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Entry version 60 (10 Feb 2021)
Sequence version 1 (17 Oct 2006)
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Protein

Monacolin J acid methylbutanoyltransferase

Gene

ATEG_09964

Organism
Aspergillus terreus (strain NIH 2624 / FGSC A1156)
Status
Reviewed-Annotation score:

Annotation score:4 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Monacolin J acid methylbutanoyltransferase; part of the gene cluster that mediates the biosynthesis of lovastatin (also known as mevinolin, mevacor or monacolin K), a hypolipidemic inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) (PubMed:10334994, PubMed:12929390, PubMed:21495633).

The first step in the biosynthesis of lovastatin is the production of dihydromonacolin L acid by the lovastatin nonaketide synthase lovB and the trans-acting enoyl reductase lovC via condensation of one acetyl-CoA unit and 8 malonyl-CoA units (PubMed:10334994, PubMed:10381407, PubMed:19900898, PubMed:22733743).

Dihydromonacolin L acid is released from lovB by the thioesterase lovG (PubMed:23653178).

Next, dihydromonacolin L acid is oxidized by the dihydromonacolin L monooxygenase lovA twice to form monacolin J acid (PubMed:12929390, PubMed:21495633).

The 2-methylbutyrate moiety of lovastatin is synthesized by the lovastatin diketide synthase lovF via condensation of one acetyl-CoA unit and one malonyl-CoA unit (PubMed:19530726, PubMed:21069965).

Finally, the covalent attachment of this moiety to monacolin J acid is catalyzed by the transesterase lovD to yield lovastatin (PubMed:10334994, PubMed:17113998, PubMed:18988191, PubMed:19875080, PubMed:24727900).

LovD has broad substrate specificity and can also convert monacolin J to simvastatin using alpha-dimethylbutanoyl-S-methyl-3-mercaptopropionate (DMB-S-MMP) as the thioester acyl donor, and can also catalyze the reverse reaction and function as hydrolase in vitro (PubMed:19875080).

LovD has much higher activity with LovF-bound 2-methylbutanoate than with free diketide substrates (PubMed:21069965).

13 Publications

Miscellaneous

Directed evolution toward higher catalytic activity with free diketides led to an enzyme with 1000-fold higher activity in simvastatin synthesis, due to numerous mutations that affect protein folding and promote optimal alignment of the residues that are important for substrate binding and catalysis.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

Kcat is 0.62 min(-1) for simvastatin synthesis.
  1. KM=0.78 mM for monacolin J2 Publications
  2. KM=0.67 mM for alpha-dimethylbutanoyl-S-methyl-3-mercaptopropionate2 Publications

    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: lovastatin biosynthesis

    This protein is involved in the pathway lovastatin biosynthesis, which is part of Polyketide biosynthesis.2 Publications
    View all proteins of this organism that are known to be involved in the pathway lovastatin biosynthesis and in Polyketide biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei73Monacolin JBy similarity1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei76Acyl-ester intermediateBy similarity1
    Binding sitei173Monacolin JBy similarity1
    Binding sitei188Monacolin JBy similarity1
    Binding sitei258Monacolin JBy similarity1
    Binding sitei3662-methylbutanoate; via amide nitrogenBy similarity1
    Binding sitei388Monacolin JBy similarity1
    Binding sitei390Monacolin JBy similarity1

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionAcyltransferase, Hydrolase, Transferase

    Enzyme and pathway databases

    UniPathway: a resource for the exploration and annotation of metabolic pathways

    More...
    UniPathwayi
    UPA00875

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    Monacolin J acid methylbutanoyltransferase1 Publication (EC:2.3.1.2383 Publications)
    Alternative name(s):
    Lovastatin biosynthesis cluster protein D1 Publication
    Lovastatin hydrolase
    Simvastatin synthase LovD1 Publication
    Short name:
    SV synthase1 Publication
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    ORF Names:ATEG_09964
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiAspergillus terreus (strain NIH 2624 / FGSC A1156)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri341663 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaeAspergillusAspergillus subgen. Circumdati
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000007963 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Unassembled WGS sequence

    Organism-specific databases

    Eukaryotic Pathogen, Vector and Host Database Resources

    More...
    VEuPathDBi
    FungiDB:ATEG_09964

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    <p>This subsection of the 'Pathology and Biotech' section describes the use of a specific protein in the biotechnological industry.<p><a href='/help/biotechnological_use' target='_top'>More...</a></p>Biotechnological usei

    Lovastatin acts as a hypolipidemic agent that works as inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) which reduces HMG-CoA to mevalonate and is the key step in cholesterol biosynthesis (PubMed:6933445). Lovastatin, simvastatin and related compounds are widely used to treat hypercholesteremia and reduce the risk of cardiovascular disease (PubMed:6933445). Furthermore, statins such as lovastatin were found to be anticancer agents (PubMed:29236027, PubMed:29932104).3 Publications

    <p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

    Loss of lovastatin biosynthesis.1 Publication

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004496601 – 413Monacolin J acid methylbutanoyltransferaseAdd BLAST413

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Interacts with LovF.

