Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major aminopeptidase present in normal human serum was purified to homogeneity as a 150-kDa molecular species. Western blotting confirmed the binding of an anti-aminopeptidase N antibody to the protein. The N-terminal amino acid sequence of the enzyme was determined. The first 13 amino acids of the enzyme completely matched amino acids 59-71 of the sequence predicted from the human intestinal aminopeptidase N cDNA nucleotide sequence. As reported previously, aminopeptidase N from maternal serum had 68 fewer amino acid residues at the N-terminus than the enzyme obtained from detergent-solubilized membranes. The results indicate that aminopeptidase N in normal serum is a different N-terminal processed derivative from that obtained from maternal serum.
Mol Genet Metab 1998 Apr
PMID:Aminopeptidase N in sera of healthy subjects is a different N-terminal processed derivative from the one obtained from maternal serum. 963 97

Aminopeptidase N was demonstrated in human dermal fibroblasts as an ectoenzyme. The enzyme has wide substrate specificity, with a K(m) of 0.63 mM and Vmax of 338 nmol min-1 mg-1. Addition of fetal calf serum to the culture medium increased aminopeptidase N activity up to 63% by 10% serum in a 48-h culture. Treatment of fibroblasts by dexamethasone increased ectoaminopeptidase N activity in a dose- and time-dependent manner. Maximal increase of aminopeptidase N occurred after treatment with 1 microM dexamethasone for 3 days. Actinomycin D, a blocker of RNA synthesis, and cycloheximide, an inhibitor of protein synthesis, did not alter basal aminopeptidase N activity. However, they prevented stimulation by dexamethasone. RU 38486, a glucocorticoid receptor antagonist, suppressed the dexamethasone-induced increase in aminopeptidase N activity. This study shows that human dermal fibroblasts contain ectoaminopeptidase N controlled by glucocorticoids through a receptor-mediated mechanism.
Cell Mol Life Sci 1998 Jun
PMID:Receptor-mediated induction of human dermal fibroblast ectoaminopeptidase N by glucocorticoids. 967 80

Aminopeptidase Ey (EC 3.4.11.20) from chicken (Gallus gallus domesticus) egg yolk is a homodimeric exopeptidase with a broad specificity for N-terminal amino acid residues at P1 position of the substrate. Aminopeptidase Ey is a 300-k metalloexopeptidase, containing 1.0 g atom of zinc per mole of a subunit with a relative molecular mass of 150 k. A full-length cDNA was cloned from chicken (female) liver cDNA library. Analysis of the 3196-base pairs (bp) nucleotide sequence of the cDNA revealed a single open reading frame coding for 967 amino acid residues. The coding region of aminopeptidase Ey gene, apdE, occupies 2901 bp of the cDNA. The predicted amino acid sequence of the enzyme is 66, 65, 64 and 63% identical with those of aminopeptidases N (EC 3.4.11.2) from human, pig, rabbit and rat, respectively. Aminopeptidase Ey contains the metallo-binding sequence motif, His-Glu-Xaa-His, found in zinc metallopeptidases. Zinc binding sites, His-386, His-390 and Glu-409, and catalytic site, Glu-387, were conserved in the homologous aminopeptidases N.
Comp Biochem Physiol B Biochem Mol Biol 1998 Mar
PMID:Isolation and characterization of cDNA encoding chicken egg yolk aminopeptidase Ey. 973 35

Phenotypic conversion from acute myeloid leukemia (AML) to acute lymphoblastic leukemia (ALL) is rare. A 38-year-old man was initially diagnosed as having AML (FAB-M2) associated with the t(8;21)(q22;q22) chromosomal abnormality. The blasts showed myeloperoxidase (MPO) activity and CD13 antigen expression. He showed complete remission after standard chemotherapy for AML. However, the patient relapsed with blasts showing ALL morphology (FAB-L1), MPO negativity, and CD19 antigen expression 33 months after cessation of AML therapy. Cytogenetic analysis at relapse was unsuccessful. Molecular analysis of ALL blasts revealed immunoglobulin heavy-chain gene and MLL gene rearrangements but no AML1 gene. MLL gene rearrangement or the 11q23 chromosomal abnormality has been associated with therapy-related leukemia. The subsequent ALL in our patient may have been induced by the chemotherapy including daunorubicin, known as a topoisomerase II inhibitor.
Hematopathol Mol Hematol 1998
PMID:Phenotypic conversion from t(8;21) acute myeloid leukemia to MLL gene rearrangement-positive acute lymphoblastic leukemia. 984 25

