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Information on EC 3.1.2.22 - palmitoyl[protein] hydrolase and Organism(s) Homo sapiens and UniProt Accession O75608
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3.1.2.22 palmitoyl[protein] hydrolaseIUBMB Comments
Specific for long-chain thioesters of fatty acids. Hydrolyses fatty acids from S-acylated cysteine residues in proteins, palmitoyl cysteine and palmitoyl-CoA.
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Word Map
- 3.1.2.22
-
ceroid
-
infantile
- lipofuscinosis
-
palmitoylated
- lysosomal
- neurodegenerative
- batten
-
depalmitoylation
-
ppt1-deficient
-
autofluorescent
-
grods
-
tripeptidyl
-
osmiophilic
-
s-acylated
-
late-infantile
-
lincl
-
thioesterases
-
lipid-modified
- ceroid-lipofuscinosis
- medicine
- nutrition
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
palmitoyl-protein thioesterase, palmitoyl-protein thioesterase 1, palmitoyl protein thioesterase, palmitoyl protein thioesterase 1, palmitoyl-protein thioesterase-1, palmitoyl protein thioesterase-1, acyl-protein thioesterase 1, lysophospholipase 1, palmitoyl-thioesterase, palmitoyl protein thioesterase-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Acyl protein thioester hydrolase
-
-
-
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G14
-
-
-
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GenBank AF020543-derived protein GI 2501961
-
-
-
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GenBank L42809-derived protein GI 1160967
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-
-
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Hydrolase, acyl protein thioester
-
-
-
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Hydrolase, acyl protein thioester (cattle clone pBovPPT-18 precursor reduced)
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-
-
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Hydrolase, acyl protein thioester (cattle pBovPPT-25 precursor reduced)
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-
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Hydrolase, acyl protein thioester (human clone B lysosome-associated isoenzyme 2)
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-
-
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Hydrolase, acyl protein thioester (human clone pHuPPT-5')
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-
-
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Hydrolase, acyl protein thioester (ox clone pBovPPT-18 precursor reduced)
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-
-
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Hydrolase, acyl protein thioester (ox pBovPPT-25 precursor reduced)
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-
-
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Hydrolase, acyl protein thioester (rat clone pRatPPT-44 precursor reduced)
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-
-
-
palmitoyl protein thioesterase 1
Palmitoyl-protein thioesterase
Palmitoyl-protein thioesterase (bovine clone pBovPPT-17 precursor)
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-
-
-
Palmitoyl-protein thioesterase (bovine clone pBovPPT-25 precursor)
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-
-
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Palmitoyl-protein thioesterase (human clone pHuPPT-5')
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-
-
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Palmitoyl-protein thioesterase (rat clone pRatPPT-44 precursor)
-
-
-
-
palmitoyl-protein thioesterase 1
Palmitoyl-protein thioesterase PPT2 (human clone B lysosome associated)
-
-
-
-
PPT
PPT1
Palmitoyl-protein thioesterase
-
-
-
-
PPT
-
-
-
-
PPT1
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
palmitoyl[protein] + H2O = palmitate + protein
specific for long-chain thioesters of fatty acids from S-acylated residues in proteins, palmitoyl cysteine and palmitoyl-CoA
-
palmitoyl[protein] + H2O = palmitate + protein
specific for long-chain thioesters of fatty acids from S-acylated residues in proteins, palmitoyl cysteine and palmitoyl-CoA, catalytic triad consists of Ser115, His289, and Asp233
-
palmitoyl[protein] + H2O = palmitate + protein
specific for long-chain thioesters of fatty acids from S-acylated residues in proteins, palmitoyl cysteine and palmitoyl-CoA, catalytic triad of PPT2 consists of Ser111, His283, and Asp228, mechanism, both PPT1 and PPT2 have lipid-binding grooves leading away from the active site
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of thioester
hydrolysis of thioester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
palmitoyl[protein] hydrolase
Specific for long-chain thioesters of fatty acids. Hydrolyses fatty acids from S-acylated cysteine residues in proteins, palmitoyl cysteine and palmitoyl-CoA.
