PaperBLAST

Full List of Papers Linked to VIMSS1936185

ACCD4_MYCTU / O53578 Biotin-dependent long chain acyl-coenzyme A carboxylase beta4 subunit; EC 2.1.3.- from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (see 3 papers)
Rv3799c PROBABLE PROPIONYL-CoA CARBOXYLASE BETA CHAIN 4 ACCD4 (PCCASE) (PROPANOYL-COA:CARBON DIOXIDE LIGASE) from Mycobacterium tuberculosis H37Rv

• function: Component of a biotin-dependent acyl-CoA carboxylase complex. This subunit transfers the CO2 from carboxybiotin to the CoA ester substrate (PubMed:16354663, PubMed:28222482). When associated with the alpha3 subunit AccA3, the beta5 subunit AccD5 and the epsilon subunit AccE5, forms the LCC complex, which is involved in the carboxylation of long chain acyl-CoA (PubMed:16354663, PubMed:28222482). The LCC complex can use C16-C24 substrates, the highest specific activity is obtained with carboxy-C20-CoA (PubMed:28222482). Has low activity with acetyl- CoA and propionyl-CoA (PubMed:16354663).
  subunit: The biotin-dependent long-chain acyl-CoA carboxylase (LCC) complex is composed of AccA3, which contains the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains, and AccD4, which contains the carboxyl transferase (CT) domain (PubMed:16354663, PubMed:28222482). The complex also contains the beta5 subunit AccD5 and the epsilon subunit AccE5. The four subunits are essential for activity, but AccD5, together with AccE5, probably plays a structural role rather than a catalytic one (PubMed:28222482).
• Polyphosphate kinase-1 regulates bacterial and host metabolic pathways involved in pathogenesis of Mycobacterium tuberculosis
  Chugh, Proceedings of the National Academy of Sciences of the United States of America 2024
  • “...ACC family of enzymes. These included AccA1 (Rv2501c), AccD1 (Rv2502c), AccA2 (Rv0973c), AccD2 (Rv0974c), AccD4 (Rv3799c), AccD5 (Rv3280), and AccE5 (Rv3281) ( SI Appendix , Table S1 and Dataset S1 ). Since polyP has been demonstrated to replace ATP as a phosphate donor in various metabolic...”
• Revolutionizing control strategies against Mycobacterium tuberculosis infection through selected targeting of lipid metabolism
  Kim, Cellular and molecular life sciences : CMLS 2023
  • “...Drug Regulation Function accA3 rv3285 H Down accD4- pks13fadD32 rv3799c, rv3800c, rv3801c H Down accD6 rv2247 H VAN Up Down acpM rv2244 H, Thiolactomycin Up...”
• Molecular Mechanisms of MmpL3 Function and Inhibition
  Williams, Microbial drug resistance (Larchmont, N.Y.) 2023
  • “...red) and is formed by the acyl-CoA carboxylase complex consisting of AccA3 (Rv3285) and AccD4 (Rv3799c). 42 Along the other branch, C 1618 short chain FAs are elongated by the -ketoacyl acyl carrier protein (ACP) synthase mtFabH (Rv0533c), which condenses a malonyl substrate, carried by the...”
• The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development
  Yan, Molecular biomedicine 2022
  • “...9 dfrA (Rv2763c) Dihydrofolate reductase DHFR [ 336 ] Synthesis of nucleic acid 10 accD4 (Rv3799c) AccD4-containing acyl-CoA carboxylase [ 337 ] Biosynthesis of mycolic acids 11 fabH (Rv0533c) [ 338 ] 3-oxoacyl-ACP synthase III, FabH Synthesis of mycolic acid (responsible for initiation of FAS II...”
• Identification of Mycobacterium tuberculosis Antigens with Vaccine Potential Using a Machine Learning-Based Reverse Vaccinology Approach
  Teahan, Vaccines 2021
  • “...(Rv3682), PonA1 (Rv0050), FadD15 (Rv2187), LdtB (Rv2518c), PbpB (Rv2163c), FadD30 (Rv0404), FbpC (Ag85C) (Rv0129c), AccD4 (Rv3799c), FadD32 (Rv3801c), hypothetical protein Rv3811 (Rv3811), LprQ (Rv0483), PbpA (Rv0016c), FadD19 (Rv3515c) DNA Repair RecA (Rv2737c), HtpG (Rv2299c), UvrA (Rv1638), LigD (Rv0938), RecG (Rv2973c), UvrB (Rv1633) Interaction with host immune...”
