| IED ID | IndEnz0002005128 |
| Enzyme Type ID | protease005128 |
| Protein Name |
Beta-Ala-His dipeptidase EC 3.4.13.20 CNDP dipeptidase 1 Carnosine dipeptidase 1 Glutamate carboxypeptidase-like protein 2 Serum carnosinase |
| Gene Name | CNDP1 CN1 CPGL2 UNQ1915/PRO4380 |
| 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 | MDPKLGRMAASLLAVLLLLLERGMFSSPSPPPALLEKVFQYIDLHQDEFVQTLKEWVAIESDSVQPVPRFRQELFRMMAVAADTLQRLGARVASVDMGPQQLPDGQSLPIPPVILAELGSDPTKGTVCFYGHLDVQPADRGDGWLTDPYVLTEVDGKLYGRGATDNKGPVLAWINAVSAFRALEQDLPVNIKFIIEGMEEAGSVALEELVEKEKDRFFSGVDYIVISDNLWISQRKPAITYGTRGNSYFMVEVKCRDQDFHSGTFGGILHEPMADLVALLGSLVDSSGHILVPGIYDEVVPLTEEEINTYKAIHLDLEEYRNSSRVEKFLFDTKEEILMHLWRYPSLSIHGIEGAFDEPGTKTVIPGRVIGKFSIRLVPHMNVSAVEKQVTRHLEDVFSKRNSSNKMVVSMTLGLHPWIANIDDTQYLAAKRAIRTVFGTEPDMIRDGSTIPIAKMFQEIVHKSVVLIPLGAVDDGEHSQNEKINRWNYIEGTKLFAAFFLEMAQLH |
| Enzyme Length | 507 |
| Uniprot Accession Number | Q96KN2 |
| Absorption | |
| Active Site | ACT_SITE 134; /evidence=ECO:0000250; ACT_SITE 199; /note=Proton acceptor; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: Activated by cadmium ions (PubMed:12473676). Inhibited by the metal chelator 1,10-o-phenantrolin. The inhibitory concentration 50% (IC(50)) is 5 uM. {ECO:0000269|PubMed:12473676}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Preferential hydrolysis of the beta-Ala-|-His dipeptide (carnosine), and also anserine, Xaa-|-His dipeptides and other dipeptides including homocarnosine.; EC=3.4.13.20; Evidence={ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:24891507}; CATALYTIC ACTIVITY: Reaction=carnosine + H2O = beta-alanine + L-histidine; Xref=Rhea:RHEA:59360, ChEBI:CHEBI:15377, ChEBI:CHEBI:57485, ChEBI:CHEBI:57595, ChEBI:CHEBI:57966; EC=3.4.13.20; Evidence={ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:24891507};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59361; Evidence={ECO:0000305|PubMed:12473676, ECO:0000305|PubMed:24891507}; CATALYTIC ACTIVITY: Reaction=anserine + H2O = beta-alanine + N(pros)-methyl-L-histidine; Xref=Rhea:RHEA:59576, ChEBI:CHEBI:15377, ChEBI:CHEBI:57966, ChEBI:CHEBI:58445, ChEBI:CHEBI:143076; EC=3.4.13.20; Evidence={ECO:0000269|PubMed:12473676};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59577; Evidence={ECO:0000305|PubMed:12473676}; CATALYTIC ACTIVITY: Reaction=H2O + L-alanyl-L-histidine = L-alanine + L-histidine; Xref=Rhea:RHEA:37283, ChEBI:CHEBI:15377, ChEBI:CHEBI:57595, ChEBI:CHEBI:57972, ChEBI:CHEBI:74388; Evidence={ECO:0000269|PubMed:12473676};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37284; Evidence={ECO:0000305|PubMed:12473676}; CATALYTIC ACTIVITY: Reaction=glycyl-L-histidine + H2O = glycine + L-histidine; Xref=Rhea:RHEA:67376, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305, ChEBI:CHEBI:57595, ChEBI:CHEBI:169956; Evidence={ECO:0000269|PubMed:12473676};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67377; Evidence={ECO:0000305|PubMed:12473676}; CATALYTIC ACTIVITY: Reaction=H2O + L-homocarnosine = 4-aminobutanoate + L-histidine; Xref=Rhea:RHEA:59572, ChEBI:CHEBI:15377, ChEBI:CHEBI:57595, ChEBI:CHEBI:59888, ChEBI:CHEBI:143075; EC=3.4.13.20; Evidence={ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:24891507};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59573; Evidence={ECO:0000305|PubMed:12473676, ECO:0000305|PubMed:24891507}; |
