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| | plcA | Membrane-associated phospholipase C 1 PlcA (MTP40 antigen); Hydrolyzes sphingomyelin in addition to phosphatidylcholine. Probable virulence factor implicated in the pathogenesis of M.tuberculosis at the level of intracellular survival, by the alteration of cell signaling events or by direct cytotoxicity; Belongs to the bacterial phospholipase C family. (512 aa) |
| | cpnT | Hypothetical alanine and proline rich protein; Has a dual function in uptake of nutrients and induction of host cell death. The N-terminal domain (NTD) forms an outer membrane channel and is used for uptake of nutrients across the outer membrane. The secreted C-terminal toxic domain (TNT) acts as a glycohydrolase, which hydrolyzes the essential cellular coenzyme NAD(+) in the cytosol of infected macrophages, leading to necrotic host cell death. Both functions are required for survival, replication and cytotoxicity of M.tuberculosis in macrophages. (846 aa) |
| | espB | Secreted ESX-1 substrate protein B, EspB. Conserved alanine and glycine rich protein; Required for host-cell death and may support an EsxA- independent virulence function. Secreted processed form of EspB binds to phosphatidic acid and phosphatidylserine. Inhibits IFN-gamma-induced autophagy in murine macrophages. (460 aa) |
| | espJ | ESX-1 secretion-associated protein EspJ. Conserved alanine rich protein; Could be involved in regulation of growth and intracellular survival. (280 aa) |
| | esxA | 6 kDa early secretory antigenic target EsxA (ESAT-6); A secreted protein that plays a number of roles in modulating the host's immune response to infection as well as being responsible for bacterial escape into the host cytoplasm. Acts as a strong host (human) T-cell antigen. Inhibits IL- 12 p40 (IL12B) and TNF-alpha expression by infected host (mouse) macrophages, reduces the nitric oxide response by about 75%. In mice previously exposed to the bacterium, elicits high level of IFN-gamma production by T-cells upon subsequent challenge by M.tuberculosis, in the first phase of a protecti [...] (95 aa) |
| | esxB | 10 kDa culture filtrate antigen EsxB (LHP) (CFP10); A secreted protein. Acts as a strong host (human) T-cell antigen. Involved in translocation of bacteria from the host (human) phagolysosome to the host cytoplasm. Might serve as a chaperone to prevent uncontrolled membrane lysis by its partner EsxA; native protein binds poorly to artificial liposomes in the absence or presence of EsxA. EsxA and EsxA-EsxB are cytotoxic to pneumocytes. EsxB (and EsxA-EsxB but not EsxA alone) activates human neutrophils; EsxB transiently induces host (human) intracellular Ca(2+) mobility in a dose-depend [...] (100 aa) |
| | PPE68 | PPE family protein PPE68; Plays a major role in RD1-associated pathogenesis, and may contribute to the establishment and maintenance of M.tuberculosis infection. Together with PE35, stimulates the secretion of IL-10 and MCP-1 from human macrophages, via the interaction with human Toll-like receptor 2 (TLR2). Stimulates high levels of gamma interferon secretion in peripheral blood mononuclear cells isolated from tuberculosis patients, as well as from healthy tuberculin purified protein derivative-positive donors. Does not interfere with the secretion and immunogenicity of EsxA (ESAT-6) [...] (368 aa) |
| | PE35 | PE family-related protein PE35; Plays a major role in RD1-associated pathogenesis, and may contribute to the establishment and maintenance of M.tuberculosis infection. Together with PPE68, stimulates the secretion of IL-10 and MCP-1 from human macrophages, via the interaction with human Toll-like receptor 2 (TLR2). (99 aa) |
| | espR | ESX-1 transcriptional regulatory protein EspR; Virulence regulator that has both architectural and regulatory roles. Impacts cell wall functions and pathogenesis through regulation of multiple genes, including the espACD operon, which is a key ESX-1 component. Influences target gene expression positively or negatively, depending on its binding position relative to the genes it controls. Acts by binding directly to the DNA. May play a central role in regulating virulence gene expression. (132 aa) |
| | lpqH | 19 kDa lipoprotein antigen precursor LpqH; Based on its structure might be involved in ligand transport (By similarity); Belongs to the mycobacterial 19 kDa antigen family. (159 aa) |
| | lucA | Probable conserved transmembrane protein; Required for the import of both fatty acids and cholesterol during growth in macrophages and in axenic culture. Facilitates the uptake of these lipids by stabilizing protein subunits of the Mce1 and Mce4 multi-subunit transporters, which transport fatty acids and cholesterol, respectively. Required for full virulence in vivo. (254 aa) |
| | asd | Aspartate-semialdehyde dehydrogenase; Catalyzes the NADPH-dependent formation of L-aspartate- semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl- 4-phosphate. Is essential for the growth and pathogenicity of M.tuberculosis, and for the generation of the bacterial cell wall ; Belongs to the aspartate-semialdehyde dehydrogenase family. (345 aa) |
| | crp | Transcriptional regulatory protein Crp (Crp/Fnr-family); Global transcriptional regulator that complexes with cAMP and binds to specific DNA promoter sites, causing DNA-bending, to regulate transcription. cAMP improves binding to specific DNA sequences, probably by altering protein conformation. The CRP regulon is predicted to contain about 115 genes. Some genes are activated by CRP (rpfA, whiB1) while others are repressed (fadD10). There are 2 CRP-binding sites in the promoter of whiB1, at low concentrations of CRP with or without cAMP transcription of whiB1 is enhanced via site CRP1, [...] (224 aa) |
| | Rv3655c | Conserved hypothetical protein; Effector protein that participates in the suppression of macrophage apoptosis by blocking the extrinsic pathway. Interferes with caspase-8 activation and binds to the host E3 ubiquitin-protein ligase RNF213, whose fusion partners have anti-apoptotic function. (125 aa) |
| | Rv3654c | Conserved hypothetical protein; Effector protein that participates in the suppression of macrophage apoptosis by blocking the extrinsic pathway. Recognizes the host polypyrimidine tract binding protein-associated splicing factor (PSF), which probably leads to its cleavage, diminishing the level of caspase-8 in macrophages. (84 aa) |
| | espA | ESX-1 secretion-associated protein A, EspA; Required for secretion of EsxA (ESAT-6) and EsxB (CFP-10) and for virulence. Involved in translocation of bacteria from the host (human) phagolysosome to the host cytoplasm. (392 aa) |
| | espC | ESX-1 secretion-associated protein EspC; Required for ESX-1 function. Required for either stability or expression of EspA. (103 aa) |
