snoP

Gene

Probable glutamine amidotransferase SnoP.

Rv2604c

phoP

Gene

Possible two component system response transcriptional positive regulator PhoP.

Rv0757

carA

Gene

Probable carbamoyl-phosphate synthase small chain CarA (carbamoyl-phosphate synthetase glutamine chain).

Rv1383

RNA polymerase-binding transcription factor CarD

Protein

Controls rRNA transcription by binding to the RNA polymerase (RNAP). Required for replication and persistence during infection of mice. {ECO:0000269|PubMed:19596241, ECO:0000269|PubMed:22904282}..

P9WJG3

carB

Gene

Probable carbamoyl-phosphate synthase large chain CarB (carbamoyl-phosphate synthetase ammonia chain).

Rv1384

Possible two component system response transcriptional positive regulator PhoP

Protein

Unknown.

P71814

Phosphate-specific transport system accessory protein PhoU homolog 2 (Pst system accessory protein PhoU homolog 2)

Protein

Plays a role in the regulation of phosphate uptake. In this role, it may bind, possibly as a chaperone, to PhoR, PhoP or a PhoR-PhoP complex to promote dephosphorylation of phospho-PhoP, or inhibit formation of the PhoR-PhoP transitory complex (By similarity). Important for tolerance to antibiotics. {ECO:0000250, ECO:0000269|PubMed:20360062}..

P9WI95

Phosphate-specific transport system accessory protein PhoU homolog 1 (Pst system accessory protein PhoU homolog 1)

Protein

Plays a role in the regulation of phosphate uptake. In this role, it may bind, possibly as a chaperone, to PhoR, PhoP or a PhoR-PhoP complex to promote dephosphorylation of phospho-PhoP, or inhibit formation of the PhoR-PhoP transitory complex (By similarity). {ECO:0000250}..

P9WI97

Group 2 truncated hemoglobin GlbO (Hemoglobin-like protein HbO) (Truncated hemoglobin) (trHbO)

Protein

When expressed in E.coli and M.smegmatis, HbO increases oxygen uptake. Membrane vesicles of E.coli carrying HbO show a respiration activity about twice that of membranes without HbO. HbO seems to interact with a terminal oxidase. Therefore, HbO could participate in oxygen/electron-transfer process, suggesting a function related to the facilitation of oxygen transfer during aerobic metabolism of M.tuberculosis..

P9WN23

Aminoglycoside 2'-N-acetyltransferase (EC 2.3.1.-) (AAC(2')-Ic)

Protein

May catalyze the coenzyme A-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides and confer resistance to aminoglycosides (By similarity). In vitro assays show no significant increase of resistance to aminoglycosides, possibly due to low expression in a heterologous system (PubMed:9159528). {ECO:0000250|UniProtKB:P94968, ECO:0000269|PubMed:9159528}..

P9WQG9

HTH-type transcriptional regulator Rv2034

Protein

Involved in the regulation of lipid metabolism and hypoxic response. Positively regulates transcription of various genes, such as phoP, groEL2 and dosR. Negatively regulates its own transcription. Acts by binding to a specific palindromic sequence motif in promoter regions. {ECO:0000269|PubMed:21782791, ECO:0000269|PubMed:22558408}..

O53478

Universal stress protein Rv2623 (USP Rv2623)

Protein

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..

P9WFD7

F420H(2)-dependent reductase Rv1155 (EC 1.-.-.-)

Protein

F420H(2)-dependent reductase able to catalyze the reduction of biliverdin-IXalpha to bilirubin-IXalpha in vitro. However, kinetic parameters show that it is less efficient than the biliverdin reductase Rv2074 and suggest biliverdin-IXalpha is unlikely to be the native substrate of Rv1155, which probably catalyzes the reduction of an alternative molecule in vivo (PubMed:27364382). Binds coenzyme F420, but does not bind FMN or other flavins (PubMed:25644473). Cannot use pyridoxine 5'-phosphate, pyridoxamine 5'-phosphate, pyridoxal 5'-phosphate (PLP), the anti-tuberculosis drug PA-824 or aflatoxin analogs as substrates (PubMed:25644473). {ECO:0000269|PubMed:25644473, ECO:0000269|PubMed:27364382}..

