| IED ID | IndEnz0002016086 |
| Enzyme Type ID | protease016086 |
| Protein Name |
Metacaspase-2 EC 3.4.22.- TbMCA2 Cleaved into: Large subunit p20; Small subunit p10 |
| Gene Name | MCA2 Tb927.6.940 |
| Organism | Trypanosoma brucei brucei (strain 927/4 GUTat10.1) |
| Taxonomic Lineage | cellular organisms Eukaryota Discoba Euglenozoa Kinetoplastea (kinetoplasts) Metakinetoplastina Trypanosomatida Trypanosomatidae Trypanosoma Trypanozoon Trypanosoma brucei Trypanosoma brucei brucei Trypanosoma brucei brucei (strain 927/4 GUTat10.1) |
| Enzyme Sequence | MCSLITQLCDAGQLADYVGLGWLNAVSSQPYLVQALGLQPPPRRVDVDAAFRDAKGLHGHQPWVATPLPGQTVRALFIGINYYGTSAALSGCCNDVKQMLATLQKKGLPINEAVILVDEDNFPGRTDQPTRDNIVRYMAWLVKDAKPGDVLFFHYSGHGTQCKSRGDSDEKYDQCIAPVDFQKSGCIVDDDIHKLLFSRLPEKVRLTAVFDCCHSGSIMDLPFTYVCSGGEQASGTPHMKRIREGNDVLGDVMMISGCADEQTSADVKNTATFGTGSTGAGGAATQCITCMLMNNQSLSYGKLLIETRDMLKRKGFKQVPQLSASKAIDLDQTFSLTEMFSVDRSIQ |
| Enzyme Length | 347 |
| Uniprot Accession Number | Q585F3 |
| Absorption | |
| Active Site | ACT_SITE 158; /evidence=ECO:0000250|UniProtKB:Q08601; ACT_SITE 213; /evidence=ECO:0000305|PubMed:18005666 |
| Activity Regulation | ACTIVITY REGULATION: Activated by Ca(2+) (PubMed:18005666, PubMed:23506317, PubMed:28089596, PubMed:22529389). In response to calcium binding, the 280-loop, a disordered loop consisting of residues 269-275, undergoes a conformational change which stabilizes substrates in the active site (PubMed:22529389). The binding to the substrate triggers the release of the N-terminal region resulting in the activation of the enzyme (PubMed:22529389). Proteolytic cleavage is required for catalytic activity towards large protein substrates (PubMed:28089596). {ECO:0000269|PubMed:18005666, ECO:0000269|PubMed:22529389, ECO:0000269|PubMed:23506317, ECO:0000269|PubMed:28089596}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.22.- |
| Enzyme Function | FUNCTION: Cysteine protease that cleaves specifically after arginine or lysine residues. {ECO:0000269|PubMed:18005666, ECO:0000269|PubMed:23506317}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 20-25 degrees Celsius. {ECO:0000269|PubMed:23506317}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.7. {ECO:0000269|PubMed:23506317, ECO:0000269|PubMed:28089596}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Beta strand (12); Chain (3); Helix (7); Metal binding (4); Mutagenesis (10); Propeptide (1); Region (1); Site (4); Turn (3) |
| Keywords | 3D-structure;Autocatalytic cleavage;Calcium;Endosome;Hydrolase;Metal-binding;Protease;Reference proteome;Thiol protease;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Recycling endosome {ECO:0000250|UniProtKB:Q8T8E7}. |
| Modified Residue | |
| Post Translational Modification | PTM: Auto-proteolytic cleavage of the propeptide after Lys-55 and between the large and small subunits after Lys-268 is required for catalytic activity towards large protein substrates but is dispensable towards small oligopeptide substrates (PubMed:18005666, PubMed:28089596, PubMed:22529389). After processing, the propeptide and the large and small subunits remain associated by non-covalent bonds (PubMed:18005666). In vivo, the unprocessed enzyme appears to be the predominant form (By similarity). {ECO:0000250|UniProtKB:Q8T8E7, ECO:0000269|PubMed:18005666, ECO:0000269|PubMed:22529389, ECO:0000269|PubMed:28089596}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (4) |
| Cross Reference PDB | 4AF8; 4AFP; 4AFR; 4AFV; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 37,779 |
| Kinetics | |
| Metal Binding | METAL 173; /note="Calcium"; /evidence="ECO:0000269|PubMed:22529389, ECO:0007744|PDB:4AFP"; METAL 189; /note="Calcium"; /evidence="ECO:0000269|PubMed:22529389, ECO:0007744|PDB:4AFP"; METAL 190; /note="Calcium"; /evidence="ECO:0000269|PubMed:22529389, ECO:0007744|PDB:4AFP"; METAL 220; /note="Calcium"; /evidence="ECO:0000269|PubMed:22529389, ECO:0007744|PDB:4AFP" |
| Rhea ID | |
| Cross Reference Brenda |