| | espD | ESX-1 secretion-associated protein EspD; Required for ESX-1 function. Required for the maintenance of adequate cellular levels of both EspA and EspC. Facilitates EsxA secretion. (184 aa) |
| | panC | Pantoate--beta-alanine ligase PanC (pantothenate synthetase) (pantoate activating enzyme); Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate. (309 aa) |
| | panD | Probable aspartate 1-decarboxylase precursor PanD (aspartate alpha-decarboxylase); Catalyzes the pyruvoyl-dependent decarboxylation of aspartate to produce beta-alanine; Belongs to the PanD family. (139 aa) |
| | lsr2 | Iron-regulated H-NS-like protein Lsr2; DNA-bridging protein that has both architectural and regulatory roles. Influences the organization of chromatin and gene expression by binding non-specifically to DNA, with a preference for AT-rich sequences, and bridging distant DNA segments. Binds in the minor groove of AT-rich DNA. Represses expression of multiple genes involved in a broad range of cellular processes, including major virulence factors or antibiotic-induced genes, such as iniBAC or efpA , and genes important for adaptation of changing O(2) levels. May also activate expression of [...] (112 aa) |
| | carD | Possible transcription factor; Controls rRNA transcription by binding to the RNA polymerase (RNAP). Required for replication and persistence during infection of mice; Belongs to the CarD family. (162 aa) |
| | fadE34 | Probable acyl-CoA dehydrogenase FadE34; Involved in the second cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. It contributes partly to the virulence by increasing the efficiency of beta-oxidation. Catalyzes the highly specific dehydrogenation of acyl-CoA ester side chains of 3- oxo-chol-4-en-24-oyl-CoA (3-OCO-CoA) to yield 3-oxochol-4,22-dien-24- oyl-CoA. (711 aa) |
| | kshB | Reductase component of 3-ketosteroid-9-alpha-hydroxylase KshB; Involved in the degradation of cholesterol. Catalyzes the introduction of a 9a-hydroxyl moiety into 1,4-androstadiene-3,17-dione (ADD) to yield the 9alpha-hydroxy-1,4-androstadiene-3,17-dione (9OHADD) intermediate which spontaneously form 3-hydroxy-9,10-seconandrost- 1,3,5(10)-triene-9,17-dione (HSA) via the meta-cleavage of ring B with concomitant aromatization of ring A. KSH is also able to use 4- androstene-3,17-dione (AD), 3-oxo-23,24-bisnorcholesta-4-en-22-oate (4- BNC), 3-oxo-23,24-bisnorcholesta-1,4-dien-22-oate (1,4 [...] (358 aa) |
| | fadA5 | Probable acetyl-CoA acetyltransferase FadA5 (acetoacetyl-CoA thiolase); Involved in the beta-oxidation of the cholesterol side chain. It is important for utilization of cholesterol as a sole carbon source in vitro and for full virulence in the chronic stage of mouse lung infection. Catalyzes the thiolysis of 3,22-dioxochol-4-en-24-oyl-CoA to yield 3-oxo-4-pregnene-20-carboxyl- CoA (3-OPC-CoA) and acetyl-CoA. Also able to use acetoacetyl-CoA (AcAcCoA) as substrate. (391 aa) |
| | cyp125 | Probable cytochrome P450 125 Cyp125; Involved in the utilization of cholesterol as the sole carbon and energy source by degrading the side chain during infection. Primarily catalyzes the sequential oxidation of the terminal methyl of cholest-4-en-3-one into (25S)-26- hydroxycholest-4-en-3-one (alcohol), (25S)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25S)-3-oxocholest-4- en-26-oate. Also able to sequentially oxidize cholesterol itself, not only cholest-4-en- 3-one. Belongs to the cytochrome P450 family. (433 aa) |
| | fadE28 | Probable acyl-CoA dehydrogenase FadE28; Involved in the third cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. May play an important role for the initial macrophage invasion, possibly in response to the acidification of phagosome. It contributes partly to the virulence by increasing the efficiency of beta-oxidation. Catalyzes the dehydrogenation of 2'-propanoyl-CoA ester side chains of 3-oxo-4- pregnene-20-carboxyl-CoA (3-OPC-CoA) to yield 3-oxo-4,17-pregnadiene- 20-carboxyl-CoA (3-OPDC-CoA). Also able to dehydrogenate steroyl-CoA such as 3-oxo-chol- [...] (339 aa) |
| | fadE29 | Probable acyl-CoA dehydrogenase FadE29; Involved in the third cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. Contributes partly to the virulence by increasing the efficiency of beta-oxidation. Catalyzes the dehydrogenation of 2'-propanoyl-CoA ester side chains of 3-oxo-4- pregnene-20-carboxyl-CoA (3-OPC-CoA) to yield 3-oxo-4,17-pregnadiene- 20-carboxyl-CoA (3-OPDC-CoA). Also able to dehydrogenate steroyl-CoA such as 3-oxo-chol-4-en-24-oyl-CoA (3-OCO-CoA), 1beta-(2'-propanoyl- CoA)-3a-alpha-H- 7a-beta-methylhexahydro-4-indanone (indanone-CoA ester), [...] (387 aa) |
| | kshA | Oxygenase component of 3-ketosteroid-9-alpha-hydroxylase KshA; Involved in the degradation of cholesterol. Catalyzes the introduction of a 9a-hydroxyl moiety into 1,4-androstadiene-3,17-dione (ADD) to yield the 9alpha-hydroxy-1,4-androstadiene-3,17-dione (9OHADD) intermediate which spontaneously form 3-hydroxy-9,10-seconandrost- 1,3,5(10)-triene-9,17-dione (HSA) via the meta-cleavage of ring B with concomitant aromatization of ring A. KSH is also able to use 4- androstene-3,17-dione (AD), 3-oxo-23,24-bisnorcholesta-4-en-22-oate (4- BNC), 3-oxo-23,24-bisnorcholesta-1,4-dien-22-oate (1,4 [...] (386 aa) |
| | cyp142 | Probable cytochrome P450 monooxygenase 142 Cyp142; Involved in the utilization of cholesterol as the sole carbon and energy source by degrading the side chain during infection. Primarily catalyzes the sequential oxidation of the terminal methyl of cholest-4-en-3-one into (25R)-26-hydroxycholest-4- en-3-one (alcohol), (25R)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25R)-3-oxocholest-4-en-26-oate. In vitro, Cyp142 catalyzes with equal preference the oxidation of both (25R)- and (25S)-26- hydroxycholest-4-en-3-one diastereomers to the corresponding carboxy [...] (398 aa) |
| | fadE27 | Probable acyl-CoA dehydrogenase FadE27; Involved in the first cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. It contributes partly to the virulence by increasing the efficiency of beta-oxidation. Catalyzes the dehydrogenation of acyl-CoA ester side chains of (25S)-3-oxo-cholest-4-en-26-oyl-CoA (3-OCS-CoA) to yield (24E)-3-oxo-cholest-4,24-dien-26-oyl-CoA. Also able to dehydrogenate steroyl-CoA such as 3-oxo- chol-4-en-24-oyl-CoA (3-OCO-CoA) as well as 3-oxo-4-pregnene-20- carboxyl-CoA (3-OPC-CoA). It dehydrogenates only (25S)-OCS-CoA diastereomer. (373 aa) |
| | fadE26 | Probable acyl-CoA dehydrogenase FadE26; Involved in the first cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. It contributes partly to the virulence by increasing the efficiency of beta-oxidation. Catalyzes the dehydrogenation of acyl-CoA ester side chains of (25S)-3-oxo-cholest-4-en-26-oyl-CoA (3-OCS-CoA) to yield (24E)-3-oxo-cholest-4,24-dien-26-oyl-CoA. Also able to dehydrogenate steroyl-CoA such as 3-oxo- chol-4-en-24-oyl-CoA (3-OCO-CoA) as well as 3-oxo-4-pregnene-20- carboxyl-CoA (3-OPC-CoA). It dehydrogenates only (25S)-OCS-CoA diastereomer ( [...] (400 aa) |
