P10614 · CP51_YEAST
- ProteinLanosterol 14-alpha demethylase CYP51
- GeneERG11
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids530 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Sterol 14alpha-demethylase that plays a critical role in the third module of ergosterol biosynthesis pathway, being ergosterol the major sterol component in fungal membranes that participates in a variety of functions (PubMed:105731, PubMed:369554). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane (PubMed:32679672).
Starting from lanosterol (lanosta-8,24-dien-3beta-ol), it catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of the sterol in the form of formate, and converts the sterol to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, which is critical for ergosterol biosynthesis (PubMed:105731, PubMed:3543000, PubMed:369554). Can demethylate substrates not intrinsic to yeast, such as eburicol (24-methylene-24,25-dihydrolanosterol) at a similar rate to lanosterol, and at a lower rate the 24,25-dihydrolanosterol (DHL) to 4,4-dimethyl-8,14-cholestadien-3beta-ol (PubMed:1872829, PubMed:3543000).
Starting from lanosterol (lanosta-8,24-dien-3beta-ol), it catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of the sterol in the form of formate, and converts the sterol to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, which is critical for ergosterol biosynthesis (PubMed:105731, PubMed:3543000, PubMed:369554). Can demethylate substrates not intrinsic to yeast, such as eburicol (24-methylene-24,25-dihydrolanosterol) at a similar rate to lanosterol, and at a lower rate the 24,25-dihydrolanosterol (DHL) to 4,4-dimethyl-8,14-cholestadien-3beta-ol (PubMed:1872829, PubMed:3543000).
Miscellaneous
It is the main target for antifungal compounds of the triazole family like ketoconazole which inhibits by coordinating the iron atom at the sixth ligand position.
Present with 73200 molecules/cell in log phase SD medium.
Catalytic activity
- a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] = a Delta14 steroid + formate + 4 H+ + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- a 14alpha-methyl steroid + O2 + reduced [NADPH--hemoprotein reductase] = a 14alpha-hydroxymethyl steroid + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- a 14alpha-hydroxymethyl steroid + O2 + reduced [NADPH--hemoprotein reductase] = a 14alpha-formyl steroid + H+ + 2 H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- a 14alpha-formyl steroid + O2 + reduced [NADPH--hemoprotein reductase] = a Delta14 steroid + formate + 2 H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- lanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-hydroxylanosterol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 32-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-oxolanosterol + H+ + 2 H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 32-oxolanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 2 H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
6.7 μM | lanosterol | |||||
8.7 μM | eburicol |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
11.8 nmol/min/nmol | with lanosterol | ||||
16.7 nmol/min/nmol | with eburicol |
Pathway
Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 1/6.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | oxidoreductase activity | |
Molecular Function | sterol 14-demethylase activity | |
Biological Process | ergosterol biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLanosterol 14-alpha demethylase CYP51
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionP10614
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-20 | Lumenal | ||||
Sequence: MSATKSIVGEALEYVNIGLS | ||||||
Transmembrane | 21-41 | Helical | ||||
Sequence: HFLALPLAQRISLIIIIPFIY | ||||||
Topological domain | 42-530 | Cytoplasmic | ||||
Sequence: NIVWQLLYSLRKDRPPLVFYWIPWVGSAVVYGMKPYEFFEECQKKYGDIFSFVLLGRVMTVYLGPKGHEFVFNAKLADVSAEAAYAHLTTPVFGKGVIYDCPNSRLMEQKKFVKGALTKEAFKSYVPLIAEEVYKYFRDSKNFRLNERTTGTIDVMVTQPEMTIFTASRSLLGKEMRAKLDTDFAYLYSDLDKGFTPINFVFPNLPLEHYRKRDHAQKAISGTYMSLIKERRKNNDIQDRDLIDSLMKNSTYKDGVKMTDQEIANLLIGVLMGGQHTSAATSAWILLHLAERPDVQQELYEEQMRVLDGGKKELTYDLLQEMPLLNQTIKETLRMHHPLHSLFRKVMKDMHVPNTSYVIPAGYHVLVSPGYTHLRDEYFPNAHQFNIHRWNKDSASSYSVGEEVDYGFGAISKGVSSPYLPFGGGRHRCIGEHFAYCQLGVLMSIFIRTLKWHYPEGKTVPPPDFTSMVTLPTGPAKIIWEKRNPEQKI |
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000052012 | 1-530 | Lanosterol 14-alpha demethylase CYP51 | |||
Sequence: MSATKSIVGEALEYVNIGLSHFLALPLAQRISLIIIIPFIYNIVWQLLYSLRKDRPPLVFYWIPWVGSAVVYGMKPYEFFEECQKKYGDIFSFVLLGRVMTVYLGPKGHEFVFNAKLADVSAEAAYAHLTTPVFGKGVIYDCPNSRLMEQKKFVKGALTKEAFKSYVPLIAEEVYKYFRDSKNFRLNERTTGTIDVMVTQPEMTIFTASRSLLGKEMRAKLDTDFAYLYSDLDKGFTPINFVFPNLPLEHYRKRDHAQKAISGTYMSLIKERRKNNDIQDRDLIDSLMKNSTYKDGVKMTDQEIANLLIGVLMGGQHTSAATSAWILLHLAERPDVQQELYEEQMRVLDGGKKELTYDLLQEMPLLNQTIKETLRMHHPLHSLFRKVMKDMHVPNTSYVIPAGYHVLVSPGYTHLRDEYFPNAHQFNIHRWNKDSASSYSVGEEVDYGFGAISKGVSSPYLPFGGGRHRCIGEHFAYCQLGVLMSIFIRTLKWHYPEGKTVPPPDFTSMVTLPTGPAKIIWEKRNPEQKI | ||||||
Cross-link | 116 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 353 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 454 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 458 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Expression is increased during growth on glucose, in the presence of heme, and during oxygen limiting growth conditions and, unexpectedly, during anaerobic growth (PubMed:1730736).
Two upstream activating sequences, UASl and UASZ, and an upstream repressor element, URS1, plus a second possible or cryptic repressor element, URSP, are present in promoter (PubMed:1730736).
HAP1 participates in activation from UASl but not from UAS2, whereas the ROXl repressor represses expressio of ERG11 (PubMed:1730736).
Two upstream activating sequences, UASl and UASZ, and an upstream repressor element, URS1, plus a second possible or cryptic repressor element, URSP, are present in promoter (PubMed:1730736).
HAP1 participates in activation from UASl but not from UAS2, whereas the ROXl repressor represses expressio of ERG11 (PubMed:1730736).
Interaction
Subunit
Interacts with ERG28.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P10614 | ERG25 P53045 | 3 | EBI-5127, EBI-6506 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length530
- Mass (Da)60,720
- Last updated1989-07-01 v1
- Checksum646960BBA0E17979
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 433 | in Ref. 2; AAA34546/AAA34547 | ||||
Sequence: K → N |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M18109 EMBL· GenBank· DDBJ | AAA34379.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21483 EMBL· GenBank· DDBJ | AAA34546.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21484 EMBL· GenBank· DDBJ | AAA34547.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M15663 EMBL· GenBank· DDBJ | AAA34837.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
U10555 EMBL· GenBank· DDBJ | AAB68433.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006934 EMBL· GenBank· DDBJ | DAA06695.1 EMBL· GenBank· DDBJ | Genomic DNA |