ERG24_YEAST
ID ERG24_YEAST Reviewed; 438 AA.
AC P32462; D6W0R4;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Delta(14)-sterol reductase ERG24 {ECO:0000303|PubMed:8125337};
DE EC=1.3.1.70 {ECO:0000305|PubMed:8125337};
DE AltName: Full=C-14 sterol reductase ERG24 {ECO:0000303|PubMed:8125337};
DE AltName: Full=Ergosterol biosynthetic protein 24 {ECO:0000303|PubMed:8125337};
DE AltName: Full=Sterol C14-reductase ERG24 {ECO:0000303|PubMed:8125337};
GN Name=ERG24 {ECO:0000303|PubMed:8125337}; OrderedLocusNames=YNL280C;
GN ORFNames=N0593;
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, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RX PubMed=1418625; DOI=10.1089/dna.1992.11.685;
RA Lorenz R.T., Parks L.W.;
RT "Cloning, sequencing, and disruption of the gene encoding sterol C-14
RT reductase in Saccharomyces cerevisiae.";
RL DNA Cell Biol. 11:685-692(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, ACTIVITY REGULATION, AND
RP PATHWAY.
RX PubMed=8125337; DOI=10.1016/0378-1119(94)90728-5;
RA Lai M.H., Bard M., Pierson C.A., Alexander J.F., Goebl M., Carter G.T.,
RA Kirsch D.R.;
RT "The identification of a gene family in the Saccharomyces cerevisiae
RT ergosterol biosynthesis pathway.";
RL Gene 140:41-49(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(1997).
RN [4]
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 [5]
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 [6]
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
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: Delta(14)-sterol reductase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:1418625, PubMed:8125337). 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 (PubMed:1418625, PubMed:8125337). The
CC third module or late pathway involves the ergosterol synthesis itself
CC through consecutive reactions that mainly occur in the endoplasmic
CC reticulum (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes
CC the 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:1418625, ECO:0000269|PubMed:8125337,
CC ECO:0000303|PubMed:32679672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + H(+) + NADPH;
CC Xref=Rhea:RHEA:18561, ChEBI:CHEBI:15378, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.70;
CC Evidence={ECO:0000305|PubMed:8125337};
CC -!- ACTIVITY REGULATION: Inhibited by the morpholine antifungal drug
CC fenpropimorph. {ECO:0000269|PubMed:8125337}.
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 2/6. {ECO:0000269|PubMed:1418625,
CC ECO:0000269|PubMed:8125337}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:16847258}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:16847258}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of ergosta-8,14-dienol
CC as the major sterol. {ECO:0000269|PubMed:1418625}.
CC -!- MISCELLANEOUS: Present with 1600 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
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DR EMBL; M99419; AAA18256.1; -; Genomic_DNA.
DR EMBL; S69420; AAB30203.1; -; Genomic_DNA.
DR EMBL; Z71556; CAA96192.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10280.1; -; Genomic_DNA.
DR PIR; S30769; S30769.
DR RefSeq; NP_014119.1; NM_001183118.1.
DR AlphaFoldDB; P32462; -.
DR SMR; P32462; -.
DR BioGRID; 35561; 357.
DR DIP; DIP-5155N; -.
DR IntAct; P32462; 16.
DR STRING; 4932.YNL280C; -.
DR iPTMnet; P32462; -.
DR MaxQB; P32462; -.
DR PaxDb; P32462; -.
DR PRIDE; P32462; -.
DR TopDownProteomics; P32462; -.
DR EnsemblFungi; YNL280C_mRNA; YNL280C; YNL280C.
DR GeneID; 855441; -.
DR KEGG; sce:YNL280C; -.
DR SGD; S000005224; ERG24.
DR VEuPathDB; FungiDB:YNL280C; -.
DR eggNOG; KOG1435; Eukaryota.
DR GeneTree; ENSGT00390000000417; -.
DR HOGENOM; CLU_015631_0_3_1; -.
DR InParanoid; P32462; -.
DR OMA; IKTWCEV; -.
DR BioCyc; MetaCyc:YNL280C-MON; -.
DR BioCyc; YEAST:YNL280C-MON; -.
DR Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR Reactome; R-SCE-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-SCE-9013106; RHOC GTPase cycle.
DR Reactome; R-SCE-9013405; RHOD GTPase cycle.
DR UniPathway; UPA00770; UER00755.
DR PRO; PR:P32462; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P32462; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0050613; F:delta14-sterol reductase activity; IDA:SGD.
DR GO; GO:0050661; F:NADP binding; ISS:UniProtKB.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; 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; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 1: Evidence at protein level;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..438
FT /note="Delta(14)-sterol reductase ERG24"
FT /id="PRO_0000207494"
FT TOPO_DOM 1..13
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:16847258"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 72..90
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..109
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 110..127
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 148..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..242
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 309..328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 329..368
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 369..387
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 388..438
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT BINDING 335
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 339
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 358
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 363
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 370..371
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 410
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 414..418
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 425
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT CONFLICT 253
FT /note="L -> S (in Ref. 2; AAB30203)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 438 AA; 50615 MW; B9368B004506C0F3 CRC64;
MVSALNPRTT EFEFGGLIGA LGISIGLPVF TIILNQMIRP DYFIKGFFQN FDIVELWNGI
KPLRYYLGNR ELWTVYCLWY GILAVLDVIL PGRVMKGVQL RDGSKLSYKI NGIAMSTTLV
LVLAIRWKLT DGQLPELQYL YENHVSLCII SILFSFFLAT YCYVASFIPL IFKKNGNGKR
EKILALGGNS GNIIYDWFIG RELNPRLGPL DIKMFSELRP GMLLWLLINL SCLHHHYLKT
GKINDALVLV NFLQGFYIFD GVLNEEGVLT MMDITTDGFG FMLAFGDLSL VPFTYSLQAR
YLSVSPVELG WVKVVGILAI MFLGFHIFHS ANKQKSEFRQ GKLENLKSIQ TKRGTKLLCD
GWWAKSQHIN YFGDWLISLS WCLATWFQTP LTYYYSLYFA TLLLHRQQRD EHKCRLKYGE
NWEEYERKVP YKIIPYVY
