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Information on EC 3.4.19.6 - pyroglutamyl-peptidase II
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3.4.19.6 pyroglutamyl-peptidase IISpecify your search results
Word Map
- 3.4.19.6
- pituitary
- adenohypophyseal
- hypothalamic
- adenohypophysis
- tsh
-
paraventricular
-
ectopeptidase
-
lactotrophs
-
trh-r1
-
trhergic
-
eminence
- tanycytes
-
deiodinase
-
hypothalamus-pituitary-thyroid
-
peptidergic
-
trh-receptor
-
mediobasal
-
hypophysiotropic
-
trh-induced
- medicine
-
trh-like
- nutrition
The enzyme appears in viruses and cellular organisms
Reaction Schemes
release of the N-terminal pyroglutamyl group from pGlu-/-His-Xaa tripeptides and pGlu-/-His-Xaa-Gly tetrapeptides
Synonyms
pyroglutamyl peptidase ii, trh-de, trh-degrading ectoenzyme, trh-degrading enzyme, pyroglutamyl aminopeptidase ii, pyroglutamate aminopeptidase ii, thyroliberinase, pap type ii, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminopeptidase, thyrotropin-releasing factor pyroglutamate
-
-
-
-
PPII
pyroglutamate aminopeptidase II
-
-
-
-
pyroglutamyl aminopeptidase II
-
-
-
-
pyroglutamyl peptidase II
thyroliberin-hydrolyzing pyroglutamate aminopeptidase
-
-
-
-
thyroliberinase
thyrotropin-releasing hormone-degrading peptidase
-
-
-
-
thyrotropin-releasing hormone-degrading pyroglutamate aminopeptidase
-
-
-
-
TRH aminopeptidase
-
-
-
-
TRH-DE
TRH-degrading ectoenzyme
TRH-specific aminopeptidase
-
-
-
-
PPII
-
-
-
-
pyroglutamyl peptidase II
-
-
-
-
thyroliberinase
-
-
-
-
TRH-DE
-
-
-
-
TRH-degrading ectoenzyme
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of the N-terminal pyroglutamyl group from pGlu-/-His-Xaa tripeptides and pGlu-/-His-Xaa-Gly tetrapeptides
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
60063-88-9
-
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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
L-pyroglutamyl-beta-naphthylamide + H2O
L-pyroglutamate + 2-naphthylamine
-
-
-
?
pyroglutamyl-7-amido-4-methylcoumarin + H2O
pyroglutamate + 7-amino-4-methylcoumarin
-
-
-
-
?
pyroglutamyl-Asn(N-benzyl)-ProNH2 + H2O
L-pyroglutamate + Asn(N-benzyl)-ProNH2
-
-
-
-
?
pyroglutamyl-Asn(N-methyl)-ProNH2 + H2O
L-pyroglutamate + Asn(N-methyl)-ProNH2
-
-
-
-
?
pyroglutamyl-His-Pro-7-amido-4-methylcoumarin + H2O
pyroglutamate + His-Pro-7-amido-4-methylcoumarin
pyroglutamyl-His-tripeptidyl naphthylamides + H2O
pyroglutamate + His-tripeptidyl naphthylamides
-
-
-
-
?
pyroglutamyl-histidyl-prolyl-7-amido-4-methylcoumarin + H2O
pyroglutamic acid + histidyl-prolyl-7-amido-4-methylcoumarin
-
-
-
-
?
pyroglutamyl-thienylalanyl-Pro-NH2 + H2O
pyroglutamate + thienylalanyl-Pro-NH2
-
-
-
-
?
thyrotropin releasing hormone-beta-naphthylamine + H2O
?
-
substrate activity assay
-
-
?
thyrotropin-releasing hormone-beta-naphthylamide + H2O
?
-
essential role of Glu408 within the exopeptidase motif for aminopeptidase activity. Ser269 and Lys463 are implicated in the generation of omegapeptidase specificity. Lys463 creates a putative salt bridge with Glu408
-
-
?
L-5-oxoprolyl 2-naphthylamide + H2O
2-naphthylamine + 5-oxoproline
-
very poor substrate
-
?
