Literature summary for 3.4.11.2 extracted from

Turner, A.J.
Membrane alanyl aminopeptidase (2004), Handbook of Proteolytic Enzymes (Barrett, J. ; Rawlings, N. D. ; Woessner, J. F. , eds. ), 1, 289-294.

No PubMed abstract available

Application

Application	Comment	Organism
diagnostics	the enzyme might be a valuable histological marker for prostate cancer	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
DNA and amino acid sequence determination and analysis	Rattus norvegicus
from a kidney library	Oryctolagus cuniculus
from an intestinal cDNA library, the gene is localized on chromosome 15, intestinal and myeloid epithelial cells use different promoters	Homo sapiens
the gene is localized on chromosome 7	Sus scrofa

Inhibitors

Inhibitors	Comment	Organism
actinonin	IC50: 0.002 mM, specific inhibitor	Sus scrofa
amastatin	slow, tight-binding inhibitor which involves a conformational change in the enzyme-inhibitor complex	Sus scrofa
bestatin	-	Sus scrofa
Metal chelating agents	-	Sus scrofa
additional information	no inhibition by sulfhydryl reagents	Sus scrofa
probestin	IC50: 50 nM	Sus scrofa
puromycin	very weak inhibition	Sus scrofa

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cell surface	CD13	Homo sapiens	9986	-
membrane	-	Lactococcus lactis	16020	-
membrane	-	Lymantria dispar	16020	-
membrane	brush border membranes	Homo sapiens	16020	-
membrane	brush border membranes	Rattus norvegicus	16020	-
membrane	brush border membranes	Sus scrofa	16020	-
membrane	brush border membranes	Oryctolagus cuniculus	16020	-
microsome	-	Homo sapiens	-	-
microsome	-	Rattus norvegicus	-	-
microsome	-	Sus scrofa	-	-
microsome	-	Oryctolagus cuniculus	-	-
plasma membrane	type II integral membrane protein located on the plasma membrane as an ectoenzyme	Homo sapiens	5886	-
plasma membrane	type II integral membrane protein located on the plasma membrane as an ectoenzyme	Rattus norvegicus	5886	-
plasma membrane	type II integral membrane protein located on the plasma membrane as an ectoenzyme	Sus scrofa	5886	-
plasma membrane	type II integral membrane protein located on the plasma membrane as an ectoenzyme	Oryctolagus cuniculus	5886	-

Metals/Ions

Metals/Ions	Comment	Organism
Zn2+	the enzyme contains a typical zinc-binding motif HEXXH, one Zn2+ per subunit	Rattus norvegicus
Zn2+	zinc-metallopeptidase, Zn2+ binds to the active site	Homo sapiens
Zn2+	zinc-metallopeptidase, Zn2+ binds to the active site	Sus scrofa

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
130000	-	kidney brush border enzyme, gel filtration	Sus scrofa

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
additional information	Sus scrofa	the brain enzyme is involved in termination of the action of neuropeptides, especially of enkephalins and angiotensin III, the kidney enzyme contributes to the extracellular catabolism of glutathione, the intestinal enzyme acts as a receptor for the transmissible gastroenteritis virus, a coronavirus, causing fatal diarrhea in newborn pigs	?	-	?
additional information	Lymantria dispar	the enzyme acts as major receptor for the CryIAc toxin of Bacillus thuringiensis	?	-	?
additional information	Homo sapiens	the enzyme in granulocytes may cooperate with neprilysin, the enzyme is involved in the metabolism of certain vasoactive peptides in vascular cells in the brain, the enzyme mediates human cytomegalovirus infection, the enzym regulates the cycle-dependent bioavailability of interleukin-8 in the endometrium, the enzyme's activity is regulated by estrogen	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Lactococcus lactis	-	gene pepN	-
Lymantria dispar	-	gypsy moth	-
Oryctolagus cuniculus	-	-	-
Rattus norvegicus	-	-	-
Sus scrofa	-	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
glycoprotein	-	Homo sapiens
glycoprotein	-	Oryctolagus cuniculus
glycoprotein	heavily glycosylated	Sus scrofa
glycoprotein	the enzyme contains 9 potential N-glycosylation sites	Rattus norvegicus

Purification (Commentary)