O06553

Dihydropteroate synthase (DHPS) (EC 2.5.1.15) (Dihydropteroate pyrophosphorylase)

Protein

Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives. {ECO:0000269|PubMed:10542185, ECO:0000269|PubMed:23118010, ECO:0000269|PubMed:23779105}.; FUNCTION: Is involved in the bioactivation of the antituberculous drug para-aminosalicylic acid (PAS). PAS is a close structural analog of pABA and acts as an alternative substrate for DHPS, leading to hydroxy-dihydropteroate (H2PtePAS). Metabolomic studies show that PAS, despite its in vitro activity as a competitive inhibitor of DHPS, does not inhibit growth of M.tuberculosis by inhibiting DHPS. PAS exerts its antimycobacterial activity through its effects on M.tuberculosis folate metabolism downstream of DHPS. PAS poisons folate-dependent pathways not only by serving as a replacement substrate for DHPS but also by the products of that reaction serving as replacement substrates and/or inhibitors of subsequent enzymes. {ECO:0000269|PubMed:23118010, ECO:0000269|PubMed:23779105}..

P9WND1

Flavin-dependent monooxygenase, reductase subunit HsaB (EC 1.5.1.36) (3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione 4-hydroxylase, reductase subunit) (Flavin:NADH reductase)

Protein

Catalyzes the reduction of free flavins (FMN or FAD) by NADH. Subsequently, the reduced flavins diffuse to the HsaA oxygenase subunit. {ECO:0000269|PubMed:20448045}..

P9WND9

Trehalose-phosphate phosphatase (TPP) (EC 3.1.3.12) (Trehalose-6-phosphate phosphatase)

Protein

Removes the phosphate from trehalose 6-phosphate to produce free trehalose. {ECO:0000269|PubMed:15158675, ECO:0000269|PubMed:15703182}..

P9WFZ5

Probable lipoprotein aminopeptidase LpqL (EC 3.4.11.1) (Leucine aminopeptidase) (Lipoprotein LpqL)

Protein

An aminopeptidase; acts on free N-terminal amino groups with a very strong preference for Leu in the first position. {ECO:0000250|UniProtKB:Q9HZQ8}..

P96264

Probable inositol 1-monophosphatase ImpA (I-1-Pase) (IMPase) (Inositol-1-phosphatase) (EC 3.1.3.25)

Protein

Catalyzes the dephosphorylation of inositol 1-phosphate (I-1-P) to yield free myo-inositol, a key metabolite in mycobacteria. {ECO:0000250}..

O53907

PE-PGRS family protein PE_PGRS30

Protein

Mediates suppression of proinflammatory immune response in macrophages via modulation of host cytokine response (PubMed:27129781). Required for full virulence. Involved in inhibition of phago-lysosome fusion (PubMed:22050772). {ECO:0000269|PubMed:22050772, ECO:0000269|PubMed:27129781}..

Q79FL8

Purine nucleoside phosphorylase (PNP) (Pu-NPase) (EC 2.4.2.1) (Inosine phosphorylase) (Inosine-guanosine phosphorylase)

Protein

The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate. Cleaves guanosine, inosine, 2'-deoxyguanosine and 2'-deoxyinosine. {ECO:0000250|UniProtKB:P77834}..

P9WP01

Probable copper-exporting P-type ATPase V (EC 7.2.2.8) (Cu(+)-exporting ATPase)

Protein

Necessary for copper homeostasis and likely functions as a copper exporter. Also required for full virulence. {ECO:0000269|PubMed:20624225}..

P9WPS3

Heme-binding protein Rv0203

Protein

Part of a heme-iron acquisition system. Acts by binding heme and delivering it to the membrane proteins MmpL3 and MmpL11. Can use free heme or heme from host hemoglobin. {ECO:0000269|PubMed:21383189, ECO:0000269|PubMed:22283334, ECO:0000269|PubMed:23760277}..

