PaperBLAST

PaperBLAST Hits for 85 a.a. (MSDGKKTKTT...)

Show query sequence

>85 a.a. (MSDGKKTKTT...)
MSDGKKTKTTVDIYGQHFTIVGEESRAHMRYVAGIVDDKMREINEKNPYLDINKLAVLTA
VNVVHDYVKLQEKCEKLERQLKEKD

Running BLASTp...

Found 10 similar proteins in the literature:

ZAPA_BACSU / P94542 Cell division protein ZapA; Z ring-associated protein ZapA from Bacillus subtilis (strain 168) (see paper)
NP_390739 regulator of cell division from Bacillus subtilis subsp. subtilis str. 168
BSU28610 cell division protein ZapA from Bacillus subtilis subsp. subtilis str. 168
100% identity, 100% coverage

• function: Activator of cell division through the inhibition of FtsZ GTPase activity, therefore promoting FtsZ assembly into bundles of protofilaments necessary for the formation of the division Z ring. It is recruited early at mid-cell but it is not essential for cell division (By similarity).
  subunit: Homodimer. Interacts with FtsZ (By similarity).
• Lateral FtsZ association and the assembly of the cytokinetic Z ring in bacteria.
  Monahan, Molecular microbiology 2009 (PubMed)
  • GeneRIF: This suggests that ZapA functions to promote the helix-to-ring transition of FtsZ by stimulating lateral FtsZ association.
• The effect of MinC on FtsZ polymerization is pH dependent and can be counteracted by ZapA.
  Scheffers, FEBS letters 2008 (PubMed)
  • GeneRIF: The inhibitory effect of MinC on FtsZ polymerization is counteracted by the presence of ZapA, a protein that promotes FtsZ filament bundling.
• A widely conserved bacterial cell division protein that promotes assembly of the tubulin-like protein FtsZ
  Gueiros-Filho, Genes & development 2002
  • “...Agrobacterium tumefaciens, NP_356887; Bacillus subtilis, NP_390739; Caulobacter vibrioides, NP_422041; Escherichia coli, NP_289478; Haemophilus influenzae,...”
• Secondary structural entropy in RNA switch (Riboswitch) identification
  Manzourolajdad, BMC bioinformatics 2015
  • “...0.2611 79 yorE BSU20410 0.825 91 2926840 2926996 reverse BSU28630 pheT -89 0.3185 1021 yshA BSU28610 0.823 92 2054401 2054557 reverse BSU18840 xynA -119 0.3822 550 pps BSU18830 0.822 93 610963 611119 reverse BSU05660 ydgI -1149 0.3121 2277 dinB BSU05630 0.822 94 3457144 3457300 reverse BSU33700...”
  • “...0.2611 79 yorE BSU20410 0.825 61 2926840 2926996 reverse BSU28630 pheT -89 0.3185 1021 yshA BSU28610 0.823 62 2054401 2054557 reverse BSU18840 xynA -119 0.3822 550 pps BSU18830 0.822 63 610963 611119 reverse BSU05660 ydgI -1149 0.3121 2277 dinB BSU05630 0.822 64 3457144 3457300 reverse BSU33700...”
• Cell division in Corynebacterineae
  Donovan, Frontiers in microbiology 2014
  • “...of Z-ring assembly Hale and De Boer, 1997 ; Slayden et al., 2006 zapA b2910 BSU28610 Positive regulator of FtsZ assembly, promotes Z-ring polymerization and protofilament bundling Gueiros-Filho and Losick, 2002 zapB b3928 Interacts with ZapA and FtsZ, stabilize Z-ring via ZapA Ebersbach et al., 2008...”

SA0988 hypothetical protein from Staphylococcus aureus subsp. aureus N315
SAR1114 conserved hypothetical protein from Staphylococcus aureus subsp. aureus MRSA252
47% identity, 86% coverage