| DNA Binding | |
| EC Number | 3.4.13.20 |
| Enzyme Function | FUNCTION: Catalyzes the peptide bond hydrolysis in Xaa-His dipeptides, displaying the highest activity toward carnosine (beta-alanyl-L-histidine) and anserine (beta-alanyl-3-methyl-histidine). {ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:24891507}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.5. {ECO:0000269|PubMed:12473676}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Beta strand (18); Chain (1); Glycosylation (2); Helix (15); Metal binding (6); Modified residue (1); Mutagenesis (3); Natural variant (3); Sequence conflict (4); Signal peptide (1); Turn (5) |
| Keywords | 3D-structure;Carboxypeptidase;Glycoprotein;Hydrolase;Metal-binding;Metalloprotease;Phosphoprotein;Protease;Reference proteome;Secreted;Signal;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12473676}. |
| Modified Residue | MOD_RES 219; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q66HG3 |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..26; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 3DLJ; |
| Mapped Pubmed ID | 14560319; 16965804; 17121880; 17205963; 17601991; 17601992; 18753673; 19373489; 19577318; 19929986; 20299368; 20332346; 20379614; 20460427; 20711718; 20851293; 20865290; 20971102; 20979941; 21573905; 22706107; 23029420; 23342076; 23402577; 24566305; 25898255; 26206726; 26439389; 27105448; 27278783; 27834319; 27834323; 28553654; 28871847; 29402779; 30610469; 32803273; 33811534; |
| Motif | |
| Gene Encoded By | |
| Mass | 56,692 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.27 uM for carnosine (at 30 degrees Celsius and in the absence of cadmium ions) {ECO:0000269|PubMed:12473676}; KM=11.00 uM for carnosine (at 30 degrees Celsius and in the presence of 200 uM cadmium ions) {ECO:0000269|PubMed:12473676}; KM=0.13 mM for carnosine {ECO:0000269|PubMed:24891507}; KM=0.20 uM for homocarnosine (at 30 degrees Celsius and in the absence of cadmium ions) {ECO:0000269|PubMed:12473676}; KM=1.0 uM for homocarnosine (at 30 degrees Celsius and in the presence of 200 uM cadmium ions) {ECO:0000269|PubMed:12473676}; KM=8.7 mM for homocarnosine {ECO:0000269|PubMed:24891507}; Vmax=8.5 umol/min/mg enzyme toward carnosine {ECO:0000269|PubMed:24891507}; Vmax=0.36 umol/min/mg enzyme toward homocarnosine {ECO:0000269|PubMed:24891507}; Note=1 hour incubation in 50 mM Tris-HCl, pH 7.5.; |
| Metal Binding | METAL 132; /note=Zinc 2; via tele nitrogen; /evidence=ECO:0000269|Ref.11; METAL 165; /note=Zinc 1; /evidence=ECO:0000269|Ref.11; METAL 165; /note=Zinc 2; /evidence=ECO:0000269|Ref.11; METAL 200; /note=Zinc 1; /evidence=ECO:0000269|Ref.11; METAL 228; /note=Zinc 2; /evidence=ECO:0000269|Ref.11; METAL 478; /note=Zinc 1; via tele nitrogen; /evidence=ECO:0000269|Ref.11 |
| Rhea ID | RHEA:59360; RHEA:59361; RHEA:59576; RHEA:59577; RHEA:37283; RHEA:37284; RHEA:67376; RHEA:67377; RHEA:59572; RHEA:59573 |
| Cross Reference Brenda | 3.4.13.20; |