I6X8R5

Inositol-1-monophosphatase SuhB (I-1-Pase) (IMPase) (Inositol-1-phosphatase) (EC 3.1.3.25)

Protein

Catalyzes the dephosphorylation of inositol 1-phosphate (I-1-P) to yield free myo-inositol, a key metabolite in mycobacteria. Is also able to hydrolyze a variety of polyol phosphates such as glucitol-6-phosphate, inositol 2-phosphate (I-2-P), glycerol-2-phosphate, and 2'-AMP, albeit with reduced efficiency. {ECO:0000269|PubMed:11914086}..

P9WKI9

Ribosome-binding factor A

Protein

One of several proteins that assist in the late maturation steps of the functional core of the 30S ribosomal subunit. Associates with free 30S ribosomal subunits (but not with 30S subunits that are part of 70S ribosomes or polysomes). Required for efficient processing of 16S rRNA. May interact with the 5'-terminal helix region of 16S rRNA. {ECO:0000255|HAMAP-Rule:MF_00003}..

P9WHJ7

Nicotinate phosphoribosyltransferase pncB2 (NAPRTase pncB2) (EC 6.3.4.21)

Protein

Involved in the Preiss-Handler pathway, which is a recycling route that permits the salvage of free nicotinamide (NM) and nicotinic acid (Na) involved in the NAD biosynthesis. Catalyzes the synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP. It is not able to use nicotinamide. PncB2 appears to be responsible for the increased salvage synthesis of NAD during infection of host tissues. {ECO:0000269|PubMed:18490451}..

P9WJI7

Nicotinate phosphoribosyltransferase pncB1 (NAPRTase pncB1) (EC 6.3.4.21)

Protein

Involved in the Preiss-Handler pathway, which is a recycling route that permits the salvage of free nicotinamide (NM) and nicotinic acid (Na) involved in the NAD biosynthesis. Catalyzes the synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP. It is not able to use nicotinamide. PncB1 contributes to basal NAD level. {ECO:0000269|PubMed:18490451}..

P9WJI9

Methionyl-tRNA formyltransferase (EC 2.1.2.9)

Protein

Attaches a formyl group to the free amino group of methionyl-tRNA(fMet). The formyl group appears to play a dual role in the initiator identity of N-formylmethionyl-tRNA by promoting its recognition by IF2 and preventing the misappropriation of this tRNA by the elongation apparatus. {ECO:0000255|HAMAP-Rule:MF_00182}..

P9WND3

Translation initiation factor IF-3

Protein

IF-3 binds to the 30S ribosomal subunit and shifts the equilibrum between 70S ribosomes and their 50S and 30S subunits in favor of the free subunits, thus enhancing the availability of 30S subunits on which protein synthesis initiation begins. {ECO:0000255|HAMAP-Rule:MF_00080}..

P9WKJ9

Probable endonuclease 4 (EC 3.1.21.2) (Endodeoxyribonuclease IV) (Endonuclease IV)

Protein

Endonuclease IV plays a role in DNA repair. It cleaves phosphodiester bonds at apurinic or apyrimidinic sites (AP sites) to produce new 5'-ends that are base-free deoxyribose 5-phosphate residues. It preferentially attacks modified AP sites created by bleomycin and neocarzinostatin. {ECO:0000255|HAMAP-Rule:MF_00152}..

P9WQ13

Ribosomal RNA small subunit methyltransferase E (EC 2.1.1.193) (16S rRNA m3U1498 methyltransferase)

Protein

Specifically methylates the N3 position of the uracil ring of uridine 1498 (m3U1498) in 16S rRNA. Acts on the fully assembled 30S ribosomal subunit (By similarity). {ECO:0000250}..

