Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII.
The lysosomal hydrolase, dipeptidyl peptidase I (DPPI), was purified from human spleen and its enzymatic activity characterized. The enzyme was purified to apparent homogeneity by a combination of differential pH solubility, heat-treatment, affinity chromatography on concanavalin A-agarose and p-hydroxymercuribenzoate-agarose, and gel filtration chromatography on Sephacryl S-300. This procedure resulted in a 1100-fold purification of DPPI protein with a yield of approximately 2% of the total DPPI activity. The enzyme was characterized as a glycoprotein with a pI of 5.4, a molecular mass of 200,000 Da as determined by gel filtration under nondenaturing conditions, and a subunit size of 24,000 Da. Amino acid sequence analysis of peptides isolated from cyanogen bromide and trypsin digests of the 24,000-Da subunit revealed extensive sequence similarity between human and rat DPPI. Purified DPPI exhibited both hydrolytic and transpeptidase (polymerase) activity. DPPI exhibited activity against a variety of dipeptide substrates including peptides with either non-polar or polar residues in the P1 position. In contrast to the reported substrate specificity of bovine and murine DPPI, the human enzyme exhibited a modest preference for peptides with nonpolar residues in the P1 position. DPPI content was found to be highest among cytotoxic lymphocytes and myeloid cells. The high level of DPPI expression in these cell populations correlates with their sensitivity to the toxic effects of leucyl-leucine methyl ester, a substrate for DPPI.
Catalysis of the hydrolysis of peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile.
J. Chromatogr. B, Biomed. Appl. 681, 251-262 (1996)[PubMed:8811434]
A procedure for the simultaneous isolation of four cysteine proteinases, cathepsins B, H, L and C, from human kidney is described. The method includes concentration of the acidified homogenate by ammonium sulphate precipitation. The resuspended and dialysed precipitate was chromatographed on DEAE-cellulose DE-32, to allow separation of cathepsins H and C from cathepsins B and L. The main isoform of cathepsin H was separated from cathepsin C by cation-exchange chromatography on CM-Sephadex C-50. These two enzymes were further purified by covalent chromatography on thiopropyl Sepharose and gel permeation on Sephacryl S-200. The last step allowed separation of cathepsin C and the minor isoform of cathepsin H. Purification of the other two enzymes, cathepsins B and L, was carried out on thiol Sepharose, followed by chromatography on CM-Sepharose C-50. In this step, pure cathepsin L was obtained, while two isoforms of cathepsin B had to be finally purified on Sephacryl S-200 columns. The purity of each enzyme was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis, isoelectric focusing on polyacrylamide gels and N-terminal sequencing. The activities of the purified cathepsins B, H and L were determined in terms of kcat/KM for three substrates, Z-Phe-Arg-MCA, Z-Arg-Arg-MCA and Arg-MCA. The method produced 25 mg of cathepsin B, 6.5 mg of cathepsin H, 1.5 mg of cathepsin L and 3.8 mg of cathepsin C from 3.5 kg of human kidney.
Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a catalytic mechanism that involves a catalytic triad consisting of a serine nucleophile that is activated by a proton relay involving an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine).
A developmental process that is a deterioration and loss of function over time. Aging includes loss of functions such as resistance to disease, homeostasis, and fertility, as well as wear and tear. Aging includes cellular senescence, but is more inclusive. May precede death (GO:0016265) and may succeed developmental maturation (GO:0021700).
J. Biol. Chem. 272, 10260-10265 (1997)[PubMed:9092576]
Dipeptidyl-peptidase I, a lysosomal cysteine proteinase, is important in intracellular degradation of proteins and appears to be a central coordinator for activation of many serine proteinases in immune/inflammatory cells. Little is known about the molecular genetics of the enzyme. In the present investigation the gene for dipeptidyl-peptidase I was cloned and characterized. The gene spans approximately 3.5 kilobases and consists of two exons and one intron. The genomic organization is distinct from the complex structures of the other members of the papain-type cysteine proteinase family. By fluorescence in situ hybridization, the gene was mapped to chromosomal region 11q14.1-q14.3. Analysis of the sequenced 5'-flanking region revealed no classical TATA or CCAAT box in the GC-rich region upstream of cap site. A number of possible regulatory elements that could account for tissue-specific expression were identified. Northern analyses demonstrated that the dipeptidyl-peptidase I message is expressed at high levels in lung, kidney, and placenta, at moderate to low levels in many organs, and at barely detectable levels in the brain, suggesting tissue-specific regulation. Among immune/inflammatory cells, the message is expressed at high levels in polymorphonuclear leukocytes and alveolar macrophages and their precursor cells. Treatment of lymphocytes with interleukin-2 resulted in a significant increase in dipeptidyl-peptidase I mRNA levels, suggesting that this gene is subjected to transcriptional regulation. The results provide initial insights into the molecular basis for the regulation of human dipeptidyl-peptidase I.