| | lprN | Possible Mce-family lipoprotein LprN (Mce-family lipoprotein Mce4E); Stimulates the host (mouse) immune response; lipidated protein produced in E.coli stimulates T-cell proliferation in mice previously sensitized with LprN. Spleenocytes from these mice produce increased amounts of TNF-alpha and IFN-gamma, as well as somewhat increased nitric oxide levels, upon subsequent challenge with LprN. Previously sensitized mice infected with M.tuberculosis have an exacerbated disease response, suggesting this lipoprotein may down- regulate the host's immune response. (384 aa) |
| | esxU | Rv3445c, (MTCY77.17c), len: 105 aa. EsxU, ESAT-6 like protein (see citations below), showing weak similarity to O30373|VCD|PA2257 pyoverdine biosynthesis protein from Pseudomonas aeruginosa (215 aa), FASTA scores: opt: 103,E(): 5.6, (32.35% identity in 133 aa overlap). Seems to belong to the ESAT6 family. Start changed since first submission (-20 aa); Belongs to the WXG100 family. CFP-10 subfamily. (105 aa) |
| | PPE57 | PPE family protein PPE57; Plays a key role in regulating innate and adaptive immune responses through human Toll-like receptor 2 (TLR2). Interacts with TLR2, leading to the subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kappa-B) signaling pathways. Induces macrophage activation by augmenting the expression of several cell surface molecules (CD40, CD80, CD86 and MHC class II) and pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-12p40) within macrophages. Also participates in adaptive immunity by directing Th1- polarised immune respo [...] (176 aa) |
| | whiB3 | Transcriptional regulatory protein WhiB-like WhiB3. Contains [4FE-4S] cluster; A redox-sensitive transcriptional regulator. Maintains intracellular redox homeostasis by regulating catabolic metabolism and polyketide biosynthesis. Regulates expression of the redox buffer ergothioneine (ERG) in a carbon-source- dependent manner; loss of ERG or mycothiol (MSH, the other major redox buffer in this bacteria) leads to respiratory alterations and bioenergetic deficiencies that negatively impact virulence. In response to low external pH (like that found in host macrophage phagosomes) alters en [...] (102 aa) |
| | sigD | Probable alternative RNA polymerase sigma-D factor SigD; Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma factors are held in an inactive form by an anti-sigma factor until released by regulated intramembrane proteolysis. (212 aa) |
| | choD | Cholesterol oxidase ChoD (cholesterol-O2 oxidoreductase); Catalyzes the oxidation and isomerization of cholesterol to cholestenone (4-cholesten-3-one), which is an initial step in the cholesterol degradation process. Required for virulence. Belongs to the GMC oxidoreductase family. Highly divergent. (578 aa) |
| | rpfD | Probable resuscitation-promoting factor RpfD; Factor that stimulates resuscitation of dormant cells. Has peptidoglycan (PG) hydrolytic activity. Active in the pM concentration range. Has little to no effect on actively-growing cells. PG fragments could either directly activate the resuscitation pathway of dormant bacteria or serve as a substrate for endogenous Rpf, resulting in low molecular weight products with resuscitation activity. Belongs to the transglycosylase family. Rpf subfamily. (154 aa) |
| | Rv3378c | Diterpene synthase; Tuberculosinyl transferase that catalyzes the condensation of adenosine and tuberculosinyl diphosphate (TbPP) to generate 1- tuberculosinyladenosine (1-TbAd), which acts as an antiacid that directly protects M.tuberculosis from acid pH and physically remodels M.tuberculosis phagolysosomes. In addition, acts as a phosphatase that catalyzes the diphosphate-removal from TbPP to produce both tuberculosinol (TOH) and isotuberculosinol (iso-TOH). Has broad substrate specificity, and can also use the 3 labdadienyl diphosphates, copalyl diphosphate (CDP), ent-CDP and syn-CD [...] (296 aa) |
| | Rv3364c | Conserved protein; Effector protein that binds to the host serine protease cathepsin G on the macrophage cell membrane, inhibiting its enzymatic activity and the downstream activation of caspase-1-dependent apoptosis. Thus prevents macrophage pyroptosis and helps M.tuberculosis survival within host cells; Belongs to the mycobacterial serine protease inhibitor Rv3364c family. (130 aa) |
| | mtp | Secreted protein antigen; Structural subunit of M.tuberculosis pili (MTP), which are thin (2- to 3-nm wide), flexible, coiled-coil, aggregative fibers. Has a strong affinity for laminin but lacks significant binding affinity for fibronectin or type IV collagen. Mediates adhesion to the extracellular matrix, an event that would facilitate direct interaction with the host epithelium during infection in the lung or other tissues. (103 aa) |
| | sapM | Acid phosphatase (acid phosphomonoesterase) (phosphomonoesterase) (glycerophosphatase); Virulence factor that plays an important role in blocking phagosome-lysosome fusion and thus participates in the intracellular survival of the pathogen. Acts as a phosphatase that dephosphorylates phosphatidylinositol 3-phosphate (PI3P), a membrane trafficking regulatory lipid essential for phagosomal acquisition of lysosomal constituents. Therefore, SapM eliminates PI3P from the phagosomal membrane by catalyzing its hydrolysis, and thus contributes to inhibition of phagosome maturation. Also interf [...] (299 aa) |
| | ctpC | Probable metal cation-transporting P-type ATPase C CtpC; High affinity, slow turnover Mn(2+) transporting ATPase, which is required for virulence. Controls the Mn(2+) cytoplasmic quota and is involved in the uploading of Mn(2+) into secreted metalloproteins. Required for tolerance to Zn(2+) and oxidative stress. Plays a crucial role in the ability to resist zinc poisoning in human macrophages. Shows a preference for Mn(2+), but Zn(2+), Co(2+) and Cu(2+) can act as alternative substrates although at slower turnover rates ; Belongs to the cation transport ATPase (P-type) (TC 3.A.3) famil [...] (718 aa) |
| | nuoG | Probable NADH dehydrogenase I (chain G) NuoG (NADH-ubiquinone oxidoreductase chain G); NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be menaquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient (By similarity). (806 aa) |
| | Rv3131 | Conserved protein; Stimulates pro-inflammatory cytokine expression via TLR2 signaling pathway. Activation of TLR2 results in the phosphorylation and activation of NF-kappa-B. Also induces TLR2 expression. May influence the innate immune responses to facilitate the survival of M.tuberculosis in the granulomatous microenvironment. Belongs to the nitroreductase family. (332 aa) |
