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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
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lactotrophs
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trh-r1
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trhergic
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eminence
- tanycytes
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deiodinase
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hypothalamus-pituitary-thyroid
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peptidergic
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trh-receptor
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mediobasal
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hypophysiotropic
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trh-induced
- medicine
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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
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PPII
pyroglutamate aminopeptidase II
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pyroglutamyl aminopeptidase II
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pyroglutamyl peptidase II
thyroliberin-hydrolyzing pyroglutamate aminopeptidase
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thyroliberinase
thyrotropin-releasing hormone-degrading peptidase
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thyrotropin-releasing hormone-degrading pyroglutamate aminopeptidase
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TRH aminopeptidase
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TRH-DE
TRH-degrading ectoenzyme
TRH-specific aminopeptidase
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PPII
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pyroglutamyl peptidase II
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thyroliberinase
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TRH-DE
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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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-
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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
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-
-
?
pyroglutamyl-7-amido-4-methylcoumarin + H2O
pyroglutamate + 7-amino-4-methylcoumarin
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-
-
-
?
pyroglutamyl-Asn(N-benzyl)-ProNH2 + H2O
L-pyroglutamate + Asn(N-benzyl)-ProNH2
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-
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-
?
pyroglutamyl-Asn(N-methyl)-ProNH2 + H2O
L-pyroglutamate + Asn(N-methyl)-ProNH2
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?
pyroglutamyl-His-Pro-7-amido-4-methylcoumarin + H2O
pyroglutamate + His-Pro-7-amido-4-methylcoumarin
pyroglutamyl-His-tripeptidyl naphthylamides + H2O
pyroglutamate + His-tripeptidyl naphthylamides
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-
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?
pyroglutamyl-histidyl-prolyl-7-amido-4-methylcoumarin + H2O
pyroglutamic acid + histidyl-prolyl-7-amido-4-methylcoumarin
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?
pyroglutamyl-thienylalanyl-Pro-NH2 + H2O
pyroglutamate + thienylalanyl-Pro-NH2
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?
thyrotropin releasing hormone-beta-naphthylamine + H2O
?
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substrate activity assay
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?
thyrotropin-releasing hormone-beta-naphthylamide + H2O
?
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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
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?
L-5-oxoprolyl 2-naphthylamide + H2O
2-naphthylamine + 5-oxoproline
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very poor substrate
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?
L-5-oxoprolyl 2-naphthylamide + H2O
2-naphthylamine + 5-oxoproline
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very poor substrate
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?
pyroglutamyl-His-Pro-7-amido-4-methylcoumarin + H2O
pyroglutamate + His-Pro-7-amido-4-methylcoumarin
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?
pyroglutamyl-His-Pro-7-amido-4-methylcoumarin + H2O
pyroglutamate + His-Pro-7-amido-4-methylcoumarin
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?
thyroliberin + H2O
?
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may control the biological activity of the neuronally released thyrotropin
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?
thyroliberin + H2O
?
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involved in the conversion of thyrotropin-releasing hormone into histidyl-proline diketopiperazine
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?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
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i.e. pyroglutamyl-His-Pro-NH2, thyrotropin-releasing hormone
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?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
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i.e. pyroglutamyl-His-Pro-NH2, thyrotropin-releasing hormone
pyroglutamic acid + histidyl-proline diketopiperazine
?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
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rapid stereospecific cleavage only of the pyroglutamyl-histidine bond of thyroliberin and closely related peptides
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?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
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cleavage at the pyroglutamyl-histidine bond
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?
thyroliberin + H2O
pyroglutamic acid + His-Pro-NH2
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i.e. pyroglutamyl-His-Pro-NH2, thyrotropin-releasing hormone
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?
additional information
?
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no hydrolysis of pyroglutamyl peptides containing more than three amino acids
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?
additional information
?
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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
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?
additional information
?
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no hydrolysis of dipeptides containing N-terminal pyroglutamic acid
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?
additional information
?
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no hydrolysis of pyroglutamyl-His decapeptide LHRH
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?
additional information
?
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no hydrolysis of ring opened Glu1-thyrotropin
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?
additional information
?
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no hydrolysis of pyroglutamyl-His-Pro-Ala naphthylamide
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?
additional information
?
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no hydrolysis of pyroglutamyl-His bond of the dipeptide pyroglutamyl-His naphthylamide
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?
additional information
?
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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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?
additional information
?
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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
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?
additional information
?
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moderately bulky, uncharged P1' residues preferentially bind to the enzyme
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?
additional information
?
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no hydrolysis of pyroglutamyl-Ala or pyroglutamyl 2-naphthylamide (known substrates of the serum enzyme)
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?
additional information
?
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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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?
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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
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-
?
thyroliberin + H2O
?
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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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-
?
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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
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66% inhibition at 1 mM, 97% inhibition at 10 mM
Glp-Asn-Pro-D-Tyr-D-TrpNH2
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potent inhibitor of TRH-DE. Competetive, fully reversible and not time dependent inhibition
Thyroliberin analogues
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LLD-thyroliberin, pyroglutamyl-His-Pro-NHCH3, pyroglutamyl-His-Pro-Gly-NHCH3, pyroglutamyl-Phe-Pro-NH2
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Glp-PSI[P(O)(OH)CH2]-His-Pro-NH2
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phosphinic analogue of thyrotropin releasing hormone, ED50 170 nM
Glp-PSI[P(O)(OH)CH2]-His-Pro-NH2
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phosphinic analogue of thyrotropin releasing hormone
Hermodice carunculata inhibitor
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the inhibitor is found in Hermodice carunculata and purified, MW below 1000 Da, the inhibitor is not a peptide
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additional information
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no inhibition by aspartyl protease inhibitors; no inhibition by cysteine protease inhibitors; no inhibition by serine protease inhibitors
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additional information
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no inhibition by bacitracin; no inhibition by puromycin
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additional information
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PPII inhibitory activity als detected in Phallusia nigra, Palythoa caribaeorum and Mycale microsigmatosa
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additional information
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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
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additional information
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no inhibition by NEM; no inhibition by serine protease inhibitors; no inhition by 2-iodoacetamide
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additional information
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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
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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
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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
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-