PaperBLAST

Full List of Papers Linked to VIMSS1936099

P9WGP5 bacterial ABC-type protein transporter (EC 7.4.2.5) from Mycobacterium tuberculosis (see 2 papers)
TC 3.A.5.2.2 / P0A5Y8 Protein translocase subunit secA 1, component of The general secretory pathway. SecA1 is the housekeeping protein; SecA2 is the accessory protein, essential for normal physiology and virulence from Mycobacterium tuberculosis (see 3 papers)
Rv3240c translocase from Mycobacterium tuberculosis H37Rv
YP_177950 protein translocase subunit SecA from Mycobacterium tuberculosis H37Rv

• substrates: proteins
  tcdb comment: The functions of SecA2 have been reviewed (Bensing et al. 2013)
• Impact of the elderly lung mucosa on <i>Mycobacterium tuberculosis</i> transcriptional adaptation during infection of alveolar epithelial cells
  Olmo-Fontánez, Microbiology spectrum 2024
  • “...tag M.tb gene A i vs A E i vs E Product/function Sec secretion system Rv3240C secA1 0.5768 1.2521 Probable preprotein translocase SecA1 1 subunit/involved in protein export Rv1821 secA2 0.4800 0.1331 Possible preprotein translocase ATPase SecA2/involved in protein export Rv2587C secD 0.1348 0.0324 Probable protein-export...”
• The unfoldase ClpC1 of Mycobacterium tuberculosis regulates the expression of a distinct subset of proteins having intrinsically disordered termini
  Lunge, The Journal of biological chemistry 2020 (secret)
• Systematic Identification of Mycobacterium tuberculosis Effectors Reveals that BfrB Suppresses Innate Immunity
  He, Molecular & cellular proteomics : MCP 2017
  • “...In addition, there are 2 (Rv0462, Rv3339c) and 3 (Rv3240c, Rv0203 and Rv2164c) unique membrane or secreted proteins that interact with proteins from the THP-1...”
  • “...(Rv0462) (20, 55), SahH (Rv3248c) (22), Rv3655c (23), SecA1 (Rv3240c) (56), FadD13 (Rv3089) (57), BfrA (Rv1876) (41, 51) and BfrB (Rv3841) (41, 51, 58) are...”
• Use of whole-genome sequencing to distinguish relapse from reinfection in a completed tuberculosis clinical trial
  Witney, BMC medicine 2017
  • “...Rv0530 S 1315992 pks4 NS 1540497 Rv1367c CP, non-essential S 2788333 plsB2 033 NS 3618159 Rv3240c, secA1 Protein export, essential 036 S 923816 lysT NS 924229 Rvnt13, pheU tRNA NS 924234 Rvnt13, pheU tRNA S 924263 pheU NS 1476973 Rvnr03, rrf 5S rRNA Function assigned using...”
• Comparative Genome and Network Centrality Analysis to Identify Drug Targets of Mycobacterium tuberculosis H37Rv
  Melak, BioMed research international 2015
  • “...0.0479375 2GQ3; 3S9I; 3S9Z; 3SAD; 3SAZ; 3SB0 Rv0467 23928.854 0.00293969 53 0.0481574 1F61; 1F8I; 1F8M Rv3240c 22790.56 0.00369075 64 0.0481586 1NKT; 1NL3 Rv0216 20616.273 0.01939864 57 0.0482126 2BI0 Rv1611 17798.758 0.00289133 57 0.0481961 3QJA; 3T40; 3T44; 3T55; 3T78; 4FB7 Rv2773c 17351.877 0.00189925 52 0.0480259 1C3V; 1P9L;...”
• A complex regulatory network controlling intrinsic multidrug resistance in Mycobacterium smegmatis
  Bowman, Molecular microbiology 2014
  • “...ID M. tuberculosis ID Protein ID 4 MSMEG_0059 Rv3868 ATPase, AAA family protein 9 MSMEG_1881 Rv3240c preprotein translocase subunit SecA 10 MSMEG_6091 Rv3596c negative regulator of genetic competence ClpC/mecB 16, 17 MSMEG_0456 Rv0006 DNA gyrase subunit A 15 MSMEG_0005 Rv0005 DNA gyrase subunit B 30 MSMEG_1670...”
• The ins and outs of Mycobacterium tuberculosis protein export
  Ligon, Tuberculosis (Edinburgh, Scotland) 2012
  • “...E. coli growth a M. tuberculosis homolog Required for M. tuberculosis growth b SecA yes Rv3240c (SecA1) yes Rv1821 (SecA2) no * 45 SecY yes Rv0732 yes SecE yes Rv0638 yes SecG no Rv1440 no SecD no Rv2587c yes SecF no Rv2586c yes YajC no Rv2588c...”
• Protein-protein interaction networks suggest different targets have different propensities for triggering drug resistance
