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Entry version 8 (17 Jun 2020)
Sequence version 1 (05 Jun 2019)
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Protein

Cytochrome P450 monooxygenase ascH

Gene

ascH

Organism
Acremonium egyptiacum (Oospora egyptiaca)
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

Cytochrome P450 monooxygenase; part of the asc-2 gene cluster that mediates the biosynthesis of ascofuranone, a strong inhibitor of cyanide-insensitive alternative oxidases and a promising drug candidate against African trypanosomiasis (PubMed:30952781).

The first step in the pathway is performed by the non-reducing polyketide synthase ascC that produces orsellinic acid by condensing acetyl-CoA with 3 malonyl-CoA units (PubMed:30952781).

Orsellinic acid is then prenylated by the prenyltransferase ascA to yield ilicicolinic acid B (PubMed:30952781).

Ilicicolinic acid B is further reduced to ilicicolin B by the reductase ascB (PubMed:30952781).

The halogenase ascD then chlorinates ilicicolin B to produce ilicicolin A which is converted to ilicicolin A epoxide by the cytochrome P450 monooxygenase ascE that catalyzes stereoselective epoxidation of the terminal double bond of the prenyl group (PubMed:30952781).

Ilicicolin A epoxide is the last common precursor for the biosynthesis of ascofuranone and ascochlorin (PubMed:30952781).

The terpene cyclase ascF produces a monocyclic terpene, and the cyclization reaction is proposed to be initiated by protonation of the terminal epoxide of ilicicolin A epoxide to generate a monocyclic tertiarycation, which is followed by a series of hydride and methyl shifts with abstraction of proton, leading to the formation of the (14S,15R,19R)-trimethylcyclohexanone ring structure of ilicicolin C, which is finally reduced to ascochlorin by the dehydrogenase ascG (PubMed:30952781).

On the other hand, ilicicolin A epoxide is hydroxylated by the cytochrome P450 monooxygenase ascH, and the resultant product is cyclized by the terpene cyclase ascI to ascofuranol via protonation-initiated epoxide ring opening, which facilitates the 6-endo-tet cyclization to form the tetrahy-drofuran ring (PubMed:30952781).

Finally, ascofuranol is oxidized into ascofuranone by ascJ (PubMed:30952781).

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 provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

hemeBy similarity

<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: terpenoid biosynthesis

This protein is involved in the pathway terpenoid biosynthesis, which is part of Secondary metabolite biosynthesis.1 Publication
View all proteins of this organism that are known to be involved in the pathway terpenoid biosynthesis and in Secondary metabolite biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi458Iron (heme axial ligand)By 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

GO - Biological processi

<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 functionMonooxygenase, Oxidoreductase
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

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

More...
UniPathwayi
UPA00213

<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:
Cytochrome P450 monooxygenase ascH1 Publication (EC:1.14.14.-1 Publication)
Alternative name(s):
Ascofuranone/ascochlorin biosynthesis clusters protein H1 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
Name:ascH1 Publication
<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>OrganismiAcremonium egyptiacum (Oospora egyptiaca)
<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 identifieri749675 [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 lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaSordariomycetesHypocreomycetidaeHypocrealesHypocreales incertae sedisAcremonium

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei12 – 32HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Membrane

<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

Ascofuranone is a specific inhibitor of trypanosome alternative oxidase (TAO), and quickly kills African trypanosomes in vitro and cures infected mice. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host.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

Impairs the production of ascofuranone and leads to the accumulation of ilicicolin A epoxide.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_00004490011 – 512Cytochrome P450 monooxygenase ascHAdd BLAST512

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi272N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi277N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1

Keywords - PTMi

Glycoprotein

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Expression is induced on AF medium.1 Publication

<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

<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 cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
1.10.630.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR001128, Cyt_P450
IPR017972, Cyt_P450_CS
IPR002401, Cyt_P450_E_grp-I
IPR036396, Cyt_P450_sf

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00067, p450, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00463, EP450I
PR00385, P450

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48264, SSF48264, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00086, CYTOCHROME_P450, 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.

A0A455R624-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGLSLGYSPD RGSIGSWICA APLILALFVI SYRLFQSVID YRLSHRNGCK
60 70 80 90 100
PPPTYPHKDW YLGLHHVFGL LKAKKENRLP TAFSELFDAS GPDVHTLGHY
110 120 130 140 150
VLGKKSYWTR DPENIKAVLS SKFNDWGLPS ARKATFRTCL GGGIFGVDGK
160 170 180 190 200
EWEHSRAMLK PSFTRTQIGD TATLSKHADN LIARIPEGET VDLAELFPLL
210 220 230 240 250
TMDVGTEMLF GESVGSLDPA EIKQATRFTT SFDYIVQTMS KHMALPILTK
260 270 280 290 300
LRDKTLQGCV EFVDDFAADV VNRTIANESK TEKPSSLGKY IFPTELAKMG
310 320 330 340 350
LPEKQIRIEV INIMVAGRDT TAALLSLIWW YLAKRPDAVM KLHQELEPLG
360 370 380 390 400
GRPPTGEEVK KMKYLRNFVN EILRLHPINP LNSRTAAKDT TLPRGGGPDG
410 420 430 440 450
KSPVFIRKGT QLMFSSAALQ RRKDLYGEDA LDLRPERWER IRPSAFEYIP
460 470 480 490 500
FGGGPRICPG QQLALTEASY FTARLLQEFQ GVTSESSGPF QEAFAILVTS
510
GDGVKVKFHK KH
Length:512
Mass (Da):57,116
Last modified:June 5, 2019 - 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:iC0961FA00B32AA01
GO

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
LC406757 Genomic DNA Translation: BBF25322.1

<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
LC406757 Genomic DNA Translation: BBF25322.1

3D structure databases

Database of comparative protein structure models

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ModBasei
Search...

SWISS-MODEL Interactive Workspace

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SWISS-MODEL-Workspacei
Submit a new modelling project...

Enzyme and pathway databases

UniPathwayiUPA00213

Family and domain databases

Gene3Di1.10.630.10, 1 hit
InterProiView protein in InterPro
IPR001128, Cyt_P450
IPR017972, Cyt_P450_CS
IPR002401, Cyt_P450_E_grp-I
IPR036396, Cyt_P450_sf
PfamiView protein in Pfam
PF00067, p450, 1 hit
PRINTSiPR00463, EP450I
PR00385, P450
SUPFAMiSSF48264, SSF48264, 1 hit
PROSITEiView protein in PROSITE
PS00086, CYTOCHROME_P450, 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 nameiASCH_ACREG
<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: A0A455R624
<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: February 26, 2020
Last sequence update: June 5, 2019
Last modified: June 17, 2020
This is version 8 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

Documents

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