UniProtKB - P53045 (ERG25_YEAST)
C-4 methylsterol oxidase ERG25
ERG25
Functioni
C-4 methylsterol oxidase; part of the third module of ergosterol biosynthesis pathway that includes the late steps of the pathway (PubMed:8552601, PubMed:12880870) (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. 10). 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 Publication23 PublicationsMiscellaneous
Catalytic activityi
- 4,4-dimethyl-5α-cholesta-8,24-dien-3β-ol + 6 Fe(II)-[cytochrome b5] + 5 H+ + 3 O2 = 4β-methylzymosterol-4α-carboxylate + 6 Fe(III)-[cytochrome b5] + 4 H2O2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 4α-methylzymosterol + 6 Fe(II)-[cytochrome b5] + 5 H+ + 3 O2 = 4α-carboxyzymosterol + 6 Fe(III)-[cytochrome b5] + 4 H2O1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
: zymosterol biosynthesis Pathwayi
This protein is involved in step 3 of the subpathway that synthesizes zymosterol from lanosterol.2 Publications This subpathway is part of the pathway zymosterol biosynthesis, which is itself part of Steroid biosynthesis.View all proteins of this organism that are known to be involved in the subpathway that synthesizes zymosterol from lanosterol, the pathway zymosterol biosynthesis and in Steroid biosynthesis.
Pathwayi: ergosterol biosynthesis
This protein is involved in the pathway ergosterol biosynthesis, which is part of Steroid metabolism.2 PublicationsView all proteins of this organism that are known to be involved in the pathway ergosterol biosynthesis and in Steroid metabolism.
GO - Molecular functioni
- C-4 methylsterol oxidase activity Source: SGD
- iron ion binding Source: InterPro
- oxidoreductase activity Source: GO_Central
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 | Iron, NAD |
Enzyme and pathway databases
Reactomei | R-SCE-191273, Cholesterol biosynthesis R-SCE-192105, Synthesis of bile acids and bile salts |
UniPathwayi | UPA00768 UPA00770;UER00756 |
Names & Taxonomyi
Protein namesi | Recommended name: C-4 methylsterol oxidase ERG251 Publication (EC:1.14.18.-2 Publications)Alternative name(s): Ergosterol biosynthetic protein 251 Publication Sterol-C4-methyl oxidase ERG251 Publication Short name: SMO1 Publication |
Gene namesi | Ordered Locus Names:YGR060W |
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 | S000003292, ERG25 |
VEuPathDBi | FungiDB:YGR060W |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 3 Publications; Single-pass membrane protein 3 Publications
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: SGD
Plasma Membrane
- plasma membrane Source: SGD
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 56 – 76 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000117039 | 1 – 309 | C-4 methylsterol oxidase ERG25Add BLAST | 309 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 96 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources |
Keywords - PTMi
Isopeptide bond, Ubl conjugationProteomic databases
MaxQBi | P53045 |
PaxDbi | P53045 |
PRIDEi | P53045 |
PTM databases
iPTMneti | P53045 |
Interactioni
Subunit structurei
Heterotetramer of ERG25, ERG26, ERG27 and ERG28. ERG28 acts as a scaffold to tether ERG27 and other 4,4-demethylation-related enzymes, forming a demethylation enzyme complex, in the endoplasmic reticulum.
Interacts with ERG27 and ERG28.
