UniprotKB/SwissProt ID: P9WIA1 (P9WIA1)
Gene Name:
ptpA
Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Function: Key virulence factor required for mycobacterial survival within host macrophages (PubMed:16085396, PubMed:18474358, PubMed:22087003, PubMed:25187516, PubMed:25642820, PubMed:27698396). Exhibits protein tyrosine phosphatase activity (PubMed:10986245, PubMed:12066895, PubMed:17975835, PubMed:23102706, PubMed:25187516, PubMed:32142609). Shows no detectable activity towards substrates containing phosphoserine/threonine residues (PubMed:10986245, PubMed:12066895) Supports mycobacteria survival during infection by modulation of the phagosome maturation and modulation of the normal host signaling pathways, including host innate immune responses and cell apoptosis (PubMed:18474358, PubMed:22087003, PubMed:25187516, PubMed:25642820, PubMed:27698396). Affects the phagocytosis process by preventing phagosome acidification and maturation in the macrophage (PubMed:16085396, PubMed:18474358, PubMed:22087003). This inhibition depends on both PtpA phosphatase activity and its ability to bind to host vacuolar-H(+)-ATPase (V-ATPase) machinery (PubMed:22087003). Enters into the host cytosol and binds to subunit H of the human V-ATPase machinery to block V-ATPase trafficking and phagosome acidification (PubMed:22087003). Dephosphorylates and inactivates host VPS33B protein, which inhibits phagosome maturation, fusion with the lysosome and promotes bacteria survival (PubMed:18474358, PubMed:22087003). Dephosphorylation of VPS33B requires interaction of PtpA with host V-ATPase and ubiquitin (PubMed:22087003, PubMed:25642820). Binding to host ubiquitin also leads to the dephosphorylation of phosphorylated Jnk and MAPK p38, leading to suppression of innate immunity (PubMed:25642820). Dephosphorylates host GSK-3 alpha on Tyr-279, which leads to modulation of GSK-3 alpha anti-apoptotic activity, promoting pathogen survival early during infection (PubMed:25187516). In vitro, dephosphorylates two subunits of the trifunctional enzyme TFP (ECHA/ ECHB), which means that it may also affect pathways involved in cell energy metabolism (PubMed:25743628). Furthermore, blocks innate immune system responses mediated by the host adapter TAB3 and dependent on NF-kappa-B by competitively binding the ubiquitin-interacting domain of TAB3, in a phosphatase activity-independent manner (PubMed:25642820). Antagonizes TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis through competitively binding to the RING domain of TRIM27 (PubMed:27698396). In addition, PtpA enters the nucleus of host cells and regulates the expression of several host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration, either by directly binding to the promoters of its target genes, or in an indirect manner (PubMed:28811474). In vitro, can bind directly to the promoter region of GADD45A, a gene encoding a protein involved in cell division, cell death and senescence, and DNA-damage repair (PubMed:28811474)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Secreted. Host cytoplasmic vesicle, host phagosome. Host cytoplasm. Host nucleus
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