L-5-oxoprolyl 2-naphthylamide + H2O
2-naphthylamine + 5-oxoproline
-
very poor substrate
-
?
pyroglutamyl-His-Pro-7-amido-4-methylcoumarin + H2O
pyroglutamate + His-Pro-7-amido-4-methylcoumarin
-
-
-
-
?
pyroglutamyl-His-Pro-7-amido-4-methylcoumarin + H2O
pyroglutamate + His-Pro-7-amido-4-methylcoumarin
-
-
-
-
?
thyroliberin + H2O
?
-
may control the biological activity of the neuronally released thyrotropin
-
-
?
thyroliberin + H2O
?
-
involved in the conversion of thyrotropin-releasing hormone into histidyl-proline diketopiperazine
-
-
?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
-
i.e. pyroglutamyl-His-Pro-NH2, thyrotropin-releasing hormone
-
-
?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
-
i.e. pyroglutamyl-His-Pro-NH2, thyrotropin-releasing hormone
pyroglutamic acid + histidyl-proline diketopiperazine
?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
-
rapid stereospecific cleavage only of the pyroglutamyl-histidine bond of thyroliberin and closely related peptides
-
?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
-
cleavage at the pyroglutamyl-histidine bond
-
-
?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
-
i.e. pyroglutamyl-His-Pro-NH2, thyrotropin-releasing hormone
-
-
?
additional information
?
-
-
no hydrolysis of pyroglutamyl peptides containing more than three amino acids
-
-
?
additional information
?
-
-
specific for tripeptides, tripeptide-amides, and tetrapeptides possessing the N-terminal sequence pyroglutamyl-His and as such is specific for thyrotropin releasing hormone or only very closely related peptides
-
-
?
additional information
?
-
-
no hydrolysis of dipeptides containing N-terminal pyroglutamic acid
-
-
?
additional information
?
-
-
no hydrolysis of pyroglutamyl-His decapeptide LHRH
-
-
?
additional information
?
-
-
no hydrolysis of ring opened Glu1-thyrotropin
-
-
?
additional information
?
-
-
no hydrolysis of pyroglutamyl-His-Pro-Ala naphthylamide
-
-
?
additional information
?
-
-
no hydrolysis of pyroglutamyl-His bond of the dipeptide pyroglutamyl-His naphthylamide
-
-
?
additional information
?
-
-
detection of a RNA species derived from an alternative processing at the exon 14intron 14 boundary. The alternatively processed RNA encodes a shorter version of PPII (PPII*), lacking part of the C-terminal domain. PPII* is expressed in COS-7 (or C6 glioma) cells but it does not exhibit any PPII activity. Co-transfection of PPII and increasing amounts of PPII* expression vectors results in a dose-dependent reduction in PPII activity and the formation of covalent PPIIPPII* heterodimers. PPII* is therefore a powerful dominant-negative isoform of PPII, and heterodimerization may be its mechanism of action. Natural expression of shortened versions of M1 aminopeptidases may constitute a new mode of regulation of their activity
-
-
?
additional information
?
-
-
hydrolyzing of substrates with the general structure pGlu-X-Y, X being a moderately bulky and uncharged residue and Y, either Pro, Ala, Trp, Pro-Gly, ProNH2, Pro-beta-naphthylamine, or Pro-7-amino-4-methyl coumarin
-
-
?
additional information
?
-
-
moderately bulky, uncharged P1' residues preferentially bind to the enzyme
-
-
?
additional information
?
-
-
no hydrolysis of pyroglutamyl-Ala or pyroglutamyl 2-naphthylamide (known substrates of the serum enzyme)
-
-
?
additional information
?
-
-
no hydrolysis of thyroliberin analogues LLD-thyroliberin, pyroglutamyl-His-Pro-NHCH3, pyroglutamyl-His-Pro-Gly-NHCH3 or pyroglutamyl-Phe-Pro-NH2
-
-
?
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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
?
-
-
detection of a RNA species derived from an alternative processing at the exon 14intron 14 boundary. The alternatively processed RNA encodes a shorter version of PPII (PPII*), lacking part of the C-terminal domain. PPII* is expressed in COS-7 (or C6 glioma) cells but it does not exhibit any PPII activity. Co-transfection of PPII and increasing amounts of PPII* expression vectors results in a dose-dependent reduction in PPII activity and the formation of covalent PPIIPPII* heterodimers. PPII* is therefore a powerful dominant-negative isoform of PPII, and heterodimerization may be its mechanism of action. Natural expression of shortened versions of M1 aminopeptidases may constitute a new mode of regulation of their activity
-
-
?
thyroliberin + H2O
?
