ERG28_YEAST
ID ERG28_YEAST Reviewed; 148 AA.
AC P40030; D3DLU4;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Ergosterol biosynthetic protein 28 {ECO:0000303|PubMed:11160377};
GN Name=ERG28 {ECO:0000303|PubMed:11160377}; Synonyms=BUD18;
GN OrderedLocusNames=YER044C;
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=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(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.
RX PubMed=11160377;
RA Gachotte D., Eckstein J., Barbuch R., Hughes T., Roberts C., Bard M.;
RT "A novel gene conserved from yeast to humans is involved in sterol
RT biosynthesis.";
RL J. Lipid Res. 42:150-154(2001).
RN [5]
RP FUNCTION, SUBUNIT, INTERACTION WITH ERG25 AND ERG27, 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 [6]
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 [7]
RP FUNCTION, AND INTERACTION WITH ERG6.
RX PubMed=15522820; DOI=10.1016/j.bbalip.2004.08.001;
RA Mo C., Valachovic M., Bard M.;
RT "The ERG28-encoded protein, Erg28p, interacts with both the sterol C-4
RT demethylation enzyme complex as well as the late biosynthetic protein, the
RT C-24 sterol methyltransferase (Erg6p).";
RL Biochim. Biophys. Acta 1686:30-36(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH ERG1; ERG3; ERG5; ERG6; ERG11; ERG25; ERG26
RP AND ERG27.
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 [9]
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 [10]
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: Part of the third module of ergosterol biosynthesis pathway
CC that includes the late steps of the pathway (PubMed:11160377,
CC PubMed:12119386, PubMed:15522820, PubMed:15995173). ERG28 has a role as
CC a scaffold to help anchor the catalytic components of the C-4
CC demethylation complex ERG25, ERG26 and ERG27 to the endoplasmic
CC reticulum (PubMed:12119386, PubMed:15522820, PubMed:15995173). 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:11160377, ECO:0000269|PubMed:12119386,
CC ECO:0000269|PubMed:15522820, ECO:0000269|PubMed:15995173,
CC ECO:0000303|PubMed:32679672}.
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, ERG26 and ERG27. Also interacts with ERG1, ERG3,
CC ERG5, ERG6 and ERG11. {ECO:0000269|PubMed:12119386,
CC ECO:0000269|PubMed:15522820, ECO:0000269|PubMed:15995173}.
CC -!- INTERACTION:
CC P40030; P53045: ERG25; NbExp=3; IntAct=EBI-22518, EBI-6506;
CC P40030; P53199: ERG26; NbExp=3; IntAct=EBI-22518, EBI-6514;
CC P40030; Q12452: ERG27; NbExp=6; IntAct=EBI-22518, EBI-38132;
CC P40030; P51533: PDR10; NbExp=2; IntAct=EBI-22518, EBI-3761544;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:12119386}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:12119386}.
CC -!- MISCELLANEOUS: Present with 377 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the ERG28 family. {ECO:0000305}.
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DR EMBL; U18796; AAB64579.1; -; Genomic_DNA.
DR EMBL; AY558453; AAS56779.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07698.1; -; Genomic_DNA.
DR PIR; S50547; S50547.
DR RefSeq; NP_010962.1; NM_001178935.1.
DR AlphaFoldDB; P40030; -.
DR BioGRID; 36780; 33.
DR DIP; DIP-2672N; -.
DR IntAct; P40030; 14.
DR MINT; P40030; -.
DR STRING; 4932.YER044C; -.
DR MaxQB; P40030; -.
DR PaxDb; P40030; -.
DR PRIDE; P40030; -.
DR EnsemblFungi; YER044C_mRNA; YER044C; YER044C.
DR GeneID; 856767; -.
DR KEGG; sce:YER044C; -.
DR SGD; S000000846; ERG28.
DR VEuPathDB; FungiDB:YER044C; -.
DR eggNOG; KOG3455; Eukaryota.
DR GeneTree; ENSGT00390000010925; -.
DR HOGENOM; CLU_114589_0_0_1; -.
DR InParanoid; P40030; -.
DR OMA; SEWLIFG; -.
DR BioCyc; MetaCyc:MON3O-271; -.
DR BioCyc; YEAST:MON3O-271; -.
DR PRO; PR:P40030; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P40030; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:SGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IDA:SGD.
DR InterPro; IPR005352; Erg28.
DR PANTHER; PTHR15451; PTHR15451; 1.
DR Pfam; PF03694; Erg28; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..148
FT /note="Ergosterol biosynthetic protein 28"
FT /id="PRO_0000193908"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 47..92
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 114..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..148
FT /note="Lumenal"
FT /evidence="ECO:0000255"
SQ SEQUENCE 148 AA; 17135 MW; F1BD39AFA180E367 CRC64;
MFSLQDVITT TKTTLAAMPK GYLPKWLLFI SIVSVFNSIQ TYVSGLELTR KVYERKPTET
THLSARTFGT WTFISCVIRF YGAMYLNEPH IFELVFMSYM VALFHFGSEL LIFRTCKLGK
GFMGPLVVST TSLVWMYKQR EYYTGVAW
