Literature summary for 3.4.11.3 extracted from

De Bundel, D.; Fafouri, A.; Csaba, Z.; Loyens, E.; Lebon, S.; El Ghouzzi, V.; Peineau, S.; Vodjdani, G.; Kiagiadaki, F.; Aourz, N.; Coppens, J.; Walrave, L.; Portelli, J.; Vanderheyden, P.; Chai, S.Y.; Thermos, K.; Bernard, V.; Collingridge, G.; Auvin, S.; Gressens, P.; Smolders, I.; Dournaud, P.
Trans-modulation of the somatostatin type 2A receptor trafficking by insulin-regulated aminopeptidase decreases limbic seizures (2015), J. Neurosci., 35, 11960-11975 .

Application

Application	Comment	Organism
pharmacology	enzyme IRAP is a therapeutic target for the treatment of limbic seizures	Rattus norvegicus

Protein Variants

Protein Variants	Comment	Organism
additional information	downregulation of enzyme IRAP by shRNA	Rattus norvegicus

Inhibitors

Inhibitors	Comment	Organism	Structure
angiotensin IV	IRAP ligands are on the one hand competitive inhibitors of the enzymatic activity of IRAP and on the other hand regulators of its trafficking	Rattus norvegicus
LVV hemorphin 7	LVV-H7, IRAP ligands are on the one hand competitive inhibitors of the enzymatic activity of IRAP and on the other hand regulators of its trafficking	Rattus norvegicus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
additional information	at the cellular level, IRAP immunoreactivity in neurons is associated with the trans-Golgi apparatus and vesicular structures in the proximity of the Golgi cisternae	Rattus norvegicus	-	-
plasma membrane	-	Rattus norvegicus	5886	-
vesicle	-	Rattus norvegicus	31982	-

Organism

Organism	UniProt	Comment	Textmining
Rattus norvegicus	P97629	-	-
Rattus norvegicus Wistar	P97629	-	-

Purification (Commentary)

Purification (Comment)	Organism
native enzyme in subcellular fractions	Rattus norvegicus

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Rattus norvegicus	-
embryo	-	Rattus norvegicus	-
hippocampus	-	Rattus norvegicus	-
additional information	enzyme IRAP is highly expressed in brain areas associated with cognition and epilepsy, regions that also display the highest densities of sst2A receptor immunoreactivity. Immunohistochemic analysis, quantitative analysis of immunofluorescence	Rattus norvegicus	-
neuron	embryonic hippocampal neurons, tissue culture	Rattus norvegicus	-

Synonyms

Synonyms	Comment	Organism
insulin-regulated aminopeptidase	-	Rattus norvegicus
IRAP	-	Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Rattus norvegicus

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Rattus norvegicus

General Information

General Information	Comment	Organism
physiological function	the insulin-regulated aminopeptidase (IRAP) is involved in vesicular trafficking and shares common regional distribution with the major somatostatin (SRIF) receptor subtype, the sst2A receptor, which is localized at postsynaptic sites of the principal neurons where it modulates neuronal activity. IRAP regulates the trafficking of the sst2A receptor, it is a negative regulator of sst2A receptor recycling. Following agonist exposure, this receptor rapidly internalizes and recycles slowly through the trans-Golgi network. IRAP ligands display anticonvulsive properties involving the sst2A receptor. IRAP ligands accelerate the recycling of the sst2A receptor that has internalized in neurons in vitro or in vivo. Most importantly, because IRAP ligands increase the density of this inhibitory receptor at the plasma membrane, they also potentiate the neuropeptide SRIF inhibitory effects on seizure activity. In addition to its aminopeptidase activity involved in peptide hormone processing, IRAP also acts as a receptor for the endogenous ligands angiotensin IV (Ang IV) and LVV hemorphin 7 (LVV-H7). IRAP ligands are on the one hand competitive inhibitors of the enzymatic activity of IRAP and on the other hand regulators of its trafficking with memory- and cognitive-enhancing effects of IRAP ligands. The extracellular part of IRAP contains the aminopeptidase activity, whereas its intracellular domain interacts with cytosolic proteins that contribute to GLUT4 vesicle retention and translocation to the plasma membrane	Rattus norvegicus