-
may control the biological activity of the neuronally released thyrotropin
-
-
?
thyroliberin + H2O
?
-
involved in the conversion of thyrotropin-releasing hormone into histidyl-proline diketopiperazine
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CoSO4
-
161% enhancement of activity at 0.1 mM and 559% enhancement at 1 mM. 1 mM, 587% reactivation of the enzyme inactivated by EDTA
Zn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-(2-aminoethyl)-benzenesulfonylfluoride
-
66% inhibition at 1 mM, 97% inhibition at 10 mM
Glp-Asn-Pro-D-Tyr-D-TrpNH2
-
potent inhibitor of TRH-DE. Competetive, fully reversible and not time dependent inhibition
Thyroliberin analogues
-
LLD-thyroliberin, pyroglutamyl-His-Pro-NHCH3, pyroglutamyl-His-Pro-Gly-NHCH3, pyroglutamyl-Phe-Pro-NH2
-
Glp-PSI[P(O)(OH)CH2]-His-Pro-NH2
-
phosphinic analogue of thyrotropin releasing hormone, ED50 170 nM
Glp-PSI[P(O)(OH)CH2]-His-Pro-NH2
-
phosphinic analogue of thyrotropin releasing hormone
Hermodice carunculata inhibitor
-
the inhibitor is found in Hermodice carunculata and purified, MW below 1000 Da, the inhibitor is not a peptide
-
additional information
-
no inhibition by aspartyl protease inhibitors; no inhibition by cysteine protease inhibitors; no inhibition by serine protease inhibitors
-
additional information
-
no inhibition by bacitracin; no inhibition by puromycin
-
additional information
-
PPII inhibitory activity als detected in Phallusia nigra, Palythoa caribaeorum and Mycale microsigmatosa
-
additional information
-
expression of PPII is downregulated in amygdala of yoked rats (immersed in a tank with no platform or spatial cues) and rats trained to find a hidden platform in water after 5 min of day 1 and 5. In hippocampus, no significant variations are observed for PPII expression at any time
-
additional information
-
no inhibition by NEM; no inhibition by serine protease inhibitors; no inhition by 2-iodoacetamide
-
additional information
-
no inhibition by chlordiazepoxide; no inhibition by DTNB; no inhibition by NEM; no inhibition by pepstatin; no inhition by 2-iodoacetamide
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DMSO
-
activity using substrates containing 2% v/v DMSO is 5% higher than that using substrate containing no DSMO
additional information
-
no requirement for sulfhydryl-reducing agents
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenoma
Analysis of thyrotropin-releasing hormone-signaling components in pituitary adenomas of patients with acromegaly.
Hyperthyroidism
Thyroid status regulates particulate but not soluble TRH-degrading pyroglutamate aminopeptidase activity in the rat liver.
Hypothyroidism
Minireview: the neural regulation of the hypothalamic-pituitary-thyroid axis.
Liver Diseases
Turnover of thyrotropin-releasing hormone in patients with chronic renal failure and chronic alcoholic liver disease.
Retinoblastoma
Inhibition of pyroglutamyl peptidase II synthesis by phorbol ester in the Y-79 retinoblastoma cell.
Retinoblastoma
Occurrence of pyroglutamyl peptidase II, a specific TRH degrading enzyme in rabbit retinal membranes and in human retinoblastoma cells.
Retinoblastoma
Rapid inactivation and phosphorylation of pyroglutamyl peptidase II in Y-79 human retinoblastoma cells after exposure to phorbol ester.
