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Information on EC 3.4.11.3 - cystinyl aminopeptidase and Organism(s) Rattus norvegicus and UniProt Accession P97629
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3.4.11.3 cystinyl aminopeptidaseSpecify your search results
Word Map
- 3.4.11.3
- envelope
- pregnancy
- cd4
- epitope
- lymphocyte
- angiotensin
- vaccinia
- viruses
- women
- aminopeptidases
-
hiv-1-infected
-
humoral
- t-cells
- virion
-
simian
- macaque
-
hiv-specific
-
immunodominant
- nef
- seroconversion
- chimpanzee
-
anti-hiv-1
-
seronegative
- insipidus
-
syncytium
-
prime-boost
- furin
-
vaccinees
-
seropositive
-
vaccine-induced
-
glut4-containing
-
hiv-seronegative
- desmopressin
- shiv
-
ddavp
-
hiv-1iiib
-
anti-cd4
-
intrarectal
-
sivmac239
- medicine
-
alum
-
seroconverted
-
1-infected
-
non-neutralizing
- diagnostics
-
oligosaccharyltransferase
-
virus-neutralizing
-
cross-neutralizing
- pharmacology
-
coreceptors
-
cross-presentation
-
nephrogenic
-
radioimmunoprecipitation
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Release of an N-terminal amino acid, Cys-/-Xaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl arylamides exceed that for the cystinyl derivative, however
Synonyms
gp160, oxytocinase, p-lap, insulin-regulated aminopeptidase, vasopressinase, at4 receptor, cystine aminopeptidase, placental leucine aminopeptidase, otase, lnpep, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-Aminoacyl-peptide hydrolase
-
-
-
-
aminopeptidase, cystyl
-
-
-
-
CAP-I
-
-
-
-
CAP-II
-
-
-
-
cysteine aminopeptidase
-
-
-
-
cystine aminopeptidase
-
-
-
-
Cystinyl aminopeptidase
-
-
-
-
cystyl aminopeptidase
-
-
-
-
GP160
Insulin-regulated membrane aminopeptidase
Insulin-responsive aminopeptidase
-
-
-
-
IRAP
L-cystine aminopeptidase
-
-
-
-
OTase
-
-
-
-
oxytocin peptidase
-
-
-
-
oxytocinase
P-LAP
-
-
-
-
Placental leucine aminopeptidase
vasopresssinase
-
-
-
-
Vesicle protein of 165 kDa
-
-
-
-
Vp165
yscXVI
-
-
-
-
GP160
-
-
-
-
Insulin-regulated membrane aminopeptidase
-
-
-
-
IRAP
-
-
-
-
oxytocinase
-
-
-
-
Placental leucine aminopeptidase
-
-
-
-
Vp165
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9031-41-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
leucyl-beta-naphthylamide + H2O
leucine + beta-naphthylamine
-
-
-
?
L-cystine-di-beta-naphthylamide + 2 H2O
L-cystine + 2 beta-naphthylamine
-
-
-
?
L-cystine-di-beta-naphthylamide + 2 H2O
L-cystine + 2 beta-naphthylamine
in the presence of thiol, the substrate is converted to L-cystine beta-naphthylamide
-
-
?
additional information
?
-
-
activity is greatly increased in rats with mammary tumors. The activity may be involved in the promotion and progression of breast cancer through oxytocin, vasopressin and/or renin-angiotensin system misregulation
-
-
?
additional information
?
-
-
the enzyme is involved in the metabolism of angiotensin
-
-
?
additional information
?
-
-
the enzyme plays a role as a mediator for the effects of angiotensin IV and related peptides on extracellular dopamine levels in striatum
-
-
?
additional information
?
-
-
the enzyme plays diverse physiological roles in the rat central nervous system
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
activity is greatly increased in rats with mammary tumors. The activity may be involved in the promotion and progression of breast cancer through oxytocin, vasopressin and/or renin-angiotensin system misregulation
-
-
?
additional information
?
-
-
the enzyme is involved in the metabolism of angiotensin
-
-
?
additional information
?
-
-
the enzyme plays a role as a mediator for the effects of angiotensin IV and related peptides on extracellular dopamine levels in striatum
-
-
?
additional information
?
