PaperBLAST

Full List of Papers Linked to NP_464946.1

TC 3.A.1.12.8 / Q93A35 BilEA aka OpuBA protein, component of A proline/glycine betaine uptake system. Also reported to be a bile exclusion system that exports oxgall and other bile compounds, BilEA/EB or OpuBA/BB (required for normal virulence) from Listeria monocytogenes (see 2 papers)
NP_464946 glycine/betaine ABC transporter ATP-binding protein from Listeria monocytogenes EGD-e
lmo1421 similar to glycine betaine/carnitine/choline ABC transporter (ATP-binding protein) from Listeria monocytogenes EGD-e

• substrates: Glycine betaine, Proline
• Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract
  Watson, BMC microbiology 2008
  • “...(accession number NC_003210) uncovered the presence of two Open Reading Frames (ORFs) bilEA (accession number NP_464946 and GI number GI:16803461) and bilEB (accession number is NP_464947.1 and GI number is GI:16803462), oriented in the same direction and overlapping by five nucleotides. PCR primers with incorporated Xba...”
• Effects of intrinsic and extrinsic growth factors on virulence gene expression of foodborne pathogens in vitro and in food model systems; a review
  Hosseini, Food science & nutrition 2024
  • “...ham under HPP. The regulation of prfA , plcA , hly , sigB , and lmo1421 virulence genes was severely downregulated in one strain compared in another strain (PrezBaltar etal., 2021 ). L . monocytogenes can become more adaptable to HPP and other stressful conditions due...”
• Impact of High-Pressure Processing (HPP) on Listeria monocytogenes-An Overview of Challenges and Responses
  Wiśniewski, Foods (Basel, Switzerland) 2023
  • “...Boor K.J. Wiedmann M. SigmaB -dependent expression patterns of compatible solute transporter genes opuCA and lmo1421 and the conjugated bile salt hydrolase gene bsh in Listeria monocytogenes Microbiology 2003 149 3247 3256 10.1099/mic.0.26526-0 14600237 137. Bowman J.P. Bittencourt C.R. Ross T. Differential gene expression of Listeria...”
  • “...5 2 2 strains 450 10 16 prfA , plcA , hly , sigB , lmo1421 [ 128 ] 600 5 3 1 strain 200 3 12 luxS Upregulation Trypticase soy broth (TSB) [ 15 ] 400 4 2 strains 200 8 8 sigB , hpf...”
• Human Listeriosis
  Koopmans, Clinical microbiology reviews 2023 (secret)
• Effect of high pressure processing on the inactivation and the relative gene transcription patterns of Listeria monocytogenes in dry-cured ham
  Pérez-Baltar, Lebensmittel-Wissenschaft + [i.e. und] Technologie. Food science + technology. Science + technologie alimentaire 2021
• Characterization of the biofilm phenotype of a Listeria monocytogenes mutant deficient in agr peptide sensing
  Zetzmann, MicrobiologyOpen 2019
  • “...be involved in resistance to cell wall and osmotic stress (Supplementary File S1). For example, lmo1421 , lmo1425 , lmo1426 , and lmo1427 encode for components of the ABC transporters OpuA and OpuC, which are required for transport of the compatible solutes glycine/betaine, carnitine, and ornithine...”
• Food-Associated Stress Primes Foodborne Pathogens for the Gastrointestinal Phase of Infection
  Horn, Frontiers in microbiology 2018
  • “...) and in salami, acidic ( B and lmo0669 ) and osmotic ( gbuA and lmo1421 ) stress-related genes were upregulated ( Mataragas et al., 2015 ). Table 2 Effect of food products on virulence potential of foodborne pathogens. Pathogen Food Virulence potential Reference Bacillus spp....”
  • “...et al., 2010 Salami Acidic ( B and lmo0669 ) and osmotic ( gbuA and lmo1421 ) stress-related genes were upregulated Mataragas et al., 2015 Pear and Melon Increased adhesion and invasion of Caco-2 cells after 2 days of storage Cols-Med et al., 2017 Milk Increased...”
• Cyclic di-AMP targets the cystathionine beta-synthase domain of the osmolyte transporter OpuC
  Huynh, Molecular microbiology 2016
  • “...the carnitine transporter component OpuCA. (A) Domain organization of OpuCA (Lmo1428), GbuA (Lmo1014), and BilE (Lmo1421). (B) Binding of OpuCA, GbuA, and BilE to c-di-AMP as measured by DRaCALA to full-length (FL), ATP-binding (ATP), or CBS domains. (C) Binding titration for the OpuCA full-length OpuCA protein...”