Starvation
Neonatal Maternal Separation Alters, in a Sex-Specific Manner, the Expression of TRH, of TRH-Degrading Ectoenzyme in the Rat Hypothalamus, and the Response of the Thyroid Axis to Starvation.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00679
thyrotropin-releasing hormone-beta-naphthylamide
-
mutant enzyme S269A
0.00942
thyrotropin-releasing hormone-beta-naphthylamide
-
wild-type enzyme
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000029
Glp-Asn-Pro-D-Tyr-D-Trp-D-Trp-7-amido-4-methyl-coumarin
-
-
0.00097
pyroglutamyl-Asn-Pro-7-amido-4-methyl coumarin
-
pH 7.5, 37°C, hydrolysis of pyroglutamyl-His-Pro-7-amido-4-methylcoumarin
0.0175
pyroglutamyl-Asn-Pro-NH2
-
pH 7.5, 37°C, hydrolysis of pyroglutamyl-His-Pro-7-amido-4-methylcoumarin
0.069
pyroglutamyl-Gln-Pro-NH2
-
pH 7.5, 37°C, hydrolysis of pyroglutamyl-His-Pro-7-amido-4-methylcoumarin
0.5
pyroglutamyl-homoprolyl-Pro-NH2
-
pH 7.5, 37°C, hydrolysis of pyroglutamyl-His-Pro-7-amido-4-methylcoumarin
0.356
pyroglutamyl-L-alpha-phenylglycyl-Pro-NH2
-
pH 7.5, 37°C, hydrolysis of pyroglutamyl-His-Pro-7-amido-4-methylcoumarin
0.232
pyroglutamyl-Trp-Pro-NH2
-
pH 7.5, 37°C, hydrolysis of pyroglutamyl-His-Pro-7-amido-4-methylcoumarin
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.7 - 8.5
-
pH 5.7: about 35% of maximal activity, pH 8.5: about 45% of maximal activity
5.8 - 8.4
-
pH 5.8: about 45% of maximal activity, pH 8.4: about 20% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 56
-
25°C: 16% of maximal activity, 37°C: 70% of maximal activity, 45°C: maximal activity
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
orchidectomy increases activity of pyrrolidone carboxypeptidase type II, testosterone replacement returns it to control levels
brenda
12 to 14% of cell profiles express pyroglutamyl peptidase II mRNA in the medial septum-diagonal band of Broca, in this region the specific activity of the enzyme is relatively high. Injection of the pyroglutamyl peptidase II inhibitor p-Glu-Asn-Pro-7-amido-4-methylcoumarin into the medial septum enhances the effect of thyrotropin-releasing hormone. The injection of a phosphinic thyrotropin-releasing hormone analog, a higher affinity inhibitor of pyroglutamyl peptidase II, diminishes the duration of ethanol-induced loss of righting reflex by itself
brenda
additional information
-
expression of wild-type and mutant enzymes in COS-7 cells and C6 glioma
brenda
-
changes in enzyme activity caused by kindling relate to regulation of the expression of TRH receptors and degrading enzyme
brenda
-
no change in pyrrolidone carboxypeptidase type II after orchidectomy, activity increases after administration of testosterone
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the physicochemical properties are distinct from the soluble enzyme
-
brenda
-
the physicochemical properties are distinct from the particulate enzyme
-
brenda
soluble and membrane-bound forms. Membrane-bound activity is highest in kidney, heart (atrium and ventricle) and liver, the lowest activities is observed in testis and lung
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
metabolism
fasting enhances pyroglutamyl peptidase II activity in tanycytes of the mediobasal hypothalamus of male adult rats
metabolism
high cholesterol intake modifies pyroglutamyl aminopeptidase activity in serum and different tissues of male and female mice. High cholesterol alters the regulation of this activity on their specific biologically active peptide substrates, mainly TRH and TRH-like peptides, and modifies their specific functions on target organs. Cholesterol administration in females significantly increases membrane-bound pyroglutamyl aminopeptidase-specific activity in liver by 62.03%, but significantly decreases activity in atrium by 56.56%
metabolism
long-term changes in dietary Zn down-regulate pyroglutamyl aminopeptidase II activity independently of triiodothyronine, increasing thyrotropin serum concentration, overall resembling sub-clinical hypothyroidism
physiological function
in the medial septum pyroglutamyl peptidase II activity may limit thyrotropin-releasing hormone action, presumably by reducing the concentration of thyrotropin-releasing hormone in the extracellular fluid around cells coexpressing pyroglutamyl peptidase II and thyrotropin-releasing hormone-receptor 1
physiological function
-
thyrotropin releasing hormone regulates action potential shape in pyramidal cortical neurons, and degrading enzyme pyroglutamyl peptidase II controls its action in this region
physiological function