-
-
the enzyme plays diverse physiological roles in the rat central nervous system
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
angiotensin IV
AngIV, induces an increase in the intracellular calcium concentration in pinealocytes by 72% at 10 nM, but AngIV does not alter cAMP levels
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
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Insulin
insulin activates the enzyme migration from the intracellular vesicles to the cellular membrane
-
Insulin
insulin effectively stimulates CysAP activity trafficking from low (LDM) density microsomes toward plasma membrane in all animal groups under study, while the insulin-stimulated traffic of LeuAP activity in adipocytes does not change as a function of metabolic challenges applied
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
activity is greatly increased in rats with mammary tumors. The activity may be involved in the promotion and progression of breast cancer through oxytocin, vasopressin and/or renin-angiotensin system misregulation
-
expression of the enzyme is increased during the differentiation of the cells into neuronal cells
-
cystinyl aminopeptidase is 100% higher in the left than in the right prefrontal cortex
additional information
AT4 receptor/IRAP is found in neurons in the cortex, hippocampus and basal ganglia
expressed in magnocellular neurones of the supraoptic (SON) and paraventricular (PVN) nuclei
-
highly expressed in selected olfactory regions, in septal and hypothalamic nuclei, throughout the hippocampal formation and cerebral cortex, and in motor and motor associated nuclei. IRAP is expressed exclusively in neurons in these regions
-
cystinyl aminopeptidase is 300% higher in the left than in the right hippocampus
-
colocalization with the potential in vivo substrates, oxytocin and vasopression
-
blocking of alpha-1adrenoceptor by doxazosin increases enzyme activity in male, but not in female
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
additional information
organ distribution in adult male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with or without treatment with captopril, overview. Soluble or membrane-bound activities are generally higher in SHR compared to WKY notably in hypothalamus and kidney than in the other tissues. Captopril mainly decreases CysAP in SHR whereas it increases in WKY. The distribution of soluble CysAP is more homogeneous among tissues of WKY than SHR. In contrast, the distribution of membrane-bound CysAP is more heterogeneous than soluble CysAP in both WKY and SHR
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
enzyme IRAP is localized in intracellular vesicles which can translocate to the cell membrane under insulin stimulation
-
high (HDM) and low (LDM) density microsomal fractions. LDM consists of microsomes without ribosomes and with portions of endoplasmatic reticulum (ER) and fragments of Golgi apparatus. HDM consists of microsomes with ribosomes adhered to its outer surface. The inner side of microsomes is biochemically equivalent to the lumen of the ER
-
-
the enzyme translocates to the cell surface within GLUT4 vesicles in response to insulin
-
IRAP vesicles represent a IgE-sensitive exocytotic compartment in mast cells, which is regulated differently from secretory granules
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
-
enzyme IRAP is localized in intracellular vesicles which can translocate to the cell membrane under insulin stimulation
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
the type of dietary fat does not influence latency period, incidence of animals with tumors, incidence of mortality, or tumor yield per rat. However, changes are observed in tumor volume and the histopathology. The type of dietary fat also differently modifies the enzymes involved in RAS regulation. Both insulin-regulated aminopeptidase (IRAP) and angiotensin IV forming activities are involved in this animal model of breast pathogenesis. The increase in serum IRAP activity can be an indicator of a misregulation of vasopressin (AVP) function
physiological function
evolution
IRAP is a member of the M1 family of zinc-dependent metalloproteinases
evolution
IRAP is a type-2 membrane glycoprotein from the M1 family of zinc-dependent aminopeptidases
malfunction
inhibition of central enzyme activity by injection of amastatin in anaesthetised suckling mothers increases the frequency of reflex milk ejections
malfunction
catalytic preference and insulin-regulated traffic of IRAP in adipocytes are disturbed by obesity and are interrelated with comprehensive roles of endogenous substrates with N-terminal cysteine pair in energy metabolism homeostasis
physiological function
