Border Color Location
  Extracellular
  Cell membrane
  Cytoplasm
  Organelle
  Bacterial membrane or virus envelope
  Other
Backgound Color Node Shape Object Type
  Box Protein or gene
  Box Protein of gene complex
  Ellipse Pathway or action
  Box Eukaryotic cell or cell component
  Box Microorganism or its component
  Box Microbe-host cell complex

Phinet Name: Mycobacterium tuberculosis

Phinet Information
Pathogen Name: Mycobacterium tuberculosis
Pathogen NIAID Category: NIAID Category C
Bio-objects
Bio-object 1: apoptosis
  • Type: Other
  • Location: Other
  • Function: Other
Bio-object 2: BAD
  • GI Number: 14670387
  • Accession Number:
  • DB Links: BCL2-antagonist of cell death
  • Type: Protein or gene
  • Location: Mitochondria
  • Function: Signal transducer
  • Description: The protein encoded by this gene is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase, as well as protein phosphatase calcineurin were found to be involved in the regulation of this protein. Alternative splicing of this gene results in two transcript variants which encode the same isoform.
Bio-object 3: Bax
  • GI Number: 163659849
  • Accession Number:
  • DB Links: Homo sapiens BCL2-associated X protein
  • Type: Protein or gene
  • Location: Organelle
  • Function: Signal transducer
  • Description: The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene.
Bio-object 4: Bcl-w
  • GI Number: 1572492
  • Accession Number:
  • Type: Protein or gene
  • Location: Organelle
  • Function: Other
Bio-object 5: BCL2
  • GI Number: 72198188]
  • Accession Number:
  • Type: Protein or gene
  • Location: Mitochondria
  • Function: Signal transducer
  • Description: This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends.
Bio-object 6: BCL2L1
  • GI Number: 20336334
  • Accession Number:
  • Type: Protein or gene
  • Location: Organelle
  • Function: Signal transducer
  • Description: The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC regulates mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported. The longer isoform acts as an apoptotic inhibitor and the shorter form acts as an apoptotic activator.
Bio-object 7: calcium uptake in cells
  • Type: Cell membrane
  • Location: Mitochondria
  • Function: Signal transducer
  • Description: (<a href="#reference8676">Rojas et al., 2000</a>)
Bio-object 8: CASP10
  • GI Number: 843
  • Accession Number:
  • Type: Protein or gene
  • Location: Cytoplasm
  • Function: Enzyme
  • Description: This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with apoptosis defects seen in type II autoimmune lymphoproliferative syndrome. Three alternatively spliced transcript variants encoding different isoforms have been described for this gene.
Bio-object 9: CASP3
  • GI Number: 836
  • Accession Number:
  • Type: Protein or gene
  • Location: Cytoplasm
  • Function: Enzyme
  • Description: This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein.
Bio-object 10: CASP8
  • Accession Number:
  • Type: Protein or gene
  • Location: Cytoplasm
  • Function: Chaperone
  • Description: This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined.
Bio-object 11: CASP9
  • GI Number: 842
  • Accession Number:
  • Type: Protein or gene
  • Location: Cytoplasm
  • Function: Enzyme
  • Description: This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspase APAF1; this step is thought to be one of the earliest in the caspase activation cascade. Alternative splicing results in two transcript variants which encode different isoforms.
Bio-object 12: Cord Factors
  • DB Links: trehalose 6,6'-dimycolate
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Infection
  • Description: Cord Factors. Toxic glycolipids composed of trehalose dimycolate derivatives. They are produced by MYCOBACTERIUM TUBERCULOSIS and other species of MYCOBACTERIUM. They induce cellular dysfunction in animals.
Bio-object 13: cytochrome C
  • GI Number: 11128019
  • Accession Number:
  • Type: Protein
  • Location: Organelle
  • Function: Other
  • Description: This gene encodes cytochrome c, a component of the electron transport chain in mitochondria. The heme group of cytochrome c accepts electrons from the b-c1 complex and transfers electrons to the cytochrome oxidase complex. Cytochrome c is also involved in initiation of apoptosis. Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor which activates the apoptotic initiator procaspase 9. Many cytochrome c pseudogenes exist, scattered throughout the human genome.
Bio-object 14: IL10
  • Type: Protein or gene
  • Location: Extracellular
  • Function: Signal transducer
  • Description: The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract.
Bio-object 15: IL12
  • GI Number: 4323579
  • Accession Number:
  • DB Links: interleukin 12; natural killer cell stimulatory factor; cytotoxic lymphocyte maturation factor 35kDa subunit; p35
  • Type: Protein or gene
  • Location: Cytoplasm
  • Function: Signal transducer
  • Description: Interleukin 12 is a disulfide-linked heterodimer composed of a 40 kD cytokine receptor like subunit encoded by IL12B, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children.