pyroglutamyl peptidase II is a thyrotropin releasing hormone (TRH)-degrading ectoenzyme that controls the amount of TRH that reaches the anterior pituitary
physiological function
the enzyme degrades thyrotropin-releasing hormone (TRH) released from the median eminence and participates in hypothalamus-pituitary-thyroid (HPT) axis function by regulating TRH-induced thyrotropin release from adenohypophysis
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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). TRHDE_HUMAN
1024
1
117000
Swiss-Prot
other Location (Reliability: 3)
TRHDE_MOUSE
1025
1
117458
Swiss-Prot
other Location (Reliability: 3)
TRHDE_RAT
1025
1
117287
Swiss-Prot
other Location (Reliability: 3)
B4PIY4_DROYA
223
0
24851
TrEMBL
other Location (Reliability: 3)
B4L128_DROMO
219
0
24330
TrEMBL
other Location (Reliability: 3)
B4LGU4_DROVI
221
0
24421
TrEMBL
other Location (Reliability: 3)
B3NHN5_DROER
223
0
24787
TrEMBL
other Location (Reliability: 2)
Q2M1A3_DROPS
223
0
24462
TrEMBL
other Location (Reliability: 2)
A0A0Q9XC53_DROMO
259
0
29143
TrEMBL
Mitochondrion (Reliability: 2)
G3H4Q4_CRIGR
239
0
27394
TrEMBL
other Location (Reliability: 1)
B3M732_DROAN
225
0
24512
TrEMBL
other Location (Reliability: 3)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
116000
230000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
additional information
-
a number of protein bands varying in MW from 55000 to 141000 Da are detected by SDS-PAGE
additional information
-
proteolytically truncated and enzymatically fully active enzyme consists of two subunits that are associated noncovalently by protein-protein interactions but not via S-S bridges
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
the brain enzyme contains a oligomannose/hybrid glycostructure, the serum and the liver enzyme belong to the groups of glycoproteins with a glycostructure of the complex type, carbohydrate content of the liver enzyme is 22%, the carbohydrate content of the brain enzyme is 16%
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C279S
-
specific activity is 10fold lower than that of the wild-type enzyme
C68S
-
specific enzymatic activities are similar to that of the wild-type enzyme
K463N
-
mutant losses omega-peptidase but displays alanyl-aminopeptidase activity
S269A
-
mutant shows a 40% decrease in activity with thyrotropin-releasing hormone-beta-naphthylamide as substrate
S269E
-
mutant is inactive with thyrotropin-releasing hormone-beta-naphthylamide as substrate
S269Q
-
mutant is inactive with thyrotropin-releasing hormone-beta-naphthylamide as substrate
S269Q/K463N
-
mutant is inactive with thyrotropin-releasing hormone-beta-naphthylamide as substrate
S269Q/K463R
-
mutant is inactive with thyrotropin-releasing hormone-beta-naphthylamide as substrate
additional information
-
detection of a RNA species derived from an alternative processing at the exon 14intron 14 boundary. The alternatively processed RNA encodes a shorter version of PPII (PPII*), lacking part of the C-terminal domain. PPII* is expressed in COS-7 (or C6 glioma) cells but it does not exhibit any PPII activity. Co-transfection of PPII and increasing amounts of PPII* expression vectors results in a dose-dependent reduction in PPII activity and the formation of covalent PPIIPPII* heterodimers. PPII* is therefore a powerful dominant-negative isoform of PPII, and heterodimerization may be its mechanism of action. Natural expression of shortened versions of M1 aminopeptidases may constitute a new mode of regulation of their activity
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
1% w/v bovine serum albumin greatly improves stability with 88% of the activity remaining after 4 days at 4°C and 93% of the activity remaining after 21 days at -80°C
-
addition of 20% v/v glyceriol affords no protection of the enzyme stored at 4°C and only moderate protection at -20°C and -80°C
-
after one cycle of freezing at -80°C and thawing, the activity of the purified enzyme preparation containing 0.3, 0.1, 0.03 or 0.01 mg protein/ml decreases by 18%, 36%, 73% and 99%, respectively
-
below a critical protein concentration of 1 mg/ml the enzyme is sensitive to freezing and thawing
-
inclusion of 50% glycerol prevents most of the harmful effect of freezing in imidazole buffer
-
presence of bovine serum albumin, 1%, sucrose, glycerol or trehalose prevents inactivation during freezing and thawing
-
trypsin is the most effective protease, above 0.001 mg/ml, the solubilized enzyme st stable for 14 days at 4°C, approximately 80% of the activity remains after 14 days at -20°C
