| IED ID | IndEnz0002014309 |
| Enzyme Type ID | protease014309 |
| Protein Name |
Cytosolic non-specific dipeptidase EC 3.4.13.18 CNDP dipeptidase 2 Glutamate carboxypeptidase-like protein 1 Peptidase A Threonyl dipeptidase |
| Gene Name | CNDP2 CN2 CPGL HEL-S-13 PEPA |
| 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 | MAALTTLFKYIDENQDRYIKKLAKWVAIQSVSAWPEKRGEIRRMMEVAAADVKQLGGSVELVDIGKQKLPDGSEIPLPPILLGRLGSDPQKKTVCIYGHLDVQPAALEDGWDSEPFTLVERDGKLYGRGSTDDKGPVAGWINALEAYQKTGQEIPVNVRFCLEGMEESGSEGLDELIFARKDTFFKDVDYVCISDNYWLGKKKPCITYGLRGICYFFIEVECSNKDLHSGVYGGSVHEAMTDLILLMGSLVDKRGNILIPGINEAVAAVTEEEHKLYDDIDFDIEEFAKDVGAQILLHSHKKDILMHRWRYPSLSLHGIEGAFSGSGAKTVIPRKVVGKFSIRLVPNMTPEVVGEQVTSYLTKKFAELRSPNEFKVYMGHGGKPWVSDFSHPHYLAGRRAMKTVFGVEPDLTREGGSIPVTLTFQEATGKNVMLLPVGSADDGAHSQNEKLNRYNYIEGTKMLAAYLYEVSQLKD |
| Enzyme Length | 475 |
| Uniprot Accession Number | Q96KP4 |
| Absorption | |
| Active Site | ACT_SITE 101; /evidence=ECO:0000250; ACT_SITE 166; /note=Proton acceptor; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by p-hydroxymercurybenzoate. The inhibitory concentration 50% (IC(50)) is 13 uM. Inhibited by bestatin. The inhibitory concentration 50% (IC(50)) is 7 nM at pH 9.5. {ECO:0000269|PubMed:12473676}. |
| Binding Site | BINDING 195; /note=Substrate; via carbonyl oxygen; /evidence=ECO:0000250; BINDING 228; /note=Substrate; shared with homodimeric partner; /evidence=ECO:0000250; BINDING 330; /note=Substrate; shared with homodimeric partner; /evidence=ECO:0000250; BINDING 343; /note=Substrate; /evidence=ECO:0000250; BINDING 417; /note=Substrate; via amide nitrogen and carbonyl oxygen; /evidence=ECO:0000250; BINDING 445; /note=Substrate; /evidence=ECO:0000250 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Hydrolysis of dipeptides, preferentially hydrophobic dipeptides including prolyl amino acids.; EC=3.4.13.18; Evidence={ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:19346245}; CATALYTIC ACTIVITY: Reaction=H2O + L-threonyl-L-threonine = 2 L-threonine; Xref=Rhea:RHEA:67360, ChEBI:CHEBI:15377, ChEBI:CHEBI:57926, ChEBI:CHEBI:169953; Evidence={ECO:0000250|UniProtKB:Q9D1A2};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67361; Evidence={ECO:0000250|UniProtKB:Q9D1A2}; CATALYTIC ACTIVITY: Reaction=H2O + L-threonyl-L-serine = L-serine + L-threonine; Xref=Rhea:RHEA:67364, ChEBI:CHEBI:15377, ChEBI:CHEBI:33384, ChEBI:CHEBI:57926, ChEBI:CHEBI:169954; Evidence={ECO:0000250|UniProtKB:Q9D1A2};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67365; Evidence={ECO:0000250|UniProtKB:Q9D1A2}; CATALYTIC ACTIVITY: Reaction=H2O + L-seryl-L-threonine = L-serine + L-threonine; Xref=Rhea:RHEA:67372, ChEBI:CHEBI:15377, ChEBI:CHEBI:33384, ChEBI:CHEBI:57926, ChEBI:CHEBI:169955; Evidence={ECO:0000250|UniProtKB:Q9D1A2};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67373; Evidence={ECO:0000250|UniProtKB:Q9D1A2}; CATALYTIC ACTIVITY: Reaction=H2O + L-cysteinylglycine = glycine + L-cysteine; Xref=Rhea:RHEA:28783, ChEBI:CHEBI:15377, ChEBI:CHEBI:35235, ChEBI:CHEBI:57305, ChEBI:CHEBI:61694; Evidence={ECO:0000269|PubMed:19346245};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28784; Evidence={ECO:0000305|PubMed:19346245}; CATALYTIC ACTIVITY: Reaction=H2O + L-alanyl-L-cysteine = L-alanine + L-cysteine; Xref=Rhea:RHEA:67380, ChEBI:CHEBI:15377, ChEBI:CHEBI:35235, ChEBI:CHEBI:57972, ChEBI:CHEBI:169958; Evidence={ECO:0000269|PubMed:19346245};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67381; Evidence={ECO:0000305|PubMed:19346245}; CATALYTIC