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Information on EC 3.4.11.3 - cystinyl aminopeptidase and Organism(s) Mus musculus and UniProt Accession Q8C129
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3.4.11.3 cystinyl aminopeptidaseSpecify your search results
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- 3.4.11.3
- envelope
- pregnancy
- cd4
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- lymphocyte
- angiotensin
- vaccinia
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- aminopeptidases
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hiv-1-infected
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humoral
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immunodominant
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vaccine-induced
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glut4-containing
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hiv-seronegative
- desmopressin
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ddavp
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hiv-1iiib
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anti-cd4
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intrarectal
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sivmac239
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alum
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1-infected
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non-neutralizing
- diagnostics
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oligosaccharyltransferase
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virus-neutralizing
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cross-neutralizing
- pharmacology
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coreceptors
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cross-presentation
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nephrogenic
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radioimmunoprecipitation
The taxonomic range for the selected organisms is: Mus musculus
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, insulin-responsive aminopeptidase, 
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
-
-
-
-
Insulin-responsive aminopeptidase
-
-
-
-
IRAP
-
-
-
-
oxytocinase
-
-
-
-
P-LAP
-
-
-
-
Placental leucine aminopeptidase
-
-
-
-
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
vasopressin + H2O
hydrolyzed vasopressin
-
vasopressin is a physiological substrate
N-terminal processing
-
?
additional information
?
-
recombinant IRAP bound to TUG, and this interaction is mapped to a short peptide in IRAP which is critical for GLUT4 intracellular retention. TUG controls vesicle translocation by interacting with IRAP as well as GLUT4
-
-
?
additional information
?
-
-
recombinant IRAP bound to TUG, and this interaction is mapped to a short peptide in IRAP which is critical for GLUT4 intracellular retention. TUG controls vesicle translocation by interacting with IRAP as well as GLUT4
-
-
?
additional information
?
-
-
IRAP is required for maintenance of key constituents of endosome-derived vesicles in cardiac muscle cells
-
-
?
additional information
?
-
-
IRAP is involved in glucose transporter GLUT4 storage vesicle trafficking
-
-
?
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
vasopressin + H2O
hydrolyzed vasopressin
-
vasopressin is a physiological substrate
N-terminal processing
-
?
additional information
?
-
recombinant IRAP bound to TUG, and this interaction is mapped to a short peptide in IRAP which is critical for GLUT4 intracellular retention. TUG controls vesicle translocation by interacting with IRAP as well as GLUT4
-
-
?
additional information
?
-
-
recombinant IRAP bound to TUG, and this interaction is mapped to a short peptide in IRAP which is critical for GLUT4 intracellular retention. TUG controls vesicle translocation by interacting with IRAP as well as GLUT4
-
-
?
additional information
?
-
-
IRAP is required for maintenance of key constituents of endosome-derived vesicles in cardiac muscle cells
-
-
?
additional information
?
-
-
IRAP is involved in glucose transporter GLUT4 storage vesicle trafficking
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
inhibitory potency in decreasing order: angiotensin IV, angiotensin III, divalinal/angiotensin IV, LVV-hemorphin 7, angiotensin 4-8, angiotensin III
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
T-tubule-enriched membrane fractions from quadriceps muscles isolated of fasting mice
-
immunodetection of enzyme with large 100-200 nm vesicles in hippocampal neurons
-
P-LAP is located in the periphery in early gestation, located in both the periphery and inner cells during mid-gestation, located only in inner cells in late gestation
-
among hematopoietic cells in fetal liver only megakaryocytes show strong expression of P-LAP
-
treatment with cyclosporin increases the activity of cystyl aminopeptidase as well as neutral, basic, prolyl imino and pyroglutamyl soluble aminopeptidase in the renal cortex
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
TUG regulates IRAP cell surface targeting in 3T3-L1 adipocytes
in adipose and muscle cells, insulin stimulates the exocytic translocation of vesicles containing GLUT4, a glucose transporter, and insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. TUG regulates IRAP cell surface targeting in 3T3-L1 adipocytes
-
insulin-stimulated translocation of IRAP remains intact despite substantial knock-down of glucose transporter GLUT4. By contrast, insulin-stimulated GLUT4 translocation is impaired upon IRAP knock-down. Tankyrase knock-down alters the basal partitioning of GLUT4 and IRAP within endosomal compartments
