| IED ID | IndEnz0002016245 |
| Enzyme Type ID | protease016245 |
| Protein Name |
Chaperonin GroEL 2 EC 5.6.1.7 60 kDa chaperonin 2 65 kDa antigen Antigen A Cell wall protein A Chaperonin-60 2 Cpn60 2 Heat shock protein 65 HSP65 Cleaved into: Cleaved form |
| Gene Name | groEL2 cpn60.2 groL2 hsp65 Rv0440 mtc28 MTV037.04 |
| 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 | MAKTIAYDEEARRGLERGLNALADAVKVTLGPKGRNVVLEKKWGAPTITNDGVSIAKEIELEDPYEKIGAELVKEVAKKTDDVAGDGTTTATVLAQALVREGLRNVAAGANPLGLKRGIEKAVEKVTETLLKGAKEVETKEQIAATAAISAGDQSIGDLIAEAMDKVGNEGVITVEESNTFGLQLELTEGMRFDKGYISGYFVTDPERQEAVLEDPYILLVSSKVSTVKDLLPLLEKVIGAGKPLLIIAEDVEGEALSTLVVNKIRGTFKSVAVKAPGFGDRRKAMLQDMAILTGGQVISEEVGLTLENADLSLLGKARKVVVTKDETTIVEGAGDTDAIAGRVAQIRQEIENSDSDYDREKLQERLAKLAGGVAVIKAGAATEVELKERKHRIEDAVRNAKAAVEEGIVAGGGVTLLQAAPTLDELKLEGDEATGANIVKVALEAPLKQIAFNSGLEPGVVAEKVRNLPAGHGLNAQTGVYEDLLAAGVADPVKVTRSALQNAASIAGLFLTTEAVVADKPEKEKASVPGGGDMGGMDF |
| Enzyme Length | 540 |
| Uniprot Accession Number | P9WPE7 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Conditions that promote oligomer formation increase the ATPase activity (PubMed:22834700). Chaperone activity is fundamentally influenced by the interdomain communication, even if oligomerization and the ability to recognize the substrates are retained (PubMed:26553853). {ECO:0000269|PubMed:22834700, ECO:0000269|PubMed:26553853}. |
| Binding Site | BINDING 413; /note=ATP; via amide nitrogen; /evidence=ECO:0000255|HAMAP-Rule:MF_00600; BINDING 492; /note=ATP; /evidence=ECO:0000255|HAMAP-Rule:MF_00600 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide.; EC=5.6.1.7; Evidence={ECO:0000255|HAMAP-Rule:MF_00600}; |
| DNA Binding | |
| EC Number | 5.6.1.7 |
| Enzyme Function | FUNCTION: Together with its co-chaperonin GroES, plays an essential role in assisting protein folding. The GroEL-GroES system forms a nano-cage that allows encapsulation of the non-native substrate proteins and provides a physical environment optimized to promote and accelerate protein folding (By similarity). Prevents aggregation of substrate proteins and promotes their refolding (PubMed:15327959, PubMed:18227175, PubMed:22834700). In vitro, activity may be independent of the presence or absence of the GroES co-chaperonin or ATP (PubMed:15327959). Shows weak ATPase activity (PubMed:15327959, PubMed:21802426). {ECO:0000255|HAMAP-Rule:MF_00600, ECO:0000269|PubMed:15327959, ECO:0000269|PubMed:18227175, ECO:0000269|PubMed:21802426, ECO:0000269|PubMed:22834700}.; FUNCTION: Mediates association of bacteria with macrophages (PubMed:19470749, PubMed:20633027). Acts as an adhesin that binds CD43 on the host macrophage surface (PubMed:20633027). The full-length protein elicits robust proinflammatory responses from dendritic cells (DCs) and promotes DC maturation and antigen presentation to T-cells. DCs exposed to full-length GroEL2 induce strong antigen-specific gamma interferon (IFN-gamma), interleukin-2 (IL-2), and IL-17A cytokine responses from CD4(+) T-cells (PubMed:29133346). Recombinant extracellular protein activates expression of NF-kappa-B in immortalized human dermal endothelial cells in a TLR4-dependent, TLR2-independent manner. Activation occurs via MYD88-dependent and -independent pathways and requires TIRAP, TRIF, TRAM and