UniProtKB - P32476 (ERG1_YEAST)
Squalene epoxidase ERG1
ERG1
Functioni
Squalene epoxidase; part of the third module of ergosterol biosynthesis pathway that includes the late steps of the pathway (PubMed:1743514, PubMed:8358382, PubMed:9450962) (Probable).
The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane (Probable). Firstly, the squalene synthase ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to form squalene, which is the precursor of all steroids (PubMed:1807826, PubMed:8323279).
Squalene synthase is crucial for balancing the incorporation of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene synthesis (PubMed:9742963).
Secondly, the squalene epoxidase ERG1 catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, which is considered to be a rate-limiting enzyme in steroid biosynthesis (PubMed:1743514, PubMed:8358382, PubMed:9450962).
Then, the lanosterol synthase ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol core (PubMed:1731628, PubMed:12842197).
In the next steps, lanosterol is transformed to zymosterol through a complex process involving various demethylation, reduction and desaturation reactions (Probable). The lanosterol 14-alpha-demethylase ERG11 (also known as CYP51) catalyzes C14-demethylation of lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol, which is critical for ergosterol biosynthesis (PubMed:369554, PubMed:105731).
The C-14 reductase ERG24 reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4-dimethyl-cholesta-8,24-dienol (PubMed:8125337).
4,4-dimethyl-cholesta-8,24-dienol is substrate of the C-4 demethylation complex ERG25-ERG26-ERG27 in which ERG25 catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, ERG26 catalyzes the oxidative decarboxylation that results in a reduction of the 3-beta-hydroxy group at the C-3 carbon to an oxo group, and ERG27 is responsible for the reduction of the keto group on the C-3 (PubMed:8663358, PubMed:12880870).
ERG28 has a role as a scaffold to help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and ERG29 regulates the activity of the iron-containing C4-methylsterol oxidase ERG25 (PubMed:12119386, PubMed:15522820, PubMed:15995173, PubMed:29773647).
Then, the sterol 24-C-methyltransferase ERG6 catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to form fecosterol (PubMed:6363386).
The C-8 sterol isomerase ERG2 catalyzes the reaction which results in unsaturation at C-7 in the B ring of sterols and thus converts fecosterol to episterol (Ref. 9). The sterol-C5-desaturase ERG3 then catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol (PubMed:1864507).
The C-22 sterol desaturase ERG5 further converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double bond in the sterol side chain (PubMed:8543054, PubMed:8635732).
Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28) sterol reductase ERG4 to produce ergosterol (PubMed:8125337).
1 Publication22 PublicationsMiscellaneous
Catalytic activityi
- O2 + reduced [NADPH—hemoprotein reductase] + squalene = (S)-2,3-epoxysqualene + H+ + H2O + oxidized [NADPH—hemoprotein reductase]3 PublicationsEC:1.14.14.173 Publications
Cofactori
Activity regulationi
Kineticsi
- KM=13.5 µM for squalene1 Publication
pH dependencei
: lanosterol biosynthesis Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes lanosterol from farnesyl diphosphate.3 Publications This subpathway is part of the pathway lanosterol biosynthesis, which is itself part of Terpene metabolism.View all proteins of this organism that are known to be involved in the subpathway that synthesizes lanosterol from farnesyl diphosphate, the pathway lanosterol biosynthesis and in Terpene metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 56 | FADBy similarity | 1 | |
Sitei | 90 | Important for enzyme activityBy similarity | 1 | |
Binding sitei | 158 | FADBy similarity | 1 | |
Binding sitei | 335 | FADBy similarity | 1 | |
Binding sitei | 348 | FAD; via amide nitrogenBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 28 – 29 | FADBy similarity | 2 | |
Nucleotide bindingi | 48 – 49 | FADBy similarity | 2 |
GO - Molecular functioni
- flavin adenine dinucleotide binding Source: InterPro
- squalene monooxygenase activity Source: SGD
GO - Biological processi
- ergosterol biosynthetic process Source: SGD
- sterol biosynthetic process Source: GO_Central
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism |
Ligand | FAD, Flavoprotein |
Enzyme and pathway databases
Reactomei | R-SCE-191273, Cholesterol biosynthesis |
UniPathwayi | UPA00767;UER00752 |
Names & Taxonomyi
Protein namesi | Recommended name: Squalene epoxidase ERG11 Publication (EC:1.14.14.173 Publications)Short name: SE1 Publication Alternative name(s): Ergosterol biosynthetic protein 11 Publication Squalene monooxygenase ERG1Curated |
Gene namesi | Name:ERG11 Publication Ordered Locus Names:YGR175C |
Organismi | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
Taxonomic identifieri | 559292 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › |
Proteomesi |
|
Organism-specific databases
SGDi | S000003407, ERG1 |
VEuPathDBi | FungiDB:YGR175C |
Subcellular locationi
Endoplasmic reticulum
- Microsome membrane 1 Publication; Multi-pass membrane protein Curated
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein Curated
Other locations
- Lipid droplet 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: SGD
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB-KW
- lipid droplet Source: SGD
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 16 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 17 – 37 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 38 – 474 | LumenalSequence analysisAdd BLAST | 437 | |
Transmembranei | 475 – 495 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 496 | CytoplasmicSequence analysis | 1 |
Keywords - Cellular componenti
Endoplasmic reticulum, Lipid droplet, Membrane, MicrosomePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000209851 | 1 – 496 | Squalene epoxidase ERG1Add BLAST | 496 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 284 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 289 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources | ||
Cross-linki | 311 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources |
Keywords - PTMi
Isopeptide bond, Ubl conjugationProteomic databases
MaxQBi | P32476 |
PaxDbi | P32476 |
PRIDEi | P32476 |
TopDownProteomicsi | P32476 |
PTM databases
iPTMneti | P32476 |
Interactioni
Subunit structurei
Interacts with ERG28.
