UniProtKB - P10614 (CP51_YEAST)
Lanosterol 14-alpha demethylase CYP51
ERG11
Functioni
Lanosterol 14-alpha demethylase; part of the third module of ergosterol biosynthesis pathway that includes the late steps of the pathway (PubMed:369554, PubMed:105731) (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. 9). 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 Publication22 PublicationsMiscellaneous
Catalytic activityi
- lanosterol + 3 O2 + 3 reduced [NADPH—hemoprotein reductase] = 4,4-dimethyl-5α-cholesta-8,14,24-trien-3β-ol + formate + 4 H+ + 4 H2O + 3 oxidized [NADPH—hemoprotein reductase]2 PublicationsEC:1.14.14.1542 PublicationsThis reaction proceeds in the forward2 Publications direction.
Cofactori
: zymosterol biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes zymosterol from lanosterol. 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.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 126 | LanosterolCombined sources1 Publication | 1 | |
Binding sitei | 314 | Itraconazole; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 470 | Iron (heme axial ligand)Combined sources1 Publication | 1 |
GO - Molecular functioni
- heme binding Source: InterPro
- iron ion binding Source: InterPro
- monooxygenase activity Source: GO_Central
- oxidoreductase activity Source: GO_Central
- sterol 14-demethylase activity Source: SGD
GO - Biological processi
- ergosterol biosynthetic process Source: SGD
- sterol metabolic process Source: GO_Central
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 1.14.14.154, 984 |
Reactomei | R-SCE-191273, Cholesterol biosynthesis R-SCE-211976, Endogenous sterols |
UniPathwayi | UPA00770;UER00754 |
Names & Taxonomyi
Protein namesi | Recommended name: Lanosterol 14-alpha demethylase CYP511 Publication (EC:1.14.14.1542 Publications)Alternative name(s): Cytochrome P450 51Curated Cytochrome P450-14DM1 Publication Cytochrome P450-LIA11 Publication Short name: CYPLI1 Publication Ergosterol biosynthetic protein 111 Publication Sterol 14-alpha demethylaseCurated |
Gene namesi | Ordered Locus Names:YHR007C |
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 | S000001049, ERG11 |
VEuPathDBi | FungiDB:YHR007C |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane Curated; Single-pass membrane protein 2 Publications
Endoplasmic reticulum
- endoplasmic reticulum Source: SGD
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 20 | Lumenal2 PublicationsAdd BLAST | 20 | |
Transmembranei | 21 – 41 | Helical2 PublicationsAdd BLAST | 21 | |
Topological domaini | 42 – 530 | Cytoplasmic2 PublicationsAdd BLAST | 489 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Chemistry databases
DrugBanki | DB06890, (2R)-2-PHENYL-N-PYRIDIN-4-YLBUTANAMIDE DB07568, (2S)-2-[(2,1,3-BENZOTHIADIAZOL-4-YLSULFONYL)AMINO]-2-PHENYL-N-PYRIDIN-4-YLACETAMIDE DB07572, 3-{[(4-methylphenyl)sulfonyl]amino}propyl pyridin-4-ylcarbamate DB07635, 4,4'-Dihydroxybenzophenone DB07569, CIS-4-METHYL-N-[(1S)-3-(METHYLSULFANYL)-1-(PYRIDIN-4-YLCARBAMOYL)PROPYL]CYCLOHEXANECARBOXAMIDE DB07560, N-[(1S)-2-methyl-1-(pyridin-4-ylcarbamoyl)propyl]cyclohexanecarboxamide |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000052012 | 1 – 530 | Lanosterol 14-alpha demethylase CYP51Add BLAST | 530 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 116 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources | ||
Cross-linki | 353 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources | ||
Cross-linki | 454 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources | ||
Modified residuei | 458 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | P10614 |
PaxDbi | P10614 |
PRIDEi | P10614 |
TopDownProteomicsi | P10614 |
PTM databases
iPTMneti | P10614 |
Expressioni
Inductioni
Interactioni
Subunit structurei
Interacts with ERG28.
1 PublicationBinary interactionsi
P10614
With | #Exp. | IntAct |
---|---|---|
ERG25 [P53045] | 3 | EBI-5127,EBI-6506 |
Protein-protein interaction databases
BioGRIDi | 36434, 491 interactors |
DIPi | DIP-7886N |
IntActi | P10614, 73 interactors |
MINTi | P10614 |
STRINGi | 4932.YHR007C |
Miscellaneous databases
RNActi | P10614, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P10614 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00930000151026 |
HOGENOMi | CLU_001570_15_0_1 |
InParanoidi | P10614 |
OMAi | FMLHWAP |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00465, EP450IV PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MSATKSIVGE ALEYVNIGLS HFLALPLAQR ISLIIIIPFI YNIVWQLLYS
60 70 80 90 100
LRKDRPPLVF YWIPWVGSAV VYGMKPYEFF EECQKKYGDI FSFVLLGRVM
110 120 130 140 150
TVYLGPKGHE FVFNAKLADV SAEAAYAHLT TPVFGKGVIY DCPNSRLMEQ
160 170 180 190 200
KKFVKGALTK EAFKSYVPLI AEEVYKYFRD SKNFRLNERT TGTIDVMVTQ
210 220 230 240 250
PEMTIFTASR SLLGKEMRAK LDTDFAYLYS DLDKGFTPIN FVFPNLPLEH
260 270 280 290 300
YRKRDHAQKA ISGTYMSLIK ERRKNNDIQD RDLIDSLMKN STYKDGVKMT
310 320 330 340 350
DQEIANLLIG VLMGGQHTSA ATSAWILLHL AERPDVQQEL YEEQMRVLDG
360 370 380 390 400
GKKELTYDLL QEMPLLNQTI KETLRMHHPL HSLFRKVMKD MHVPNTSYVI
410 420 430 440 450
PAGYHVLVSP GYTHLRDEYF PNAHQFNIHR WNKDSASSYS VGEEVDYGFG
460 470 480 490 500
AISKGVSSPY LPFGGGRHRC IGEHFAYCQL GVLMSIFIRT LKWHYPEGKT
510 520 530
VPPPDFTSMV TLPTGPAKII WEKRNPEQKI
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 433 | K → N in AAA34546 (PubMed:3046615).Curated | 1 | |
Sequence conflicti | 433 | K → N in AAA34547 (PubMed:3046615).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M18109 Genomic DNA Translation: AAA34379.1 M15663 Genomic DNA Translation: AAA34837.1 M21483 Genomic DNA Translation: AAA34546.1 M21484 Genomic DNA Translation: AAA34547.1 U10555 Genomic DNA Translation: AAB68433.1 BK006934 Genomic DNA Translation: DAA06695.1 |
PIRi | A27491 |
RefSeqi | NP_011871.1, NM_001179137.1 |
Genome annotation databases
EnsemblFungii | YHR007C_mRNA; YHR007C; YHR007C |
GeneIDi | 856398 |
KEGGi | sce:YHR007C |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M18109 Genomic DNA Translation: AAA34379.1 M15663 Genomic DNA Translation: AAA34837.1 M21483 Genomic DNA Translation: AAA34546.1 M21484 Genomic DNA Translation: AAA34547.1 U10555 Genomic DNA Translation: AAB68433.1 BK006934 Genomic DNA Translation: DAA06695.1 |
PIRi | A27491 |
RefSeqi | NP_011871.1, NM_001179137.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4LXJ | X-ray | 1.90 | A | 1-530 | [»] | |
5EQB | X-ray | 2.19 | A | 1-530 | [»] | |
SMRi | P10614 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 36434, 491 interactors |
DIPi | DIP-7886N |
IntActi | P10614, 73 interactors |
MINTi | P10614 |
STRINGi | 4932.YHR007C |
Chemistry databases
DrugBanki | DB06890, (2R)-2-PHENYL-N-PYRIDIN-4-YLBUTANAMIDE DB07568, (2S)-2-[(2,1,3-BENZOTHIADIAZOL-4-YLSULFONYL)AMINO]-2-PHENYL-N-PYRIDIN-4-YLACETAMIDE DB07572, 3-{[(4-methylphenyl)sulfonyl]amino}propyl pyridin-4-ylcarbamate DB07635, 4,4'-Dihydroxybenzophenone DB07569, CIS-4-METHYL-N-[(1S)-3-(METHYLSULFANYL)-1-(PYRIDIN-4-YLCARBAMOYL)PROPYL]CYCLOHEXANECARBOXAMIDE DB07560, N-[(1S)-2-methyl-1-(pyridin-4-ylcarbamoyl)propyl]cyclohexanecarboxamide |
PTM databases
iPTMneti | P10614 |
Proteomic databases
MaxQBi | P10614 |
PaxDbi | P10614 |
PRIDEi | P10614 |
TopDownProteomicsi | P10614 |
Genome annotation databases
EnsemblFungii | YHR007C_mRNA; YHR007C; YHR007C |
GeneIDi | 856398 |
KEGGi | sce:YHR007C |
Organism-specific databases
SGDi | S000001049, ERG11 |
VEuPathDBi | FungiDB:YHR007C |
Phylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00930000151026 |
HOGENOMi | CLU_001570_15_0_1 |
InParanoidi | P10614 |
OMAi | FMLHWAP |
Enzyme and pathway databases
UniPathwayi | UPA00770;UER00754 |
BRENDAi | 1.14.14.154, 984 |
Reactomei | R-SCE-191273, Cholesterol biosynthesis R-SCE-211976, Endogenous sterols |
Miscellaneous databases
PROi | PR:P10614 |
RNActi | P10614, protein |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00465, EP450IV PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CP51_YEAST | |
Accessioni | P10614Primary (citable) accession number: P10614 Secondary accession number(s): D3DKV1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
Last sequence update: | July 1, 1989 | |
Last modified: | February 23, 2022 | |
This is version 202 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
3D-structure, Reference proteomeDocuments
- Yeast
Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD - Yeast chromosome VIII
Yeast (Saccharomyces cerevisiae) chromosome VIII: entries and gene names - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families