ACTIVITY: Reaction=(S)-lactate + L-phenylalanine = H2O + N-[(S)-lactoyl]-L-phenylalanine; Xref=Rhea:RHEA:66724, ChEBI:CHEBI:15377, ChEBI:CHEBI:16651, ChEBI:CHEBI:58095, ChEBI:CHEBI:167456; Evidence={ECO:0000269|PubMed:25964343};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66725; Evidence={ECO:0000305|PubMed:25964343};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:66726; Evidence={ECO:0000305|PubMed:25964343}; |
| DNA Binding | |
| EC Number | 3.4.13.18 |
| Enzyme Function | FUNCTION: Catalyzes the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides (By similarity). Mediates threonyl dipeptide catabolism in a tissue-specific way (By similarity). Has high dipeptidase activity toward cysteinylglycine, an intermediate metabolite in glutathione metabolism (PubMed:19346245, PubMed:12473676). Metabolizes N-lactoyl-amino acids, both through hydrolysis to form lactic acid and amino acids, as well as through their formation by reverse proteolysis (PubMed:25964343). Plays a role in the regulation of cell cycle arrest and apoptosis (PubMed:17121880, PubMed:24395568). {ECO:0000250|UniProtKB:Q9D1A2, ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:17121880, ECO:0000269|PubMed:19346245, ECO:0000269|PubMed:24395568, ECO:0000269|PubMed:25964343}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Beta strand (21); Binding site (6); Chain (1); Helix (16); Initiator methionine (1); Metal binding (6); Modified residue (4); Natural variant (1); Region (1); Sequence conflict (2); Site (1); Turn (4) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Carboxypeptidase;Cytoplasm;Direct protein sequencing;Hydrolase;Manganese;Metal-binding;Metalloprotease;Phosphoprotein;Protease;Reference proteome |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:17121880}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"; MOD_RES 9; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 58; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q6Q0N1"; MOD_RES 299; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 4RUH; |
| Mapped Pubmed ID | 17220478; 18753673; 19373489; 19805454; 20199107; 21573905; 22128300; 22410244; 24705354; 24885395; 25814554; 28871847; 29056506; 29402779; 31537175; |
| Motif | |
| Gene Encoded By | |
| Mass | 52,878 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.04 mM for L-serylglutamine (at pH 7.5 and in the presence of 0.1 mM manganese ions) {ECO:0000269|PubMed:12473676}; KM=0.6 mM for L-cysteinylglycine (at pH 8.0 and in the presence of 50 uM manganese ions) {ECO:0000269|PubMed:19346245}; KM=15 mM for carnosine (at pH 9.5 and in the presence of 0.1 mM manganese ions) {ECO:0000269|PubMed:12473676}; |
| Metal Binding | METAL 99; /note=Manganese 2; via tele nitrogen; /evidence=ECO:0000269|Ref.19; METAL 132; /note=Manganese 1; /evidence=ECO:0000269|Ref.19; METAL 132; /note=Manganese 2; /evidence=ECO:0000269|Ref.19; METAL 167; /note=Manganese 1; /evidence=ECO:0000269|Ref.19; METAL 195; /note=Manganese 2; /evidence=ECO:0000269|Ref.19; METAL 445; /note=Manganese 1; via tele nitrogen; /evidence=ECO:0000269|Ref.19 |
| Rhea ID | RHEA:67360; RHEA:67361; RHEA:67364; RHEA:67365; RHEA:67372; RHEA:67373; RHEA:28783; RHEA:28784; RHEA:67380; RHEA:67381; RHEA:66724; RHEA:66725; RHEA:66726 |
| Cross Reference Brenda | 3.4.13.18; |