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C or -20°C, 24 h, decrease of more than 50% of activity of the enzyme solubilized by sodium deoxycholate or Triton X-100, the CHAPS solubilized enzyme is slightly more stable with approximately 90% and 40% of the activity remaining after 72 h at 4°C and -20°C
-
stable at 4°C for more than 2 months or for 24 h at 25°C, in phosphate or diethylmalonate buffer, pH 7.3, irrespective of the protein concentration
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
detection of a RNA species derived from an alternative processing at the exon 14intron 14 boundary. The alternatively processed RNA encodes a shorter version of PPII (PPII*), lacking part of the C-terminal domain. PPII* is expressed in COS-7 (or C6 glioma) cells but it does not exhibit any PPII activity. Co-transfection of PPII and increasing amounts of PPII* expression vectors results in a dose-dependent reduction in PPII activity and the formation of covalent PPIIPPII* heterodimers. PPII* is therefore a powerful dominant-negative isoform of PPII, and heterodimerization may be its mechanism of action. Natural expression of shortened versions of M1 aminopeptidases may constitute a new mode of regulation of their activity
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
nutrition
-
animals drinking a 2.5% NaCl solution for 7 d present body weight reduction. Despite their negative energy balance, they avoid food and have increased hypothalamic paraventricular nucleus thyrotropin releasing hormone expression and thyroid-stimulating hormone serum levels. Increased medial basal hypothalamic pyroglutamyl-aminopeptidase II activity in dehydration-induced anorexia rats might counteract their high thyrotropin releasing hormone release
medicine
-
inhibitors of the enzyme may be used to enhance the therapeutic actions of TRH and to investigate the functions of thyrotropin-releasing hormone and pyroglutamyl-peptidase II
medicine
-
involvement of thyrotropin-releasing hormone during emotionally charged situations, which is inactivated by PPII
medicine
-
pyroglutamyl peptidase II inhibitors may be used to enhance the therapeutic actions of thyrotropin releasing hormone
medicine
-
animals drinking a 2.5% NaCl solution for 7 d present body weight reduction. Despite their negative energy balance, they avoid food and have increased hypothalamic paraventricular nucleus thyrotropin releasing hormone expression and thyroid-stimulating hormone serum levels. Increased medial basal hypothalamic pyroglutamyl-aminopeptidase II activity in dehydration-induced anorexia rats might counteract their high thyrotropin releasing hormone release
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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Cavia porcellus
brenda
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Bos taurus
brenda
Scharfmann, R.; Morgat, J.L.; Aratan-Spire, S.
Presence of a particulate thyrotropin-releasing hormone-degrading pyroglutamate aminopeptidase activity in rat liver
Neuroendocrinology
49
442-448
1989
Rattus norvegicus
brenda
Bauer, K.; Nowak, P.
Characterization of a thyroliberin-degrading serum enzyme catalyzing the hydrolysis of thyroliberin at the pyroglutamyl-histidine bond
Eur. J. Biochem.
99
239-246
1979
Sus scrofa
brenda
Elmore, M.A.; Griffiths, E.C.; O'Connor, B.; O'Cuinn, G.
Further characterization of the substrate specificity of a TRH hydrolyzing pyroglutamate aminopeptidase from guinea pig brain
Neuropeptides
15
31-36
1990
Cavia porcellus
brenda
Wilk, S.; Wilk, E.K.
Pyroglutamyl peptidase II, a thyrotropin releasing hormone degrading enzyme: purification and specificity studies of the rabbit brain enzyme
Neurochem. Int.
15
81-89
1989
Oryctolagus cuniculus
brenda
Emerson, C.H.
Primary thyrotropin-releasing hormone-degrading enzymes
Methods Enzymol.
168
365-371
1989
Oryctolagus cuniculus
brenda
Bauer, K.; Nowak, P.; Kleinkauf, H.
Specificity of a serum peptidase hydrolyzing thyroliberin at pyroglutamyl-histidine bone
Eur. J. Biochem.
118
173-176
1981
Sus scrofa
brenda
Bauer, K.
Purification and characterization of the thyrotropin-releasing-hormone-degrading ectoenzyme
Eur. J. Biochem.
224
387-396
1994
Rattus norvegicus, Sus scrofa
brenda
Greaney, A.; Phelan, J.; O'Cuinn, G.
Localization of thyroliberin pyroglutamyl peptidase on synaptosomal-membrane preparations of guinea-pig brain tissue
Biochem. Soc. Trans.
8
423
1980
Cavia porcellus
brenda
Kelly, J.A.; Slator, G.R.; Tipton, K.F.; Williams, C.H.; Bauer, K.
