I1S4E7 · ERG26_GIBZE
- ProteinSterol-4-alpha-carboxylate 3-dehydrogenase ERG26, decarboxylating
- GeneERG26
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids303 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
function
Sterol-4-alpha-carboxylate 3-dehydrogenase; part of the third module of ergosterol biosynthesis pathway that includes the late steps of the pathway (By similarity).
ERG26 is a catalytic component of the C-4 demethylation complex that catalyzes the conversion of 4,4-dimethylfecosterol into fecosterol via 4-methylfecosterol (By similarity).
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, squalene is converted into lanosterol by the consecutive action of the squalene epoxidase ERG1 and the lanosterol synthase ERG7. Then, the delta24-sterol C-methyltransferase ERG6 methylates lanosterol at C-24 to produce eburicol. Eburicol is the substrate of the sterol 14-alpha demethylase encoded by CYP51A, CYP51B and CYP51C, to yield 4,4,24-trimethyl ergosta-8,14,2428-trienol. CYP51B encodes the enzyme primarily responsible for sterol 14-alpha-demethylation, and plays an essential role in ascospore formation. CYP51A encodes an additional sterol 14-alpha-demethylase, induced on ergosterol depletion and responsible for the intrinsic variation in azole sensitivity. The third CYP51 isoform, CYP51C, does not encode a sterol 14-alpha-demethylase, but is required for full virulence on host wheat ears. The C-14 reductase ERG24 then reduces the C14=C15 double bond which leads to 4,4-dimethylfecosterol. A sequence of further demethylations at C-4, involving the C-4 demethylation complex containing the C-4 methylsterol oxidases ERG25, the sterol-4-alpha-carboxylate 3-dehydrogenase ERG26 and the 3-keto-steroid reductase ERG27, leads to the production of fecosterol via 4-methylfecosterol. ERG28 has a role as a scaffold to help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum. The C-8 sterol isomerase ERG2 then 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-desaturases ERG3A and ERG3BB then catalyze the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturases ERG5A and ERG5B further convert 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).
ERG26 is a catalytic component of the C-4 demethylation complex that catalyzes the conversion of 4,4-dimethylfecosterol into fecosterol via 4-methylfecosterol (By similarity).
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, squalene is converted into lanosterol by the consecutive action of the squalene epoxidase ERG1 and the lanosterol synthase ERG7. Then, the delta24-sterol C-methyltransferase ERG6 methylates lanosterol at C-24 to produce eburicol. Eburicol is the substrate of the sterol 14-alpha demethylase encoded by CYP51A, CYP51B and CYP51C, to yield 4,4,24-trimethyl ergosta-8,14,2428-trienol. CYP51B encodes the enzyme primarily responsible for sterol 14-alpha-demethylation, and plays an essential role in ascospore formation. CYP51A encodes an additional sterol 14-alpha-demethylase, induced on ergosterol depletion and responsible for the intrinsic variation in azole sensitivity. The third CYP51 isoform, CYP51C, does not encode a sterol 14-alpha-demethylase, but is required for full virulence on host wheat ears. The C-14 reductase ERG24 then reduces the C14=C15 double bond which leads to 4,4-dimethylfecosterol. A sequence of further demethylations at C-4, involving the C-4 demethylation complex containing the C-4 methylsterol oxidases ERG25, the sterol-4-alpha-carboxylate 3-dehydrogenase ERG26 and the 3-keto-steroid reductase ERG27, leads to the production of fecosterol via 4-methylfecosterol. ERG28 has a role as a scaffold to help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum. The C-8 sterol isomerase ERG2 then 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-desaturases ERG3A and ERG3BB then catalyze the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturases ERG5A and ERG5B further convert 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
In Fusarium, the biosynthesis pathway of the sterol precursors leading to the prevalent sterol ergosterol differs from yeast. The ringsystem of lanosterol in S.cerevisiae is firstly demethylised in three enzymatic steps leading to the intermediate zymosterol and secondly a methyl group is added to zymosterol by the sterol 24-C-methyltransferase to form fecosterol. In Fusarium, lanosterol is firstly transmethylated by the sterol 24-C-methyltransferase leading to the intermediate eburicol and secondly demethylated in three steps to form fecosterol.
Pathway
Steroid metabolism; ergosterol biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 8-9 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SL | ||||||
Binding site | 30-32 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: TAS | ||||||
Binding site | 71 | substrate | ||||
Sequence: S | ||||||
Binding site | 102 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 102 | substrate | ||||
Sequence: Y | ||||||
Active site | 106 | Proton donor | ||||
Sequence: K | ||||||
Binding site | 106 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 128-131 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: IPGI |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | |
Biological Process | sterol biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSterol-4-alpha-carboxylate 3-dehydrogenase ERG26, decarboxylating
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Hypocreomycetidae > Hypocreales > Nectriaceae > Fusarium
Accessions
- Primary accessionI1S4E7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000454364 | 1-303 | Sterol-4-alpha-carboxylate 3-dehydrogenase ERG26, decarboxylating | |||
Sequence: MPKLQLRSLASQDKIEEIFERFKPHAVIHTASPSYMDTKKTLMSKNVDGTKALLEAARTCSDTKAFVFTSSDEAIMPTQEPTSEENAHRYDENNAPNAPNTYALSKALAKRLVIAANSEELYTSVIRIPGIYGKYDDNFIPQLVSSMREKEHKMQVGNNTKVFEFLYVNKAAEAHIMAMKALLNPSTRDQVGGEDFFISDGKPQGLFDFCRRIYAAAGSPVRPEEVTSIPLSVMQTMASTMEWVYWVFTLGTVQPSLRRISMDHLDTGCCWSLDKARRILGYEPVQDQDKVIERTMDWTMKTF |
Interaction
Subunit
Heterotetramer of ERG25, ERG26, ERG27 and ERG28 (By similarity).
ERG28 acts as a scaffold to tether ERG27 and other 4,4-demethylation-related enzymes, forming a demethylation enzyme complex, in the endoplasmic reticulum (By similarity).
ERG28 acts as a scaffold to tether ERG27 and other 4,4-demethylation-related enzymes, forming a demethylation enzyme complex, in the endoplasmic reticulum (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Sequence
- Sequence statusComplete
- Length303
- Mass (Da)34,289
- Last updated2012-06-13 v1
- ChecksumA8C88BAC11EAEEAC
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
HG970332 EMBL· GenBank· DDBJ | CEF72100.1 EMBL· GenBank· DDBJ | Genomic DNA |