| | virS | Virulence-regulating transcriptional regulator VirS (AraC/XylS family); Regulates the expression of the mymA operon (Rv3083-Rv3089). (340 aa) |
| | pknK | Serine/threonine-protein kinase transcriptional regulatory protein PknK (protein kinase K) (STPK K); Key microbial factor involved in regulation of early and late events in tuberculosis infection, and in host-pathogen interactions. Modulates host immunity during early infection. Slows mycobacterial growth during chronic infection in host and during a variety of stress conditions in vitro. Regulates the expression of a large subset of tRNA genes as a means to facilitate adaptation to changing growth environments. In vitro, directs the inhibition of transcription and translation processe [...] (1110 aa) |
| | lppX | Probable conserved lipoprotein LppX; Might be involved in translocating phthiocerol dimycocerosates (PDIM) from the cell membrane to the outer membrane; PDIM forms part of the cell wall; Belongs to the LppX/LprAFG lipoprotein family. (233 aa) |
| | mmpL7 | Conserved transmembrane transport protein MmpL7; Required for export of phthiocerol dimycocerosate (PDIM) to the cell wall. Essential for normal replication during the active-growth phase of the murine tuberculosis model. (920 aa) |
| | tesA | Probable thioesterase TesA; Involved in the synthesis of both phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), which are structurally related lipids non-covalently bound to the outer cell wall layer of M.tuberculosis and are important virulence factors. In vitro, TesA has both thioesterase and esterase activities. Exhibits thioesterase activity on acyl-CoA derivatives such as palmitoyl-CoA and decanoyl-CoA. Also displays hydrolytic activity on ester substrates, being more active on pNP esters with short carbon chain lengths (C2-C5) than with those bearing medium and [...] (261 aa) |
| | pknI | Serine/threonine-protein kinase PknI; Plays an important role in slowing down the growth of mycobacteria within the infected host; Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. (585 aa) |
| | PE_PGRS47 | PE-PGRS family protein PE_PGRS47; Contributes to evasion of both innate and adaptive immunity. Inhibits autophagy in infected host phagocytes and inhibits major histocompatibility complex (MHC) class II antigen presentation by mycobacteria-infected dendritic cells. Has an important role in the growth and survival of M.tuberculosis, particularly during intracellular growth and in the later chronic phase of infection. (525 aa) |
| | TB31.7 | Universal stress protein family protein TB31.7; May play a role in the establishment of a persistent infection (latency) in the host, as strains without this gene are hypervirulent. Overexpression of the protein retards growth in culture; Glu-15 and Ala-117 mutant proteins which bind less ATP do not show this retardation, suggesting growth may be regulated through an ATP- dependent function. (297 aa) |
| | pimA | Alpha-mannosyltransferase PimA; Involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIM) which are early precursors in the biosynthesis of lipomannans (LM) and lipoarabinomannans (LAM). Catalyzes the addition of a mannosyl residue from GDP-D-mannose (GDP-Man) to the position 2 of the carrier lipid phosphatidyl-myo-inositol (PI) to generate a phosphatidyl-myo-inositol bearing an alpha-1,2-linked mannose residue (PIM1). PimA plays an essential role for growth in macrophages and during both the acute and chronic phases of infection. (378 aa) |
| | lipQ | Probable carboxylesterase LipQ; Shows lipase activity. Is highly immunogenic and may play an important role in the virulence and pathogenesis of M.tuberculosis infection, by altering the balance of cytokines. Significantly down-regulates the expression level of pro- inflammatory cytokines (TNF-alpha and IFN-gamma) and up-regulates the level of anti-inflammatory cytokines such as IL-4 and IL-10 as compared to LPS stimulated macrophages. Also inhibits the expression of iNOS, TLR2 and transcription factor NF-kappa-B in LPS stimulated macrophages whereas the expression of TLR-4 remains unc [...] (421 aa) |
| | rpfE | Probable resuscitation-promoting factor RpfE; Factor that stimulates resuscitation of dormant cells. Has peptidoglycan (PG) hydrolytic activity. Active in the pM concentration range. Has little to no effect on actively-growing cells. PG fragments could either directly activate the resuscitation pathway of dormant bacteria or serve as a substrate for endogenous Rpf, resulting in low molecular weight products with resuscitation activity. Belongs to the transglycosylase family. Rpf subfamily. (172 aa) |
| | PE25 | PE family protein PE25; The PE25/PPE41 dimer induces both a strong humoral and cellular immune response. PE25 protein alone induces low response. The dimer induces necrosis, but not apoptosis, in mouse macrophage cells. It also induces activation and maturation of mouse dendritic cells and drives Th2-biased immune responses. (99 aa) |
| | PPE41 | PPE family protein PPE41; The PE25/PPE41 dimer induces both a strong humoral and cellular immune response. The dimer induces necrosis, but not apoptosis, in mouse macrophage cells. It also induces activation and maturation of mouse dendritic cells and drives Th2-biased immune responses. (194 aa) |
| | Rv1931c | Probable transcriptional regulatory protein; Controls the expression of genes important for virulence. (259 aa) |
| | pafA | Proteasome accessory factor a PafA; Catalyzes the covalent attachment of the prokaryotic ubiquitin-like protein modifier Pup to the proteasomal substrate proteins, thereby targeting them for proteasomal degradation. This tagging system is termed pupylation. The ligation reaction involves the side-chain carboxylate of the C-terminal glutamate of Pup and the side- chain amino group of a substrate lysine. PafA is required to confer resistance against the lethal effects of reactive nitrogen intermediates (RNI), antimicrobial molecules produced by activated macrophages and other cell types. (452 aa) |
| | prcA | Proteasome alpha subunit PrcA; Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues. In complex with the ATPase Mpa, degrades protein targets conjugated to a prokaryotic ubiquitin-like protein (Pup). Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins. One function of the proteasome is to contribute to M.tuberculosis ability [...] (248 aa) |
| | prcB | Proteasome beta subunit PrcB; Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues. In complex with the ATPase Mpa, degrades protein targets conjugated to a prokaryotic ubiquitin-like protein (Pup). Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins. One function of the proteasome is to contribute to M.tuberculosis ability [...] (291 aa) |
