PaperBLAST

PaperBLAST Hits for 96 a.a. (MTAALTWEKH...)

Show query sequence

>96 a.a. (MTAALTWEKH...)
MTAALTWEKHNDVLALTGELDRDTLMSFWTARQAQMDCVRTVDVSGLAHVDSAGLAMLVR
LKSEQGDTPLVLAGVSPNLQMLISLYGVASEFSDNQ

Running BLASTp...

Found 7 similar proteins in the literature:

ETAE_0508 putative anti-sigma B factor antagonist from Edwardsiella tarda EIB202
40% identity, 81% coverage

• Genome sequence of the versatile fish pathogen Edwardsiella tarda provides insights into its adaptation to broad host ranges and intracellular niches
  Wang, PloS one 2009
  • “...rpoN RNA polymerase factor sigma-54 RpoN ETAE_2873 rpoS RNA polymerase factor sigma-38 RpoS Anti-sigma factor ETAE_0508 Putative anti-sigma B factor antagonist ETAE_0576 dnaK Molecular chaperone ETAE_1223 flgM Anti-sigma 28 factor ETAE_1867 pspA Phage shock protein A, suppresses 54 -dependent transcription ETAE_2684 Anti-sigma regulatory factor (Ser/Thr protein...”

y0142 hypothetical protein from Yersinia pestis KIM
41% identity, 88% coverage

• A transposon site hybridization screen identifies galU and wecBC as important for survival of Yersinia pestis in murine macrophages
  Klein, Journal of bacteriology 2012
  • “...pestis biovar 2.MED, pCD1 pMT1 pPCP1 pgm KIM6 phoP127-429 KIM6 y0142 nt 61-y0145 nt 724 KIM6 y0157 nt 22-y0159 nt 151 KIM6 gshA40-1560 KIM6 wecB nt 46-wecC nt...”
  • “...was constructed by deleting a region of the chromosome encoding y0142 to y0145 (Table 1). A summary of the genes inactivated in KIM6 and the phenotypes of the...”

SG3199 possible anti-sigma factor antagonist from Salmonella enterica subsp. enterica serovar Gallinarum str. 287/91
38% identity, 94% coverage

• Chemical Conjugation in Drug Delivery Systems
  Eras, Frontiers in chemistry 2022
  • “...Initial U.S. Approval: 2021, 2021 ). Zynlonta comprises a humanized mAb Anti CD19 conjugated to SG3199, a cytotoxic pyrrolobenzodiazepine (PBD) dimer alkylating agent, through a protease-cleavable valinealanine linker, and using maleimido caproyl and eight PEG units ( Figure 8G ). This ADC is used for adult...”
• 33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018
  , Journal for immunotherapy of cancer 2018
  • “...colon cancer-derived cell lines, MC38 and CT26. All three cell lines were highly sensitive to SG3199, the PBD dimer toxin of sur301, irrespective of their CD25-status. In vivo, sur301 anti-tumor activity was investigated in the syngeneic MC38 and CT26 models, two immunogenic colon cancer models with...”

Z4554 No description from Escherichia coli O157:H7 EDL933
34% identity, 71% coverage

• Disruption of rcsB by a duplicated sequence in a curli-producing Escherichia coli O157:H7 results in differential gene expression in relation to biofilm formation, stress responses and metabolism
  Sharma, BMC microbiology 2017
  • “...and lipid metabolism pgsA Z3000 Phosphatidylglycerophosphate synthetase +1.47 0.01 plsC Z4372 1-acyl-sn-glycerol-3-phosphate +1.30 2.3E-03 yrbB Z4554 Phospholipid ABC transporter 1.87 2.0E-03 yrbC Z4555 Phospholipid ABC transporter 1.97 3.0E-04 Phosphate metabolism phoU Z5215 Transcriptional regulator 2.09 4.0E-03 pstB Z5216 Phosphate transporter ATP-binding protein 2.02 0.02 pstA Z5217...”