    2 Publications

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    3D structure databases

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...
    SMRi
    Q0C8M0

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Belongs to the class-A beta-lactamase family.Curated

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    ENOG502S4UR, Eukaryota

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    CLU_020027_11_1_1

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    TYGFYGD

    Database of Orthologous Groups

    More...
    OrthoDBi
    1268012at2759

    Family and domain databases

    Gene3D Structural and Functional Annotation of Protein Families

    More...
    Gene3Di
    3.40.710.10, 1 hit

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR001466, Beta-lactam-related
    IPR012338, Beta-lactam/transpept-like

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF00144, Beta-lactamase, 1 hit

    Superfamily database of structural and functional annotation

    More...
    SUPFAMi
    SSF56601, SSF56601, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    Q0C8M0-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MGSIIDAAAA ADPVVLMETA FRKAVKSRQI PGAVIMARDC SGNLNYTRCF
    60 70 80 90 100
    GARTVRRDEC NQLPPLQVDT PCRLASATKL LTTIMALQCM ERGLVDLDET
    110 120 130 140 150
    VDRLLPDLSA MPVLEGFDDA GNARLRERRG KITLRHLLTH TSGLSYVFLH
    160 170 180 190 200
    PLLREYMAQG HLQSAEKFGI QSRLAPPAVN DPGAEWIYGA NLDWAGKLVE
    210 220 230 240 250
    RATGLDLEQY LQENICAPLG ITDMTFKLQQ RPDMLARRAD QTHRNSADGR
    260 270 280 290 300
    LRYDDSVYFR ADGEECFGGQ GVFSGPGSYM KVLHSLLKRD GLLLQPQTVD
    310 320 330 340 350
    MMFQPALEPR LEEQMNQHMD ASPHINYGGP MPMVLRRSFG LGGIIALEDL
    360 370 380 390 400
    DGEDWRRKGS LTFGGGPNIV WQIDPKAGLC TLAFFQLEPW NDPVCRDLTR
    410
    TFEHAIYAQY QQG
    Length:413
    Mass (Da):46,056
    Last modified:October 17, 2006 - v1
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i33DD09B7BF0D2732
    GO

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...
    DDBJi
    Links Updated
    CH476609 Genomic DNA Translation: EAU29413.1

    NCBI Reference Sequences

    More...
    RefSeqi
    XP_001209266.1, XM_001209266.1

    Genome annotation databases

    Ensembl fungal genome annotation project

    More...
    EnsemblFungii
    EAU29413; EAU29413; ATEG_09964

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    4319610

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    CH476609 Genomic DNA Translation: EAU29413.1
    RefSeqiXP_001209266.1, XM_001209266.1

    3D structure databases

    SMRiQ0C8M0
    ModBaseiSearch...

    Genome annotation databases

    EnsemblFungiiEAU29413; EAU29413; ATEG_09964
    GeneIDi4319610

    Organism-specific databases

    VEuPathDBiFungiDB:ATEG_09964

    Phylogenomic databases

    eggNOGiENOG502S4UR, Eukaryota
    HOGENOMiCLU_020027_11_1_1
    OMAiTYGFYGD
    OrthoDBi1268012at2759

    Enzyme and pathway databases

    UniPathwayiUPA00875

    Family and domain databases

    Gene3Di3.40.710.10, 1 hit
    InterProiView protein in InterPro
    IPR001466, Beta-lactam-related
    IPR012338, Beta-lactam/transpept-like
    PfamiView protein in Pfam
    PF00144, Beta-lactamase, 1 hit
    SUPFAMiSSF56601, SSF56601, 1 hit

    MobiDB: a database of protein disorder and mobility annotations

    More...
    MobiDBi
    Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiLOVD_ASPTN
    <p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q0C8M0
    <p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 22, 2020
    Last sequence update: October 17, 2006
    Last modified: February 10, 2021
    This is version 60 of the entry and version 1 of the sequence. See complete history.
    <p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    <p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families
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