| | dop | Deamidase of pup Dop; Specifically catalyzes the deamidation of the C-terminal glutamine of the prokaryotic ubiquitin-like protein Pup to glutamate, thereby rendering Pup competent for conjugation. Also displays depupylase (DPUP) activity, removing conjugated Pup from target proteins; is thus involved in the recycling of Pup and may function similarly to deubiquitinases (DUBs) in eukaryotes to prevent or promote proteasomal degradation of certain proteins. Belongs to the Pup ligase/Pup deamidase family. Pup deamidase subfamily. (554 aa) |
| | mpa | Mycobacterial proteasome ATPase Mpa; ATPase which is responsible for recognizing, binding, unfolding and translocation of pupylated proteins into the bacterial 20S proteasome core particle. May be essential for opening the gate of the 20S proteasome via an interaction with its C-terminus, thereby allowing substrate entry and access to the site of proteolysis. Thus, the C-termini of the proteasomal ATPase may function like a 'key in a lock' to induce gate opening and therefore regulate proteolysis. Is required but not sufficient to confer resistance against the lethal effects of reactiv [...] (609 aa) |
| | Rv2181 | Alpha(1->2)mannosyltransferase; Responsible for the addition of alpha-(1-2) mannose branches to the linear mannan core on the biosynthetic pathway to mature lipoarabinomannan (LAM). (427 aa) |
| | pimB | Mannosyltransferase PimB; Involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIM) which are early precursors in the biosynthesis of lipomannans (LM) and lipoarabinomannans (LAM). Catalyzes the addition of a mannosyl residue from GDP-D-mannose (GDP- Man) to the position 6 of a phosphatidyl-myo-inositol bearing an alpha- 1,2-linked mannose residue (PIM1) to generate phosphatidyl-myo-inositol bearing alpha-1,2- and alpha-1,6-linked mannose residues (Ac1PIM2). PimB also catalyzes the addition of a mannosyl residue from GDP-Man to the position 6 of phosphatidyl-myo-inosit [...] (385 aa) |
| | dlaT | DlaT, dihydrolipoamide acyltransferase, E2 component of pyruvate dehydrogenase; Component of the pyruvate dehydrogenase (PDH) complex, that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). Appears to be essential for Mtb pathogenesis. (553 aa) |
| | glnA1 | Glutamine synthetase GlnA1 (glutamine synthase) (GS-I); Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia. Also able to use GTP. D-glutamate is a poor substrate, and DL-glutamate shows about 50% of the standard specific activity. Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion. Involved in cell wall biosynthesis via the production of the major component p [...] (478 aa) |
| | caeA | Probable carboxylesterase CaeA; Involved in virulence. Catalyzes the cleavage of ester bonds. Esterase activity increases with increasing carbon chain length of the substrate. (520 aa) |
| | ptpA | Phosphotyrosine protein phosphatase PtpA (protein-tyrosine-phosphatase) (PTPase) (LMW phosphatase); Mediates host-pathogen interaction and interferes with vesicular trafficking in the infected macrophage. Inhibits host phagolysosomal fusion in M.tuberculosis-infected macrophages to promote bacteria survival. Dephosphorylates host VPS33B protein, which induces a block of the host phagosome maturation within macrophage cells. Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates; Belongs to the low molecular weight phosphotyrosine prot [...] (163 aa) |
| | esxO | Putative ESAT-6 like protein EsxO (ESAT-6 like protein 6); Plays an important role in mycobacterial pathogenesis in the context of innate immunity. Aids host cell invasion and intracellular bacillary persistence. Increases host oxidative stress response, leading to genomic instability and decrease in macrophage viability. Also induces autophagy and modulates the immune function of macrophages; Belongs to the WXG100 family. ESAT-6 subfamily. (94 aa) |
| | plcB | Membrane-associated phospholipase C 2 PlcB; Hydrolyzes sphingomyelin in addition to phosphatidylcholine. Probable virulence factor implicated in the pathogenesis of M.tuberculosis at the level of intracellular survival, by the alteration of cell signaling events or by direct cytotoxicity. (512 aa) |
| | pknB | Transmembrane serine/threonine-protein kinase B PknB (protein kinase B) (STPK B); Protein kinase that regulates many aspects of mycobacterial physiology, and is critical for growth in vitro and survival of the pathogen in the host. Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, PbpA, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA. Also catalyzes the phosphorylation of the core proteasome alpha-subunit (PrcA), and thereby regulates th [...] (626 aa) |
| | pknA | Transmembrane serine/threonine-protein kinase A PknA (protein kinase A) (STPK A); Protein kinase that regulates many aspects of mycobacterial physiology, and is critical for growth in vitro and survival of the pathogen in the host. Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins such as FtsZ, Wag31, GlmU, FhaB, PstP, EmbR and Rv1422. Also catalyzes the phosphorylation of the proteasome alpha-subunit (PrcA) and unprocessed proteasome beta-subunit (pre-PrcB), which results in the inhibitio [...] (431 aa) |
| | whiB5 | Probable transcriptional regulatory protein WhiB-like WhiB5; A transcription factor that is probably redox-responsive. Probably plays a role in immunomodulation and reactivation after chronic infection. Its induction results in transcription of a number of genes including sigM, and the genes for 2 type VII secretion systems ESX-2 and ESX-4. Seems to negatively regulate its own expression. The apo-form has been shown to act as a protein disulfide reductase. The apo- but not holo-form probably binds DNA. (139 aa) |
| | Rv0079 | Unknown protein; Involved in translation regulation. Inhibits protein synthesis and decreases bacterial growth when expressed in E.coli. Can also stimulate macrophages and peripheral blood mononuclear cells (PBMC) to secrete important cytokines that may be significant in granuloma formation and its maintenance. Increases secretion of IFN-gamma, TNF-alpha, IL-1 beta and IL-8 through human Toll-like receptor 2 (TLR2) signaling pathway. (273 aa) |
| | PE3 | PE family protein PE3; Plays significant roles in mycobacterial persistence during infection and modulates host immune response. (468 aa) |
| | Rv0183 | Possible lysophospholipase; Involved in the hydrolysis of exogenous host lipids during chronic infection. Catalyzes the hydrolysis of both monoacylglycerols (MAG) and diacylglycerols (DAG). It hydrolyzes 2-MAG, 1-3-MAG and MAG with short, medium and long chain fatty acids such as 1-monobutyroyl- rac-glycerol (MC4), 1-mono-octanoyl-rac-glycerol (MC8), 1-monodecanoyl- rac-glycerol (MC10), 1-monolauroyl-rac-glycerol (MC12), 1- monomyristoyl-rac-glycerol (MC14) and 1-mono-oleyl-rac-glycerol (MC18:1). Also able to hydrolyze DAG with short (DiC6) and medium (DiC10) fatty acid chains, but not [...] (279 aa) |
