ERG26_YEAST
ID ERG26_YEAST Reviewed; 349 AA.
AC P53199; D6VUD7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase ERG26, decarboxylating {ECO:0000303|PubMed:9811880};
DE EC=1.1.1.170 {ECO:0000269|PubMed:9811880};
DE AltName: Full=C-3 sterol dehydrogenase ERG26 {ECO:0000303|PubMed:9811880};
DE AltName: Full=C-4 decarboxylase ERG26 {ECO:0000303|PubMed:9811880};
DE AltName: Full=Ergosterol biosynthetic protein 26 {ECO:0000303|PubMed:9811880};
GN Name=ERG26 {ECO:0000303|PubMed:9811880}; OrderedLocusNames=YGL001C;
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=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(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 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 [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9811880; DOI=10.1073/pnas.95.23.13794;
RA Gachotte D., Barbuch R., Gaylor J., Nickel E., Bard M.;
RT "Characterization of the Saccharomyces cerevisiae ERG26 gene encoding the
RT C-3 sterol dehydrogenase (C-4 decarboxylase) involved in sterol
RT biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:13794-13799(1998).
RN [5]
RP ERRATUM OF PUBMED:9811880.
RA Gachotte D., Barbuch R., Gaylor J., Nickel E., Bard M.;
RL Proc. Natl. Acad. Sci. U.S.A. 96:1810-1810(1999).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ERG25 AND ERG27.
RX PubMed=11279045; DOI=10.1074/jbc.m100274200;
RA Baudry K., Swain E., Rahier A., Germann M., Batta A., Rondet S.,
RA Mandala S., Henry K., Tint G.S., Edlind T., Kurtz M., Nickels J.T. Jr.;
RT "The effect of the erg26-1 mutation on the regulation of lipid metabolism
RT in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 276:12702-12711(2001).
RN [7]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR 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 [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 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 [10]
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 [11]
RP ACTIVITY REGULATION.
RX PubMed=26456460; DOI=10.1038/ncomms9613;
RA Helliwell S.B., Karkare S., Bergdoll M., Rahier A., Leighton-Davis J.R.,
RA Fioretto C., Aust T., Filipuzzi I., Frederiksen M., Gounarides J.,
RA Hoepfner D., Hofmann A., Imbert P.E., Jeker R., Knochenmuss R., Krastel P.,
RA Margerit A., Memmert K., Miault C.V., Rao Movva N., Muller A.,
RA Naegeli H.U., Oberer L., Prindle V., Riedl R., Schuierer S., Sexton J.A.,
RA Tao J., Wagner T., Yin H., Zhang J., Roggo S., Reinker S., Parker C.N.;
RT "FR171456 is a specific inhibitor of mammalian NSDHL and yeast Erg26p.";
RL Nat. Commun. 6:8613-8613(2015).
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: Sterol-4-alpha-carboxylate 3-dehydrogenase; part of the third
CC module of ergosterol biosynthesis pathway that includes the late steps
CC of the pathway (PubMed:9811880, PubMed:15995173). ERG26 is a catalytic
CC component of the C-4 demethylation complex that catalyzes the oxidative
CC decarboxylation that results in a reduction of the 3-beta-hydroxy group
CC at the C-3 carbon to an oxo group (PubMed:9811880). The third module or
CC 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:15995173, ECO:0000269|PubMed:9811880,
CC ECO:0000303|PubMed:32679672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3-
CC dehydro-4-methylzymosterol + CO2 + NADPH; Xref=Rhea:RHEA:33447,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:50593, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:64925; EC=1.1.1.170;
CC Evidence={ECO:0000269|PubMed:9811880};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33448;
CC Evidence={ECO:0000305|PubMed:9811880};
CC -!- ACTIVITY REGULATION: Inhibited by FR171456, a natural product with
CC broad antifungal activity. {ECO:0000269|PubMed:26456460}.
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 4/6. {ECO:0000269|PubMed:9811880}.
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 {ECO:0000269|PubMed:11279045, ECO:0000269|PubMed:12119386,
CC ECO:0000269|PubMed:15995173}.
CC -!- INTERACTION:
CC P53199; P40030: ERG28; NbExp=3; IntAct=EBI-6514, EBI-22518;
CC P53199; P38132: MCM7; NbExp=2; IntAct=EBI-6514, EBI-4300;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11279045, ECO:0000269|PubMed:12119386,
CC ECO:0000269|PubMed:15716577}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12119386, ECO:0000269|PubMed:15716577}.
CC -!- MISCELLANEOUS: Present with 2580 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Z72523; CAA96701.1; -; Genomic_DNA.
DR EMBL; AY693026; AAT93045.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA08098.1; -; Genomic_DNA.
DR PIR; S64003; S64003.
DR RefSeq; NP_011514.1; NM_001180866.1.
DR AlphaFoldDB; P53199; -.
DR SMR; P53199; -.
DR BioGRID; 33244; 290.
DR DIP; DIP-6786N; -.
DR IntAct; P53199; 23.
DR MINT; P53199; -.
DR STRING; 4932.YGL001C; -.
DR SwissLipids; SLP:000001310; -.
DR iPTMnet; P53199; -.
DR MaxQB; P53199; -.
DR PaxDb; P53199; -.
DR PRIDE; P53199; -.
DR EnsemblFungi; YGL001C_mRNA; YGL001C; YGL001C.
DR GeneID; 852883; -.
DR KEGG; sce:YGL001C; -.
DR SGD; S000002969; ERG26.
DR VEuPathDB; FungiDB:YGL001C; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000158229; -.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; P53199; -.
DR OMA; WGPGDTQ; -.
DR BioCyc; MetaCyc:YGL001C-MON; -.
DR BioCyc; YEAST:YGL001C-MON; -.
DR BRENDA; 1.1.1.170; 984.
DR Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR Reactome; R-SCE-193048; Androgen biosynthesis.
DR Reactome; R-SCE-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-SCE-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-SCE-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-SCE-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-SCE-194002; Glucocorticoid biosynthesis.
DR UniPathway; UPA00770; UER00757.
DR PRO; PR:P53199; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P53199; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:InterPro.
DR GO; GO:0103066; F:4alpha-carboxy-4beta-methyl-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-oxidoreductase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0103067; F:4alpha-carboxy-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-dehydrogenase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0000252; F:C-3 sterol dehydrogenase (C-4 sterol decarboxylase) activity; IDA:SGD.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0047012; F:sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IDA:SGD.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane; NAD;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT CHAIN 1..349
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase ERG26,
FT decarboxylating"
FT /id="PRO_0000087798"
FT ACT_SITE 155
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 11..17
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 62..63
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 84..86
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A0A059TC02"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 155
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
FT BINDING 179..182
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51110"
SQ SEQUENCE 349 AA; 38706 MW; 87CA8FF8D64B0327 CRC64;
MSKIDSVLII GGSGFLGLHL IQQFFDINPK PDIHIFDVRD LPEKLSKQFT FNVDDIKFHK
GDLTSPDDME NAINESKANV VVHCASPMHG QNPDIYDIVN VKGTRNVIDM CKKCGVNILV
YTSSAGVIFN GQDVHNADET WPIPEVPMDA YNETKAIAED MVLKANDPSS DFYTVALRPA
GIFGPGDRQL VPGLRQVAKL GQSKFQIGDN NNLFDWTYAG NVADAHVLAA QKLLDPKTRT
AVSGETFFIT NDTPTYFWAL ARTVWKADGH IDKHVIVLKR PVAICAGYLS EWVSKMLGKE
PGLTPFRVKI VCAYRYHNIA KAKKLLGYTP RVGIEEGINK TLAWMDEGL
