| IED ID | IndEnz0002016016 |
| Enzyme Type ID | protease016016 |
| Protein Name |
Serine protease Hip1 EC 3.4.21.- Hydrolase important for pathogenesis 1 Serine hydrolase Hip1 |
| Gene Name | hip1 caeA Rv2224c MTCY427.05c |
| Organism | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Actinobacteria Actinomycetia (high G+C Gram-positive bacteria) Corynebacteriales Mycobacteriaceae Mycobacterium Mycobacterium tuberculosis complex Mycobacterium tuberculosis Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Enzyme Sequence | MGMRLSRRDKIARMLLIWAALAAVALVLVGCIRVVGGRARMAEPKLGQPVEWTPCRSSNPQVKIPGGALCGKLAVPVDYDRPDGDVAALALIRFPATGDKIGSLVINPGGPGESGIEAALGVFQTLPKRVHERFDLVGFDPRGVASSRPAIWCNSDADNDRLRAEPQVDYSREGVAHIENETKQFVGRCVDKMGKNFLAHVGTVNVAKDLDAIRAALGDDKLTYLGYSYGTRIGSAYAEEFPQRVRAMILDGAVDPNADPIEAELRQAKGFQDAFNNYAADCAKNAGCPLGADPAKAVEVYHSLVDPLVDPDNPRISRPARTKDPRGLSYSDAIVGTIMALYSPNLWQHLTDGLSELVDNRGDTLLALADMYMRRDSHGRYNNSGDARVAINCVDQPPVTDRDKVIDEDRRAREIAPFMSYGKFTGDAPLGTCAFWPVPPTSQPHAVSAPGLVPTVVVSTTHDPATPYKAGVDLANQLRGSLLTFDGTQHTVVFQGDSCIDEYVTAYLIGGTTPPSGAKC |
| Enzyme Length | 520 |
| Uniprot Accession Number | P9WHR3 |
| Absorption | |
| Active Site | ACT_SITE 228; /note=Nucleophile; /evidence=ECO:0000305|PubMed:28346784; ACT_SITE 463; /evidence=ECO:0000305|PubMed:28346784; ACT_SITE 490; /note=Proton donor; /evidence=ECO:0000305|PubMed:28346784 |
| Activity Regulation | ACTIVITY REGULATION: Protease activity is inhibited by serine protease inhibitors but not by cysteine protease inhibitors. {ECO:0000269|PubMed:24830429}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.21.- |
| Enzyme Function | FUNCTION: 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). {ECO:0000269|PubMed:18172199, ECO:0000269|PubMed:24830429, ECO:0000269|PubMed:28346784}.; FUNCTION: 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 proinflammatory 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 proinflammatory cytokines such as IL-12, impairs Ag presentation, and modulates the nature of Ag-specific T-cell responses (PubMed:24659689). {ECO:0000269|PubMed:18172199, ECO:0000269|PubMed:21947769, ECO:0000269|PubMed:24659689}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (14); Chain (1); Disulfide bond (5); Domain (1); Helix (21); Lipidation (2); Mutagenesis (3); Signal peptide (1); Turn (2) |
| Keywords | 3D-structure;Cell membrane;Disulfide bond;Hydrolase;Lipoprotein;Membrane;Palmitate;Reference proteome;Signal;Virulence |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell envelope {ECO:0000269|PubMed:18172199}. Cell membrane {ECO:0000255|PROSITE-ProRule:PRU00303, ECO:0000269|PubMed:18172199}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..30; /evidence=ECO:0000255|PROSITE-ProRule:PRU00303 |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 5UGQ; 5UNO; 5UOH; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 55,924 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.19 mM for GroEL2 {ECO:0000269|PubMed:28346784}; Note=kcat is 0.45 min(-1) with GroEL2 as substrate. {ECO:0000269|PubMed:28346784}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |