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Protein

Squalene monooxygenase

Gene

ERG1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.1 Publication

Catalytic activityi

Squalene + [reduced NADPH--hemoprotein reductase] + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication

Cofactori

Enzyme regulationi

Inhibited by the allylamine antimycotic drugs.

Kineticsi

  1. KM=13.5 µM for squalene1 Publication

    pH dependencei

    Optimum pH is 7.5.1 Publication

    Pathwayi: lanosterol biosynthesis

    This protein is involved in step 2 of the subpathway that synthesizes lanosterol from farnesyl diphosphate.
    Proteins known to be involved in the 3 steps of the subpathway in this organism are:
    1. Squalene synthase (ERG9)
    2. Squalene monooxygenase (ERG1)
    3. Lanosterol synthase (ERG7)
    This subpathway is part of the pathway lanosterol biosynthesis, which is itself part of Terpene metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes lanosterol from farnesyl diphosphate, the pathway lanosterol biosynthesis and in Terpene metabolism.

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi21 – 4828FADSequence analysisAdd
    BLAST

    GO - Molecular functioni

    • drug binding Source: SGD
    • flavin adenine dinucleotide binding Source: InterPro
    • squalene monooxygenase activity Source: SGD

    GO - Biological processi

    • ergosterol biosynthetic process Source: SGD
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    FAD, Flavoprotein, NADP

    Enzyme and pathway databases

    BioCyciMetaCyc:YGR175C-MONOMER.
    YEAST:YGR175C-MONOMER.
    ReactomeiR-SCE-191273. Cholesterol biosynthesis.
    R-SCE-2426168. Activation of gene expression by SREBF (SREBP).
    UniPathwayiUPA00767; UER00752.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Squalene monooxygenase (EC:1.14.14.171 Publication)
    Alternative name(s):
    Squalene epoxidase1 Publication
    Short name:
    SE
    Gene namesi
    Name:ERG1
    Ordered Locus Names:YGR175C
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    Proteomesi
    • UP000002311 Componenti: Chromosome VII

    Organism-specific databases

    EuPathDBiFungiDB:YGR175C.
    SGDiS000003407. ERG1.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1616CytoplasmicSequence analysisAdd
    BLAST
    Transmembranei17 – 3721HelicalSequence analysisAdd
    BLAST
    Topological domaini38 – 474437LumenalSequence analysisAdd
    BLAST
    Transmembranei475 – 49521HelicalSequence analysisAdd
    BLAST
    Topological domaini496 – 4961CytoplasmicSequence analysis

    GO - Cellular componenti

    • endoplasmic reticulum Source: SGD
    • endoplasmic reticulum membrane Source: UniProtKB-SubCell
    • integral component of membrane Source: UniProtKB-KW
    • lipid particle Source: SGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Chemistry

    ChEMBLiCHEMBL1888.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 496496Squalene monooxygenasePRO_0000209851Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki284 – 284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki311 – 311Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

    Keywords - PTMi

    Isopeptide bond, Ubl conjugation

    Proteomic databases

    MaxQBiP32476.
    PeptideAtlasiP32476.
    TopDownProteomicsiP32476.

    Interactioni

    Subunit structurei

    Interacts with ERG28.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CSG2P352061EBI-6545,EBI-2051140
    ERG25P530451EBI-6545,EBI-6506
    ERG4P253401EBI-6545,EBI-6558
    ERP1Q053591EBI-6545,EBI-6581
    ERP4Q124501EBI-6545,EBI-6598
    ERV25P548371EBI-6545,EBI-6642
    ERV29P533371EBI-6545,EBI-23662
    GOT1Q035541EBI-6545,EBI-2057821
    PIS1P061971EBI-6545,EBI-13458
    SNA3P143591EBI-6545,EBI-26122
    SWP1Q027951EBI-6545,EBI-12666
    YHR146WP388451EBI-6545,EBI-24770
    YVH1Q022561EBI-6545,EBI-14322

    Protein-protein interaction databases

    BioGridi33428. 41 interactions.
    DIPiDIP-6325N.
    IntActiP32476. 19 interactions.
    MINTiMINT-1324933.

    Structurei

    3D structure databases

    ProteinModelPortaliP32476.
    SMRiP32476. Positions 15-52.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the squalene monooxygenase family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    GeneTreeiENSGT00390000011759.
    HOGENOMiHOG000174713.
    InParanoidiP32476.
    KOiK00511.
    OMAiIGAAACT.
    OrthoDBiEOG7KM62S.

    Family and domain databases

    Gene3Di3.50.50.60. 2 hits.
    InterProiIPR023753. FAD/NAD-binding_dom.
    IPR013698. Squalene_epoxidase.
    [Graphical view]
    PfamiPF08491. SE. 1 hit.
    [Graphical view]
    SUPFAMiSSF51905. SSF51905. 3 hits.

    Sequencei

    Sequence statusi: Complete.