• Differential gene expression profiling of Listeria monocytogenes in Cacciatore and Felino salami to reveal potential stress resistance biomarkers
  Mataragas, Food microbiology 2015 (PubMed)
  • “...and ripening of Cacciatore, whereas gbuA and lmo1421 were up-regulated during the ripening of Felino and Cacciatore, respectively. sigB expression was...”
  • “...gene expression profiling analysis suggested that sigB and lmo1421 or sigB and gbuA could be used as different types of stress resistance biomarkers to...”
• Refinement of the Listeria monocytogenes σB regulon through quantitative proteomic analysis
  Mujahid, Microbiology (Reading, England) 2013
  • “...D protein Lmo1422 is encoded in an operon that includes lmo1421 (which was also identified as sBdependent; Group C, Table S2). This operon is preceded by a sB...”
  • “...et al., 2003; Sue et al., 2003). While lmo1421 and lmo1422 were initially annotated as glycine betaine/carnitine/choline ABC transporters, they have been...”
• Protein level identification of the Listeria monocytogenes sigma H, sigma L, and sigma C regulons
  Mujahid, BMC microbiology 2013
  • “...not identified as positively regulated by any of the alternative factors include Lmo1540, Lmo2610, Lmo1422, Lmo1421, Lmo1602, Lmo1426, Lmo1428, Lmo2205, Lmo2398, Lmo1601, Lmo0554, Lmo1634, Lmo0110, Lmo2558, Lmo0783, Lmo0134, and Lmo0098. Table 4 Proteins found to be differentially regulated by at least two of the three alternative...”
• Transcriptome analysis of alkali shock and alkali adaptation in Listeria monocytogenes 10403S
  Giotis, Foodborne pathogens and disease 2010
  • “...2.57 2.39 4.38 4.41 4.13 lmo2497 NA lmo1422 NA lmo1421 NA lmo1428 opuCA LMOf2365_1446 opuCB lmo1426 opuCC Symbol 15 30 60 AA Subfunctional category Gene=protein...”
  • “...the choline uptake system OpuB of B. subtilis (lmo1421 and lmo1422) (Sleator and Hill, 2005). Upregulation of osmolyte transporter systems has been reported in...”
• Listeria monocytogenes {sigma}B has a small core regulon and a conserved role in virulence but makes differential contributions to stress tolerance across a diverse collection of strains
  Oliver, Applied and environmental microbiology 2010
  • “...lineage I strains; these genes include opuCA and lmo1421, which encode a known compatible solute transporter protein and a putative compatible solute...”
  • “...lmo1072 lmo1121 lmo1226 lmo1242 lmo1243 lmo1360 lmo1388 lmo1421 lmo1426 lmo1427 lmo1527 lmo1534 lmo1571 lmo1580 lmo1622 lmo1635 lmo1637 lmo1666 lmo1681 lmo1636...”
• Temporal transcriptomic analysis of the Listeria monocytogenes EGD-e sigmaB regulon
  Hain, BMC microbiology 2008
  • “...been shown for the osmotic induction of both opuC (encoding an ABC carnitine transporter) and lmo1421 (encoding a putative transporter) [ 20 ], and for one of the two prfA promoters upstream of prfA [ 21 ]. Furthermore, a deletion in the sigB gene has been...”
  • “...citrulline produced might be used to generate ornithine. Further a operon comprising the genes for lmo1421 and lmo1422 encoding the bile exclusion system BilE was confirmed to be B -regulated [ 30 ]. Together with the bile salt hydrolase bsh ( lmo2067 ) [ 31 ],...”
• Modulation of stress and virulence in Listeria monocytogenes
  Chaturongakul, Trends in microbiology 2008
  • “...34 Sue D 2003 B -dependent expression patterns of compatible solute transporter genes opuCA and lmo1421 and a conjugated bile salt hydrolase bsh in Listeria monocytogenes Microbiology 149 3247 3256 14600237 35 Fraser KR 2003 The role of B in regulating compatible solute uptake systems of...”
• Proteomic analyses of a Listeria monocytogenes mutant lacking sigmaB identify new components of the sigmaB regulon and highlight a role for sigmaB in the utilization of glycerol
  Abram, Applied and environmental microbiology 2008
  • “...B promoters (upstream from lmo0596, prfA, fri, gbuA, lmo1421, lmo0699, lmo1433, lmo2230, opuCA, inlA, lmo2434, bsh, and rsbV) (4, 9, 24, 30, 32). The...”