An aminopeptidase N (APN) isozyme having the molecular weight of 90 kDa, was released by phosphatidylinositol-specific phospholipase C (PI-PLC) and purified homogeneously, from the brush border membrane of Bombyx mori. From the result of cDNA cloning, the primary structure of 90 kDa APN proved to consist of 948 amino acid residues, containing a typical metalloprotease-specific zinc-binding motif in the deduced sequence. Moreover, the primary sequence contained two hydrophobic segments on N- and C-termini. The N-terminal one showed characteristics of leader peptide for secretion and the C-terminal one contained a possible glycosylphosphatidylinositol (GPI) anchoring site, suggesting that the APN encoded by the cDNA is not only a zinc-binding enzyme, but also a GPI-anchored protein. The primary sequence is significantly homologous with those of insect and mammalian APNs, and contains four conserved segments around the zinc-binding motif, two potential N-glycosylation sites and four conserved Cys residues. The deduced primary sequence had 30.7% identity with that of B. mori 110 kDa APN, and did not contain the N-terminal and internal amino acid sequences of B. mori 100 kDa APN, revealing B. mori 90 kDa APN to be the third isozyme on the midgut brush border membrane. On the other hand, the primary sequence of 90 kDa APN showed high homology with Manduca sexta APN2 (65.1% identity) and Plutella xylostella APN2 (63.8% identity). It appears that the B. mori 90 kDa APN should be classified in the insect apn2 cluster and differentiated from insect apn1 and mammalian apn clusters by phylogenetic analysis. These results suggest that 90 kDa APN isozyme encoded by the cDNA is a product of B. mori apn2 gene.
Comp Biochem Physiol B Biochem Mol Biol 1998 Oct
PMID:Cloning and sequence analysis of the aminopeptidase N isozyme (APN2) from Bombyx mori midgut. 997 96

Three types of binding assays were used to study the binding of Bacillus thuringiensis delta-endotoxin Cry1Ac to brush border membrane vesicle (BBMV) membranes and a purified putative receptor of the target insect Manduca sexta. Using hybrid proteins consisting of Cry1Ac and the related Cry1C protein, it was shown that domain III of Cry1Ac is involved in specificity of binding as observed by all three techniques. In ligand blotting experiments using SDS-PAGE-separated BBMV proteins as well as the purified putative receptor aminopeptidase N (APN), the presence of domain III of Cry1Ac in a hybrid with Cry1C was necessary and sufficient for specific binding to APN. Using the surface plasmon resonance (SPR) technique with immobilized APN, it was shown that the presence of domain III of Cry1Ac in a hybrid is sufficient for binding to one of the two previously identified Cry1Ac binding sites, whereas the second site requires the full Cry1Ac toxin for binding. In addition, the role of domain III in the very specific inhibition of Cry1Ac binding by the amino sugar N-acetylgalactosamine (GalNac) was determined. Both in ligand blotting and in surface plasmon resonance experiments, as well as in binding assays using intact BBMVs, it was shown that the presence of domain III of Cry1Ac in a toxin molecule is sufficient for the inhibition of binding by GalNAc. These and other results strongly suggest that domain III of delta-endotoxins play a role in insect specificity through their involvement in specific binding to insect gut epithelial receptors.
Mol Microbiol 1999 Jan
PMID:Domain III of the Bacillus thuringiensis delta-endotoxin Cry1Ac is involved in binding to Manduca sexta brush border membranes and to its purified aminopeptidase N. 1002 64

