Gene Rv3875 (esat-6)
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Unknown. Elicits high level of inf-gamma from memory effector cells during the first phase of a protective immune response. Exported protein cotranscribed with Rv3874|MT3988|MTV027.09|LHP|CFP10. |
| Product | 6 kDa early secretory antigenic target EsxA (ESAT-6) |
| Comments | Rv3875, (MT3989, MTV027.10), len: 95 aa. EsxA, early secretory antigenic target (see citations below), identical to Q57165|O84901|ESAT6 early secretory antigenic target from Mycobacterium bovis (94 aa), FASTA scores: opt: 596, E(): 4.6e-33, (100.0% identity in 94 aa overlap). Also similar to Q50206|ESA6_MYCLE|ESAT6|ESX|L45|ML0049|MLCB628.12c 6 KDA early secretory antigenic target homolog (ESAT-6-like protein) (L-ESAT) from Mycobacterium leprae (95 aa), FASTA scores: opt: 236, E(): 3.3e-09, (36.25% identity in 91 aa overlap); and weak similarity with others proteins ESAT-like from Mycobacterium leprae. Also some similarity with O53266|ES69_MYCTU|Rv3019c|MT3104|MTV012.33c putative secreted ESAT-6 like protein 9 from Mycobacterium tuberculosis (96 aa), FASTA scores: opt: 131, E(): 0.03, (26.15% identity in 88 aa overlap); and other ESAT-like protein. Contains probable coiled-coil from 56 to 92 aa. Belongs to the ESAT6 family. Note that previously known as esat-6. A core mycobacterial gene; conserved in mycobacterial strains (See Marmiesse et al., 2004). Predicted possible vaccine candidate (See Zvi et al., 2008). EspD|Rv3614c expression but not secretion is required for EsxA|Rv3875 secretion (See Chen et al., 2012). |
| Functional category | Cell wall and cell processes |
| Proteomics | The product of this CDS corresponds to spots 3875 identified in short term culture filtrate and cell wall by proteomics at the Statens Serum Institute (Denmark) (see some citations below). Identified in immunodominant fractions of M. tuberculosis H37Rv culture filtrate using 2D-LPE, 2D-PAGE, and LC-MS or LC-MS/MS (See Covert et al., 2001). Identified in the membrane fraction of M. tuberculosis H37Rv using 1D-SDS-PAGE and uLC-MS/MS (See Gu et al., 2003). Identified in the culture supernatant of M. tuberculosis H37Rv using mass spectrometry (See Mattow et al., 2003). Identified in culture filtrates of M. tuberculosis H37Rv (See Malen et al., 2007). Identified by mass spectrometry in Triton X-114 extracts of M. tuberculosis H37Rv (See Malen et al., 2010). Translational start site supported by proteomics data (See de Souza et al., 2011) (See Kelkar et al., 2011). |
| Transcriptomics | mRNA identified by RT-PCR (See Amoudy et al., 2006). |
| Mutant | Non-essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Non-essential gene for in vitro growth of H37Rv, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). SCID mice infected with M. tuberculosis H37Rv Rv3874-Rv3875 mutant survive longer than those infected with wild-type (See Hsu et al., 2003). In THP-1 cells, M. tuberculosis H37Rv Rv3875 mutant is attenuated for growth and cytotoxicity; in C57BL/6 mouse lungs, growth and histopathology are attenuated; Rv3874 protein levels are reduced in cell pellet and not detected in culture filtrate, by ELISPOT (See Guinn et al., 2003). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 4352609 | 4352896 | + |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv3875|esxA
MTEQQWNFAGIEAAASAIQGNVTSIHSLLDEGKQSLTKLAAAWGGSGSEAYQGVQQKWDATATELNNALQNLARTISEAGQAMASTEGNVTGMFA
Bibliography
- Sørensen AL et al. [1995]. Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis. Proteomics
- Berthet FX et al. [1998]. A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Proteomics
- Skjot RL, Oettinger T, Rosenkrands I, Ravn P, Brock I, Jacobsen S and Andersen P [2000]. Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens. Proteomics