YrbB / b3191 intermembrane phospholipid transport system protein MlaB from Escherichia coli K-12 substr. MG1655 (see 7 papers)
MLAB_ECOLI / P64602 Intermembrane phospholipid transport system binding protein MlaB from Escherichia coli (strain K12) (see 3 papers)
TC 3.A.1.27.3 / P64602 Probable phospholipid ABC transporter-binding protein mlaB, component of ABC transporter maintaining outer membrane (OM) lipid asymmetry, MlaABCDEF (YrbABCDEF) (Malinverni and Silhavy, 2009). MlaA (VacJ) is a "spreading" protein, essential for Shigella from Escherichia coli (strain K12) (see 3 papers)
NP_417658 intermembrane phospholipid transport system protein MlaB from Escherichia coli str. K-12 substr. MG1655
b3191 orf, hypothetical protein from Escherichia coli str. K-12 substr. MG1655
34% identity, 95% coverage

• function: Part of the ABC transporter complex MlaFEDB, which is involved in a phospholipid transport pathway that maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane (PubMed:19383799, PubMed:27529189). MlaB plays critical roles in both the assembly and activity of the complex. May act by modulating MlaF structure and stability (PubMed:27529189).
  subunit: The complex is composed of two ATP-binding proteins (MlaF), two transmembrane proteins (MlaE), two cytoplasmic solute-binding proteins (MlaB) and six periplasmic solute-binding proteins (MlaD).
  disruption phenotype: Mutation leads to accumulation of phospholipid in the outer leaflet of the outer membrane and increased outer membrane permeability. It confers sensitivity to SDS-EDTA.
• substrates: phospholipids
  tcdb comment: pathogenicity (Suzuki et al., 1994). The ABC transporter, MlaEFBD, provides energy for maintaining OM lipid asymmetry via the transport of aberrantly localized phospholipids (PLs) from the OM to the inner membrane (IM) (Thong et al. 2016). MlaD forms stable hexamers within the complex, functions in substrate binding with strong affinity for PLs, and modulates ATP hydrolytic activity. MlaB plays critical roles in both the assembly and activity of the transporter. MlaA forms a complex with OmpC and OmpF in the outer membrane to extract PLs from the outer leaflet of the OM (Chong et al. 2015). MlaA is a monomeric α-helical OM protein that functions as a phospholipid translocation channel, forming a ~20-Å-thick doughnut embedded in the inner leaflet of the OM with a central, amphipathic pore (Abellón-Ruiz et al. 2017). This architecture prevents access of inner leaflet phospholipids to the pore, but allows outer leaflet phospholipids to bind to a pronounced ridge surrounding the channel
• Structure of MlaFB uncovers novel mechanisms of ABC transporter regulation.
  Kolich, eLife 2020
  • GeneRIF: Structure of MlaFB uncovers novel mechanisms of ABC transporter regulation.
• Defining key roles for auxiliary proteins in an ABC transporter that maintains bacterial outer membrane lipid asymmetry.
  Thong, eLife 2016
  • GeneRIF: The authors further demonstrate that MlaD forms extremely stable hexamers within the complex, functions in substrate binding with strong affinity for phospholipids, and modulates ATP hydrolytic activity. In addition, MlaB plays critical roles in both the assembly and activity of the MlaFEDB ATP-binding cassette transporter.
• The Mla system and its role in maintaining outer membrane barrier function in Stenotrophomonas maltophilia
  Coves, Frontiers in cellular and infection microbiology 2024
  • “...Ttg2ABCDE (PA4452-PA4456) or VacJ (PA2800) and E. coli K-12 substr. MG1655 genes encoding MlaFEDCB (b3195- b3191) or MlaA (b2346) were identified as follows. Protein sequences were first analyzed using BLAST, PSI-BLAST and CDD within NCBI ( http://ncbi.nlm.nih.gov/ ). Orthologous sequences in other species were searched using...”

SO3950 SpoIIAA family protein from Shewanella oneidensis MR-1
34% identity, 91% coverage

• Global transcriptome analysis of Shewanella oneidensis MR-1 exposed to different terminal electron acceptors
  Beliaev, Journal of bacteriology 2005
  • “...was displayed by genes encoding putative spoIIA family (SO3950) and aerobic respiration control (arcA, SO3988) proteins. In addition, over fourfold increase in...”

VP2660 putative anti-sigma B factor antagonist from Vibrio parahaemolyticus RIMD 2210633
33% identity, 79% coverage

• Insights into virulence: structure classification of the Vibrio parahaemolyticus RIMD mobilome
  Kinch, mSystems 2023
  • “...MlaE (VP2663) and MlaF (VP2664), retaining 27% and 37% sequence identity, respectively. The classic MlaB (VP2660) SpoIIaa-like domain is instead fused to the HGT MlaE-like VP1361 ( Fig. 3D , teal), and the periplasmic HGT MlaD-like VP1364 has an additional helical domain at the C-terminus (...”

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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.