Purification (Comment)	Organism
native enzyme from kidney and from small intestine, the kidney brush border enzyme is purified by proteinase treatment or detergent solubilization and chromatographical steps, e.g. affinity chromatography on a 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate resin followed by a concanavalin A resin, the small intestinal enzyme is purified by immunoadsorbent chromatography	Sus scrofa

Source Tissue

Source Tissue	Comment	Organism	Textmining
astrocyte	-	Sus scrofa	-
blood vessel	lung endothelium	Sus scrofa	-
blood vessel endothelium	lung blood vessels	Sus scrofa	-
brain	-	Homo sapiens	-
brain	endothelial cells, synaptic membranes of astro- and pericytes	Sus scrofa	-
granulocyte	-	Homo sapiens	-
hematopoietic cell	CD13	Homo sapiens	-
hematopoietic stem cell	-	Homo sapiens	-
intestine	-	Homo sapiens	-
kidney	-	Sus scrofa	-
kidney	-	Oryctolagus cuniculus	-
liver	-	Sus scrofa	-
lung	located on endothelial cells in blood vessels	Sus scrofa	-
lymphocyte	-	Homo sapiens	-
melanoma cell	-	Homo sapiens	-
monocyte	-	Homo sapiens	-
additional information	wide tissue distribution	Homo sapiens	-
additional information	wide tissue distribution	Rattus norvegicus	-
additional information	wide tissue distribution	Sus scrofa	-
additional information	wide tissue distribution	Oryctolagus cuniculus	-
mucosa	-	Sus scrofa	-
myeloid leukemia cell	-	Homo sapiens	-
pericyte	-	Sus scrofa	-
placenta	-	Sus scrofa	-
prostate cancer cell	-	Homo sapiens	-
small intestine	mucosa	Sus scrofa	-
T-lymphocyte	activated	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
Cys-Gly + H2O	-	Homo sapiens	Cys + Gly	-	?
Cys-Gly + H2O	-	Rattus norvegicus	Cys + Gly	-	?
Cys-Gly + H2O	-	Sus scrofa	Cys + Gly	-	?
Cys-Gly + H2O	-	Oryctolagus cuniculus	Cys + Gly	-	?
enkephalin + H2O	hydrolysis of the Tyr1-Gly2 bond	Homo sapiens	?	-	?
enkephalin + H2O	hydrolysis of the Tyr1-Gly2 bond	Rattus norvegicus	?	-	?
enkephalin + H2O	hydrolysis of the Tyr1-Gly2 bond	Sus scrofa	?	-	?
enkephalin + H2O	hydrolysis of the Tyr1-Gly2 bond	Oryctolagus cuniculus	?	-	?
L-Ala-2-naphthylamide + H2O	-	Homo sapiens	L-Ala + 2-naphthylamine	-	?
L-Ala-2-naphthylamide + H2O	-	Rattus norvegicus	L-Ala + 2-naphthylamine	-	?
L-Ala-2-naphthylamide + H2O	-	Sus scrofa	L-Ala + 2-naphthylamine	-	?
L-Ala-2-naphthylamide + H2O	-	Oryctolagus cuniculus	L-Ala + 2-naphthylamine	-	?
L-Ala-4-nitroanilide + H2O	-	Homo sapiens	L-Ala + 4-nitroaniline	-	?
L-Ala-4-nitroanilide + H2O	-	Rattus norvegicus	L-Ala + 4-nitroaniline	-	?
L-Ala-4-nitroanilide + H2O	-	Sus scrofa	L-Ala + 4-nitroaniline	-	?
L-Ala-4-nitroanilide + H2O	-	Oryctolagus cuniculus	L-Ala + 4-nitroaniline	-	?
L-Ala-7-amido-4-methylcoumarin + H2O	-	Homo sapiens	L-Ala + 7-amino-4-methylcoumarin	-	?
L-Ala-7-amido-4-methylcoumarin + H2O	-	Rattus norvegicus	L-Ala + 7-amino-4-methylcoumarin	-	?
L-Ala-7-amido-4-methylcoumarin + H2O	-	Sus scrofa	L-Ala + 7-amino-4-methylcoumarin	-	?
L-Ala-7-amido-4-methylcoumarin + H2O	-	Oryctolagus cuniculus	L-Ala + 7-amino-4-methylcoumarin	-	?
additional information	the brain enzyme is involved in termination of the action of neuropeptides, especially of enkephalins and angiotensin III, the kidney enzyme contributes to the extracellular catabolism of glutathione, the intestinal enzyme acts as a receptor for the transmissible gastroenteritis virus, a coronavirus, causing fatal diarrhea in newborn pigs	Sus scrofa	?	-	?
additional information	the enzyme acts as major receptor for the CryIAc toxin of Bacillus thuringiensis	Lymantria dispar	?	-	?
additional information	the enzyme in granulocytes may cooperate with neprilysin, the enzyme is involved in the metabolism of certain vasoactive peptides in vascular cells in the brain, the enzyme mediates human cytomegalovirus infection, the enzym regulates the cycle-dependent bioavailability of interleukin-8 in the endometrium, the enzyme's activity is regulated by estrogen	Homo sapiens	?	-	?
additional information	substrate specificity, overview, chain length influencs the activity rate, dipeptides are readily hydrolyzed, the enzyme prefers substrates with N-terminal L-Ala residues, the specificity for N-terminal residues is descending order is Ala, Phe, Tyr, Leu, Arg, Thr, Trp, Lys, Ser, Asp, His, Val. Pro- and alpha- or gamma-Glu-derivatives are slowly hydrolyzed, when a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide	Homo sapiens	?	-	?
additional information	substrate specificity, overview, chain length influencs the activity rate, dipeptides are readily hydrolyzed, the enzyme prefers substrates with N-terminal L-Ala residues, the specificity for N-terminal residues is descending order is Ala, Phe, Tyr, Leu, Arg, Thr, Trp, Lys, Ser, Asp, His, Val. Pro- and alpha- or gamma-Glu-derivatives are slowly hydrolyzed, when a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide	Rattus norvegicus	?	-	?
additional information	substrate specificity, overview, chain length influencs the activity rate, dipeptides are readily hydrolyzed, the enzyme prefers substrates with N-terminal L-Ala residues, the specificity for N-terminal residues is descending order is Ala, Phe, Tyr, Leu, Arg, Thr, Trp, Lys, Ser, Asp, His, Val. Pro- and alpha- or gamma-Glu-derivatives are slowly hydrolyzed, when a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide	Oryctolagus cuniculus	?	-	?
additional information	substrate specificity, overview, chain length influencs the activity rate, dipeptides are readily hydrolyzed, the enzyme prefers substrates with N-terminal L-Ala residues, the specificity for N-terminal residues is descending order is Ala, Phe, Tyr, Leu, Arg, Thr, Trp, Lys, Ser, Asp, His, Val. Pro- and alpha- or gamma-Glu-derivatives are slowly hydrolyzed, when a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide. Glu350 is involved in catalysis, the enzyme in lung is identical with the p146 type II alveolar epithelial cell antigen	Sus scrofa	?	-	?