2 PublicationsBinary interactionsi
P53045
With | #Exp. | IntAct |
---|---|---|
ERG11 [P10614] | 3 | EBI-6506,EBI-5127 |
ERG27 [Q12452] | 4 | EBI-6506,EBI-38132 |
ERG28 [P40030] | 3 | EBI-6506,EBI-22518 |
ERG3 [P32353] | 3 | EBI-6506,EBI-6554 |
Protein-protein interaction databases
BioGRIDi | 33305, 314 interactors |
DIPi | DIP-2799N |
IntActi | P53045, 60 interactors |
MINTi | P53045 |
STRINGi | 4932.YGR060W |
Miscellaneous databases
RNActi | P53045, protein |
Structurei
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 147 – 282 | Fatty acid hydroxylaseSequence analysisAdd BLAST | 136 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 287 – 309 | DisorderedSequence analysisAdd BLAST | 23 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 160 – 164 | Histidine box-11 Publication | 5 | |
Motifi | 173 – 177 | Histidine box-21 Publication | 5 | |
Motifi | 257 – 263 | Histidine box-31 Publication | 7 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0873, Eukaryota |
GeneTreei | ENSGT00940000158012 |
HOGENOMi | CLU_047036_5_0_1 |
InParanoidi | P53045 |
OMAi | PGFIFQF |
Family and domain databases
InterProi | View protein in InterPro IPR006694, Fatty_acid_hydroxylase |
Pfami | View protein in Pfam PF04116, FA_hydroxylase, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MSAVFNNATL SGLVQASTYS QTLQNVAHYQ PQLNFMEKYW AAWYSYMNND
60 70 80 90 100
VLATGLMFFL LHEFMYFFRC LPWFIIDQIP YFRRWKLQPT KIPSAKEQLY
110 120 130 140 150
CLKSVLLSHF LVEAIPIWTF HPMCEKLGIT VEVPFPSLKT MALEIGLFFV
160 170 180 190 200
LEDTWHYWAH RLFHYGVFYK YIHKQHHRYA APFGLSAEYA HPAETLSLGF
210 220 230 240 250
GTVGMPILYV MYTGKLHLFT LCVWITLRLF QAVDSHSGYD FPWSLNKIMP
260 270 280 290 300
FWAGAEHHDL HHHYFIGNYA SSFRWWDYCL DTESGPEAKA SREERMKKRA
ENNAQKKTN
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 302 | N → K in AAS56153 (PubMed:17322287).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U31885 Genomic DNA Translation: AAC49139.1 DQ115391 Genomic DNA Translation: AAZ22473.1 Z72845 Genomic DNA Translation: CAA97062.1 AY557827 Genomic DNA Translation: AAS56153.1 BK006941 Genomic DNA Translation: DAA08156.1 |
PIRi | S64354 |
RefSeqi | NP_011574.3, NM_001181189.3 |
Genome annotation databases
EnsemblFungii | YGR060W_mRNA; YGR060W; YGR060W |
GeneIDi | 852951 |
KEGGi | sce:YGR060W |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U31885 Genomic DNA Translation: AAC49139.1 DQ115391 Genomic DNA Translation: AAZ22473.1 Z72845 Genomic DNA Translation: CAA97062.1 AY557827 Genomic DNA Translation: AAS56153.1 BK006941 Genomic DNA Translation: DAA08156.1 |
PIRi | S64354 |
RefSeqi | NP_011574.3, NM_001181189.3 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 33305, 314 interactors |
DIPi | DIP-2799N |
IntActi | P53045, 60 interactors |
MINTi | P53045 |
STRINGi | 4932.YGR060W |
PTM databases
iPTMneti | P53045 |
Proteomic databases
MaxQBi | P53045 |
PaxDbi | P53045 |
PRIDEi | P53045 |
Genome annotation databases
EnsemblFungii | YGR060W_mRNA; YGR060W; YGR060W |
GeneIDi | 852951 |
KEGGi | sce:YGR060W |
Organism-specific databases
SGDi | S000003292, ERG25 |
VEuPathDBi | FungiDB:YGR060W |
Phylogenomic databases
eggNOGi | KOG0873, Eukaryota |
GeneTreei | ENSGT00940000158012 |
HOGENOMi | CLU_047036_5_0_1 |
InParanoidi | P53045 |
OMAi | PGFIFQF |
Enzyme and pathway databases
UniPathwayi | UPA00768 UPA00770;UER00756 |
Reactomei | R-SCE-191273, Cholesterol biosynthesis R-SCE-192105, Synthesis of bile acids and bile salts |
Miscellaneous databases
PROi | PR:P53045 |
RNActi | P53045, protein |
Family and domain databases
InterProi | View protein in InterPro IPR006694, Fatty_acid_hydroxylase |
Pfami | View protein in Pfam PF04116, FA_hydroxylase, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ERG25_YEAST | |
Accessioni | P53045Primary (citable) accession number: P53045 Secondary accession number(s): D6VUJ5, E9P8T3, Q45U26 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 177 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
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