O93875 · ERG3_CANAX
- ProteinDelta(7)-sterol 5(6)-desaturase
- GeneERG3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids386 (go to sequence)
- Protein existenceEvidence at transcript 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 pathwa (PubMed:10433965, PubMed:20733039, PubMed:9000517).
ERG3 catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol (PubMed:10433965).
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 (Probable).
ERG3 catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol (PubMed:10433965).
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 (Probable).
Miscellaneous
Defects in C-5 sterol desaturation results in antibiotic and azole resistance of Candida albicans during infection, particularly in AIDS patients.
Catalytic activity
- a Delta7-sterol + 2 Fe(II)-[cytochrome b5] + O2 + 2 H+ = a Delta5,Delta7-sterol + 2 Fe(III)-[cytochrome b5] + 2 H2OThis reaction proceeds in the forward direction.
Cofactor
Pathway
Steroid metabolism; ergosterol biosynthesis; ergosterol from zymosterol: step 3/5.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum lumen | |
Cellular Component | endoplasmic reticulum 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 |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDelta(7)-sterol 5(6)-desaturase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Debaryomycetaceae > Candida/Lodderomyces clade > Candida
Accessions
- Primary accessionO93875
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Transmembrane | 120-140 | Helical | |||
Transmembrane | 172-192 | Helical | |||
Transmembrane | 206-226 | Helical | |||
Transmembrane | 272-292 | Helical | |||
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Natural variant | 97 | in strain: azole-resistant isolates | |||
Natural variant | 147 | in strain: azole-resistant isolates | |||
Natural variant | 193 | in strain: azole-resistant isolates | |||
Natural variant | 237 | in strain: azole-resistant isolates | |||
Natural variant | 243 | in strain: azole-resistant isolates | |||
Natural variant | 330 | in strain: azole-resistant isolates | |||
Natural variant | 353 | in strain: azole-resistant isolates | |||
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 7 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000117020 | 1-386 | Delta7-sterol 56-desaturase | ||
Expression
Induction
Expression is repressed during spider biofilm formation.
Interaction
Chemistry
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 214-337 | Fatty acid hydroxylase | |||
Motif | 226-230 | Histidine box-1 | |||
Motif | 239-243 | Histidine box-2 | |||
Motif | 314-318 | Histidine box-3 | |||
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
Family and domain databases
Sequence
- Sequence statusComplete
- Length386
- Mass (Da)45,447
- Last updated1999-05-01 v1
- MD5 ChecksumBBC85BF91A89D4053F76E8DC60A2219A
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF069752 EMBL· GenBank· DDBJ | AAC99343.1 EMBL· GenBank· DDBJ | Genomic DNA |