P9WGX1

UvrABC system protein A (UvrA protein) (Excinuclease ABC subunit A)

Protein

The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by UvrB, the UvrA molecules dissociate. Alone it slightly inhibits RecA-mediated DNA strand exchange, in concert with UvrD1 greatly inhibits RecA-mediated DNA strand exchange. {ECO:0000255|HAMAP-Rule:MF_00205, ECO:0000269|PubMed:20455546, ECO:0000269|PubMed:22467787}..

P9WQK7

Heme oxygenase (mycobilin-producing) (EC 1.14.99.57) (Mycobacterial heme utilization, degrader) (MHUD)

Protein

Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron. {ECO:0000269|PubMed:19917297, ECO:0000269|PubMed:23420845}..

P9WKH3

N-acetylmuramoyl-L-alanine amidase CwlM (EC 3.5.1.28) (Peptidoglycan hydrolase CwlM)

Protein

Cell-wall hydrolase that hydrolyzes the amide bond between N-acetylmuramic acid and L-alanine in cell-wall glycopeptides. Is able to lyse whole mycobacteria, release peptidoglycan from the cell wall of M.luteus and M.smegmatis, and cleave N-acetylmuramoyl-L-alanyl-D-isoglutamine, releasing free N-acetylmuramic acid and dipeptide. {ECO:0000269|PubMed:15680239}..

L7N653

Nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) (EC 3.6.1.8)

Protein

Required to maintain the full capacity of the mycobacterium to respond to oxidative stress via the degradation of oxidation-induced damaged nucleotides. Hydrolyzes all canonical (d)NTPs, as well as mutagenic dUTP and 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP). Also involved in the transcriptional activation of RelA in response to oxidative stress. {ECO:0000269|PubMed:20529853}..

P96379

Mycosin-1 (EC 3.4.21.-) (MycP1 protease)

Protein

May play a dual role in regulation of ESX-1 secretion and virulence. Acts as a protease that cleaves EspB. Essential for ESX-1 function, required for early replication in macrophages and full virulence in mice. {ECO:0000269|PubMed:20227664}..

O05461

Ribosome maturation factor RimM

Protein

An accessory protein needed during the final step in the assembly of 30S ribosomal subunit, possibly for assembly of the head region. Probably interacts with S19. Essential for efficient processing of 16S rRNA. May be needed both before and after RbfA during the maturation of 16S rRNA. It has affinity for free ribosomal 30S subunits but not for 70S ribosomes. {ECO:0000255|HAMAP-Rule:MF_00014}..

P9WH19

Neutral ceramidase (N-CDase) (NCDase) (EC 3.5.1.23) (Acylsphingosine deacylase) (N-acylsphingosine amidohydrolase)

Protein

Catalyzes the cleavage of the N-acyl linkage of the ceramides (Cers) to yield sphingosine (Sph) and free fatty acid. Also catalyzes the synthesis of Cers from Sph and fatty acid. Cers containning C6-C24 fatty acids are well hydrolyzed, and Cers with mono unsaturated fatty acids are much more hydrolyzed than those with saturated fatty acids. {ECO:0000269|PubMed:10593963, ECO:0000269|PubMed:20139604}..

O06769

Mycocerosic acid synthase-like polyketide synthase (MAS-like PKS) (EC 2.3.1.-) (Polyketide synthase Pks5)

Protein

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. {ECO:0000269|PubMed:12855735, ECO:0000305}..

O53901

Diacylglycerol acyltransferase/mycolyltransferase Ag85C (DGAT) (EC 2.3.1.122) (EC 2.3.1.20) (Acyl-CoA:diacylglycerol acyltransferase) (Antigen 85 complex C) (85C) (Ag85C) (Fibronectin-binding protein C) (Fbps C)

Protein

The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria to fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM. {ECO:0000269|PubMed:1830294, ECO:0000269|PubMed:9162010}..