Kinetic investigation of the specificity of porcine brain thyrotropin-releasing hormone-degrading ectoenzyme for thyrotropin-releasing hormone-like peptides
J. Biol. Chem.
275
16746-16751
2000
Sus scrofa
brenda
Schmitmeier, S.; Thole, H.; Bader, A.; Bauer, K.
Purification and characterization of the thyrotropin-releasing hormone (TRH)-degrading serum enzyme and its identification as a product of liver origin
Eur. J. Biochem.
269
1278-1286
2002
Bos taurus, Rattus norvegicus, Sus scrofa
brenda
Papadopoulos, T.; Heuer, H.; Bauer, K.
Analysis of the thyrotropin-releasing hormone-degrading ectoenzyme by site-directed mutagenesis of cysteine residues. Cys68 is involved in disulfide-linked dimerization
Eur. J. Biochem.
267
2617-2623
2000
Rattus norvegicus
brenda
Pascual, I.; Gil-Parrado, S.; Cisneros, M.; Joseph-Bravo, P.; Diaz, J.; Possani, L.D.; Charli, J.L.; Chavez, M.
Purification of a specific inhibitor of pyroglutamyl aminopeptidase II from the marine annelide Hermodice carunculata. in vivo effects in rodent brain
Int. J. Biochem. Cell Biol.
36
138-152
2004
Mus musculus, Rattus norvegicus
brenda
Kelly, J.A.; Scalabrino, G.A.; Slator, G.R.; Cullen, A.A.; Gilmer, J.F.; Lloyd, D.G.; Bennett, G.W.; Bauer, K.; Tipton, K.F.; Williams, C.H.
Structure-activity studies with high-affinity inhibitors of pyroglutamyl-peptidase II
Biochem. J.
389
569-576
2005
Rattus norvegicus
brenda
Garcia-Lopez, M.J.; Martinez-Martos, J.M.; Mayas, M.D.; Carrera, M.P.; Ramirez-Exposito, M.J.
Effects of orchidectomy and testosterone replacement on mouse pyrrolidone carboxypeptidase activity in the HPA axis
Horm. Metab. Res.
36
131-135
2004
Mus musculus
brenda
Chavez-Gutierrez, L.; Matta-Camacho, E.; Osuna, J.; Horjales, E.; Joseph-Bravo, P.; Maigret, B.; Charli, J.L.
Homology modeling and site-directed mutagenesis of pyroglutamyl peptidase II. Insights into omega-versus aminopeptidase specificity in the M1 family
J. Biol. Chem.
281
18581-18590
2006
Rattus norvegicus
brenda
Chavez-Gutierrez, L.; Bourdais, J.; Aranda, G.; Vargas, M.A.; Matta-Camacho, E.; Ducancel, F.; Segovia, L.; Joseph-Bravo, P.; Charli, J.L.
A truncated isoform of pyroglutamyl aminopeptidase II produced by exon extension has dominant-negative activity
J. Neurochem.
92
807-817
2005
Rattus norvegicus
brenda
de Gortari, P.; Uribe, R.M.; Garcia-Vazquez, A.; Aguilar-Valles, A.; Martinez, A.; Valdes, A.; Charli, J.L.; Fernandez-Guardiola, A.; Joseph-Bravo, P.
Amygdala kindling differentially regulates the expression of the elements involved in TRH transmission
Neurochem. Int.
48
31-42
2006
Rattus norvegicus
brenda
de Gortari, P.; Vargas, M.A.; Martinez, A.; Garcia-Vazquez, A.I.; Uribe, R.M.; Chavez-Gutierrez, L.; Magdaleno, V.; Boileau, G.; Charli, J.L.; Joseph-Bravo, P.
Stage-specific modulation of neprilysin and aminopeptidase N in the limbic system during kindling progression
J. Mol. Neurosci.
33
252-261
2007
Rattus norvegicus
brenda
Aguilar-Valles, A.; Sanchez, E.; de Gortari, P.; Garcia-Vazquez, A.I.; Ramirez-Amaya, V.; Bermudez-Rattoni, F.; Joseph-Bravo, P.
The expression of TRH, its receptors and degrading enzyme is differentially modulated in the rat limbic system during training in the Morris water maze
Neurochem. Int.
50
404-417
2007
Rattus norvegicus
brenda
Scalabrino, G.A.; Hogan, N.; OBoyle, K.M.; Slator, G.R.; Gregg, D.J.; Fitchett, C.M.; Draper, S.M.; Bennett, G.W.; Hinkle, P.M.; Bauer, K.; Williams, C.H.; Tipton, K.F.; Kelly, J.A.