1 PublicationProtein-protein interaction databases
BioGRIDi | 33428, 73 interactors |
DIPi | DIP-6325N |
IntActi | P32476, 17 interactors |
MINTi | P32476 |
STRINGi | 4932.YGR175C |
Miscellaneous databases
RNActi | P32476, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1298, Eukaryota |
GeneTreei | ENSGT00390000011759 |
HOGENOMi | CLU_026390_0_0_1 |
InParanoidi | P32476 |
OMAi | KSKFWGL |
Family and domain databases
Gene3Di | 3.50.50.60, 1 hit |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR013698, Squalene_epoxidase IPR040125, Squalene_monox |
PANTHERi | PTHR10835, PTHR10835, 1 hit |
Pfami | View protein in Pfam PF08491, SE, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MSAVNVAPEL INADNTITYD AIVIGAGVIG PCVATGLARK GKKVLIVERD
60 70 80 90 100
WAMPDRIVGE LMQPGGVRAL RSLGMIQSIN NIEAYPVTGY TVFFNGEQVD
110 120 130 140 150
IPYPYKADIP KVEKLKDLVK DGNDKVLEDS TIHIKDYEDD ERERGVAFVH
160 170 180 190 200
GRFLNNLRNI TAQEPNVTRV QGNCIEILKD EKNEVVGAKV DIDGRGKVEF
210 220 230 240 250
KAHLTFICDG IFSRFRKELH PDHVPTVGSS FVGMSLFNAK NPAPMHGHVI
260 270 280 290 300
LGSDHMPILV YQISPEETRI LCAYNSPKVP ADIKSWMIKD VQPFIPKSLR
310 320 330 340 350
PSFDEAVSQG KFRAMPNSYL PARQNDVTGM CVIGDALNMR HPLTGGGMTV
360 370 380 390 400
GLHDVVLLIK KIGDLDFSDR EKVLDELLDY HFERKSYDSV INVLSVALYS
410 420 430 440 450
LFAADSDNLK ALQKGCFKYF QRGGDCVNKP VEFLSGVLPK PLQLTRVFFA
460 470 480 490
VAFYTIYLNM EERGFLGLPM ALLEGIMILI TAIRVFTPFL FGELIG
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 251 | L → F in strain: A2-M8; confers resistance to the allylamine antifungal terbinafine. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M64994 Genomic DNA Translation: AAA34592.1 Z72960 Genomic DNA Translation: CAA97201.1 BK006941 Genomic DNA Translation: DAA08271.1 |
PIRi | S64489 |
RefSeqi | NP_011691.1, NM_001181304.1 |
Genome annotation databases
EnsemblFungii | YGR175C_mRNA; YGR175C; YGR175C |
GeneIDi | 853086 |
KEGGi | sce:YGR175C |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M64994 Genomic DNA Translation: AAA34592.1 Z72960 Genomic DNA Translation: CAA97201.1 BK006941 Genomic DNA Translation: DAA08271.1 |
PIRi | S64489 |
RefSeqi | NP_011691.1, NM_001181304.1 |
3D structure databases
SMRi | P32476 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 33428, 73 interactors |
DIPi | DIP-6325N |
IntActi | P32476, 17 interactors |
MINTi | P32476 |
STRINGi | 4932.YGR175C |
Chemistry databases
ChEMBLi | CHEMBL1888 |
PTM databases
iPTMneti | P32476 |
Proteomic databases
MaxQBi | P32476 |
PaxDbi | P32476 |
PRIDEi | P32476 |
TopDownProteomicsi | P32476 |
Genome annotation databases
EnsemblFungii | YGR175C_mRNA; YGR175C; YGR175C |
GeneIDi | 853086 |
KEGGi | sce:YGR175C |
Organism-specific databases
SGDi | S000003407, ERG1 |
VEuPathDBi | FungiDB:YGR175C |
Phylogenomic databases
eggNOGi | KOG1298, Eukaryota |
GeneTreei | ENSGT00390000011759 |
HOGENOMi | CLU_026390_0_0_1 |
InParanoidi | P32476 |
OMAi | KSKFWGL |
Enzyme and pathway databases
UniPathwayi | UPA00767;UER00752 |
Reactomei | R-SCE-191273, Cholesterol biosynthesis |
Miscellaneous databases
PROi | PR:P32476 |
RNActi | P32476, protein |
Family and domain databases
Gene3Di | 3.50.50.60, 1 hit |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR013698, Squalene_epoxidase IPR040125, Squalene_monox |
PANTHERi | PTHR10835, PTHR10835, 1 hit |
Pfami | View protein in Pfam PF08491, SE, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ERG1_YEAST | |
Accessioni | P32476Primary (citable) accession number: P32476 Secondary accession number(s): D6VUW0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1993 |
Last sequence update: | October 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 196 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Yeast
Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD - Yeast chromosome VII
Yeast (Saccharomyces cerevisiae) chromosome VII: entries and gene names - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families