P9WQN9

Diacylglycerol acyltransferase/mycolyltransferase Ag85B (DGAT) (EC 2.3.1.122) (EC 2.3.1.20) (30 kDa extracellular protein) (Acyl-CoA:diacylglycerol acyltransferase) (Antigen 85 complex B) (85B) (Ag85B) (Extracellular alpha-antigen) (Fibronectin-binding protein B) (Fbps B)

Protein

The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria for fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM. {ECO:0000269|PubMed:12010501, ECO:0000269|PubMed:3141278, ECO:0000269|PubMed:9162010}..

P9WQP1

D-aminoacyl-tRNA deacylase (DTD) (EC 3.1.1.96) (Gly-tRNA(Ala) deacylase) (EC 3.1.1.-)

Protein

An aminoacyl-tRNA editing enzyme that deacylates mischarged D-aminoacyl-tRNAs. Also deacylates mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS. Acts via tRNA-based rather than protein-based catalysis; rejects L-amino acids rather than detecting D-amino acids in the active site. By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality. {ECO:0000255|HAMAP-Rule:MF_00518}..

P9WNS9

Lipid uptake coordinator A

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. {ECO:0000269|PubMed:28708968}..

O69690

L-threonine dehydratase biosynthetic IlvA (EC 4.3.1.19) (Threonine deaminase)

Protein

Catalyzes the anaerobic formation of alpha-ketobutyrate and ammonia from threonine in a two-step reaction. The first step involved a dehydration of threonine and a production of enamine intermediates (aminocrotonate), which tautomerizes to its imine form (iminobutyrate). Both intermediates are unstable and short-lived. The second step is the nonenzymatic hydrolysis of the enamine/imine intermediates to form 2-ketobutyrate and free ammonia. In the low water environment of the cell, the second step is accelerated by RidA (By similarity). {ECO:0000250}..

P9WG95

Copper-sensing transcriptional repressor CsoR (Copper-sensitive operon repressor)

Protein

Copper-sensitive repressor that has a key role in copper homeostasis. It is part of the cso operon involved in the cellular response to increasing concentrations of copper inside the bacterium, which can be highly toxic. In the presence of copper, CsoR fully dissociates from the promoter in the cso operon, leading to the transcription of its genes. Binds to a GC-rich pseudopallindromic sequence, 5'-GTAGCCCACCCCCAGTGGGGTGGGA-3', in the cso promoter region. {ECO:0000269|PubMed:17143269}..

P9WP49

Chaperone protein DnaJ 1

Protein

Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins and by disaggregating proteins, also in an autonomous, DnaK-independent fashion. Unfolded proteins bind initially to DnaJ; upon interaction with the DnaJ-bound protein, DnaK hydrolyzes its bound ATP, resulting in the formation of a stable complex. GrpE releases ADP from DnaK; ATP binding to DnaK triggers the release of the substrate protein, thus completing the reaction cycle. Several rounds of ATP-dependent interactions between DnaJ, DnaK and GrpE are required for fully efficient folding. Also involved, together with DnaK and GrpE, in the DNA replication of plasmids through activation of initiation proteins. {ECO:0000255|HAMAP-Rule:MF_01152}..

P9WNV9

Chaperone protein DnaJ 2

Protein

Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins and by disaggregating proteins, also in an autonomous, DnaK-independent fashion. Unfolded proteins bind initially to DnaJ; upon interaction with the DnaJ-bound protein, DnaK hydrolyzes its bound ATP, resulting in the formation of a stable complex. GrpE releases ADP from DnaK; ATP binding to DnaK triggers the release of the substrate protein, thus completing the reaction cycle. Several rounds of ATP-dependent interactions between DnaJ, DnaK and GrpE are required for fully efficient folding. Also involved, together with DnaK and GrpE, in the DNA replication of plasmids through activation of initiation proteins (By similarity). Inhibits the beta-lactamase and RNase activity of RNase J. {ECO:0000255|HAMAP-Rule:MF_01152, ECO:0000269|PubMed:21568871}..