CAS REGISTRY NUMBER
COMMENTARY
150605-49-5
-
158210-90-3
hydrolase, acyl protein thioester (rat clone pRatPPT-44 precursor reduced) /palmitoyl-protein thioesterase (rat clone pRatPPT-44 precursor)
158210-92-5
hydrolase, acyl protein thioester (cattle clone pBovPPT-18 precursor reduced) /hydrolase, acyl protein thioester (ox clone pBovPPT-18 precursor reduced) /palmitoyl-protein thioesterase (bovine clone pBovPPT-17 precursor)
158210-93-6
hydrolase, acyl protein thioester (cattle pBovPPT-25 precursor reduced) /hydrolase, acyl protein thioester (ox pBovPPT-25 precursor reduced) /palmitoyl-protein thioesterase (bovine clone pBovPPT-25 precursor)
179801-10-6
hydrolase, acyl protein thioester (human clone pHuPPT-5') /GenBank L42809-derived protein GI 1160967 /palmitoyl-protein thioesterase (human clone pHuPPT-5')
199619-79-9
hydrolase, acyl protein thioester (human clone B lysosome-associated isoenzyme 2) /genBank AF020543-derived protein GI 2501961 /palmitoyl-protein thioesterase PPT2 (human clone B lysosome associated)
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
1-palmitoyl lysophosphatidylcholine + H2O
glycerophosphocholine + palmitate
-
-
-
?
palmitoyl-peptide + H2O
palmitate + peptide
residue 3 to 14 of RGS4 protein with palmitoyl group attached at Cys12 of RGS4 protein
-
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
4-methylumbelliferyl 6-thio-beta-D-glucoside + palmitate
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
palmitate + 4-methylumbelliferyl 6-thio-beta-D-glucoside
palmitoyl-[MfNACsa protein] + H2O
palmitate + MfNACsa protein
-
substrate of isoform APT1
-
-
r
palmitoylthio-beta-glucoside + H2O
palmitate + thio-beta-glucoside
-
-
-
?
palmitoyl[beta-D-thioglucoside] + H2O
palmitate + 1-thio-beta-D-glucopyranose
-
-
-
-
?
S-palmitoyl-N-acetyl-O-carboxymethyl-cysteine + H2O
N-acetyl-O-carboxymethyl-cysteine + palmitate
-
enzyme form PPT1, not PPT2
-
?
S-palmitoyl-N-acetylcysteamine + H2O
N-acetylcysteamine + palmitate
-
enzyme form PPT1, not PPT2
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
4-methylumbelliferyl 6-thio-beta-D-glucoside + palmitate
-
-
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
4-methylumbelliferyl 6-thio-beta-D-glucoside + palmitate
-
-
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
4-methylumbelliferyl 6-thio-beta-D-glucoside + palmitate
-
-
-
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
4-methylumbelliferyl 6-thio-beta-D-glucoside + palmitate
-
-
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
palmitate + 4-methylumbelliferyl 6-thio-beta-D-glucoside
-
-
-
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
palmitate + 4-methylumbelliferyl 6-thio-beta-D-glucoside
-
-
-
?
4-methylumbelliferyl 6-S-palmitoyl-6-thio-beta-D-glucoside + H2O
palmitate + 4-methylumbelliferyl 6-thio-beta-D-glucoside
-
-
-
-
?
palmitoyl-[protein] + H2O
palmitate + protein
-
various S-acylated proteins
-
?
palmitoyl-[protein] + H2O
palmitate + protein
-
palmitoylation plays critical roles in diverse biological functions, including membrane anchorage, vesicular transport, signal transduction and the maintenance of cellular architecture
-
-
r
additional information
?
-
-
structural differences in the 2 enzyme fomrs PPT1 and PPT2, PPT2 does not hydrolyze substrates with bulky head groups
-
?
additional information
?
-
-
mutations in the enzyme protein cause the neurodegenerative disorder infantile neuronal ceroid lipofuscinosis
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-
?
additional information
?
-
-
defect in the palmitoyl-(protein) hydrolase gene causes a neurodegenerative disorder. Depalmitoylation of the still uncharacterized substrate(s) of the enzyme is critical for postnatal development or maintainance of cortical neurons
-
-
?
additional information
?
-
-
the enzyme is required for the efficient lysosomal degradation of thioesters derived from S-acylated proteins
-
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological and granular osmiophilic deposits, GROD, and infantile neuronal ceroid lipofuscinosis
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL, a lysosomal storage disorder
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL, molecular basis
-
?
additional information
?