Discovery of a dual action first-in-class peptide that mimics and enhances CNS-mediated actions of thyrotropin-releasing hormone
Neuropharmacology
52
1472-1481
2007
Rattus norvegicus
brenda
Gutierrez-Mariscal, M.; de Gortari, P.; Lopez-Rubalcava, C.; Martinez, A.; Joseph-Bravo, P.
Analysis of the anxiolytic-like effect of TRH and the response of amygdalar TRHergic neurons in anxiety
Psychoneuroendocrinology
33
198-213
2008
Rattus norvegicus
brenda
Sanchez, E.; Vargas, M.A.; Singru, P.S.; Pascual, I.; Romero, F.; Fekete, C.; Charli, J.L.; Lechan, R.M.
Tanycyte pyroglutamyl peptidase II contributes to regulation of the hypothalamic-pituitary-thyroid axis through glial-axonal associations in the median eminence
Endocrinology
150
2283-2291
2009
Rattus norvegicus
brenda
Matziari, M.; Bauer, K.; Dive, V.; Yiotakis, A.
Synthesis of the phosphinic analogue of thyrotropin releasing hormone
J. Org. Chem.
73
8591-8593
2008
Mammalia
brenda
Rodriguez-Molina, V.; Vargas, M.A.; Joseph-Bravo, P.; Charli, J.L.
NMDA receptor up-regulates pyroglutamyl peptidase II activity in the rat hippocampus
Neurosci. Lett.
449
211-214
2009
Rattus norvegicus
brenda
Cruz, R.; Vargas, M.A.; Uribe, R.M.; Pascual, I.; Lazcano, I.; Yiotakis, A.; Matziari, M.; Joseph-Bravo, P.; Charli, J.L.
Anterior pituitary pyroglutamyl peptidase II activity controls TRH-induced prolactin release
Peptides
29
1953-1964
2008
Rattus norvegicus
brenda
Rodriguez-Molina, V.; Patino, J.; Vargas, Y.; Sanchez-Jaramillo, E.; Joseph-Bravo, P.; Charli, J.L.
TRH regulates action potential shape in cerebral cortex pyramidal neurons
Brain Res.
1571
1-11
2014
Rattus norvegicus
brenda
Alvarez-Salas, E.; Aceves, C.; Anguiano, B.; Uribe, R.M.; Garcia-Luna, C.; Sanchez, E.; de Gortari, P.
Food-restricted and dehydrated-induced anorexic rats present differential TRH expression in anterior and caudal PVN. Role of type 2 deiodinase and pyroglutamyl aminopeptidase II
Endocrinology
153
4067-4076
2012
Rattus norvegicus
brenda
Lazcano, I.; Uribe, R.M.; Martinez-Chavez, E.; Vargas, M.A.; Matziari, M.; Joseph-Bravo, P.; Charli, J.L.
Pyroglutamyl peptidase II inhibition enhances the analeptic effect of thyrotropin-releasing hormone in the rat medial septum
J. Pharmacol. Exp. Ther.
342
222-231
2012
Rattus norvegicus (Q10836), Rattus norvegicus
brenda
Ramirez-Exposito, M.; Martinez-Martos, J.
High cholesterol intake modifies pyroglutamyl aminopeptidase activity in serum and different tissues of male and female mice
Curr. Top. Pept. Protein Res.
18
103-108
2017
Mus musculus (Q9UKU6)
-
brenda
Lazcano, I.; Cabral, A.; Uribe, R.M.; Jaimes-Hoy, L.; Perello, M.; Joseph-Bravo, P.; Sanchez-Jaramillo, E.; Charli, J.L.
Fasting enhances pyroglutamyl peptidase II activity in Tanycytes of the mediobasal hypothalamus of male adult rats
Endocrinology
156
2713-2723
2015
Rattus norvegicus (Q10836)
brenda
Alvarez-Salas, E.; Alcantara-Alonso, V.; Matamoros-Trejo, G.; Vargas, M.A.; Morales-Mulia, M.; de Gortari, P.
Mediobasal hypothalamic and adenohypophyseal TRH-degrading enzyme (PPII) is down-regulated by zinc deficiency
Int. J. Dev. Neurosci.
46
115-124
2015
Rattus norvegicus (Q10836)
brenda
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