analysis of enzyme activity in high (HDM) and low (LDM) density microsomal fractions, and plasma membrane fraction (MF) from isolated adipocytes of healthy (C), food deprived (FD) and monosodium glutamate (MSG) obese rats on aminoacyl substrates with N-terminal Cys or Leu, in absence or presence of insulin, overview. The hydrolytic activity trafficking from LDM to MF under influence of insulin in C, MSG and FD acts only on N-terminal Cys. The pathophysiological significance of IRAP in adipocytes seems to be linked to comprehensive energy metabolism related roles of endogenous substrates with N-terminal cysteine pair such as vasopressin and oxytocin. Insulin-dependent traffic of CysAP activity has important pathophysiological implications
physiological function
functional roles of soluble (Sol) and membrane-bound (MB) cystinylaminopeptidase (CysAP) activities, overview. Soluble and membrane-bound CysAP activities, acting separately or in concert and mainly in renal medulla, regulate the function of their susceptible endogenous substrates, and may participate meaningfully in the control of blood pressure and fluid balance
physiological function
the AT4 receptor identified as the IRAP is found in neurons in the cortex, hippocampus and basal ganglia. The presence of aminopeptidases A and N in the pineal gland suggests local production of Ang IV that could act through its specific receptor (IRAP)/AT4 to modulate melatonin synthesis, analysis of the role of enzyme inhibitor Ang IV on melatonin synthesis using isolated pinealocyte cultures, overview. IRAP is an enzyme that is mostly associated with cellular membranes, and its translocation appears to be regulated by insulin, which activates its migration from the intracellular vesicles to the cellular membrane together with the glucose transporter, Glut4. IRAP plays either the role of a true receptor, the (IRAP)/AT4 receptor, inducing intracellular signaling pathways, or the role of an enzyme that metabolizes several peptides, such as oxytocin and arginine vasopressin
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). LCAP_RAT
1025
1
117201
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
the increase in serum IRAP activity can be an indicator of a misregulation of vasopressin (AVP) function
pharmacology
enzyme IRAP is a therapeutic target for the treatment of limbic seizures
medicine
medicine
-
activities of soluble cystyl aminopeptidase do not differ between diabetic and control rats in both hippocampus and hypothalamus. Membrane-bound cystyl aminopeptidase is about 2.5foldincreased in the hypothalamus and 5fold increased in the hippocampus
medicine
-
blocking of alpha-1adrenoceptor by doxazosin increases enzyme activity in male, but not in female thalamus. Increased capacity of males to degrade vasopressin and to regulate cardiovascular homeostasis
medicine
-
Otsuka Long Evans Tokushima Fatty rats, model of type II Diabetes mellitus, show significantly lower cell surface IRAP equilibrium activity than control. Time to reach equilibrium is significantly longer and adipocytes isolated from the model rats demonstrate both a delay and a reduction in 3-O-methyl-D-glucose uptake
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Burbach, J.P.H.; De Bree, F.M.; Terwel, D.; Tan, A.; Maskova, H.P.; Van der Kleij, A.A.M.
Properties of aminopeptidase activity involved in the conversion of vasopressin by rat brain membranes [published erratum appears in Peptides 1994;15(5):933
Peptides
14
807-813
1993
Rattus norvegicus
Banegas, I.; Prieto, I.; Alba, F.; Vives, F.; Araque, A.; Segarra, A.B.; Duran, R.; de Gasparo, M.; Ramirez, M.
Angiotensinase activity is asymmetrically distributed in the amygdala, hippocampus and prefrontal cortex of the rat
Behav. Brain Res.
156
321-326
2005
Rattus norvegicus
Pilar Carrera, M.; Ramirez-Exposito, M.J.; Duenas, B.; Dolores Mayas, M.; Jesus Garcia, M.; de la Chica, S.; Cortes, P.; Ruiz-Sanjuan, M.; Martinez-Martos, J.M.
Insulin-regulated aminopeptidase/placental leucil Aminopeptidase (IRAP/P-lAP) and angiotensin IV-forming activities are modified in serum of rats with breast cancer induced by N-methyl-nitrosourea
Anticancer Res.
26
1011-1014
2006
Rattus norvegicus
Tsujimoto, M.; Hattori, A.
The oxytocinase subfamily of M1 aminopeptidases
Biochim. Biophys. Acta
1751
9-18
2005
Homo sapiens, Rattus norvegicus
Alponti, R.F.; Zambotti-Villela, L.; Murena-Nunes, C.; Marinho, C.E.; do Amaral Olivo, R.; Silveira, P.F.
Cystyl aminopeptidase activity in the plasma, viscera and brain of the snake Bothrops jararaca
Comp. Biochem. Physiol. A
141
336-352
2005
Bothrops jararaca, Rattus norvegicus
Nomura, S.; Tsujimoto, M.; Mizutani, S.
Cystinyl aminopeptidase, oxytocinase and insulin-regulated aminopeptidase
Handbook of proteolytic enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. ) Academic Press
1
307-311
2004
Homo sapiens, Rattus norvegicus
-
Fernando, R.N.; Larm, J.; Albiston, A.L.; Chai, S.Y.
Distribution and cellular localization of insulin-regulated aminopeptidase in the rat central nervous system
J. Comp. Neurol.
487
372-390
2005
Rattus norvegicus
Stragier, B.; Sarre, S.; Vanderheyden, P.; Vauquelin, G.; Fournie-Zaluski, M.C.; Ebinger, G.; Michotte, Y.
