Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 32 (17 Jun 2020)
Sequence version 1 (22 Jul 2008)
Previous versions | rss
Help videoAdd a publicationFeedback
Protein

FAD-linked oxidoreductase hmp9

Gene

hpm9

Organism
Hypomyces subiculosus (Nectria subiculosa)
Status
Reviewed-Annotation score:

Annotation score:3 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

FAD-linked oxidoreductase; part of the gene cluster that mediates the biosynthesis of hypothemycin, a resorcylic acid lactone (RAL) that irreversibly inhibits a subset of protein kinases with a conserved cysteine in the ATP binding site such as human ERK2 (PubMed:18567690). The first step is performed by both PKSs hmp3 and hmp8 and leads to the production of 7',8'-dehydrozearalenol (DHZ) (PubMed:18567690, PubMed:20222707). The highly reducing PKS hpm8 synthesizes the reduced hexaketide (7S,11S,2E,8E)-7,11-dihydroxy-dodeca-2,8-dienoate, which is transferred downstream to the non-reducing PKS hpm3 (PubMed:20222707). Hpm3 then extends the reduced hexaketide to a nonaketide, after which regioselective cyclization and macrolactonization affords DHZ (PubMed:20222707). The next step is the conversion of DHZ into aigialomycin C and is performed by the O-methyltransferase hmp5, the FAD-binding monooxygenase hmp7, and the cytochrome P450 monooxygenase hmp1 (PubMed:18567690). The wide substrate tolerance of the hmp5 and hmp7 implies that the reactions from DHZ to aigialomycin C can occur in any order (PubMed:18567690). The steps from aigialomycin C to hypothemycin are less well established (PubMed:18567690). The FAD-linked oxidoreductase hmp9 presumably catalyzes oxidation of the C-6' hydroxyl to a ketone (PubMed:18567690). The timing of this oxidation is important, since the resulting enone functional group is a Michael acceptor that can react spontaneously with glutathione, an abundant metabolite in fungal cells (PubMed:18567690). The glutathione S-transferase hmp2 catalyzes cis-trans isomerization of the 7',8' double bond with equilibrium favoring the trans isomer (PubMed:18567690). The hpm6-encoded transporter might preferentially pump hypothemycin out of the cell relative to the trans isomer aigialomycin A. The cis-to-trans isomerization may be coupled with C-4' hydroxylation, since all known hypothemycin analogs containing the enone functional group also have hydroxyl groups at both C-4' and C-5' (PubMed:18567690).2 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: Secondary metabolite biosynthesis

This protein is involved in Secondary metabolite biosynthesis.1 Publication
View all proteins of this organism that are known to be involved in Secondary metabolite biosynthesis.

<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 functionOxidoreductase

<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:
FAD-linked oxidoreductase hmp9Curated (EC:1.-.-.-Curated)
Alternative name(s):
Hypothemycin biosynthesis cluster protein hpm91 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:hpm91 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>OrganismiHypomyces subiculosus (Nectria subiculosa)
<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 identifieri193393 [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 lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaSordariomycetesHypocreomycetidaeHypocrealesHypocreaceaeHypomyces

<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

Hypothemycin is an antifungal agent that exhibits excellent activity against Peronophythora litchii, which could be helpful for the storage of harvest litchi fruit (PubMed:24106914). Hypothemycin is a strong inhibitor of a subset of MAP kinases such as human ERK2 (PubMed:18571434, PubMed:20118535, PubMed:26371861). It can therefore be used as an anti-cancer drug thanks to its inhibitory activity of Ras-mediated cellular signals (PubMed:10595743, PubMed:10421424). It can also inhibit Trypanosoma brucei kinase TbCLK1 which is a good candidate as a therapeutic target for African trypanosomiasis (PubMed:23853713). Finally, hypothemycin has also inhibitor activity of T cell activation (PubMed:10598882).8 Publications

<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 denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 29Sequence analysisAdd BLAST29
<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_500764011230 – 628FAD-linked oxidoreductase hmp9Sequence analysisAdd BLAST599

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>Glycosylationi80N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi133N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi356N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1

Keywords - PTMi

Glycoprotein

<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
B3FWS5

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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini152 – 337FAD-binding PCMH-typePROSITE-ProRule annotationAdd BLAST186

<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

Keywords - Domaini

Signal

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR016166, FAD-bd_PCMH
IPR036318, FAD-bd_PCMH-like_sf
IPR006094, Oxid_FAD_bind_N

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF01565, FAD_binding_4, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF56176, SSF56176, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS51387, FAD_PCMH, 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.

<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 in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

B3FWS5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MFCIIRAQLL LLLHLLVLAL LLVGTVCNAH PQHGHPSELE PLALKRGGSP
60 70 80 90 100
RDDGNTLAPR CRCIPGEACW PSTQIWDSFN RTIGGSLIKT APLAESCYPG
110 120 130 140 150
PKKNTRKCAV VSRKWTDQDF QTDSPVGRTY PYNITCAPVN YFAGQRPTTC
160 170 180 190 200
SLGQLPVYAI DARTRQSVAQ GLRFAKDNNL RVTVVSTGHD LLGRADGYGS
210 220 230 240 250
LEIWLRHHRN EIRFERQYMA TDGCRESGWT GSAIDIDGAY QWRDVHIKAR
260 270 280 290 300
ANNVIVVGGG SVSPGAIGGW PSGGGHGPAS RNYGLGADQI LEAEVMLADG
310 320 330 340 350
SVVLANHCQH TDLFRALRGG GPGFGVVLKT KIKAYPNVAS VSVHHLTITP
360 370 380 390 400
IRQTPNNSDL LDAVAVLMQA YPKLSDDGYA GYAFWLRNCK SFFIGSAKSG
410 420 430 440 450
YRHGIWMIGK TTEEAEHSFA PVREALDKFK SKLTISESYM TYNDYWSFYT
460 470 480 490 500
SESGLYESVG TTSVLTSRLI DRPAVEDYNR VREAVEVIGG KPEDYATNVM
510 520 530 540 550
MLVSNGQVFA DAADKSSGLN PAWRVSPYVV ISSRGIPMVV DQASRKEVAD
560 570 580 590 600
DITYVKGAAL QKLAPNTGGY MNEGDRNDPN YIKNFFGTIY PTHLATKKKY
610 620
DPWGLFYCPT CVGAELFEET SRGELCRR
Length:628
Mass (Da):68,958
Last modified:July 22, 2008 - 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:i54D18D0A7DD57277
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
EU520417 Genomic DNA Translation: ACD39759.1
EU520418 Genomic DNA Translation: ACD39768.1

<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
EU520417 Genomic DNA Translation: ACD39759.1
EU520418 Genomic DNA Translation: ACD39768.1

3D structure databases

SMRiB3FWS5
ModBaseiSearch...

Family and domain databases

InterProiView protein in InterPro
IPR016166, FAD-bd_PCMH
IPR036318, FAD-bd_PCMH-like_sf
IPR006094, Oxid_FAD_bind_N
PfamiView protein in Pfam
PF01565, FAD_binding_4, 1 hit
SUPFAMiSSF56176, SSF56176, 1 hit
PROSITEiView protein in PROSITE
PS51387, FAD_PCMH, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

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 nameiHPM9_HYPSB
<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: B3FWS5
<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: November 2, 2016
Last sequence update: July 22, 2008
Last modified: June 17, 2020
This is version 32 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again