-
enzyme is enriched in low density microsome, and exhibits lower levels in high density microsomes. Co-localization with the vesicular marker VAMP2
-
-
after exposure of 3T3-L1 adipocytes to insulin, IRAP translocates to the plasma membrane
-
comparison of enzyme activity in membranes of COS-7 cells, HEK-293 cells, SK-N-MC cells, CHO-K1 cells and MDBK cells. Comparatively, CHO-K1 cells display the highest level of enzyme. In all cell types, the enzyme predominates over aminopeptidase N
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
insulin stimulates the exocytic translocation of vesicles containing GLUT4 glucose transporters and insulin-regulated aminopeptidase (IRAP). Insulin acts through TUG proteins to control IRAP targeting, similar to GLUT4, the activity of vasopressin, an IRAP substrate, is reduced in mice with disrupted TUG action in muscle. TUG regulates vasopressin action. Exocytic translocation of vesicles in muscle coordinates vasopressin inactivation by IRAP with glucose uptake
physiological function
the enzyme inactivates vasopressin in the muscle and adipose tissue regulated by TUG. Vasopressin regulates water permeability in the renal collecting system by both minute-to-minute effects on AQP2 targeting and hour-to-daylong effects on AQP2 abundance. Recombinant IRAP binds to TUG, and this interaction is mapped to a short peptide in IRAP that is critical for GLUT4 intracellular retention
additional information
insulin-responsive aminopeptidase (IRAP) is identified as an S-acylated protein in adipocytes and other tissues, semi-quantitative acyl-RAC technique shows that approximately 60% of IRAP is S-acylated in 3T3-L1 adipocytes
malfunction
in IRAP knockout mice, the half-life of circulating vasopressin is increased 3fold, and plasma concentrations are increased 2fold. Transgenic mice with constitutive TUG proteolysis in muscle consume much more water than wild-type control mice. The transgenic mice lose more body weight during water restriction, and the abundance of renal AQP2 water channels is reduced, implying that vasopressin activity is decreased. To compensate for accelerated vasopressin degradation, vasopressin secretion is increased, as assessed by the cosecreted protein copeptin. IRAP abundance is increased in T-tubule fractions of fasting transgenic mice, when compared with controls
malfunction
protein S-acylation (also referred to as palmitoylation) is a post-translational modification (PTM) involving the attachment of palmitate and other fatty acids to cysteine residues of proteins via thioester linkage, no effects of mutating the modified cysteines on the plasma membrane localisation of IRAP in transfected HEK-293T cells are detected
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_MOUSE
1025
1
117304
Swiss-Prot
other Location (Reliability: 1)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S-acylation
insulin-responsive aminopeptidase (IRAP) is identified as an S-acylated protein in adipocytes and other tissues, semi-quantitative acyl-RAC technique shows that approximately 60% of IRAP is S-acylated in 3T3-L1 adipocytes, palmitoylation. Mapping of the sites of S-acylation on IRAP to two cysteine residues, one of which is predicted to lie in the cytoplasmic side of the single transmembrane domain and the other which is just upstream of this transmembrane domain, these cysteines, C103, and C114, may be modified in a mutually-exclusive manner. Although S-acylation regulates the intracellular trafficking of several transmembrane proteins, no effects of mutating the modified cysteines on the plasma membrane localisation of IRAP in transfected HEK-293T cells are detected, suggesting that S-acylation is not essential for the movement of IRAP through the secretory pathway
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C103A/C114A
no effects of mutating the modified cysteines on the plasma membrane localisation of IRAP in transfected HEK-293T cells are detected. Combined mutation of both C103A and C114A leads to a complete loss of IRAP S-acylation
C35A/C103A/C114A
no effects of mutating the modified cysteines on the plasma membrane localisation of IRAP in transfected HEK-293T cells are detected. Combined mutation of both C103A and C114A leads to a complete loss of IRAP S-acylation
L76A/L77A
-
mutation results in rapid default of the enzyme to the cell surface. In presence of a dominant interfering mutant of clathrin adaptor GGA1, insulin-stimulated translocation of wild-type enzyme, but not of mutant L76A/L77A is inhibited
additional information
additional information
construction of IRAP knockout mice, phenotype, overview
additional information
-
construction of IRAP knockout mice, phenotype, overview
additional information
-
adipocytes and skeletal muscle cells of IRAP-/- mice do not process vasopressin and oxytocin from their N-terminus. In IRAP-/- mice, plasma vasopressin level is elevated twofold and vasopressin levels in mutant mice brains show a compensatory decrease
additional information
-
alanine-substitution of 9 residues amino- or carboxy-terminal to the dileucine motif at positions 76, 77 does not perturb basal intracellular sequestration of the enzyme
additional information
-
IRAP knockout mice with an accelerated, age-realted decline in spatial memory
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of HA-tagged wild-type and mutant enzymes in HEK-293T cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Garza, L.A.; Birnbaum, M.J.