Metabolism of angiotensin II is required for its in vivo effect on dopamine release in the striatum of the rat
J. Neurochem.
90
1251-1257
2004
Rattus norvegicus
Chai, S.Y.; Fernando, R.; Ye, S.; Peck, G.R.; Albiston, A.L.
Insulin-regulated aminopeptidase
Proteases in Biology and Disease (Hooper, N. M. ; Lendeckel, U. , eds. ) Springer
2
61-81
2004
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
-
Liao, H.; Keller, S.R.; Castle, J.D.
Insulin-regulated aminopeptidase marks an antigen-stimulated recycling compartment in mast cells
Traffic
7
155-167
2006
Rattus norvegicus
Zambotti-Villela, L.; Yamasaki, S.C.; Villarroel, J.S.; Murena-Nunes, C.; Silveira, P.F.
Prolyl, cystyl and pyroglutamyl peptidase activities in the hippocampus and hypothalamus of streptozotocin-induced diabetic rats
Peptides
28
1586-1595
2007
Rattus norvegicus
de la Chica-Rodriguez, S.; Cortes-Denia, P.; Ramirez-Exposito, M.J.; Martinez-Martos, J.M.
Effects of alpha1-adrenergic receptor blockade by doxazosin on renin-angiotensin system-regulating aminopeptidase and vasopressin-degrading activities in male and female rat thalamus
Horm. Metab. Res.
39
813-817
2007
Rattus norvegicus
Takeuchi, M.; Itakura, A.; Okada, M.; Mizutani, S.; Kikkawa, F.
Impaired insulin-regulated membrane aminopeptidase translocation to the plasma membrane in adipocytes of Otsuka Long Evans Tokushima Fatty rats
Nagoya J. Med. Sci.
68
155-163
2006
Rattus norvegicus
De Bundel, D.; Demaegdt, H.; Lahoutte, T.; Caveliers, V.; Kersemans, K.; Ceulemans, A.G.; Vauquelin, G.; Clinckers, R.; Vanderheyden, P.; Michotte, Y.; Smolders, I.
Involvement of the AT1 receptor subtype in the effects of angiotensin IV and LVV-haemorphin 7 on hippocampal neurotransmitter levels and spatial working memory
J. Neurochem.
112
1223-1234
2010
Rattus norvegicus
Tobin, V.A.; Arechaga, G.; Brunton, P.J.; Russell, J.A.; Leng, G.; Ludwig, M.; Douglas, A.J.
Oxytocinase in the female rat hypothalamus: a novel mechanism controlling oxytocin neurones during lactation
J. Neuroendocrinol.
26
205-216
2014
Rattus norvegicus (P97629)
Abrahao, M.V.; Dos Santos, N.F.T.; Kuwabara, W.M.T.; do Amaral, F.G.; do Carmo Buonfiglio, D.; Peres, R.; Vendrame, R.F.A.; Flavio da Silveira, P.; Cipolla-Neto, J.; Baltatu, O.C.; Afeche, S.C.
Identification of insulin-regulated aminopeptidase (IRAP) in the rat pineal gland and the modulation of melatonin synthesis by angiotensin IV
Brain Res.
1704
40-46
2019
Rattus norvegicus (P97629)
Ruixadz-Sanjuan, M.; Martinez-Martos, J.; Carrera-Gonzalez, M.; Mayas, M.; Garcia, M.; Arrazola, M.; Ramirez-Exposito, M.
Normolipidic dietary fat modifies circulating renin-angiotensin system-regulating aminopeptidase activities in rat with breast cancer
Integr. Cancer Ther.
14
149-155
2015
Rattus norvegicus (P97629)
-
Alponti, R.F.; Viana, L.G.; Yamanouye, N.; Silveira, P.F.
Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by obesity
J. Mol. Endocrinol.
55
1-8
2015
Rattus norvegicus (P97629), Rattus norvegicus Wistar (P97629)
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
J. Neurosci.
35
11960-11975
2015
Rattus norvegicus (P97629), Rattus norvegicus Wistar (P97629)
Prieto, I.; Villarejo, A.B.; Segarra, A.B.; Wangensteen, R.; Banegas, I.; de Gasparo, M.; Vanderheyden, P.; Zorad, S.; Vives, F.; Ramirez-Sanchez, M.
Tissue distribution of CysAP activity and its relationship to blood pressure and water balance
Life Sci.
134
73-78
2015
Rattus norvegicus (P97629), Rattus norvegicus Wistar-Kyoto (P97629)
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