  Padiadpu, Systems and synthetic biology 2010
  • “...category, while CcdA (Rv0527), IniA (Rv0342) and SecA1 (Rv3240c) are examples of the second, third and fourth categories respectively. Previously, we had...”
  • “...(Rv2720), Rv0818 Genes implicated in HGT SecA1 (Rv3240c), SecA2 (Rv1821), Rv3659c, Rv3660c Cytochromes CcdA (Rv0527), CcsA (Rv0529), CtaB (Rv1451), CtaC...”
• Polymerase chain reaction of secA1 on sputum or oral wash samples for the diagnosis of pulmonary tuberculosis
  Davis, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2009
  • “...with a PCR assay targeting the M. TB gene coding for the protein secA1(locus tag Rv3240c, GeneID 888860), a component of the major pathway of protein secretion across the cytoplasmic membrane.[ 13 ] Specimens were processed by ultrasonication for 15 minutes in a sodium-dodecyl-sulfate-Tris-HCl buffer with...”
• Mycobacterium tuberculosis interactome analysis unravels potential pathways to drug resistance
  Raman, BMC microbiology 2008
  • “...(Rv1629), LexA (Rv2720) Genes implicated in horizontal gene transfer [ 7 , 32 ] SecA1 (Rv3240c), SecA2 (Rv1821), Rv3659c, Rv3660c Cytochromes [ 32 ] CcdA (Rv0527), CcsA (Rv0529), CtaB (Rv1451), CtaC (Rv2200c), CtaD (Rv3043c), CtaE (Rv2193), CydA (Rv1623c), CydB (Rv1622c), CydC (Rv1620c), CydD (Rv1621c), Cyp121 (Rv2276),...”
  • “...-(569)Rv2687c 0.0901 Rv2243 -(2) Rv2245 -(565)Rv0340 -(447) Rv0342 0.1151 Rv0642c (MmaA4) -(350) Rv3248c (sahH) -(486) Rv3240c -(323)Rv3239c 0.1365 Rv0642c -(350) Rv3248c -(350) Rv1988 0.1385 Rv1350 -(90) Rv2245 -(596) Rv2737c -(429) Rv2882c (Frr) -(584)Rv0783c (EmrB) 0.3169 Rv2245 -(369) Rv1908c (KatG) -(350) Rv1988 0.3833 Rv0242c -(276) Rv2245 -(369)...”
• Two nonredundant SecA homologues function in mycobacteria
  Braunstein, Journal of bacteriology 2001
  • “...and 107 kDa, respectively. Subsequently, a secA1 homologue (rv3240c) was identified in the complete genome sequence of M. tuberculosis (8). Each of these secA1...”
• In Silico Drug Discovery Strategies Identified ADMET Properties of Decoquinate RMB041 and Its Potential Drug Targets against Mycobacterium tuberculosis
  Knoll, Microbiology spectrum 2022
  • “...Thr A:223, Val A:255, Asp A:257, Phe A:259, Ser A:281, Leu A:288 SecA1 (Rv3240) 1NKT P9WGP5 4.90 6.6 Gln A:80, Phe A:83, Gln A:86, Lys A:107, Leu A:109, Arg A:137, Trp A:141, Asp A:493, Asn A:499, Asp A:501, Arg A:573 GlnA1 (Rv2220) 2bvc P9WN39 4.71 6.5...”
• In Vitro Interaction of the Housekeeping SecA1 with the Accessory SecA2 Protein of Mycobacterium tuberculosis.
  Prabudiansyah, PloS one 2015
  • GeneRIF: The housekeeping protein SecA1 forms heterodimers with the accessory SecA2 protein of Mycobacterium tuberculosis in solution.
• Structural Similarities and Differences between Two Functionally Distinct SecA Proteins, Mycobacterium tuberculosis SecA1 and SecA2.
  Swanson, Journal of bacteriology 2015
  • GeneRIF: Many of the structural features of SecA1 are conserved in the SecA2 structure, including putative contacts with the SecYEG channel.
• ADP-dependent conformational changes distinguish Mycobacterium tuberculosis SecA2 from SecA1.
  D'Lima, The Journal of biological chemistry 2014
  • GeneRIF: conformational change involving closure of the clamp in SecA2 may provide a mechanism for the cell to direct protein export through the conventional SecA1 pathway under normal growth conditions
• ATPase activity of Mycobacterium tuberculosis SecA1 and SecA2 proteins and its importance for SecA2 function in macrophages.
  Hou, Journal of bacteriology 2008
  • GeneRIF: Here, M. tuberculosis SecA1 and SecA2 are shown to bind ATP with high affinity

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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.