P9WNV7

Copper-sensing transcriptional repressor RicR (Regulated in copper repressor)

Protein

Under low copper conditions, represses the expression of lpqS, Rv2963, mymT, socA, socB, mmcO and its own expression. In the presence of copper, RicR dissociates from DNA, leading to the expression of the target genes. Members of the RicR regulon are important for copper resistance during infections and full virulence in a mouse model of infection. {ECO:0000269|PubMed:21166899, ECO:0000269|PubMed:24549843}..

O07434

Lipoprotein LprA

Protein

Constitutes a host TLR2 agonist (toll-like receptor), shown experimentally for human and mouse (PubMed:19362712). In host cells full-length (acylated) protein acts as a TLR2 agonist, inducing human and murine macrophages to produce cytokines, inducing murine dendritic cell maturation and cytokine production and inhibiting antibody processing in murine macrophages (PubMed:16785538). Binds diacylated phosphatidyl-myo-inositol mannosides (PIMs) (PubMed:20694006). Does not induce murine macrophage apoptosis or necrosis (PubMed:16785538). Non-acylated protein does not act as a TLR2 agonist (PubMed:20694006). Requires only host TLR2 as receptors to elicit host response in mouse, although TLR6 may play a redundant role, also requires CD14 and CD16 as accessory receptors (PubMed:19362712). {ECO:0000269|PubMed:16785538, ECO:0000269|PubMed:19362712, ECO:0000269|PubMed:20694006}..

P9WK55

Diacylglycerol acyltransferase/mycolyltransferase Ag85A (DGAT) (EC 2.3.1.122) (EC 2.3.1.20) (Acyl-CoA:diacylglycerol acyltransferase) (Antigen 85 complex A) (85A) (Ag85A) (Fibronectin-binding protein A) (Fbps A)

Protein

The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria for fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan, and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM. FbpA mediates triacylglycerol (TAG) formation with long-chain acyl-CoA as the acyl donor and 1,2-dipalmitoyl-sn-glycerol (1,2-dipalmitin) as the acyl acceptor. It has a preference for C26:0-CoA over C18:1-CoA. {ECO:0000269|PubMed:12010501, ECO:0000269|PubMed:21819455, ECO:0000269|PubMed:3141278, ECO:0000269|PubMed:9162010}..

P9WQP3

DNA topoisomerase 1 (EC 5.6.2.2) (DNA topoisomerase I) (Omega-protein) (Relaxing enzyme) (Swivelase) (Untwisting enzyme)

Protein

Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex (PubMed:8921893, PubMed:20724443). Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. {ECO:0000255|HAMAP-Rule:MF_00952, ECO:0000269|PubMed:20724443, ECO:0000269|PubMed:8921893}.; FUNCTION: The C-terminus (residues 622-934) inhibits RNA cleavage by MazF4. {ECO:0000269|PubMed:20724443}..

P9WG49

Steroid 3-ketoacyl-CoA thiolase (EC 2.3.1.16) (Acetyl-CoA acetyltransferase FadA5) (Beta-ketoacyl-CoA thiolase)

Protein

Involved in the beta-oxidation of the cholesterol side chain (PubMed:19822655). 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 (PubMed:19822655). 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 (PubMed:25482540). Also able to use acetoacetyl-CoA (AcAcCoA) as substrate (PubMed:19822655). {ECO:0000269|PubMed:19822655, ECO:0000269|PubMed:25482540}..

I6XHI4

Protein GrpE (HSP-70 cofactor)

Protein

Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins, in association with DnaK and GrpE. It is the nucleotide exchange factor for DnaK and may function as a thermosensor. Unfolded proteins bind initially to DnaJ; upon interaction with the DnaJ-bound protein, DnaK hydrolyzes its bound ATP, resulting in the formation of a stable complex. GrpE releases ADP from DnaK; ATP binding to DnaK triggers the release of the substrate protein, thus completing the reaction cycle. Several rounds of ATP-dependent interactions between DnaJ, DnaK and GrpE are required for fully efficient folding. {ECO:0000255|HAMAP-Rule:MF_01151}..

