=1.1.1.270 {ECO:0000269|PubMed:10535978};
DE AltName: Full=Ergosterol biosynthetic protein 27 {ECO:0000303|PubMed:10535978};
GN Name=ERG27 {ECO:0000303|PubMed:10535978}; OrderedLocusNames=YLR100W;
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 [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 [2]
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=10535978; DOI=10.1073/pnas.96.22.12655;
RA Gachotte D., Sen S.E., Eckstein J., Barbuch R., Krieger M., Ray B.D.,
RA Bard M.;
RT "Characterization of the Saccharomyces cerevisiae ERG27 gene encoding the
RT 3-keto reductase involved in C-4 sterol demethylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:12655-12660(1999).
RN [4]
RP FUNCTION, SUBUNIT, INTERACTION WITH ERG25 AND ERG28, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12119386; DOI=10.1073/pnas.112202799;
RA Mo C., Valachovic M., Randall S.K., Nickels J.T., Bard M.;
RT "Protein-protein interactions among C-4 demethylation enzymes involved in
RT yeast sterol biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:9739-9744(2002).
RN [5]
RP FUNCTION, INTERACTION WITH ERG7, AND SUBCELLULAR LOCATION.
RX PubMed=12842197; DOI=10.1016/s1388-1981(03)00088-x;
RA Mo C., Milla P., Athenstaedt K., Ott R., Balliano G., Daum G., Bard M.;
RT "In yeast sterol biosynthesis the 3-keto reductase protein (Erg27p) is
RT required for oxidosqualene cyclase (Erg7p) activity.";
RL Biochim. Biophys. Acta 1633:68-74(2003).
RN [6]
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 [7]
RP SUBCELLULAR LOCATION.
RX PubMed=15716577; DOI=10.1074/mcp.m400123-mcp200;
RA Natter K., Leitner P., Faschinger A., Wolinski H., McCraith S., Fields S.,
RA Kohlwein S.D.;
RT "The spatial organization of lipid synthesis in the yeast Saccharomyces
RT cerevisiae derived from large scale green fluorescent protein tagging and
RT high resolution microscopy.";
RL Mol. Cell. Proteomics 4:662-672(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-345, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [9]
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: 3-keto-steroid reductase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:10535978, PubMed:12119386, PubMed:12842197,
CC PubMed:15995173). ERG27 is a catalytic component of the C-4
CC demethylation complex that catalyze the reduction of the keto group on
CC the C-3 (PubMed:10535978). 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. 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 (PubMed:32679672). {ECO:0000269|PubMed:10535978,
CC ECO:0000269|PubMed:12119386, ECO:0000269|PubMed:12842197,
CC ECO:0000269|PubMed:15995173, ECO:0000303|PubMed:32679672}.
CC -!- FUNCTION: Facilitates the association of ERG7 with lipid particles
CC preventing its digestion in the endoplasmic reticulum and the lipid
CC particles. {ECO:0000269|PubMed:12842197}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-dehydro-4alpha-methylzymosterol + H(+) + NADPH = 4alpha-
CC methylzymosterol + NADP(+); Xref=Rhea:RHEA:36379, ChEBI:CHEBI:1949,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:136486; EC=1.1.1.270;
CC Evidence={ECO:0000269|PubMed:10535978};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36380;
CC Evidence={ECO:0000269|PubMed:10535978};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 5/6. {ECO:0000269|PubMed:10535978}.
CC -!- SUBUNIT: Heterotetramer of ERG25, ERG26, ERG27 and ERG28. ERG28 acts as
CC a scaffold to tether ERG27 and other 4,4-demethylation-related enzymes,
CC forming a demethylation enzyme complex, in the endoplasmic reticulum.
CC Interacts with ERG25 and ERG28. Also interacts with ERG7, but only in
CC lipid particles. {ECO:0000269|PubMed:12119386,
CC ECO:0000269|PubMed:12842197, ECO:0000269|PubMed:15995173}.