Binding of the insecticidal Bacillus thuringiensis Cry1Ac toxin to the putative receptor aminopeptidase N is specifically inhibited by N-acetylgalactosamine (GalNAc), suggesting that this toxin recognises GalNAc on the receptor. A possible structural basis for involvement of domain III of the toxin in carbohydrate-mediated receptor recognition was noted in the similarity between the domain III fold of the related toxin Cry3A and a carbohydrate-binding domain in the 1,4-beta-glucanase from Cellulomonas fimi. This possibility was investigated by making selected mutations in domain III of the Cry1Ac delta-endotoxin. Mutagenesis of residues Asn506, Gln509 or Tyr513 resulted in toxins with reduced binding and a slower rate of pore formation in Manduca sexta midgut membrane vesicles compared to the wild-type Cry1Ac. These mutants also showed reduced binding to the 120 kDa Cry1Ac putative receptor aminopeptidase N. Unlike the wild-type toxin, binding of the triple mutant N506D,Q509E,Y513A (Tmut) to M. sexta midgut membrane vesicles could not be inhibited by GalNAc. These data indicate that GalNAc binding is located on domain III of Cry1Ac and therefore support a lectin-like role for this domain. A preliminary analysis of the Cry1Ac crystal structure locates Asn506, Gln509 and Tyr513 in a region on and adjacent to beta-16 in domain III, which has a unique conformation compared to the other known Cry structures. These residues are in a favourable position to interact with either soluble or protein-bound carbohydrate.
J Mol Biol 1999 Apr 16
PMID:N-acetylgalactosamine on the putative insect receptor aminopeptidase N is recognised by a site on the domain III lectin-like fold of a Bacillus thuringiensis insecticidal toxin. 1022 7

Alanyl aminopeptidase (APN, CD13) is highly expressed in human monocytes, and anti-CD13 monoclonal antibodies are well established routine markers in leukaemia typing. Due to activation or malignant transformation other leukocyte subpopulations including human T cells exhibit significant APN-gene and surface expression. The function of leukocyte APN is poorly understood, especially the knowledge of physiological ligands/substrates of the enzyme is limited. Abnormal expression of APN on malignant lymphocytes, the activation-dependent induction of APN expression in peripheral T cells and the strong anti-proliferative effects of aminopeptidase inhibitors lead to the interesting hypothesis of a linkage of APN expression and/or function to leukocyte growth. In support of this hypothesis we detected mutations in the APN-gene of patients suffering from leukaemia or lymphoma. This review outlines evidence for APN contributing to the regulation and realisation of lymphocyte growth and function by modulating the mRNA expression of IL-2, IL-1 receptor antagonist, and TGF-beta1 and increasing the activity of MAP kinase p42/Erk2.
Int J Mol Med 1999 Jul
PMID:Role of alanyl aminopeptidase in growth and function of human T cells (review). 1037 32

We screened a midgut cDNA library from diamondback moth, Plutella xylostella, with a probe generated using sequence information from an aminopeptidase N gene from Manduca sexta (MsAPN-1). The sequence recovered (PxAPN-A) encodes a protein of 988 resides with a 60% sequence identity to MsAPN-1. The two proteins share a signal peptide which directs processing by the endoplasmic reticulum, a C-terminal hydrophobic region satisfying the criterion for a GPI anchor and cleavage, and the possibility of an O-glycosylated rigid stalk attached to the GPI anchor. PxAPN-A is more closely related to MsAPN-1 than it is to another aminopeptidase recently reported from P. xylostella. Sequence comparisons with other species suggests that at least one aminopeptidase gene duplication occurred in an ancestral lepidopteran.
Insect Mol Biol 1999 May
PMID:A new aminopeptidase from diamondback moth provides evidence for a gene duplication event in Lepidoptera. 1038 Jan

Nutrient interactions during intestinal digestion has been established in animals. The present study investigated the effect of different nutrients on intestinal dipeptidase, tripeptidase, carboxypeptidase (EC 3.4.12.-) and aminopeptidase N (ApN) (EC 3.4.11.2) activities in human fetuses and children. The effect of nutrients on isolated porcine kidney ApN was also studied. Sucrose, lactose and tributyrin had no effect on di-, tri-, and carboxypeptidase activities of mucosal homogenates, but tributyrin significantly (20-50%) inhibited both fetal and postnatal ApN activity in the small intestine and colon. The pH-independent inhibition of ApN is specific for tributyrin and to the product of its hydrolysis, butyric acid. Glycerol, triolein, and natural oils did not affect ApN activity. The inhibition of ApN by tributyrin was dose and time dependent and occurred in enterocyte brush border membranes as well as in the purified enzyme from porcine kidney. The kinetics of the purified ApN showed that the tributyrin effect is primarily competitive and associated mainly with an increase in K(m). These observations demonstrate the possibility of intestinal and kidney ApN regulation by lipids and products of their hydrolysis. We speculate that nutrient interactions arose quite early in the evolution and represent a mechanism for the regulation of food digestion.
Comp Biochem Physiol A Mol Integr Physiol 1999 Oct
PMID:Regulation of intestinal peptidases by nutrients in human fetuses and children. 1062 59


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