J. Chromatogr. B, Biomed. Appl. 681, 251-262 (1996)[PubMed:8811434]
A procedure for the simultaneous isolation of four cysteine proteinases, cathepsins B, H, L and C, from human kidney is described. The method includes concentration of the acidified homogenate by ammonium sulphate precipitation. The resuspended and dialysed precipitate was chromatographed on DEAE-cellulose DE-32, to allow separation of cathepsins H and C from cathepsins B and L. The main isoform of cathepsin H was separated from cathepsin C by cation-exchange chromatography on CM-Sephadex C-50. These two enzymes were further purified by covalent chromatography on thiopropyl Sepharose and gel permeation on Sephacryl S-200. The last step allowed separation of cathepsin C and the minor isoform of cathepsin H. Purification of the other two enzymes, cathepsins B and L, was carried out on thiol Sepharose, followed by chromatography on CM-Sepharose C-50. In this step, pure cathepsin L was obtained, while two isoforms of cathepsin B had to be finally purified on Sephacryl S-200 columns. The purity of each enzyme was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis, isoelectric focusing on polyacrylamide gels and N-terminal sequencing. The activities of the purified cathepsins B, H and L were determined in terms of kcat/KM for three substrates, Z-Phe-Arg-MCA, Z-Arg-Arg-MCA and Arg-MCA. The method produced 25 mg of cathepsin B, 6.5 mg of cathepsin H, 1.5 mg of cathepsin L and 3.8 mg of cathepsin C from 3.5 kg of human kidney.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic substance stimulus.
The directed killing of a target cell by a T cell through the release of granules containing cytotoxic mediators or through the engagement of death receptors.
IEAOrtholog Compara
Enzymatic activity
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.4.14.1: Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro.
CuratedUniProtKB
It requires the following cofactor
Binds 1 chloride ion per heavy chain.
CuratedUniProtKB
It is regulated in the following manner
Strongly inhibited by the cysteine peptidase inhibitors mersalyl acid, iodoacetic acid and cystatin. Inhibited by N-ethylmaleimide, Gly-Phe-diazomethane, TLCK, TPCK and, at low pH, by dithiodipyridine. Not inhibited by the serine peptidase inhibitor PMSF, the aminopeptidase inhibitor bestatin, or metal ion chelators.
The lysosomal hydrolase, dipeptidyl peptidase I (DPPI), was purified from human spleen and its enzymatic activity characterized. The enzyme was purified to apparent homogeneity by a combination of differential pH solubility, heat-treatment, affinity chromatography on concanavalin A-agarose and p-hydroxymercuribenzoate-agarose, and gel filtration chromatography on Sephacryl S-300. This procedure resulted in a 1100-fold purification of DPPI protein with a yield of approximately 2% of the total DPPI activity. The enzyme was characterized as a glycoprotein with a pI of 5.4, a molecular mass of 200,000 Da as determined by gel filtration under nondenaturing conditions, and a subunit size of 24,000 Da. Amino acid sequence analysis of peptides isolated from cyanogen bromide and trypsin digests of the 24,000-Da subunit revealed extensive sequence similarity between human and rat DPPI. Purified DPPI exhibited both hydrolytic and transpeptidase (polymerase) activity. DPPI exhibited activity against a variety of dipeptide substrates including peptides with either non-polar or polar residues in the P1 position. In contrast to the reported substrate specificity of bovine and murine DPPI, the human enzyme exhibited a modest preference for peptides with nonpolar residues in the P1 position. DPPI content was found to be highest among cytotoxic lymphocytes and myeloid cells. The high level of DPPI expression in these cell populations correlates with their sensitivity to the toxic effects of leucyl-leucine methyl ester, a substrate for DPPI.
Enzyme which catalyzes hydrolysis reaction, i.e. the addition of the hydrogen and hydroxyl ions of water to a molecule with its consequent splitting into two or more simpler molecules.
Proteolytic enzyme with a cysteine residue (Cys) in its active site. There are many families of thiol proteases. The most well known one is the papain family (C1 in MEROPS classification) which is known to exist in most eukaryotes.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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