  • “...IleS (Rv1536), LprG (Rv1411c) Response to acidic pH FadD13 (Rv3089), Tgs4 (Rv3088), Icl1 (Rv0467), AccD4 (Rv3799c) Response to hypoxia GroEL2 (Rv0440), PonA1 (Rv0050), Tgs4 (Rv3088), Icl1 (Rv0467), AccD4 (Rv3799c), PE_PGRS11 (Rv0754), Tuf (Rv0685), SdhA (Rv3318), probable succinate dehydrogenase (Rv0248c) Response to nitrosative or oxidative stress Mpa...”
• Phylogenomic Reappraisal of Fatty Acid Biosynthesis, Mycolic Acid Biosynthesis and Clinical Relevance Among Members of the Genus Corynebacterium
  Dover, Frontiers in microbiology 2021
  • “...p96927 -Hydroxyacyl-acp dehydratase subunit FAS-II hadC Rv0637 501 p9wfj9 -Hydroxyacyl-acp dehydratase subunit MA condensation accD4 Rv3799c 1,569 o53578 Biotin-dependent long chain acyl-amp carboxylase beta4 subunit MA condensation pks13 Rv3800c 5,202 o53579 Polyketide synthase MA condensation fadD32 Rv3801c 1914 o53580 Long-chain-fatty-acid-amp ligase MA condensation accD5 Rv3280 1,647...”
• The influence of AccD5 on AccD6 carboxyltransferase essentiality in pathogenic and non-pathogenic Mycobacterium
  Pawelczyk, Scientific reports 2017
  • “...suggested that among the six carboxyltransferases in M. tuberculosis AccD6 (Rv2247), AccD5 (Rv3280) and AccD4 (Rv3799c) are essential for cell viability 13 14 and are expressed at high levels during mycolic acid biosynthesis 14 15 . Thus, in recent years, efforts have been made to identify...”
  • “...vivo studies are necessary to conclusively establish the functional role of AccD5 in mycobacteria. AccD4 (Rv3799c) remains the least characterized mycobacterial carboxyltransferase. A Corynebacterium glutamicum mutant devoid of an accD4 homolog exhibited a mycolate-less phenotype and a lack of tetradecylmalonic acid, the predicted product of the...”
• A systematic review of East African-Indian family of Mycobacterium tuberculosis in Brazil
  Duarte, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 2017
  • “...Rv3711c Rv3711c_491t>C NS 13 4156503 Rv3711c Rv3711c_227g>A NS 13 4182695 Rv3731 Rv3731_938g>A NS 13 4255922 Rv3799c Rv3799c_27t>C S 34 S, synonymous; NS, non-synonymous. Our systematic review of the literature regarding EAI occurrence in studies of Mtb diversity performed in Brazil yielded 175 articles, of which 14...”
• Comparative genomics of cell envelope components in mycobacteria
  Banerjee, PloS one 2011
  • “...protein) shares significant MI and PCC with mycolate genes like Rv3801c ( fadD32 ) and Rv3799c ( accD4 ), and hence, Rv0227c may be functionally linked to mycolic acid biosynthesis ( Figure 6 ). It has also been proved to be essential for growth by Sassetti...”
  • “...biosynthesis Rv3804c 242 Rv1273c 241 Rv0503c 240 Rv0470c 239 Rv3280 99 Rv3802c 95 Rv3801c 94 Rv3799c 93 Rv2509 92 Rv1484 65 Rv0644c 51 Rv0643c 50 Arabinogalactan biosynthesis Rv3809c 248 Rv3794 246 Rv3464 243 Rv3265c 242 Rv2361c 240 Rv1086 237 Rv1302 236 Rv2152c 113 Rv1315 111 Rv2682c...”
• Disruption of cell wall fatty acid biosynthesis in Mycobacterium tuberculosis using a graph theoretic approach
  Baths, Theoretical biology & medical modelling 2011
  • “...Index) RV2501C 15 RV2967C 15 RV0973C 15 Rv3285 14.5 RV0263C 12 RV3280 11.5 RV2502C 11.5 RV3799C 11.5 RV0974C 11.5 RV2247 11.5 RV2888C 10 RV3375 10 RV3011C 10 RV1263 10 RV2363 10 RV1384 9 package nearnessindex; import java.util.Scanner; import java.util.regex .*; import java.io .*; /** * *...”
