| IED ID | IndEnz0002001368 |
| Enzyme Type ID | protease001368 |
| Protein Name |
Tripeptidyl-peptidase 1 TPP-1 EC 3.4.14.9 Cell growth-inhibiting gene 1 protein Lysosomal pepstatin-insensitive protease LPIC Tripeptidyl aminopeptidase Tripeptidyl-peptidase I TPP-I |
| Gene Name | TPP1 CLN2 GIG1 UNQ267/PRO304 |
| 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 | MGLQACLLGLFALILSGKCSYSPEPDQRRTLPPGWVSLGRADPEEELSLTFALRQQNVERLSELVQAVSDPSSPQYGKYLTLENVADLVRPSPLTLHTVQKWLLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGAEFHHYVGGPTETHVVRSPHPYQLPQALAPHVDFVGGLHRFPPTSSLRQRPEPQVTGTVGLHLGVTPSVIRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDSDLAQFMRLFGGNFAHQASVARVVGQQGRGRAGIEASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQWLMLLSNESALPHVHTVSYGDDEDSLSSAYIQRVNTELMKAAARGLTLLFASGDSGAGCWSVSGRHQFRPTFPASSPYVTTVGGTSFQEPFLITNEIVDYISGGGFSNVFPRPSYQEEAVTKFLSSSPHLPPSSYFNASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSASTPVFGGILSLINEHRILSGRPPLGFLNPRLYQQHGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP |
| Enzyme Length | 563 |
| Uniprot Accession Number | O14773 |
| Absorption | |
| Active Site | ACT_SITE 272; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967"; ACT_SITE 276; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967"; ACT_SITE 475; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967, ECO:0000305|PubMed:11054422" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by diisopropyl fluorophosphate (DFP). {ECO:0000269|PubMed:11054422}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.; EC=3.4.14.9; Evidence={ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}; |
| DNA Binding | |
| EC Number | 3.4.14.9 |
| Enzyme Function | FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:11054422, PubMed:19038966, PubMed:19038967). May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (PubMed:11054422, PubMed:19038966, PubMed:19038967). Requires substrates with an unsubstituted N-terminus (PubMed:19038966). {ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (1); Beta strand (24); Chain (1); Disulfide bond (3); Domain (1); Frameshift (1); Glycosylation (5); Helix (17); Metal binding (5); Mutagenesis (4); Natural variant (41); Propeptide (1); Sequence caution (1); Sequence conflict (2); Signal peptide (1); Turn (9) |
| Keywords | 3D-structure;Alternative splicing;Autocatalytic cleavage;Calcium;Direct protein sequencing;Disease variant;Disulfide bond;Epilepsy;Glycoprotein;Hydrolase;Lysosome;Metal-binding;Neurodegeneration;Neuronal ceroid lipofuscinosis;Protease;Reference proteome;Serine protease;Signal;Spinocerebellar ataxia;Zymogen |
| Interact With | Q9NWX5-2; Q53EZ4; Q9NSE2; Q9UKA2; Q6P3S6; Q96FW1; Q96D59; Q9BUZ4; P45974-2; O00308; Q8NAP3; E5LBV4; Q2NKJ3-1; Q9H668; O14746 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:19941651}. Melanosome {ECO:0000269|PubMed:12643545}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000269|PubMed:12643545}. |
| Modified Residue | |
| Post Translational Modification | PTM: Activated by autocatalytic proteolytical processing upon acidification (PubMed:11054422, PubMed:19038966, PubMed:19038967). N-glycosylation is required for processing and activity (PubMed:19038966, PubMed:19038967). {ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}. |
| Signal Peptide | SIGNAL 1..19; /evidence=ECO:0000269|PubMed:11054422 |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 3EDY; 3EE6; |
| Mapped Pubmed ID | 10679303; 12125808; 12134079; 12488460; 12950156; 14702339; 15143070; 15158442; 15317752; 15582991; 15733845; 16091586; 16168594; 16518810; 16539657; 17174955; 17500595; 17690061; 17959406; 18234856; 18411270; 18552385; 19246452; 19748052; 20217867; 20689811; 20711500; 21150319; 21784683; 22016395; 22832778; 22989886; 23249249; 23266810; 23587805; 23606334; 24271013; 26496610; 27553878; 27840983; 28079862; 29160297; 29378960; 29631617; 30541466; 31059981; 31256057; 31283065; 32146219; 32631363; 32735728; 33317560; |
| Motif | |
| Gene Encoded By | |
| Mass | 61,248 |
| Kinetics | |
| Metal Binding | METAL 517; /note="Calcium"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967"; METAL 518; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967"; METAL 539; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967"; METAL 541; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967"; METAL 543; /note="Calcium"; /evidence="ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967" |
| Rhea ID | |
| Cross Reference Brenda | 3.4.14.9; |