| | mmpL11 | Probable conserved transmembrane transport protein MmpL11; Part of a heme-iron acquisition system. Receives heme from the heme-binding protein Rv0203 and transports it into the mycobacterial cell. Contributes to virulence. Belongs to the resistance-nodulation-cell division (RND) (TC 2.A.6) family. MmpL subfamily. (966 aa) |
| | PE5 | PE family protein PE5; Important for the siderophore-mediated iron-acquisition function of ESX-3. May play a pivotal role in the evasion of host immune response by M.tuberculosis. Mediates production of IL-10 via activation of the p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling pathways. (102 aa) |
| | esxG | ESAT-6 like protein EsxG (conserved protein TB9.8); EsxG, in complex with EsxH, disrupts ESCRT function and impairs host phagosome maturation, thereby promoting intracellular bacterial growth. The complex acts by interacting, via EsxH, with the host hepatocyte growth factor-regulated tyrosine kinase substrate (HGS/HRS), a component of the ESCRT machinery. EsxG stabilizes EsxH in the host cytosol. (97 aa) |
| | esxH | Low molecular weight protein antigen 7 EsxH (10 kDa antigen) (CFP-7) (protein TB10.4); EsxH, in complex with EsxG, disrupts ESCRT function and impairs host phagosome maturation, thereby promoting intracellular bacterial growth. The complex acts by interacting, via EsxH, with the host hepatocyte growth factor-regulated tyrosine kinase substrate (HGS/HRS), a component of the ESCRT machinery. Belongs to the WXG100 family. ESAT-6 subfamily. (96 aa) |
| | PE_PGRS5 | PE-PGRS family protein PE_PGRS5; Involved in endoplasmic reticulum (ER) stress-mediated apoptosis through human Toll-like receptor 4 (TLR4) signaling pathway. Localizes to the host ER, leading to ER stress, disruption of intracellular Ca(2+) homeostasis and increase of nitric oxide (NO) and reactive oxygen species (ROS) levels. Stress response results in caspase-8 activation and apoptosis of macrophage cells. Apoptosis may lead to dissemination of the bacteria, thereby spreading the disease. Belongs to the mycobacterial PE family. PGRS subfamily. (591 aa) |
| | pknG | Serine/threonine-protein kinase PknG (protein kinase G) (STPK G); Phosphorylates GarA. May play a role in metabolic regulation via control of the phosphorylation status of GarA. Plays a crucial role in the survival of mycobacteria within host macrophages, by blocking the intracellular degradation of mycobacteria in lysosomes. Required for intrinsic antibiotic resistance. (750 aa) |
| | mmpL4 | Probable conserved transmembrane transport protein MmpL4; Part of an export system, which is required for biosynthesis and secretion of siderophores. Essential for normal replication during the active-growth phase of the murine tuberculosis model. (967 aa) |
| | mmpS4 | Probable conserved membrane protein MmpS4; Part of an export system, which is required for biosynthesis and secretion of siderophores. Essential for virulence. (140 aa) |
| | PPE11 | PPE family protein PPE11; May play an important role in the persistence of mycobacteria in host cells. May regulate the innate immune response of macrophages by promoting the production of pro-inflammatory cytokines and inhibiting the production of anti-inflammatory cytokines. Promotes the death of macrophages during infection. (518 aa) |
| | lpdC | Dihydrolipoyl dehydrogenase; Lipoamide dehydrogenase is an essential component of the alpha-ketoacid dehydrogenase complexes, namely the pyruvate dehydrogenase (PDH) complex, the branched-chain alpha-ketoacid dehydrogenase (BCKADH) complex, and likely also the 2-oxoglutarate dehydrogenase (ODH) complex. Catalyzes the reoxidation of dihydrolipoyl groups which are covalently attached to the lipoate acyltransferase components (E2) of the complexes. Is also able to catalyze the transhydrogenation of NADH and thio-NAD(+) in the absence of D,L- lipoamide, and the NADH-dependent reduction of [...] (464 aa) |
| | hbhA | Iron-regulated heparin binding hemagglutinin HbhA (adhesin); Required for extrapulmonary dissemination. Mediates adherence to epithelial cells by binding to sulfated glycoconjugates present at the surface of these cells; binds heparin, dextran sulfate, fucoidan and chondroitin sulfate. Promotes hemagglutination of erythrocytes of certain host species. Induces mycobacterial aggregation. To M.leprae HbhA. (199 aa) |
| | mgtA | Mannosyltransferase MgtA; Catalyzes the addition of a mannose residue from GDP-D- mannose to GlcAGroAc2 to generate 1,2-di-O-C16/C18:1-(alpha-D- mannopyranosyl)-(1-4)-(alpha-D-glucopyranosyluronic acid)-(1-3)- glycerol(ManGlcAGroAc2). (378 aa) |
| | menJ | Possible oxidoreductase; Catalyzes the reduction of a single double bond in the isoprenoid tail of menaquinone (MK-9) in M.tuberculosis, likely the beta-isoprene unit, forming the predominant form of menaquinone found in mycobacteria, MK-9(II-H2). Is required for M.tuberculosis survival in host macrophages; Belongs to the geranylgeranyl reductase family. (408 aa) |
| | TB27.3 | Conserved protein TB27.3; May function as a glyoxylase involved in the methylglyoxal detoxification pathway. Induces maturation of dendritic cells in a TLR2-dependent manner, causing increased expression of cell-surface molecules (CD80, CD86, MHC class I and II) and proinflammatory cytokines (TNF-alpha, IL-6, IL-1 beta and IL- 12p70). Acts via both the NF-kappa-B and MAPK signaling pathways. Induces Th1-polarized immune responses. (261 aa) |
| | mmpS5 | Possible conserved membrane protein MmpS5; Part of an export system, which is required for biosynthesis and secretion of siderophores. Essential for virulence. Belongs to the MmpS family. (142 aa) |
| | sigL | Probable alternative RNA polymerase sigma factor SigL; Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma factors are held in an inactive form by an anti-sigma factor until released by regulated intramembrane proteolysis. Over-expression of SigL induces 19-28 genes including polyketide synthases, secreted and membrane proteins. Might play a minor role in regulating SigB. (177 aa) |
| | rslA | Anti-sigma factor RslA; An anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigL. ECF sigma factors are held in an inactive form by an anti-sigma factor until released by regulated intramembrane proteolysis (RIP). RIP occurs when an extracytoplasmic signal triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. The membrane-spanning regulatory substrate protein is first cut extracytoplasmically (site-1 protease, S1P), then within the membrane itself (site-2 protease, S2P, Rip1), while cytoplasmic proteases finish degrading the r [...] (250 aa) |