• Comparative transcriptome analysis of Listeria monocytogenes strains of the two major lineages reveals differences in virulence, cell wall, and stress response
  Severino, Applied and environmental microbiology 2007
  • “...lmo1472 lmo2785 lmo0205 lmo0905 lmo0938 lmo2230 lmo1014 lmo1421 lmo1579 lmo2551 lmo0211 lmo1471 lmo1538 lmo2695 lmo2205 lmo0014 lmo0970 lmo1372 lmo1439 lmo1688...”
  • “...belonging to lineage Ia Gene; function M P lmo1421 lmo1426 lmo1427 lmo1428 lmo0893 lmo0894 lmo0895 lmo0896 lmo2230 lmo0783 lmo0784 lmo2398 lmo2602 lmo1539...”
• Characterization of the osmoprotectant transporter OpuC from Pseudomonas syringae and demonstration that cystathionine-beta-synthase domains are required for its osmoregulatory function
  Chen, Journal of bacteriology 2007
  • “...GbuA OpuAA OpuCA OpuBA OpuCA PSPTO_4575 Psyr4249 PA3891 YehX Lmo1421 ChoV EhuA PrbV HisV/HutV PSPTO_5273 PSPTO_0462 PSPTO_3060 c 4 105 5 109 3 1011 1 1013 5...”
  • “...of uptake in MKH13, which contains an intact yehX); Lmo1421 (3, 53); ChoV (19); EhuA (28); PrbV (1); HisV/HutV (8); and PSPTO_5273, PSPTO_0462, and PSPTO_3060...”
• Intracellular gene expression profile of Listeria monocytogenes
  Chatterjee, Infection and immunity 2006
  • “...3.17 2.52 lmo0593 lmo0880 2.72 2.39 lmo0911 lmo0956 lmo1421 5.11 2.84 2.70 lmo0911 lmo0956 lmo1421 4.60 2.84 2.35 lmo1433 lmo1539 lmo1883 lmo2085 lmo2205...”
  • “...(28). We detected the up regulation of the opuBA gene (lmo1421 and lmo0903, encoding a glycine betaine uptake system) and a gene similar to the osmC gene during...”
• Whole-genome sequence of Listeria welshimeri reveals common steps in genome reduction with Listeria innocua as compared to Listeria monocytogenes
  Hain, Journal of bacteriology 2006
  • “...locus (btlB, lmo0752-lmo0754) (1), and the bilE system (lmo1421 and lmo1422) (36) have all been implicated in the protection of the bacterium within the...”
• Molecular and physiological analysis of the role of osmolyte transporters BetL, Gbu, and OpuC in growth of Listeria monocytogenes at low temperatures
  Wemekamp-Kamphuis, Applied and environmental microbiology 2004
  • “...OpuB (identified by bioinformatic analysis and encoded by lmo1421 and lmo1422), showed no significant contribution to listerial chill tolerance. Growth of the...”
  • “...system OpuB of Bacillus subtilis. Consisting of two genes, lmo1421 and lmo1422, this operon is located approximately 2.4 kb downstream of opuC on the listerial...”
• Sigma(B)-dependent expression patterns of compatible solute transporter genes opuCA and lmo1421 and the conjugated bile salt hydrolase gene bsh in Listeria monocytogenes
  Sue, Microbiology (Reading, England) 2003 (PubMed)
  • “...compatible solute transporter genes opuCA and lmo1421 and the conjugated bile salt hydrolase gene bsh in Listeria monocytogenes David Sue, Kathryn J. Boor and...”
  • “...their expression patterns under various stress conditions. opuCA, lmo1421 and bsh were identified as putative sB-dependent genes based on the presence of a...”
• Role of sigmaB in regulating the compatible solute uptake systems of Listeria monocytogenes: osmotic induction of opuC is sigmaB dependent
  Fraser, Applied and environmental microbiology 2003
  • “...predicted to encode a compatible solute transporter subunit (lmo1421) is induced in response to elevated osmolarity. The osmotic induction of opuCA and lmo1421...”
  • “...(10). The identification of two open reading frames (lmo1421 and lmo1422) in close proximity to the opuC operon and with significant sequence similarity to...”
• Listeria monocytogenes sigma B regulates stress response and virulence functions
  Kazmierczak, Journal of bacteriology 2003
  • “...lmo2205 lmo0956 lmo1883 lmo2695 lmo1694 lmo0669 lmo0593 lmo0524 lmo1421 lmo1539 lmo2463 lmo0405 lmo2602 lmo0784 opuCD opuCC opuCB bsh inlA inlB inlC2 inlD inlE...”
  • “...both virulence genes; lmo0669, a putative metabolic gene; lmo1421 and opuCA (which encode putative and known compatible solute J. BACTERIOL. VOL. 185, 2003 5729...”