P9WMT5

ECF RNA polymerase sigma factor SigE (ECF sigma factor SigE) (Alternative RNA polymerase sigma factor SigE) (RNA polymerase sigma-E factor) (Sigma-E factor)

Protein

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. Responds to heat shock and surface stress (detergent exposure). When combined with isolated core RNA polymerase from M.smegmatis is able to guide initiation from the sigB promoter. Required for full expression of sigB, and for sigB induction after detergent exposure but not after heat shock. Controls a regulon of about 38 genes in culture (PubMed:11489128) and about 16 genes during macrophage infection (PubMed:18657035), most of which have decreased expression in a disruption mutant. Probably down regulates the host immune response to mycobacterial infection. {ECO:0000269|PubMed:11489128, ECO:0000269|PubMed:18657035, ECO:0000269|PubMed:20025669, ECO:0000269|PubMed:9139909}..

P9WGG7

SsrA-binding protein (Small protein B)

Protein

Required for rescue of stalled ribosomes mediated by trans-translation. Binds to transfer-messenger RNA (tmRNA), required for stable association of tmRNA with ribosomes. tmRNA and SmpB together mimic tRNA shape, replacing the anticodon stem-loop with SmpB. tmRNA is encoded by the ssrA gene; the 2 termini fold to resemble tRNA(Ala) and it encodes a 'tag peptide', a short internal open reading frame. During trans-translation Ala-aminoacylated tmRNA acts like a tRNA, entering the A-site of stalled ribosomes, displacing the stalled mRNA. The ribosome then switches to translate the ORF on the tmRNA; the nascent peptide is terminated with the 'tag peptide' encoded by the tmRNA and targeted for degradation. The ribosome is freed to recommence translation, which seems to be the essential function of trans-translation. {ECO:0000255|HAMAP-Rule:MF_00023}..

P9WGD3

Oxygen sensor histidine kinase response regulator DosT (EC 2.7.13.3)

Protein

Interacts with the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. Required for full induction of the DevR (DosR) regulon; required during early adaptation to anaerobiosis, to start induction of the DevR regulon (PubMed:19487478). May act as a direct hypoxia/oxygen sensor (PubMed:17609369, PubMed:17600145, PubMed:28977726). O(2) acts as a switch, with the Fe(2+)-O(2)-bound protein inactive in autophosphorylation (PubMed:17600145). Autophosphorylates under anaerobic but not aerobic conditions, binding of NO or CO has no effect on autophosphorylation (PubMed:17600145). Binds a number of gases; O(2), NO, CO (PubMed:17609369, PubMed:17600145). May be a secondary sensor for CO (PubMed:18400743). Donates a phosphate group to transcriptional regulator DevR (DosR) (PubMed:15135056, PubMed:15033981, PubMed:28977726). {ECO:0000269|PubMed:15033981, ECO:0000269|PubMed:15135056, ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:17609369, ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359, ECO:0000269|PubMed:19487478, ECO:0000269|PubMed:28977726}..

P9WGK1

Arylamine N-acetyltransferase (NAT) (EC 2.3.1.5) (TBNAT)

Protein

Catalyzes the transfer of the acetyl group from acetyl coenzyme A to the free amino group of arylamines and hydrazines (PubMed:18795795). Is able to utilize not only acetyl-CoA, but also n-propionyl-CoA and acetoacetyl-CoA as acyl donors, although at a lower rate (PubMed:19014350). As acetyl-CoA and propionyl-CoA are products of cholesterol catabolism and the nat gene is likely present in the same operon than genes involved in cholesterol degradation, this enzyme could have a role in the utilization and regulation of these CoA species (PubMed:19014350). {ECO:0000269|PubMed:18795795, ECO:0000269|PubMed:19014350}.; FUNCTION: It has been reported that overexpression of this enzyme may be responsible for increased resistance to the front-line antitubercular drug isoniazid (INH), by acetylating and hence inactivating the prodrug (PubMed:9973365). However, isoniazid is an extremely poor substrate for the enzyme; therefore, the expression of TBNAT is unlikely to be a significant cause of isoniazid resistance in M.tuberculosis (PubMed:18795795). {ECO:0000269|PubMed:18795795, ECO:0000269|PubMed:9973365}..