| | PE_PGRS11 | PE-PGRS family protein PE_PGRS11; Induces maturation and activation of human dendritic cells (DCs), via TLR2-dependent activation of ERK1/2, p38 MAPK, and NF-kappa- B signaling pathways, and enhances the ability of DCs to stimulate CD4(+) T cells. By activating DCs, could potentially contribute to the initiation of innate immune responses during tuberculosis infection and hence regulate the clinical course of tuberculosis. Involved in resistance to oxidative stress, via TLR2-dependent activation of the PI3K-ERK1/2-NF-kappa-B signaling pathway and expression of COX-2 and Bcl2. Also abol [...] (584 aa) |
| | rpfA | Possible resuscitation-promoting factor RpfA; Factor that stimulates resuscitation of dormant cells. Has peptidoglycan (PG) hydrolytic activity. Active in the pM concentration range. Has little to no effect on actively-growing cells. PG fragments could either directly activate the resuscitation pathway of dormant bacteria or serve as a substrate for endogenous Rpf, resulting in low molecular weight products with resuscitation activity. Stimulates growth of stationary phase M.bovis (a slow-growing Mycobacterium), reduces the lag phase of diluted fast-growers M.smegmatis and Micrococcus [...] (407 aa) |
| | pknD | Transmembrane serine/threonine-protein kinase D PknD (protein kinase D) (STPK D); Key microbial factor required for central nervous system tuberculosis. Required for invasion of host brain endothelia, but not macrophages, lung epithelia or other endothelia. Phosphorylates the anti-anti-sigma factor homolog Rv0516c, which inhibits binding of Rv0516c to Rv2638, another anti-anti-sigma factor. Can also phosphorylate the FHA domain of Rv1747. (664 aa) |
| | pstS2 | Periplasmic phosphate-binding lipoprotein PstS2 (PBP-2) (PstS2); Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation. Part of the ABC transporter complex PstSACB involved in phosphate import (Probable). (370 aa) |
| | pstS1 | Periplasmic phosphate-binding lipoprotein PstS1 (PBP-1) (PstS1); Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation. Binds phosphate; probably able to bind both H(2)PO(4)(-) and HPO(4)(2-). Part of the ABC transporter complex PstSACB involved in phosphate import (Probable). (374 aa) |
| | PE_PGRS17 | PE-PGRS family protein PE_PGRS17; Induces maturation and activation of human dendritic cells (DCs), via TLR2-dependent activation of ERK1/2, p38 MAPK, and NF-kappa- B signaling pathways, and enhances the ability of DCs to stimulate CD4(+) T cells. By activating DCs, could potentially contribute to the initiation of innate immune responses during tuberculosis infection and hence regulate the clinical course of tuberculosis. (331 aa) |
| | mprA | Response regulator MprA; Member of the two-component regulatory system MprB/MprA which contributes to maintaining a balance among several systems involved in stress resistance and is required for establishment and maintenance of persistent infection in the host. Functions as a transcriptional regulator that recognizes a 19-bp nucleotide motif comprizing two loosely conserved 8-bp direct DNA-binding motif repeats separated by a 3-bp spacer region. MprB/MprA is involved in regulation of numerous stress-responsive genes, including up-regulation of two sigma factors, sigE and sigB as well [...] (228 aa) |
| | mprB | Two component sensor kinase MprB; Member of the two-component regulatory system MprB/MprA which contributes to maintaining a balance among several systems involved in stress resistance and is required for establishment and maintenance of persistent infection in the host. In response to environmental signals MprB acts as both a membrane-associated protein kinase that undergoes autophosphorylation and subsequently transfers the phosphate to MprA, and a protein phosphatase that dephosphorylates phospho-MprA. MprB/MprA is involved in regulation of numerous stress-responsive genes, includin [...] (504 aa) |
| | rpfB | Probable resuscitation-promoting factor RpfB; Factor that stimulates resuscitation of dormant cells. Has peptidoglycan (PG) hydrolytic activity. Active in the pM concentration range. Has little to no effect on actively-growing cells. PG fragments could either directly activate the resuscitation pathway of dormant bacteria or serve as a substrate for endogenous Rpf, resulting in low molecular weight products with resuscitation activity; Belongs to the transglycosylase family. Rpf subfamily. (362 aa) |
| | PE9 | PE family protein PE9; Together with PE10, induces macrophage apoptosis through human Toll-like receptor 4 (TLR4) signaling pathway. Interaction with TLR4 leads to increased levels of phospho-IRF-3, increase in the transcript levels of IFN-beta and pro-apoptotic genes, up-regulation of IL-10, down-regulation of IL-1b and enhanced levels of macrophage apoptosis. (144 aa) |
| | PE10 | PE family protein PE10; Together with PE9, induces macrophage apoptosis through human Toll-like receptor 4 (TLR4) signaling pathway. Interaction with TLR4 leads to increased levels of phospho-IRF-3, increase in the transcript levels of IFN-beta and pro-apoptotic genes, up-regulation of IL-10, down-regulation of IL-1b and enhanced levels of macrophage apoptosis. (120 aa) |
| | pimE | Mannosyltransferase PimE; Catalyzes the alpha-1,2 addition of a mannose residue from polyprenol-phosphate-mannose (PPM) to a monoacyl phosphatidylinositol pentamannoside (AcPIM5) to generate a monoacyl phosphatidylinositol hexamannoside (AcPIM6). (431 aa) |
| | lpqW | Probable conserved lipoprotein LpqW; May directly or indirectly regulate the accessibility of the key branch point intermediate, monoacyl phosphatidylinositol tetramannoside (AcPIM4), to the elongating alpha-1,6 mannosyltransferases which could regulate the lipoarabinomannans (LAMs) biosynthesis; Belongs to the bacterial solute-binding protein 5 family. (635 aa) |
| | PE13 | PE family protein PE13; May play a pivotal role in the interaction between M.tuberculosis and host. Can enhance the survival within macrophages under stress conditions such as H(2)O(2), SDS and low pH. Increases the production of IL-6 and IL-1beta from macrophages, and decreases the secretion of suppressor of cytokine signaling 3 (SOCS-3). These changes probably involve the p38-ERK-NF-kappa-B signaling pathway. Also precipitates the macrophage death. (99 aa) |
| | PPE18 | PPE family protein PPE18; Could be a crucial virulence factor for intracellular survival of M.tuberculosis. Favors development of Th2-type response, and downregulates the proinflammatory and Th1-type response. Specifically interacts with the human Toll-like receptor 2 (TLR2), leading to an early and sustained activation of p38 MAPK, which induces IL-10 production and activates Th2-type immune response. Also inhibits proinflammatory cytokines IL-12p40 and TNF-alpha production. Acts by upregulating the expression as well as tyrosine phosphorylation of suppressor of cytokine signaling 3 ( [...] (391 aa) |