• Characterizing the effects of inorganic acid and alkaline shock on the Staphylococcus aureus transcriptome and messenger RNA turnover
  Anderson, FEMS immunology and medical microbiology 2010
  • “...* 5.4 2.5 30 fabD SA1244 malonyl CoA-acyl transacylase sa_c318s157_a_at * 2.7 2.5 30 fabF SA0988 acyl-carrier-protein synthase II sa_c4695s4014_a_at 5.8 2.5 2.5 SA0207 hypothetical protein sa_c6975s6099_a_at 6.3 2.5 2.5 SA0317 lipase precursor sa_c10609s11066_s_at 3.3 2.5 ND SA0390 lipase precursor sa_c1242s1022_a_at * 4.3 2.5 15 SA1240...”
  • “...2.5 2.5 fabD SA1244 malonyl CoA-acyl carrier protein transacylase sa_c318s157_a_at * 5.5 2.5 2.5 fabF SA0988 3-oxoacyl-(acyl-carrier-protein) synthase II sa_c9967s8662_at 6.4 2.5 5 fabG1 SA1245 3-oxoacyl-reductase, acyl-carrier sa_c312s155_a_at 20.3 2.5 2.5 fabH SA0987 3-oxoacyl-(acyl-carrier-protein) synthase III sa_c7805s6807_a_at 2.2 2.5 2.5 mvk SA0636 mevalonate kinase sa_c1256s1031_a_at 7.9...”
• The Staphylococcus aureus response to unsaturated long chain free fatty acids: survival mechanisms and virulence implications
  Kenny, PloS one 2009
  • “...protein 2.33 3.44E-02 SAR1086 conserved hypothetical protein 3.45 6.54E-03 SAR1095 conserved hypothetical protein 2.86 2.16E-02 SAR1114 putative cell division protein ZapA 2.38 3.96E-03 SAR1148 putative DNA-binding protein 2.38 2.66E-02 SAR1154 MraZ protein 2.50 3.00E-03 SAR1312 hypothetical protein 3.85 3.27E-02 SAR1315 hypothetical protein 2.38 2.99E-03 SAR1316 hypothetical...”

SAUSA300_1040 hypothetical protein from Staphylococcus aureus subsp. aureus USA300_FPR3757
47% identity, 86% coverage

• Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) Genetic Factors Involved in Human Endothelial Cells Damage, an Important Phenotype Correlated with Persistent Endovascular Infection
  Xiao, Antibiotics (Basel, Switzerland) 2022
  • “...epiD lantibiotic epidermin biosynthesis protein EpiD 26.84 3.46 SAUSA300_2332 hypothetical heat shock protein 26.78 8.46 SAUSA300_1040 hypothetical hypothetical protein 26.74 8.21 SAUSA300_2280 fosB fosfomycin resistance protein FosB 26.67 8.68 SAUSA300_1750 hypothetical conserved hypothetical protein 26.62 9.44 SAUSA300_0883 hypothetical putative surface protein 26.40 12.90 SAUSA300_1964 hypothetical hypothetical...”
  • “...3.61 59.90 1.08 SAUSA300_0206 hypothetical 60.82 6.24 69.33 0.48 SAUSA300_0335 hypothetical 60.15 8.31 63.35 2.06 SAUSA300_1040 EC damage 30% in 384-well plates hypothetical 26.74 8.21 30.92 a SAUSA300_1875 hypothetical 24.52 10.68 30.51 a SAUSA300_0871 hypothetical 24.49 12.19 28.60 a SAUSA300_1950 hypothetical 23.24 9.64 25.87 a SAUSA300_0253...”

SXYL_01801 cell division protein ZapA from Staphylococcus xylosus
41% identity, 89% coverage

• Adaptation of Staphylococcus xylosus to Nutrients and Osmotic Stress in a Salted Meat Model
  Vermassen, Frontiers in microbiology 2016
  • “...CTP synthase 5.7 5.2 4.3 Division SXYL_01703 ftsA Cell division protein FtsA 2.9 2.8 2.6 SXYL_01801 zapA Cell division protein ZapA 2.7 2.2 2.2 SXYL_01704 divIB Cell division protein DivIB 4.8 3.5 2.7 SXYL_00848 Cell division protein, FtsW/RodA/SpoVE family 4.1 2.6 2.0 SXYL_01212 mreD Cell shape-determining...”

EF1402 conserved domain protein from Enterococcus faecalis V583
37% identity, 55% coverage