Insulin-responsive aminopeptidase trafficking in 3T3-L1 adipocytes
J. Biol. Chem.
275
2560-2567
2000
Mus musculus
Kobayashi, H.; Nomura, S.; Mitsui, T.; Ito, T.; Kuno, N.; Ohno, Y.; Kadomatsu, K.; Muramatsu, T.; Nagasaka, T.; Mizutani, S.
Tissue distribution of placental leucine aminopeptidase/oxytocinase during mouse pregnancy
J. Histochem. Cytochem.
52
113-121
2004
Mus musculus
Abel, E.D.; Graveleau, C.; Betuing, S.; Pham, M.; Reay, P.A.; Kandror, V.; Kupriyanova, T.; Xu, Z.; Kandror, K.V.
Regulation of insulin-responsive aminopeptidase expression and targeting in the insulin-responsive vesicle compartment of glucose transporter isoform 4-deficient cardiomyocytes
Mol. Endocrinol.
18
2491-2501
2004
Mus musculus
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
-
Marinho, C.E.; Olivo, R.d.o.A.; Zambotti-Villela, L.; Ribeiro-de-Andrade, T.N.; Fernandes, C.M.; Silveira, P.F.
Renal and macrophage aminopeptidase activities in cyclosporin-treated mice
Int. Immunopharmacol.
6
415-425
2006
Mus musculus
Wallis, M.G.; Lankford, M.F.; Keller, S.R.
Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP
Am. J. Physiol. Endocrinol. Metab.
293
E1092-E1102
2007
Mus musculus
Yeh, T.Y.; Sbodio, J.I.; Tsun, Z.Y.; Luo, B.; Chi, N.W.
Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase
Biochem. J.
402
279-290
2007
Mus musculus
Demaegdt, H.; Lenaerts, P.J.; Swales, J.; De Backer, J.P.; Laeremans, H.; Le, M.T.; Kersemans, K.; Vogel, L.K.; Michotte, Y.; Vanderheyden, P.; Vauquelin, G.
Angiotensin AT4 receptor ligand interaction with cystinyl aminopeptidase and aminopeptidase N: [125I]angiotensin IV only binds to the cystinyl aminopeptidase apo-enzyme
Eur. J. Pharmacol.
546
19-27
2006
Bos taurus, Cricetulus griseus, Homo sapiens, Mus musculus
Hou, J.C.; Suzuki, N.; Pessin, J.E.; Watson, R.T.
A specific dileucine motif is required for the GGA-dependent entry of newly synthesized insulin-responsive aminopeptidase into the insulin-responsive compartment
J. Biol. Chem.
281
33457-33466
2006
Mus musculus
Fernando, R.N.; Luff, S.E.; Albiston, A.L.; Chai, S.Y.
Sub-cellular localization of insulin-regulated membrane aminopeptidase, IRAP to vesicles in neurons
J. Neurochem.
102
967-976
2007
Homo sapiens, Mus musculus
Weiland, F.; Verspohl, E.J.
Local formation of angiotensin peptides with paracrine activity by adipocytes
J. Pept. Sci.
15
767-776
2009
Mus musculus
Albiston, A.L.; Fernando, R.N.; Yeatman, H.R.; Burns, P.; Ng, L.; Daswani, D.; Diwakarla, S.; Pham, V.; Chai, S.Y.
Gene knockout of insulin-regulated aminopeptidase: loss of the specific binding site for angiotensin IV and age-related deficit in spatial memory
Neurobiol. Learn Mem.
93
19-30
2010
Mus musculus
Habtemichael, E.N.; Alcazar-Roman, A.; Rubin, B.R.; Grossi, L.R.; Belman, J.P.; Julca, O.; Loeffler, M.G.; Li, H.; Chi, N.W.; Samuel, V.T.; Bogan, J.S.
Coordinated regulation of vasopressin inactivation and glucose uptake by action of TUG protein in muscle
J. Biol. Chem.
290
14454-14461
2015
Mus musculus (Q8C129), Mus musculus, Mus musculus C57BL/6J (Q8C129)
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