| | esxL | Putative ESAT-6 like protein EsxL (ESAT-6 like protein 4); Induces apoptosis of host cells. Is immunogenic with highly specific seroreactivity towards TB patients' serum ; Belongs to the WXG100 family. ESAT-6 subfamily. (94 aa) |
| | PE15 | PE family protein PE15; May play a pivotal role in the evasion of host immune response by M.tuberculosis. Mediates production of IL-10 via activation of the p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling pathways; Belongs to the mycobacterial PE family. (102 aa) |
| | Rv1410c | Aminoglycosides/tetracycline-transport integral membrane protein; In association with lipoprotein LprG probably transports triacylglycerides (TAG) across the inner cell membrane into the periplasm; TAG probably regulates lipid metabolism and growth regulation. Confers resistance to ethidium bromide, possibly acting as an efflux pump, requires LprG lipoprotein for normal function. With LprG maintains cell wall permeability. Probably required with LprG for normal surface localization of LAM. Overexpression of LprG and Rv1410c leads to increased levels of TAG in the culture medium. Belong [...] (518 aa) |
| | lprG | Conserved lipoprotein LprG; Probably helps membrane protein Rv1410c (P55) transport triacylglycerides (TAG) across the inner cell membrane into the periplasm; TAG probably regulates lipid metabolism and growth regulation. Binds TAG and transfers it between lipid bilayers, probably to the outer membrane in vivo. Binds di- and triacylated phosphatidyl-myo-inositol mannosides (PIMs), and glycolipid lipoglycan modulins lipoarabinomannan (LAM) and lipomannan (LM), facilitating their recognition by TLR2. Binds LM > PIM6 > ManLAM > PI-LAM > PIM2 (mannose-capped LAM and phospho-myo-inositol-ca [...] (236 aa) |
| | pks5 | Probable polyketide synthase Pks5; Polyketide synthase likely involved in the biosynthesis of a polymethyl-branched fatty acid (PMB-FA) that might only be produced during host infection. Is required for the full virulence of M.tuberculosis during host infection. (2108 aa) |
| | lysX | Lysyl-tRNA synthetase 2 LysX; Catalyzes the production of L-lysyl-tRNA(Lys)transfer and the transfer of a lysyl group from L-lysyl-tRNA(Lys) to membrane-bound phosphatidylglycerol (PG), which produces lysylphosphatidylglycerol (LPG), one of the components of the bacterial membrane with a positive net charge. LPG synthesis contributes to the resistance to cationic antimicrobial peptides (CAMPs) and likely protects M.tuberculosis against the CAMPs produced by competiting microorganisms (bacteriocins). In fact, the modification of anionic phosphatidylglycerol with positively charged L-lys [...] (1172 aa) |
| | PE_PGRS30 | PE-PGRS family protein PE_PGRS30; Mediates suppression of proinflammatory immune response in macrophages via modulation of host cytokine response. Required for full virulence. Involved in inhibition of phago-lysosome fusion. (1011 aa) |
| | tlyA | 2'-O-methyltransferase TlyA; Acts as a host evasion factor, that significantly contributes to the pathogenesis of M.tuberculosis by modulating adaptive immune responses by inhibiting host-protective Th1 and Th17 cytokine responses as well as autophagy. Catalyzes the 2'-O-methylation at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA. Is likely involved in ribosomal biogenesis. Also exhibits hemolytic activity in vitro, by binding with and oligomerizing into host cell membranes. Belongs to the TlyA family. (268 aa) |
| | pknE | Probable transmembrane serine/threonine-protein kinase E PknE (protein kinase E) (STPK E); Important for survival of the bacterium in the host during infection. Promotes the survival of infected macrophages by activating multiple signaling responses and suppressing apoptosis of macrophages during nitrate stress. May contribute to the adaptation of M.tuberculosis during stress conditions by maintaining the cellular integrity. Can phosphorylate the FHA domain of Rv1747. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. (566 aa) |
| | PPE26 | PPE family protein PPE26; Probably plays a key role in regulating innate and adaptive immune responses through human Toll-like receptor 2 (TLR2). Interacts with TLR2, leading to the subsequent activation of the mitogen- activated protein kinase (MAPK) and nuclear factor kappa B (NF-kappa-B) signaling pathways. Stimulates macrophage activation by augmenting pro- inflammatory cytokine production (TNF-alpha, IL-6 and IL-12p40) and the expression of cell surface molecules (CD80, CD86, MHC class I and II). Also participates in adaptive immunity by directing Th1-polarised immune responses. (393 aa) |
| | PE_PGRS33 | PE-PGRS family protein PE_PGRS33; Induces TNF-alpha release through human Toll-like receptor 2 (TLR2) signaling pathway, leading to macrophage apoptosis. The signaling pathway involves TLR2-dependent activation of the mitogen-activated protein kinase kinase kinase 5 (ASK1), which activates the p38 and JNK MAPKs, leading to enhanced expression of TNF-alpha and tumor necrosis factor receptor superfamily member 1A (TNFRI) genes. Signals are amplified through classical caspase 8-dependent mitochondrial release of cytochrome c, leading to the activation of caspases 9 and 3. Mediates Ca(2+)- [...] (498 aa) |
| | rpfC | Probable resuscitation-promoting factor RpfC; Factor that stimulates resuscitation of dormant cells. Has peptidoglycan (PG) hydrolytic activity. Active in the pM concentration range. Has little to no effect on actively-growing cells. PG fragments could either directly activate the resuscitation pathway of dormant bacteria or serve as a substrate for endogenous Rpf, resulting in low molecular weight products with resuscitation activity. Belongs to the transglycosylase family. Rpf subfamily. (176 aa) |
| | katG | Catalase-peroxidase-peroxynitritase T KatG; Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity, oxidizing various electron donors including NADP(H). Protects M.tuberculosis against toxic reactive oxygen species (ROS) including hydrogen peroxide as well as organic peroxides and thus contributes to its survival within host macrophages by countering the phagocyte oxidative burst. Also displays efficient peroxynitritase activity, which may help the bacterium to persist in macrophages. Catalyzes the oxidative activation of the antitubercular pro- drug isoniazid (I [...] (740 aa) |
| | PPE34 | PPE family protein PPE34; Facilitates a shift in the ensuing immunity toward the Th2 phenotype and could aid in immune evasion by mycobacteria. Interacts with human Toll-like receptor 2 (TLR2) and triggers functional maturation of human dendritic cells (DCs), leading to secretion of IL- 4, IL-5 and IL-10 from CD4(+) T cells and induction of Th2 immune response. Maturation of DCs involves PI3K, ERK1/2, p38 MAPK and NF- kappa-B signaling pathways. (1459 aa) |