• Synergistic Microbicidal Effect of Auranofin and Antibiotics Against Planktonic and Biofilm-Encased S. aureus and E. faecalis
  She, Frontiers in microbiology 2019
  • “...4 E. faecalis ATCC 29212 b 0.25 >32 2 >32 EF1401 0.25 >32 1 >32 EF1402 0.25 >32 1 >32 EF1403 0.5 32 1 >32 EF1405 b 0.5 >32 2 >32 EF1407 b 0.5 >32 2 >32 EF1410 0.5 >32 2 >32 EF1411 b 0.25 >32...”
  • “...SA1435 (MRSA) FOF 32 8 0.25 0.5 No interaction AF 0.5 0.125 0.25 E. faecalis EF1402 CHL 8 1 0.125 0.375 Synergy AF 0.25 0.0625 0.25 EF1403 CHL 16 0.25 0.016 0.266 Synergy AF 0.5 0.125 0.25 Determination of the Susceptibility of Biofilms Staphylococcus aureus LZB1...”
• Enterococcus faecalis Glycolipids Modulate Lipoprotein-Content of the Bacterial Cell Membrane and Host Immune Response
  Theilacker, PloS one 2015
  • “...binding protein lipoprotein EF3256 -0.569 Pheromone cAD1 lipoprotein lipoprotein EF1548 -0.577 Ribosomal protein S1 cytoplasmic EF1402 -0.580 Conserved domain protein cytoplasmic EF1193 -0.592 DNA binding response regulator VicR cytoplasmic EF2932 -0.600 AhpC TSA family protein cytoplasmic EF1584 -0.607 Cysteine synthase cytoplasmic EF0997 -0.696 Cell division protein...”

UC7_RS12585 cell division protein ZapA from Enterococcus caccae ATCC BAA-1240
36% identity, 53% coverage

• Analysis of Temporal Changes in Growth and Gene Expression for Commensal Gut Microbes in Response to the Polyphenol Naringenin
  Firrman, Microbiology insights 2018
  • “...UC7_RS13470 Hypothetical protein 1.5 Unknown UC7_RS16155 Hypothetical protein 1.5 Unknown UC7_RS14625 Hypothetical protein 1.5 Unknown UC7_RS12585 Cell division protein ZapA 1.5 Cell division UC7_RS16570 Hypothetical protein 1.5 Unknown UC7_RS16330 Acyl carrier protein 1.5 Protein synthesis Table 6. Genes downregulated by Enterococcus caccae in response to naringenin....”

CAC2355 Hypothetical protein from Clostridium acetobutylicum ATCC 824
37% identity, 33% coverage

• A Strongly Fluorescing Anaerobic Reporter and Protein-Tagging System for Clostridium Organisms Based on the Fluorescence-Activating and Absorption-Shifting Tag Protein (FAST)
  Streett, Applied and environmental microbiology 2019
  • “...of the hypothetical FtsZ interacting cell division protein ZapA (CAC2355). The C-terminal end of C. acetobutylicum ZapA was fused to the N-terminal end of FAST...”

CD0701 hypothetical protein from Clostridium difficile 630
34% identity, 36% coverage

• Use of mCherry Red fluorescent protein for studies of protein localization and gene expression in Clostridium difficile
  Ransom, Applied and environmental microbiology 2015
  • “...pRAN473. PCR was used to amplify a zapA homolog (cd0701) from the JIR8094 chromosome with primers RP176 and RP177. The resulting PCR fragment was digested with...”
  • “...mediates tetramerization (31, 32). In C. difficile 630, locus CD0701 is annotated as a "putative cell division protein" based on its similarity to ZapA (13,...”

CAETHG_RS06665 cell division protein ZapA from Clostridium autoethanogenum DSM 10061
38% identity, 35% coverage

• Adaptive laboratory evolution of Clostridium autoethanogenum to metabolize CO₂ and H₂ enhances growth rates in chemostat and unravels proteome and metabolome alterations
  Heffernan, Microbial biotechnology 2024
  • “...metabolism were also amongst highly increased proteins in Evolved D, including a monosaccharide ABC transporter (CAETHG_RS06665) and a gluconate transporter and kinase (CAETHG_RS15960 and 15965) with log 2 FCs of 3.3, 2.0 and 2.3. Notable strongly decreased DE proteins in Evolved D included proteins related to...”

XF2012 conserved hypothetical protein from Xylella fastidiosa 9a5c
35% identity, 82% coverage

• In vitro Determination of Extracellular Proteins from Xylella fastidiosa
  Mendes, Frontiers in microbiology 2016
  • “...Phage-related protein, xfp4 30.4 XF1649 XF1379 P76513 No No 0.065 Phosphoserine aminotransferase (PSAT) 39.6 XF2326 XF2012 Q9PB19 No No 0.163 PilA2 Tfp pilus assembly protein, 15.4 XF2539 XF2216 P17837 No No 0.937 Porin O (POP) 43.7 XF0975 XF0803 P33976 No No 0.717 POP O (POP) 45...”

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Statistics

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.