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How It Works

PaperBLAST builds a database of protein sequences that are linked to scientific articles. These links come from automated text searches against the articles in EuropePMC and from manually-curated information from GeneRIF, UniProtKB/Swiss-Prot, BRENDA, CAZy (as made available by dbCAN), BioLiP, CharProtDB, MetaCyc, EcoCyc, TCDB, REBASE, the Fitness Browser, and a subset of the European Nucleotide Archive with the /experiment tag. Given this database and a protein sequence query, PaperBLAST uses protein-protein BLAST to find similar sequences with E < 0.001.

To build the database, we query EuropePMC with locus tags, with RefSeq protein identifiers, and with UniProt accessions. We obtain the locus tags from RefSeq or from MicrobesOnline. We use queries of the form "locus_tag AND genus_name" to try to ensure that the paper is actually discussing that gene. Because EuropePMC indexes most recent biomedical papers, even if they are not open access, some of the links may be to papers that you cannot read or that our computers cannot read. We query each of these identifiers that appears in the open access part of EuropePMC, as well as every locus tag that appears in the 500 most-referenced genomes, so that a gene may appear in the PaperBLAST results even though none of the papers that mention it are open access. We also incorporate text-mined links from EuropePMC that link open access articles to UniProt or RefSeq identifiers. (This yields some additional links because EuropePMC uses different heuristics for their text mining than we do.)

For every article that mentions a locus tag, a RefSeq protein identifier, or a UniProt accession, we try to select one or two snippets of text that refer to the protein. If we cannot get access to the full text, we try to select a snippet from the abstract, but unfortunately, unique identifiers such as locus tags are rarely provided in abstracts.

PaperBLAST also incorporates manually-curated protein functions:

• Proteins from NCBI's RefSeq are included if a GeneRIF entry links the gene to an article in PubMed^®. GeneRIF also provides a short summary of the article's claim about the protein, which is shown instead of a snippet.
• Proteins from Swiss-Prot (the curated part of UniProt) are included if the curators identified experimental evidence for the protein's function (evidence code ECO:0000269). For these proteins, the fields of the Swiss-Prot entry that describe the protein's function are shown (with bold headings).
• Proteins from BRENDA, a curated database of enzymes, are included if they are linked to a paper in PubMed and their full sequence is known.
• Every protein from the non-redundant subset of BioLiP, a database of ligand-binding sites and catalytic residues in protein structures, is included. Since BioLiP itself does not include descriptions of the proteins, those are taken from the Protein Data Bank. Descriptions from PDB rely on the original submitter of the structure and cannot be updated by others, so they may be less reliable. (For SitesBLAST and Sites on a Tree, we use a larger subset of BioLiP so that every ligand is represented among a group of structures with similar sequences, but for PaperBLAST, we use the non-redundant set provided by BioLiP.)
• Every protein from EcoCyc, a curated database of the proteins in Escherichia coli K-12, is included, regardless of whether they are characterized or not.
• Proteins from the MetaCyc metabolic pathway database are included if they are linked to a paper in PubMed and their full sequence is known.
• Proteins from the Transport Classification Database (TCDB) are included if they have known substrate(s), have reference(s), and are not described as uncharacterized or putative. (Some of the references are not visible on the PaperBLAST web site.)
• Every protein from CharProtDB, a database of experimentally characterized protein annotations, is included.
• Proteins from the CAZy database of carbohydrate-active enzymes are included if they are associated with an Enzyme Classification number. Even though CAZy does not provide links from individual protein sequences to papers, these should all be experimentally-characterized proteins.
• Proteins from the REBASE database of restriction enzymes are included if they have known specificity.
• Every protein with an evidence-based reannotation (based on mutant phenotypes) in the Fitness Browser is included.
• Sequence-specific transcription factors (including sigma factors and DNA-binding response regulators) with experimentally-determined DNA binding sites from the PRODORIC database of gene regulation in prokaryotes.
• Putative transcription factors from RegPrecise that have manually-curated predictions for their binding sites. These predictions are based on conserved putative regulatory sites across genomes that contain similar transcription factors, so PaperBLAST clusters the TFs at 70% identity and retains just one member of each cluster.
• Coding sequence (CDS) features from the European Nucleotide Archive (ENA) are included if the /experiment tag is set (implying that there is experimental evidence for the annotation), the nucleotide entry links to paper(s) in PubMed, and the nucleotide entry is from the STD data class (implying that these are targeted annotated sequences, not from shotgun sequencing). Also, to filter out genes whose transcription or translation was detected, but whose function was not studied, nucleotide entries or papers with more than 25 such proteins are excluded. Descriptions from ENA rely on the original submitter of the sequence and cannot be updated by others, so they may be less reliable.