• Fatty acid biosynthesis in actinomycetes
  Gago, FEMS microbiology reviews 2011
  • “...tuberculosis has not been well characterized at the biochemical level. The fact that accD4 ( Rv3799c ) is clustered with and transcribed in the same orientation as the genes pks13 ( Rv3800c ) and fadD32 ( Rv3801c ) ( Fig. 5 ), a condensase and an...”
• Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is inhibited by the antimycobacterial agent tetrahydrolipstatin
  Parker, PloS one 2009
  • “...genes involved in joining the and mero mycolates are located in a cluster, beginning with Rv3799c and extending at least until Rv3804c . The role of each enzyme encoded by these five genes is fairly well understood, except for Rv3802c . Rv3802 is one of seven...”
  • “...acid and transferring it to trehalose or arabinogalactan are located in a gene cluster from Rv3799c to at least Rv3804c ( Figure 1 ). The role of each enzyme encoded by these five genes is fairly well understood, except for the product of Rv3802c , though...”
• The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target
  Eoh, Tuberculosis (Edinburgh, Scotland) 2009
  • “...importantly, His49 of the E. coli enzyme amino acid is missing in Rv3379c. 43 Recombinant Rv3799c showed no DXS activity, 43 suggesting that Rv2682c is the only functional M. tuberculosis DXS. A.3. HTS campaign for 1-deoxy-D-xylulose 5-phosphate synthase Most reported DXS assays utilize either TLC or...”
• AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis
  Daniel, Journal of bacteriology 2007
  • “...(Rv3285) accD1 (Rv2502c) accD2 (Rv0974c) accD3 (Rv0904c) accD4 (Rv3799c) accD5 (Rv3280) accD6 (Rv2247) accE (Rv3281) sigA (Rv2703) a F, forward primer; R,...”
• Mycobacterial bacilli are metabolically active during chronic tuberculosis in murine lungs: insights from genome-wide transcriptional profiling
  Talaat, Journal of bacteriology 2007
  • “...rv0348 rv0981 rv1062 rv2080 rv2326c rv3079c rv3103c rv3685c rv3799c rv3830c rv3871 a Product PntAB Rv0348 MprA Rv1062 LppJ Rv2326c Rv3079c Rv3103c Rv3685c AccD4...”
• Targeting the formation of the cell wall core of M. tuberculosis
  Barry, Infectious disorders drug targets 2007
  • “...the biotin carboxyl carrier protein), AccD4 and AccD5 (Rv3799c and Rv3280, the two apparently required subunits of the acyl-CoA carboxylase) [155]. AccA3 and...”
  • “...Rv0503c Meromycolyl Carboxylase (AccA3) Rv3285, (AccD4) Rv3799c, (AccD5) Rv3280 Author Manuscript Fatty Acyl-AMP ligase (FadD32) Rv3801c Condensase (Pks13)...”
• Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv
  Oh, The Journal of biological chemistry 2006
  • “...The primers used for amplification of the genes Rv3285 (3), Rv3799c (4), Rv3280 (5), and Rv3281 () are listed in Table 1. All of the PCR products were cloned...”
  • “...and subcloned in pET16b or pET28a () vectors. Rv3285, Rv3799c, and Rv3280 were expressed in pET16b, and Rv3281 was expressed in pET28a (). In these vectors, the...”
• Identification of Mycobacterium avium genes that affect invasion of the intestinal epithelium
  Miltner, Infection and immunity 2005
  • “...1.8 0.1 3.1 0.4 M. tuberculosis accD4 (Rv3799c) (proninoyl-CoA carboxylase) FadE20 (Rv2724c) (acyl-CoA dehydrogenase) Rv3802c (probable membrane protein) Rv3720...”
• Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis
  Takayama, Clinical microbiology reviews 2005
  • “...No No No No accD4 accD5 fadD32 pks13 Rv3799c Rv3280 Rv3801c Rv3800c Acyl-CoA carboxylase Acyl-CoA carboxylase Fatty acyl-AMP ligase Polyketide synthase-13 Yes...”

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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.