Subunits

Subunits	Comment	Organism
monomer	-	Oryctolagus cuniculus
More	the enzyme contains a small cytoplasmic domain, a 24-amino-acid hydrophobic segment close to the N-terminus which serves as membrane anchor, and the bulk domain including the active site as ectodomain	Rattus norvegicus

Synonyms

Synonyms	Comment	Organism
aminopeptidase M	-	Sus scrofa
aminopeptidase N	-	Homo sapiens
aminopeptidase N	-	Rattus norvegicus
aminopeptidase N	-	Sus scrofa
aminopeptidase N	-	Oryctolagus cuniculus
aminopeptidase N	-	Lactococcus lactis
aminopeptidase N	-	Lymantria dispar
CD13	cluster differentiation antigen	Homo sapiens
Cys-Gly-dipeptidase	-	Sus scrofa
cysteinyl-glycinase	-	Sus scrofa
mAAP	-	Homo sapiens
mAAP	-	Rattus norvegicus
mAAP	-	Sus scrofa
mAAP	-	Oryctolagus cuniculus
mAAP	-	Lactococcus lactis
mAAP	-	Lymantria dispar
p146 type II alveolar epithelial cell antigen	-	Sus scrofa

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7	7.5	dependent on substrate concentration	Homo sapiens
7	7.5	dependent on substrate concentration	Sus scrofa

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.00002	-	amastatin	preincubation of the enzyme with the inhibitor	Sus scrofa

pI Value

Organism	Comment	pI Value Maximum	pI Value
Sus scrofa	about	-	5

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.00005	-	IC50: 50 nM	Sus scrofa	probestin
0.002	-	IC50: 0.002 mM, specific inhibitor	Sus scrofa	actinonin