Serine protease that promotes tuberculosis (TB) pathogenesis by promoting the processing and the extracellular release of the M.tuberculosis (Mtb) heat-shock protein GroEL2 (PubMed:18172199, PubMed:24830429, PubMed:28346784). Hip1-dependent cleavage of multimeric GroEL2 results in release of cleaved monomeric GroEL2 into the extracellular milieu. Conversion of multimeric GroEL2 into monomeric GroEL2 is likely to be a mechanism for regulating GroEL2 functions during Mtb pathogenesis (PubMed:24830429). In vitro, exhibits proteolytic activity against synthetic peptides and the general protease substrate azocasein, and exhibits esterase activity against the ester substrate p-nitrophenylbutyrate (PubMed:24830429, PubMed:28346784). Key immunomodulatory virulence factor, which promotes survival in host macrophages and modulates host immune responses (PubMed:18172199, PubMed:21947769, PubMed:24659689). Impacts host innate immune responses by preventing robust macrophage activation (PubMed:18172199, PubMed:21947769). Dampens macrophage pro-inflammatory responses by limiting toll-like receptor 2 (TLR2) activation. It also dampens TLR2-independent activation of the inflammasome and limits secretion of interleukin-18 (IL-18). May act by masking cell surface interactions between TLR2 agonists on Mtb and TLR2 on macrophages (PubMed:21947769). In addition, impacts host adaptive immune responses. It prevents robust maturation of infected dendritic cells (DCs), limits the secretion of key pro-inflammatory cytokines such as IL-12, impairs Ag presentation, and modulates the nature of Ag-specific T-cell responses (PubMed:24659689). Protease activity is inhibited by serine protease inhibitors but not by cysteine protease inhibitors. kcat is 0.45 min(-1) with GroEL2 as substrate. Interacts with GroEL2. Shows esterase activity in active, dormant, and reactivating Mtb cultures. The active site region is accessed through a large opening that suggests that the enzyme has endopeptidase activity rather than exopeptidase activity. Disruption of the gene leads to growth defects and attenuates the virulence of Mtb (PubMed:18172199, PubMed:19011036). Disruption of the gene enhances host innate immune responses, compromises the intracellular survival of Mtb in macrophages, and increases its susceptibility to lysozyme. It prolongs survival and reduces lung immunopathology of infected mice (PubMed:18172199). Disruption leads to earlier and significantly higher levels of key pro-inflammatory cytokines and chemokines (PubMed:21947769). Mutant induces enhanced levels of the key Th1-inducing cytokine IL-12, as well as other pro-inflammatory cytokines (IL-23, IL-6, TNF-alpha, IL-1beta, and IL-18) in DCs via MyD88- and TLR2/9-dependent pathways (PubMed:24659689). Infection with the hip1 mutant also induces higher levels of MHC class II and costimulatory molecules CD40 and CD86 (PubMed:24659689). At low pH, mutants are hypersensitive to antibiotics, sodium dodecyl sulfate, heat shock, and reactive oxygen and nitrogen intermediates (PubMed:19011036). GroEL2 remains uncleaved in the hip1 mutant (PubMed:24830429). Hip1 is an attractive target for developing immunomodulatory therapeutics against Mtb. Belongs to the peptidase S33 family.