Bio-object 16: IL1B
  • GI Number: 278894305
  • Accession Number:
  • DB Links: Interleukin 1, beta
  • Type: Protein or gene
  • Location: Cytoplasm
  • Function: Signal transducer
  • Description: The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.
Bio-object 17: KanLM
  • DB Links: M. kansasii lipomannan
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Ligand binding or carrier
  • Description:
Bio-object 18: LAM of M. smegmatis
  • DB Links: Lipoarabinomannan isolated from Mycobacterium smegmatis (a non-pathogenic species)
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Ligand binding or carrier
  • Description: (<a href="#reference8680">Ghosh et al., 1998</a>)
Bio-object 19: LMs
  • DB Links: lipomannans
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Ligand binding or carrier
  • Description: (<a href="#reference8678">Dao et al., 2004</a>)
Bio-object 20: LPS
  • DB Links: lipopolysaccharide
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Chaperone
Bio-object 21: M. bovis bacillus Calmette-Guérin (BCG)
  • DB Links: ATCC® Number: 19015™
  • Type: Microorganism or its component
  • Location: Other
  • Function: Other
Bio-object 22: M. tuberculosis H37Ra
  • DB Links: ATCC Number: 25177
  • Type: Microorganism or its component
  • Location: Other
  • Function: Other
  • Description: attenuated M. tuberculosis (<a href="#reference8658">Riendeau and Kornfeld, 2003</a>)
Bio-object 23: M. tuberculosis H37Rv
  • DB Links: ATCC Number: 25618
  • Type: Microorganism or its component
  • Location: Other
  • Function: Other
  • Description: virulent wild-type M. tuberculosis
Bio-object 24: ManLAM
  • DB Links: mannosylated lipoarabinomannan
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Other
  • Description: (<a href="#reference8676">Rojas et al., 2000</a>)
Bio-object 25: MCL1
  • GI Number: 33519459, 33519457
  • Accession Number:
  • Type: Protein or gene
  • Location: Organelle
  • Function: Chaperone
  • Description: The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. The longer gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene product (isoform 2) promotes apoptosis and is death-inducing.
Bio-object 26: Mn superoxide dismutase
  • GI Number: 34710
  • Accession Number:
  • Type: Protein or gene
  • Location: Organelle
  • Function: Enzyme
Bio-object 27: mycolic acid
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Other
  • Description: (<a href="#reference8672">Nuzzo et al., 2002</a>)
Bio-object 28: MYD88
  • DB Links: myeloid differentiation primary response gene
  • Type: Protein or gene
  • Location: Cytoplasm
  • Function: Signal transducer
Bio-object 29: p19
  • DB Links: 19-kDa M. tuberculosis glycolipoprotein
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Other
  • Description: (<a href="#reference8674">López et al., 2003</a>)(<a href="#reference8675">Ciaramella et al., 2000</a>)(<a href="#reference8673">Ciaramella et al., 2004</a>)
Bio-object 30: PI-3K
  • GI Number: 472991
  • Accession Number:
  • DB Links: phosphatidylinositol 3-kinase
  • Type: Enzyme
  • Location: Cytoplasm
  • Function: Signal transducer
Bio-object 31: PILAM
  • DB Links: phosphoinositol-capped LAM
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Other
  • Description: (<a href="#reference8678">Dao et al., 2004</a>)
Bio-object 32: PKC
  • DB Links: Protein Kinase C
  • Type: Enzyme
  • Location: Cytoplasm
  • Function: Signal transducer
Bio-object 33: sTNFR2
  • DB Links: soluble TNFR2
  • Type: Protein or gene
  • Location: Extracellular
  • Function: Ligand binding or carrier
  • Description:
Bio-object 34: TLR-4
  • GI Number: 2459627
  • Accession Number:
  • Type: Cell membrane
  • Location: Cell membrane
  • Function: Ligand binding or carrier
  • Description: The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta, and in myelomonocytic subpopulation of the leukocytes. It has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness. Also, several transcript variants of this gene have been found, but the protein coding potential of most of them is uncertain.
Bio-object 35: TLR2
  • GI Number: 2459623
  • Accession Number:
  • DB Links: Toll-like receptor 2
  • Type: Cell membrane
  • Location: Cell membrane
  • Function: Signal transducer
Bio-object 36: TNF-alpha
  • GI Number: 37209
  • Accession Number:
  • Type: Protein or gene
  • Location: Extracellular
  • Function: Ligand binding or carrier
  • Description: This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine.
