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:22087003, PubMed:16085396, PubMed:18474358). 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). H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate Phosphatase activity is stimulated by phosphorylation (PubMed:25535696). Inhibited by sodium molybdate, sodium orthovanadate and sodium tungstate (PubMed:10986245, PubMed:17975835). Inhibited by S-nitrosylation (PubMed:20830431, PubMed:23102706). Subjected to substrate activation, triggered by pNPP or by phosphotyrosine. Is also activated by phosphoserine, with serine being ineffective in enhancing PtpA activity (PubMed:32142609). kcat is 12.6 sec(-1) with pNPP as substrate at pH 5.0. kcat is 1313 sec(-1) with pNPP as substrate at pH 6.0. kcat is 1334 sec(-1) with pNPP as substrate at pH 7.0 (PubMed:17975835). kcat is 13.73 sec(-1) with pNPP as substrate. kcat is 6.71 with pNPP as substrate (in the presence of S-nitrosoglutathione) (PubMed:23102706). kcat is 0.87 sec(-1) with pNPP as substrate. kcat is 0.69 sec(-1) with phosphotyrosine as substrate (PubMed:32142609). Interacts with the host VPS33B protein in macrophages (PubMed:18474358). Interacts with subunit H of host V-ATPase (PubMed:22087003). Interacts with host GSK-3 alpha (PubMed:25187516). Interacts with host ubiquitin and host adapter TAB3 (PubMed:25642820). Interacts with host TRIM27 (PubMed:27698396). Translocates into the host cytosol by crossing the host phagosomal membrane during human macrophage infection. Colocalizes with host VPS33B in macrophage cytosol and associates with phagosomes. Up-regulated upon infection of human monocytes. The activation most likely occurs via a reversible conformational rearrangement of the enzyme, leading to a catalytically competent form (PubMed:32142609). Both the P- and D-loop form part of the binding interface (PubMed:22888002). Phosphorylated on tyrosines 128 and 129 by PtkA (PubMed:19366344, PubMed:22888002, PubMed:25535696). Both Tyr-128 and Tyr-129 together are essential for PtpA phosphatase activity (PubMed:25535696). In vitro, can be phosphorylated by several eukaryotic-like Ser/Thr protein kinases, such as protein kinase A (PknA), which phosphorylates PtpA at Thr-45 and increases its activity (PubMed:25535696). S-nitrosylation at Cys-53 decreases activity (PubMed:20830431). Modification does not affect substrate affinity, but decreases protein thermal stability and promotes a local effect in the surroundings of the Cys-53 residue, which interferes in both protein stability and function (PubMed:23102706). Deletion mutant is attenuated in human macrophages (PubMed:18474358). The mutant is not defective when grown in vitro and also shows no growth defect in a mouse infection model (PubMed:18752626). The important role played by PtpA in virulence makes it a highly promising target for the treatment of tuberculosis infections. Several classes of potent inhibitors have been developed and studied to date. Drug candidates include, among others, stevastelins, roseophilins, prodigiosins, hydroxypyrrole benzoic acids, difluoromethylphosphonic acid (DFMP) and chalcone derivatives. Belongs to the low molecular weight phosphotyrosine protein phosphatase family.