CC -!- INTERACTION:
CC Q12452; P53045: ERG25; NbExp=4; IntAct=EBI-38132, EBI-6506;
CC Q12452; P40030: ERG28; NbExp=6; IntAct=EBI-38132, EBI-22518;
CC Q12452; P38604: ERG7; NbExp=4; IntAct=EBI-38132, EBI-6572;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12119386, ECO:0000269|PubMed:12842197,
CC ECO:0000269|PubMed:15716577}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12119386, ECO:0000269|PubMed:12842197,
CC ECO:0000269|PubMed:15716577}. Lipid droplet
CC {ECO:0000269|PubMed:12119386, ECO:0000269|PubMed:12842197,
CC ECO:0000269|PubMed:15716577}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. ERG27 subfamily. {ECO:0000305}.
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DR EMBL; U53876; AAB67544.1; -; Genomic_DNA.
DR EMBL; Z73272; CAA97664.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09417.1; -; Genomic_DNA.
DR PIR; S64936; S64936.
DR RefSeq; NP_013201.1; NM_001181987.1.
DR AlphaFoldDB; Q12452; -.
DR SMR; Q12452; -.
DR BioGRID; 31374; 330.
DR DIP; DIP-1237N; -.
DR IntAct; Q12452; 22.
DR MINT; Q12452; -.
DR STRING; 4932.YLR100W; -.
DR iPTMnet; Q12452; -.
DR MaxQB; Q12452; -.
DR PaxDb; Q12452; -.
DR PRIDE; Q12452; -.
DR TopDownProteomics; Q12452; -.
DR EnsemblFungi; YLR100W_mRNA; YLR100W; YLR100W.
DR GeneID; 850790; -.
DR KEGG; sce:YLR100W; -.
DR SGD; S000004090; ERG27.
DR VEuPathDB; FungiDB:YLR100W; -.
DR eggNOG; KOG1478; Eukaryota.
DR GeneTree; ENSGT00390000013340; -.
DR HOGENOM; CLU_029944_1_0_1; -.
DR InParanoid; Q12452; -.
DR OMA; ASYEGSK; -.
DR BioCyc; MetaCyc:YLR100W-MON; -.
DR BioCyc; YEAST:YLR100W-MON; -.
DR BRENDA; 1.1.1.270; 984.
DR UniPathway; UPA00770; UER00758.
DR PRO; PR:Q12452; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q12452; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0005811; C:lipid droplet; IDA:SGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; HDA:SGD.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IMP:SGD.
DR GO; GO:0102176; F:cycloeucalenone reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:SGD.
DR CDD; cd08941; 3KS_SDR_c; 1.
DR InterPro; IPR042829; HSD17B7/Erg27.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid droplet; Lipid metabolism;
KW Membrane; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Steroid biosynthesis.
FT CHAIN 1..347
FT /note="3-keto-steroid reductase ERG27"
FT /id="PRO_0000054595"
FT ACT_SITE 202
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q12634"
FT BINDING 43..79
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12634"
FT MOD_RES 345
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17330950"
SQ SEQUENCE 347 AA; 39725 MW; D9A0589C049D8C49 CRC64;
MNRKVAIVTG TNSNLGLNIV FRLIETEDTN VRLTIVVTSR TLPRVQEVIN QIKDFYNKSG
RVEDLEIDFD YLLVDFTNMV SVLNAYYDIN KKYRAINYLF VNAAQGIFDG IDWIGAVKEV
FTNPLEAVTN PTYKIQLVGV KSKDDMGLIF QANVFGPYYF ISKILPQLTR GKAYIVWISS
IMSDPKYLSL NDIELLKTNA SYEGSKRLVD LLHLATYKDL KKLGINQYVV QPGIFTSHSF
SEYLNFFTYF GMLCLFYLAR LLGSPWHNID GYKAANAPVY VTRLANPNFE KQDVKYGSAT
SRDGMPYIKT QEIDPTGMSD VFAYIQKKKL EWDEKLKDQI VETRTPI