P9WJI5

Oxygen sensor histidine kinase response regulator DevS/DosS (EC 2.7.13.3)

Protein

Member of the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response (PubMed:12953092). Regulates an approximately 48-member regulon (PubMed:12953092, PubMed:11416222, PubMed:15033981, PubMed:18400743). Required for full induction of the DevR (DosR) regulon; acts later than DosT to positively regulate expression of the DevR regulon during adaptation to anaerobiosis (PubMed:19487478). Characterized as an oxygen sensor; O(2) acts as a switch, with O(2)-bound Fe(2+) protein inactive in autophosphorylation (PubMed:17371046, PubMed:17600145, PubMed:18975917, PubMed:19463006, PubMed:28977726). Has also been suggested to act as a redox sensor, or perhaps as a dual oxygen/redox sensor (PubMed:17609369). Autophosphorylates under anaerobic but not aerobic conditions, binding of NO or CO does not dramatically change the level of autophosphorylation of Fe(2+) protein, binding of O(2) inactivates kinase activity (PubMed:17600145, PubMed:18975917, PubMed:27235395). Binds O(2), NO, CO (PubMed:17371046, PubMed:17609369, PubMed:17600145, PubMed:18975917, PubMed:27235395). It is probably reduced by flavin nucleotides such as FMN and FAD (PubMed:19276084). May be the primary sensor for CO (PubMed:18400743). Donates a phosphate group to transcriptional regulator DevR (DosR) (PubMed:15033981, PubMed:15073296, PubMed:28977726). {ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:12953092, ECO:0000269|PubMed:15033981, ECO:0000269|PubMed:15073296, ECO:0000269|PubMed:17371046, ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:17609369, ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359, ECO:0000269|PubMed:18975917, ECO:0000269|PubMed:19463006, ECO:0000269|PubMed:19487478, ECO:0000269|PubMed:27235395, ECO:0000269|PubMed:28977726}..

P9WGK3

Decaprenylphosphoryl-beta-D-ribose oxidase (EC 1.1.98.3) (Decaprenylphospho-beta-D-ribofuranose 2-dehydrogenase) (Decaprenylphosphoryl-beta-D-ribofuranose 2'-epimerase subunit DprE1) (Decaprenyl-phosphoribose 2'-epimerase subunit 1) (Decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase) (Decaprenylphosphoryl-beta-D-ribose 2-epimerase flavoprotein subunit) (FAD-dependent decaprenylphosphoryl-beta-D-ribofuranose 2-oxidase)

Protein

Component of the DprE1-DprE2 complex that catalyzes the 2-step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-phospho-arabinose (DPA), a key precursor that serves as the arabinose donor required for the synthesis of cell-wall arabinans (PubMed:16291675, PubMed:19299584). DprE1 catalyzes the first step of epimerization, namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX) (PubMed:22733761). The intermediate DPX is then transferred to DprE2 subunit of the epimerase complex, most probably through a 'substrate channel' at the interface of DprE1-DprE2 complex (PubMed:25789990). Can also use farnesyl-phosphoryl-beta-D-ribofuranose (FPR) as substrate in vitro (PubMed:25427196). Appears to be essential for the growth and survival of M.tuberculosis (PubMed:12657046, PubMed:24517327). {ECO:0000269|PubMed:12657046, ECO:0000269|PubMed:16291675, ECO:0000269|PubMed:19299584, ECO:0000269|PubMed:22733761, ECO:0000269|PubMed:24517327, ECO:0000269|PubMed:25427196, ECO:0000305|PubMed:25789990}.; FUNCTION: DprE1 is a highly vulnerable and fully validated tuberculosis drug target. {ECO:0000303|PubMed:20629622, ECO:0000303|PubMed:24037308, ECO:0000303|PubMed:24245764}..

P9WJF1