| IED ID | IndEnz0002004223 |
| Enzyme Type ID | protease004223 |
| Protein Name |
Granzyme A EC 3.4.21.78 CTL tryptase Cytotoxic T-lymphocyte proteinase 1 Fragmentin-1 Granzyme-1 Hanukkah factor H factor HF |
| Gene Name | GZMA CTLA3 HFSP |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MRNSYRFLASSLSVVVSLLLIPEDVCEKIIGGNEVTPHSRPYMVLLSLDRKTICAGALIAKDWVLTAAHCNLNKRSQVILGAHSITREEPTKQIMLVKKEFPYPCYDPATREGDLKLLQLMEKAKINKYVTILHLPKKGDDVKPGTMCQVAGWGRTHNSASWSDTLREVNITIIDRKVCNDRNHYNFNPVIGMNMVCAGSLRGGRDSCNGDSGSPLLCEGVFRGVTSFGLENKCGDPRGPGVYILLSKKHLNWIIMTIKGAV |
| Enzyme Length | 262 |
| Uniprot Accession Number | P12544 |
| Absorption | |
| Active Site | ACT_SITE 69; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:12819769, ECO:0000269|PubMed:12819770"; ACT_SITE 114; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:12819769, ECO:0000269|PubMed:12819770"; ACT_SITE 212; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:12819769, ECO:0000269|PubMed:12819770, ECO:0000305|PubMed:32299851" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Hydrolysis of proteins, including fibronectin, type IV collagen and nucleolin. Preferential cleavage: -Arg-|-Xaa-, -Lys-|-Xaa- >> -Phe-|-Xaa- in small molecule substrates.; EC=3.4.21.78; Evidence={ECO:0000269|PubMed:12819770, ECO:0000269|PubMed:32299851}; |
| DNA Binding | |
| EC Number | 3.4.21.78 |
| Enzyme Function | FUNCTION: Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubMed:3257574, PubMed:3262682, PubMed:3263427, PubMed:32299851, PubMed:12819770). It cleaves after Lys or Arg (PubMed:32299851, PubMed:12819770). Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-B (GSDMB), releasing the pore-forming moiety of GSDMB, thereby triggering pyroptosis and target cell death (PubMed:32299851). Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity (PubMed:12524539). Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA (PubMed:11555662, PubMed:12628186, PubMed:16818237). {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:12819770, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:32299851, ECO:0000269|PubMed:3257574, ECO:0000269|PubMed:3262682, ECO:0000269|PubMed:3263427}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Beta strand (17); Chain (1); Disulfide bond (4); Domain (1); Glycosylation (1); Helix (2); Mutagenesis (1); Natural variant (1); Propeptide (1); Sequence conflict (6); Signal peptide (1); Turn (2) |
| Keywords | 3D-structure;Alternative promoter usage;Cytolysis;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Protease;Reference proteome;Secreted;Serine protease;Signal;Zymogen |
| Interact With | |
| Induction | INDUCTION: Dexamethasone (DEX) induces expression of isoform beta and represses expression of isoform alpha. The alteration in expression is mediated by binding of glucocorticoid receptor to independent promoters adjacent to the alternative first exons of isoform alpha and isoform beta. {ECO:0000269|PubMed:17180578}. |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform alpha]: Secreted {ECO:0000269|PubMed:3257574}. Cytoplasmic granule {ECO:0000269|PubMed:3257574}. Note=Delivered into the target cell by perforin. {ECO:0000269|PubMed:20038786, ECO:0000269|PubMed:32299851}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..26; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 1OP8; 1ORF; |
| Mapped Pubmed ID | 11060286; 11909973; 15238416; 15998831; 16440001; 17116752; 17138956; 17308307; 17703412; 18317234; 18485875; 18776661; 18951048; 19014932; 19059912; 19258923; 19343046; 19506301; 19875524; 20503287; 20536382; 20711500; 21068403; 21349256; 21709155; 22476618; 24505135; 24673566; 25437548; 25745046; 25921628; 25928296; 26025597; 26032366; 26051682; 26156785; 26522261; 26752517; 27343190; 28094457; 29167233; 31993061; 32574709; 32640217; 32830401; 33397791; 34413857; |
| Motif | |
| Gene Encoded By | |
| Mass | 28,999 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.78; |