Detail Information for IndEnz0010001052
IED ID IndEnz0010001052
Enzyme Type ID esterase001052
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 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). {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