P32353 · ERG3_YEAST

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).

Miscellaneous

Present with 36200 molecules/cell in log phase SD medium.

Catalytic activity

Cofactor

Fe cation (UniProtKB | Rhea| CHEBI:24875 )

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

AspectTerm
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum lumen
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmembrane
Molecular FunctionC-5 sterol desaturase activity
Molecular Functiondelta7-sterol 5(6)-desaturase activity
Molecular Functioniron ion binding
Biological Processergosterol biosynthetic process
Biological Processsterol biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Delta(7)-sterol 5(6)-desaturase ERG3
  • EC number
  • Alternative names
    • C-5 sterol desaturase ERG3
    • Ergosterol Delta(5,6) desaturase ERG3
    • Ergosterol biosynthetic protein 3
    • Sterol-C5-desaturase

Gene names

    • Name
      ERG3
    • Synonyms
      PSO6, SYR1
    • ORF names
      L2150
    • Ordered locus names
      YLR056W

Organism names

Accessions

  • Primary accession
    P32353
  • Secondary accessions
    • D6VY58

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-92Cytoplasmic
Transmembrane93-113Helical
Topological domain114-140Lumenal
Transmembrane141-161Helical
Topological domain162-242Cytoplasmic
Transmembrane243-263Helical
Topological domain264-365Lumenal

Keywords

Phenotypes & Variants

Disruption phenotype

Abolishes the production of ergosterol (PubMed:37604855).
Resistance to aescin (PubMed:37604855).

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, cross-link.

TypeIDPosition(s)Description
ChainPRO_00001170271-365Delta7-sterol 56-desaturase ERG3
Cross-link324Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Keywords

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).

Interaction

Subunit

Interacts with ERG28.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY P32353ERG25 P530453EBI-6554, EBI-6506

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, motif.

TypeIDPosition(s)Description
Domain187-311Fatty acid hydroxylase
Motif200-204Histidine box-1
Motif213-217Histidine box-2
Motif288-292Histidine 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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    365
  • Mass (Da)
    42,730
  • Last updated
    1993-10-01 v1
  • Checksum
    7F441DA6927A711C
MDLVLEVADHYVLDDLYAKVLPASLAANIPVKWQKLLGLNSGFSNSTILQETLNSKNAVKECRRFYGQVPFLFDMSTTSFASLLPRSSILREFLSLWVIVTIFGLLLYLFTASLSYVFVFDKSIFNHPRYLKNQMAMEIKLAVSAIPWMSMLTVPWFVMELNGHSKLYMKIDYENHGVRKLIIEYFTFIFFTDCGVYLAHRWLHWPRVYRALHKPHHKWLVCTPFASHSFHPVDGFLQSISYHIYPLILPLHKVSYLILFTFVNFWTVMIHDGQYLSNNPAVNGTACHTVHHLYFNYNYGQFTTLWDRLGGSYRRPDDSLFDPKLRDAKETWDAQVKEVEHFIKEVEGDDNDRIYENDPNTKKNN

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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