- Rosenkrands I et al. [2000]. Towards the proteome of Mycobacterium tuberculosis. Proteomics
- Rosenkrands I, Weldingh K, Jacobsen S, Hansen CV, Florio W, Gianetri I and Andersen P [2000]. Mapping and identification of Mycobacterium tuberculosis proteins by two-dimensional gel electrophoresis, microsequencing and immunodetection. Proteomics
- Covert BA et al. [2001]. The application of proteomics in defining the T cell antigens of Mycobacterium tuberculosis. Proteomics
- Gey Van Pittius NC, Gamieldien J, Hide W, Brown GD, Siezen RJ and Beyers AD [2001]. The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria. Secondary Phylogeny
- Hsu T et al. [2003]. The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Mutant
- Pym AS, Brodin P, Majlessi L, Brosch R, Demangel C, Williams A, Griffiths KE, Marchal G, Leclerc C and Cole ST [2003]. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Gene
- Gu S et al. [2003]. Comprehensive proteomic profiling of the membrane constituents of a Mycobacterium tuberculosis strain. Proteomics
- Mattow J, Schaible UE, Schmidt F, Hagens K, Siejak F, Brestrich G, Haeselbarth G, Muller EC, Jungblut PR and Kaufmann SH [2003]. Comparative proteome analysis of culture supernatant proteins from virulent Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen. Proteomics
- Marmiesse M, Brodin P, Buchrieser C, Gutierrez C, Simoes N, Vincent V, Glaser P, Cole ST and Brosch R [2004]. Macro-array and bioinformatic analyses reveal mycobacterial 'core' genes, variation in the ESAT-6 gene family and new phylogenetic markers for the Mycobacterium tuberculosis complex. Homology
- Demangel C et al. [2004]. Cell envelope protein PPE68 contributes to Mycobacterium tuberculosis RD1 immunogenicity independently of a 10-kilodalton culture filtrate protein and ESAT-6. Biochemistry
- Guinn KM et al. [2004]. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mutant
- Renshaw PS et al. [2005]. Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. Structure
- Champion PA et al. [2006]. C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis. Biochemistry
- Amoudy HA et al. [2006]. Identification of transcriptionally active open reading frames within the RD1 genomic segment of Mycobacterium tuberculosis. Transcriptome
- Målen H et al. [2007]. Comprehensive analysis of exported proteins from Mycobacterium tuberculosis H37Rv. Proteomics
- de Jonge MI et al. [2007]. ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP-10 under acidic conditions and exhibits membrane-lysing activity. Biochemistry
- Zvi A et al. [2008]. Whole genome identification of Mycobacterium tuberculosis vaccine candidates by comprehensive data mining and bioinformatic analyses. Immunology
- Lightbody KL, Ilghari D, Waters LC, Carey G, Bailey MA, Williamson RA, Renshaw PS and Carr MD [2008]. Molecular features governing the stability and specificity of functional complex formation by Mycobacterium tuberculosis CFP-10/ESAT-6 family proteins. Biophysics Structure
- [2009]. Systematic genetic nomenclature for type VII secretion systems. Nomenclature
- Målen H et al. [2010]. Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv. Proteomics
- Kelkar DS et al. [2011]. Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Proteomics Sequence
- de Souza GA et al. [2011]. Proteogenomic analysis of polymorphisms and gene annotation divergences in prokaryotes using a clustered mass spectrometry-friendly database. Proteomics Sequence
- Chen JM et al. [2012]. EspD is critical for the virulence-mediating ESX-1 secretion system in Mycobacterium tuberculosis. Biochemistry
- DeJesus MA et al. [2017]. Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. Mutant
- Minato Y et al. [2019]. Genomewide Assessment of Mycobacterium tuberculosis Conditionally Essential Metabolic Pathways. Mutant