Except for GeneRIF and ENA, the curated entries include a short curated description of the protein's function. For entries from BioLiP, the protein's function may not be known beyond binding to the ligand. Many of these entries also link to articles in PubMed.

For more information see the PaperBLAST paper (mSystems 2017) or the code. You can download PaperBLAST's database here.

Changes to PaperBLAST since the paper was written:

• November 2023: incorporated PRODORIC and RegPrecise. Many PRODORIC entries were not linked to a protein sequence (no UniProt identifier), so we added this information.
• February 2023: BioLiP changed their download format. PaperBLAST now includes their non-redundant subset. SitesBLAST and Sites on a Tree use a larger non-redundant subset that ensures that every ligand is represented within each cluster. This should ensure that every binding site is represented.
• June 2022: incorporated some coding sequences from ENA with the /experiment tag.
• March 2022: incorporated BioLiP.
• April 2020: incorporated TCDB.
• April 2019: EuropePMC now returns table entries in their search results. This has expanded PaperBLAST's database, but most of the new entries are of low relevance, and the resulting snippets are often just lists of locus tags with annotations.
• February 2018: the alignment page reports the conservation of the hit's functional sites (if available from from Swiss-Prot or UniProt)
• January 2018: incorporated BRENDA.
• December 2017: incorporated MetaCyc, CharProtDB, CAZy, REBASE, and the reannotations from the Fitness Browser.
• September 2017: EuropePMC no longer returns some table entries in their search results. This has shrunk PaperBLAST's database, but has also reduced the number of low-relevance hits.

Many of these changes are described in Interactive tools for functional annotation of bacterial genomes.

Secrets

PaperBLAST cannot provide snippets for many of the papers that are published in non-open-access journals. This limitation applies even if the paper is marked as "free" on the publisher's web site and is available in PubmedCentral or EuropePMC. If a journal that you publish in is marked as "secret," please consider publishing elsewhere.

Omissions from the PaperBLAST Database

Many important articles are missing from PaperBLAST, either because the article's full text is not in EuropePMC (as for many older articles), or because the paper does not mention a protein identifier such as a locus tag, or because of PaperBLAST's heuristics. If you notice an article that characterizes a protein's function but is missing from PaperBLAST, please notify the curators at UniProt or add an entry to GeneRIF. Entries in either of these databases will eventually be incorporated into PaperBLAST. Note that to add an entry to UniProt, you will need to find the UniProt identifier for the protein. If the protein is not already in UniProt, you can ask them to create an entry. To add an entry to GeneRIF, you will need an NCBI Gene identifier, but unfortunately many prokaryotic proteins in RefSeq do not have corresponding Gene identifers.

References

PaperBLAST: Text-mining papers for information about homologs.
M. N. Price and A. P. Arkin (2017). mSystems, 10.1128/mSystems.00039-17.

Europe PMC in 2017.
M. Levchenko et al (2017). Nucleic Acids Research, 10.1093/nar/gkx1005.

Gene indexing: characterization and analysis of NLM's GeneRIFs.
J. A. Mitchell et al (2003). AMIA Annu Symp Proc 2003:460-464.

UniProt: the universal protein knowledgebase.
The UniProt Consortium (2016). Nucleic Acids Research, 10.1093/nar/gkw1099.

BRENDA in 2017: new perspectives and new tools in BRENDA.
S. Placzek et al (2017). Nucleic Acids Research, 10.1093/nar/gkw952.

The EcoCyc database: reflecting new knowledge about Escherichia coli K-12.
I. M. Keeseler et al (2016). Nucleic Acids Research, 10.1093/nar/gkw1003.

The MetaCyc database of metabolic pathways and enzymes.
R. Caspi et al (2018). Nucleic Acids Research, 10.1093/nar/gkx935.

CharProtDB: a database of experimentally characterized protein annotations.
R. Madupu et al (2012). Nucleic Acids Research, 10.1093/nar/gkr1133.

The carbohydrate-active enzymes database (CAZy) in 2013.
V. Lombard et al (2014). Nucleic Acids Research, 10.1093/nar/gkt1178.

The Transporter Classification Database (TCDB): recent advances
M. H. Saier, Jr. et al (2016). Nucleic Acids Research, 10.1093/nar/gkv1103.

REBASE - a database for DNA restriction and modification: enzymes, genes and genomes.
R. J. Roberts et al (2015). Nucleic Acids Research, 10.1093/nar/gku1046.

Deep annotation of protein function across diverse bacteria from mutant phenotypes.
M. N. Price et al (2016). bioRxiv, 10.1101/072470.