    P32476-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSAVNVAPEL INADNTITYD AIVIGAGVIG PCVATGLARK GKKVLIVERD
    60 70 80 90 100
    WAMPDRIVGE LMQPGGVRAL RSLGMIQSIN NIEAYPVTGY TVFFNGEQVD
    110 120 130 140 150
    IPYPYKADIP KVEKLKDLVK DGNDKVLEDS TIHIKDYEDD ERERGVAFVH
    160 170 180 190 200
    GRFLNNLRNI TAQEPNVTRV QGNCIEILKD EKNEVVGAKV DIDGRGKVEF
    210 220 230 240 250
    KAHLTFICDG IFSRFRKELH PDHVPTVGSS FVGMSLFNAK NPAPMHGHVI
    260 270 280 290 300
    LGSDHMPILV YQISPEETRI LCAYNSPKVP ADIKSWMIKD VQPFIPKSLR
    310 320 330 340 350
    PSFDEAVSQG KFRAMPNSYL PARQNDVTGM CVIGDALNMR HPLTGGGMTV
    360 370 380 390 400
    GLHDVVLLIK KIGDLDFSDR EKVLDELLDY HFERKSYDSV INVLSVALYS
    410 420 430 440 450
    LFAADSDNLK ALQKGCFKYF QRGGDCVNKP VEFLSGVLPK PLQLTRVFFA
    460 470 480 490
    VAFYTIYLNM EERGFLGLPM ALLEGIMILI TAIRVFTPFL FGELIG
    Length:496
    Mass (Da):55,126
    Last modified:October 1, 1996 - v2
    Checksum:iBBEFD766634855E8
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti251 – 2511L → F in strain: A2-M8; confers resistance to the allylamine antifungal terbinafine.

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M64994 Genomic DNA. Translation: AAA34592.1.
    Z72960 Genomic DNA. Translation: CAA97201.1.
    BK006941 Genomic DNA. Translation: DAA08271.1.
    PIRiS64489.
    RefSeqiNP_011691.1. NM_001181304.1.

    Genome annotation databases

    EnsemblFungiiYGR175C; YGR175C; YGR175C.
    GeneIDi853086.
    KEGGisce:YGR175C.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M64994 Genomic DNA. Translation: AAA34592.1.
    Z72960 Genomic DNA. Translation: CAA97201.1.
    BK006941 Genomic DNA. Translation: DAA08271.1.
    PIRiS64489.
    RefSeqiNP_011691.1. NM_001181304.1.

    3D structure databases

    ProteinModelPortaliP32476.
    SMRiP32476. Positions 15-52.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi33428. 41 interactions.
    DIPiDIP-6325N.
    IntActiP32476. 19 interactions.
    MINTiMINT-1324933.

    Chemistry

    ChEMBLiCHEMBL1888.

    Proteomic databases

    MaxQBiP32476.
    PeptideAtlasiP32476.
    TopDownProteomicsiP32476.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYGR175C; YGR175C; YGR175C.
    GeneIDi853086.
    KEGGisce:YGR175C.

    Organism-specific databases

    EuPathDBiFungiDB:YGR175C.
    SGDiS000003407. ERG1.

    Phylogenomic databases

    GeneTreeiENSGT00390000011759.
    HOGENOMiHOG000174713.
    InParanoidiP32476.
    KOiK00511.
    OMAiIGAAACT.
    OrthoDBiEOG7KM62S.

    Enzyme and pathway databases

    UniPathwayiUPA00767; UER00752.
    BioCyciMetaCyc:YGR175C-MONOMER.
    YEAST:YGR175C-MONOMER.
    ReactomeiR-SCE-191273. Cholesterol biosynthesis.
    R-SCE-2426168. Activation of gene expression by SREBF (SREBP).

    Miscellaneous databases

    NextBioi973064.
    PROiP32476.

    Family and domain databases

    Gene3Di3.50.50.60. 2 hits.
    InterProiIPR023753. FAD/NAD-binding_dom.
    IPR013698. Squalene_epoxidase.
    [Graphical view]
    PfamiPF08491. SE. 1 hit.
    [Graphical view]
    SUPFAMiSSF51905. SSF51905. 3 hits.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The gene encoding squalene epoxidase from Saccharomyces cerevisiae: cloning and characterization."
      Jandrositz A., Turnowsky F., Hoegenauer G.
      Gene 107:155-160(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: A2-M8.
    2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."
      Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E.
      , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K.
      Nature 387:81-84(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    3. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    4. "Enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae."
      Satoh T., Horie M., Watanabe H., Tsuchiya Y., Kamei T.
      Biol. Pharm. Bull. 16:349-352(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
    5. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
    6. Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-311.
      Strain: SUB592.
    7. "A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery."
      Hitchcock A.L., Auld K., Gygi S.P., Silver P.A.
      Proc. Natl. Acad. Sci. U.S.A. 100:12735-12740(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-284.
    8. "Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex."
      Mo C., Bard M.
      J. Lipid Res. 46:1991-1998(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ERG28.
    9. "A global topology map of the Saccharomyces cerevisiae membrane proteome."
      Kim H., Melen K., Oesterberg M., von Heijne G.
      Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY [LARGE SCALE ANALYSIS].
      Strain: ATCC 208353 / W303-1A.
    10. "Sites of ubiquitin attachment in Saccharomyces cerevisiae."
      Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.
      Proteomics 12:236-240(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiERG1_YEAST
    AccessioniPrimary (citable) accession number: P32476
    Secondary accession number(s): D6VUW0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: October 1, 1996
    Last modified: April 13, 2016
    This is version 153 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Present with 65400 molecules/cell in log phase SD medium.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families
    3. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    4. Yeast chromosome VII
      Yeast (Saccharomyces cerevisiae) chromosome VII: entries and gene names

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.