Bio-object 37: tuberculostearic acid
  • Type: Cell membrane
  • Location: Bacterial membrane or virus envelope
  • Function: Other
  • Description:
Interactions
Interaction 1: activation
Interaction 2: upregulate
  • Type: upregulate
  • Input Objects: M. tuberculosis H37Rv
  • Output Objects: Bcl-w
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8659">Spira et al., 2003</a>)
Interaction 3: upregulate
Interaction 4: downregulate
Interaction 5: upregulate
  • Type: upregulate
  • Input Objects: M. tuberculosis H37Rv
  • Output Objects: MCL1
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8660">Sly et al., 2003</a>)
Interaction 6: release
  • Type: release
  • Input Objects: M. tuberculosis H37Rv
  • Output Objects: cytochrome C
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8661">Abarca-Rojano et al., 2003</a>)
Interaction 7: activation
  • Type: activation
  • Input Objects: M. tuberculosis H37Rv
  • Output Objects: CASP3
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8662">Perskvist et al., 2002</a>)
Interaction 8: upregulate
Interaction 9: downregulate
Interaction 10: induce
  • Type: induce
  • Input Objects: Cord Factors, mycolic acid, tuberculostearic acid
  • Output Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8671">Hamasaki et al., 2000</a>)(<a href="#reference8670">Ozeki et al., 1997</a>)(<a href="#reference8672">Nuzzo et al., 2002</a>)
Interaction 11: upregulate
  • Type: Upregulate
  • Input Objects: Cord Factors, mycolic acid
  • Output Objects: BCL2
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8672">Nuzzo et al., 2002</a>)
Interaction 12: induce
  • Type: Induce
  • Input Objects: BCL2
  • Output Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
Interaction 13: singanling transduction
  • Type: signaling transduction
  • Input Objects: p19
  • Output Objects: TLR2
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8674">López et al., 2003</a>)(<a href="#reference8673">Ciaramella et al., 2004</a>)
Interaction 14: singanling transduction
  • Type: signaling transduction
  • Input Objects: TLR2
  • Output Objects: CASP8
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8674">López et al., 2003</a>)
Interaction 15: induce
  • Type: signaling transduction
  • Input Objects: CASP8
  • Output Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8674">López et al., 2003</a>)
Interaction 16: release
  • Type: release
  • Input Objects: p19
  • Output Objects: IL1B
  • GO Evidence Code: Inferred by Curator
Interaction 17: prevent
Interaction 18: induce
Interaction 19: phosphorylation
  • Type: phosphorylation
  • Input Objects: ManLAM
  • Output Objects: BAD
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8676">Rojas et al., 2000</a>)
Interaction 20: prevent
  • Type: prevent
  • Input Objects: BAD
  • Output Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8676">Rojas et al., 2000</a>)
Interaction 21: activate
  • Input Objects: ManLAM
  • Output Objects: PI-3K
  • GO Evidence Code: Inferred by Curator
Interaction 22: phosphorylation
  • Input Objects: PI-3K
  • Output Objects: BAD
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8677">Maiti et al., 2001</a>)
Interaction 23: Interaction
  • Input Objects: LMs, PILAM
  • Output Objects: TLR2
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8678">Dao et al., 2004</a>)
Interaction 24: Induce secreation
  • Input Objects: LMs, PILAM
  • Output Objects: IL12
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8677">Maiti et al., 2001</a>)
Interaction 25: Induce
  • Input Objects: KanLM
  • Output Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
  • Description: (<a href="#reference8679">Guérardel et al., 2003</a>)
Interaction 26: Inhibit
  • Input Objects: LAM of M. smegmatis
  • Output Objects: PKC
  • GO Evidence Code: Inferred by Curator
  • Description: These results clearly demonstrate that lipoarabinomannan from M. smegmatis may exert its cytotoxic activity via inhibition of protein kinase C, a key signaling molecule inside the mononuclear cells, which ultimately affects the phosphorylation of various proteins imperative for cellular defence and survival.
Interaction 27: Induce
  • Input Objects: PKC
  • Output Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
  • Description: These results clearly demonstrate that lipoarabinomannan from M. smegmatis may exert its cytotoxic activity via inhibition of protein kinase C, a key signaling molecule inside the mononuclear cells, which ultimately affects the phosphorylation of various proteins imperative for cellular defence and survival.
Interaction 28: Ligand
  • Input Objects: LPS
  • Output Objects: TLR-4
  • GO Evidence Code: Inferred by Curator
Interaction 29: Activate
  • Input Objects: TLR-4
  • Output Objects: MYD88
  • GO Evidence Code: Inferred by Curator
Interaction 30: Release
  • Input Objects: MYD88
  • Output Objects: TNF-alpha
  • GO Evidence Code: Inferred by Curator
Interaction 31: Induce
  • Input Objects: TNF-alpha
  • Output Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
Interaction 32: Release
Interaction 33: Bind and Prevent
  • Input Objects: sTNFR2
  • Output Objects: TNF-alpha
  • GO Evidence Code: Inferred by Curator
Interaction 34: Inhibit
  • Cofactors: IL10
  • Input Objects: apoptosis
  • GO Evidence Code: Inferred by Curator
Interaction 35: Release
  • Input Objects: IL10
  • Output Objects: sTNFR2
  • GO Evidence Code: Inferred by Curator
Pathways