MD-2 (some experiments done in mouse cells, mice do not usually catch tuberculosis) (PubMed:15809303). {ECO:0000269|PubMed:15809303, ECO:0000269|PubMed:19470749, ECO:0000269|PubMed:20633027, ECO:0000269|PubMed:29133346}.; FUNCTION: [Cleaved form]: Cleaved, monomeric GroEL2 is biologically relevant and significantly contributes to Hip1-mediated dampening of macrophage responses during M.tuberculosis (Mtb) infection (PubMed:24830429). Within macrophage, the cleaved form is able to detach from the bacterial surface and crosses the phagosomal membrane towards mitochondria organelles where it interacts with the host stress-70 protein (HSPA9 or mortalin) and blocks macrophage apoptosis, which promotes Mtb survival in the hostile macrophage environment (PubMed:28288970). The cleaved form is poorly immunostimulatory and is unable to promote DC maturation and antigen presentation. Proteolytic cleavage of GroEL2 allows Mtb to prevent optimal DC-T-cell cross talk during infection (PubMed:29133346). {ECO:0000269|PubMed:24830429, ECO:0000269|PubMed:28288970, ECO:0000269|PubMed:29133346}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 29..32; /note=ATP; /evidence=ECO:0000255|HAMAP-Rule:MF_00600; NP_BIND 86..90; /note=ATP; /evidence=ECO:0000255|HAMAP-Rule:MF_00600 |
| Features | Beta strand (18); Binding site (2); Chain (2); Cross-link (1); Helix (18); Mutagenesis (1); Nucleotide binding (2); Region (1); Site (1); Turn (8) |
| Keywords | 3D-structure;ATP-binding;Cell wall;Chaperone;Host mitochondrion;Isomerase;Isopeptide bond;Nucleotide-binding;Reference proteome;Secreted;Ubl conjugation;Virulence |
| Interact With | P9WI75 |
| Induction | INDUCTION: Induced in response to heat shock (45 degrees Celsius), pH 10, hyperosmolarity and starvation (PubMed:18227175). Repressed by WhiB1, activated by Cmr (PubMed:22464736). {ECO:0000269|PubMed:18227175, ECO:0000269|PubMed:22464736}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, capsule {ECO:0000269|PubMed:19470749, ECO:0000269|PubMed:20633027}. Cell surface {ECO:0000269|PubMed:19470749, ECO:0000269|PubMed:20633027}. Secreted, cell wall {ECO:0000269|PubMed:24830429}. Note=Although thought of as a cytoplasmic chaperone this protein is routinely found extracellularly in the absence of cell lysis. {ECO:0000305|PubMed:19470749}.; SUBCELLULAR LOCATION: [Cleaved form]: Secreted {ECO:0000269|PubMed:24830429}. Host mitochondrion {ECO:0000269|PubMed:28288970}. Note=Exits phagosomal membrane and reaches macrophage mitochondria. {ECO:0000269|PubMed:28288970}. |
| Modified Residue | |
| Post Translational Modification | PTM: Cleaved by the mycobacterial serine protease Hip1 (PubMed:24830429). Hip1-dependent cleavage of multimeric GroEL2 results in release of cleaved monomeric GroEL2 into the extracellular milieu (PubMed:24830429). {ECO:0000269|PubMed:24830429}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 1SJP; 3RTK; |
| Mapped Pubmed ID | 20925060; |
| Motif | |
| Gene Encoded By | |
| Mass | 56,727 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: Note=kcat for ATPase activity is 0.28 min(-1) (PubMed:15327959). kcat for ATPase activity is 0.18 min(-1) (PubMed:21802426). {ECO:0000269|PubMed:15327959, ECO:0000269|PubMed:21802426}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |