P32353 · ERG3_YEAST
- ProteinDelta(7)-sterol 5(6)-desaturase ERG3
- GeneERG3
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids365 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
C-5 sterol desaturase; part of the third module of ergosterol biosynthesis pathway that includes the late steps of the pathway (PubMed:1864507).
ERG3 catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol (PubMed:1864507).
The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to form squalene, which is the precursor of all steroids. Squalene synthase is crucial for balancing the incorporation of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene synthesis. 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. Then, the lanosterol synthase ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol core. In the next steps, lanosterol is transformed to zymosterol through a complex process involving various demethylation, reduction and desaturation reactions. 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. 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. 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. 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. Then, the sterol 24-C-methyltransferase ERG6 catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to form fecosterol. 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. The sterol-C5-desaturase ERG3 then catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturase ERG5 further converts 5-dehydroepisterol into ergosta-5,7,22,2428-tetraen-3beta-ol by forming the C-2223 double bond in the sterol side chain. Finally, ergosta-5,7,22,2428-tetraen-3beta-ol is substrate of the C-2428 sterol reductase ERG4 to produce ergosterol (PubMed:32679672).
ERG3 catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol (PubMed:1864507).
The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to form squalene, which is the precursor of all steroids. Squalene synthase is crucial for balancing the incorporation of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene synthesis. 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. Then, the lanosterol synthase ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol core. In the next steps, lanosterol is transformed to zymosterol through a complex process involving various demethylation, reduction and desaturation reactions. 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. 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. 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. 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. Then, the sterol 24-C-methyltransferase ERG6 catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to form fecosterol. 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. The sterol-C5-desaturase ERG3 then catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturase ERG5 further converts 5-dehydroepisterol into ergosta-5,7,22,2428-tetraen-3beta-ol by forming the C-2223 double bond in the sterol side chain. Finally, ergosta-5,7,22,2428-tetraen-3beta-ol is substrate of the C-2428 sterol reductase ERG4 to produce ergosterol (PubMed:32679672).
Miscellaneous
Present with 36200 molecules/cell in log phase SD medium.
Catalytic activity
- episterol + 2 Fe(II)-[cytochrome b5] + O2 + 2 H+ = 5-dehydroepisterol + 2 Fe(III)-[cytochrome b5] + 2 H2OThis reaction proceeds in the forward direction.
Cofactor
Biotechnology
Engineered yeast lacking this enzyme have an increased tolerance to the phamaceutical aescin (escine), and could therefore be useful in the production of aescin at industrial scale.
Pathway
Steroid metabolism; ergosterol biosynthesis; ergosterol from zymosterol: step 3/5.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum lumen | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | membrane | |
Molecular Function | C-5 sterol desaturase activity | |
Molecular Function | delta7-sterol 5(6)-desaturase activity | |
Molecular Function | iron ion binding | |
Biological Process | ergosterol biosynthetic process | |
Biological Process | sterol biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDelta(7)-sterol 5(6)-desaturase ERG3
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionP32353
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-92 | Cytoplasmic | ||||
Sequence: MDLVLEVADHYVLDDLYAKVLPASLAANIPVKWQKLLGLNSGFSNSTILQETLNSKNAVKECRRFYGQVPFLFDMSTTSFASLLPRSSILRE | ||||||
Transmembrane | 93-113 | Helical | ||||
Sequence: FLSLWVIVTIFGLLLYLFTAS | ||||||
Topological domain | 114-140 | Lumenal | ||||
Sequence: LSYVFVFDKSIFNHPRYLKNQMAMEIK | ||||||
Transmembrane | 141-161 | Helical | ||||
Sequence: LAVSAIPWMSMLTVPWFVMEL | ||||||
Topological domain | 162-242 | Cytoplasmic | ||||
Sequence: NGHSKLYMKIDYENHGVRKLIIEYFTFIFFTDCGVYLAHRWLHWPRVYRALHKPHHKWLVCTPFASHSFHPVDGFLQSISY | ||||||
Transmembrane | 243-263 | Helical | ||||
Sequence: HIYPLILPLHKVSYLILFTFV | ||||||
Topological domain | 264-365 | Lumenal | ||||
Sequence: NFWTVMIHDGQYLSNNPAVNGTACHTVHHLYFNYNYGQFTTLWDRLGGSYRRPDDSLFDPKLRDAKETWDAQVKEVEHFIKEVEGDDNDRIYENDPNTKKNN |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000117027 | 1-365 | Delta7-sterol 56-desaturase ERG3 | |||
Sequence: MDLVLEVADHYVLDDLYAKVLPASLAANIPVKWQKLLGLNSGFSNSTILQETLNSKNAVKECRRFYGQVPFLFDMSTTSFASLLPRSSILREFLSLWVIVTIFGLLLYLFTASLSYVFVFDKSIFNHPRYLKNQMAMEIKLAVSAIPWMSMLTVPWFVMELNGHSKLYMKIDYENHGVRKLIIEYFTFIFFTDCGVYLAHRWLHWPRVYRALHKPHHKWLVCTPFASHSFHPVDGFLQSISYHIYPLILPLHKVSYLILFTFVNFWTVMIHDGQYLSNNPAVNGTACHTVHHLYFNYNYGQFTTLWDRLGGSYRRPDDSLFDPKLRDAKETWDAQVKEVEHFIKEVEGDDNDRIYENDPNTKKNN | ||||||
Cross-link | 324 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 344 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
The ERG3 promoter contains 2 upstream activation sequences, UAS1 and UAS2 (PubMed:8772195).
UAS1 regulates gene expression but does not affect sterol regulation (PubMed:8772195).
UAS2 is required for sterol regulation (PubMed:8772195).
The absence of sterol esterification leads to a decrease of ERG3 expression (PubMed:8772195).
UAS1 regulates gene expression but does not affect sterol regulation (PubMed:8772195).
UAS2 is required for sterol regulation (PubMed:8772195).
The absence of sterol esterification leads to a decrease of ERG3 expression (PubMed:8772195).
Interaction
Subunit
Interacts with ERG28.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P32353 | ERG25 P53045 | 3 | EBI-6554, EBI-6506 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 187-311 | Fatty acid hydroxylase | ||||
Sequence: TFIFFTDCGVYLAHRWLHWPRVYRALHKPHHKWLVCTPFASHSFHPVDGFLQSISYHIYPLILPLHKVSYLILFTFVNFWTVMIHDGQYLSNNPAVNGTACHTVHHLYFNYNYGQFTTLWDRLGG | ||||||
Motif | 200-204 | Histidine box-1 | ||||
Sequence: HRWLH | ||||||
Motif | 213-217 | Histidine box-2 | ||||
Sequence: HKPHH | ||||||
Motif | 288-292 | Histidine box-3 | ||||
Sequence: HTVHH |
Domain
The histidine box domains may contain the active site and/or be involved in metal ion binding.
Sequence similarities
Belongs to the sterol desaturase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length365
- Mass (Da)42,730
- Last updated1993-10-01 v1
- Checksum7F441DA6927A711C
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M62623 EMBL· GenBank· DDBJ | AAA34594.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S46162 EMBL· GenBank· DDBJ | AAB39844.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M64989 EMBL· GenBank· DDBJ | AAA34595.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
D14299 EMBL· GenBank· DDBJ | BAA20292.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X94607 EMBL· GenBank· DDBJ | CAA64303.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z73228 EMBL· GenBank· DDBJ | CAA97586.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY692996 EMBL· GenBank· DDBJ | AAT93015.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006945 EMBL· GenBank· DDBJ | DAA09374.1 EMBL· GenBank· DDBJ | Genomic DNA |