-
-
enzyme deficiency causes the infantile form of neuronal ceroid lipofuscinosis INCL, a progressive encephalopathyof children
-
?
additional information
?
-
-
PPT1 deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
PPT1 deficiency causes, together with tripeptidyl peptidase 1 deficiency, progressive neurological disorder infantile neuronal ceroid lipofuscinosis, a group of at least 8 inherited, progressive encephalopathies that are characterized by lipofuscin-like inclusions in various tissues and have been classified as CNL1-CNL8
-
?
additional information
?
-
the most severe form of neuronal ceroid lipofuscinoses, infantile neuronal ceroid lipofuscinosis (INCL), is caused by mutations in the CLN1 gene, resulting in a deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1
-
-
?
additional information
?
-
-
PPT1 deficiency leads to abnormally low levels of soluble synaptic vesicle proteins like synaptobrevin 2 and SNAP25, that are known to undergo palmitoylation and are critical for fusion, exocytosis, recycling, and regeneration of fresh synaptic vesicles
-
-
?
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
palmitoyl-[protein] + H2O
palmitate + protein
-
palmitoylation plays critical roles in diverse biological functions, including membrane anchorage, vesicular transport, signal transduction and the maintenance of cellular architecture
-
-
r
additional information
?
-
-
mutations in the enzyme protein cause the neurodegenerative disorder infantile neuronal ceroid lipofuscinosis
-
-
?
additional information
?
-
-
defect in the palmitoyl-(protein) hydrolase gene causes a neurodegenerative disorder. Depalmitoylation of the still uncharacterized substrate(s) of the enzyme is critical for postnatal development or maintainance of cortical neurons
-
-
?
additional information
?
-
-
the enzyme is required for the efficient lysosomal degradation of thioesters derived from S-acylated proteins
-
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological and granular osmiophilic deposits, GROD, and infantile neuronal ceroid lipofuscinosis
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL, a lysosomal storage disorder
-
?
additional information
?
-
-
enzyme deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL, molecular basis
-
?
additional information
?
-
-
enzyme deficiency causes the infantile form of neuronal ceroid lipofuscinosis INCL, a progressive encephalopathyof children
-
?
additional information
?
-
-
PPT1 deficiency causes progressive neurological disorder infantile neuronal ceroid lipofuscinosis, INCL
-
?
additional information
?
-
-
PPT1 deficiency causes, together with tripeptidyl peptidase 1 deficiency, progressive neurological disorder infantile neuronal ceroid lipofuscinosis, a group of at least 8 inherited, progressive encephalopathies that are characterized by lipofuscin-like inclusions in various tissues and have been classified as CNL1-CNL8
-
?
additional information
?
-
the most severe form of neuronal ceroid lipofuscinoses, infantile neuronal ceroid lipofuscinosis (INCL), is caused by mutations in the CLN1 gene, resulting in a deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1
-
-
?
additional information
?
-
-
PPT1 deficiency leads to abnormally low levels of soluble synaptic vesicle proteins like synaptobrevin 2 and SNAP25, that are known to undergo palmitoylation and are critical for fusion, exocytosis, recycling, and regeneration of fresh synaptic vesicles
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-palmitoyl lysophosphatidylcholine
competitive inhibitor for acylprotein thioesterase activity
Chloroquine
-
inhibits the hydrolysis and leads to accumulation of lipid cysteine thioesters in the lysosomes of treated cells
leupeptin
-
inhibits the hydrolysis and leads to accumulation of lipid cysteine thioesters in the lysosomes of treated cells but has no direct inhibitory effect on the enzyme
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0222
1-palmitoyl lysophosphatidylcholine
for acylprotein thioesterase activity
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
-
exclusively localized to the basolateral side of the polarized cells
normal fibroblasts and infantile neuronal ceroid lipofuscinosis fibroblasts, deficient of PPT1
additional information
-
postmortem from patient with infantile neuronal ceroid lipofuscinosis (INCL) caused by PPT1 deficiency
additional information
-
the most common mutation results in intracellular accumulationof the enzyme polypeptide and undetectable activity in the brain
additional information
-
lymphoblasts from patients with infantile neuronal ceroid lipofuscinosis, deficient of PPT1
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the most common mutation results in intracellular accumulation of the enzyme polypeptide and undetectable activity in the brain
-
in contrast to the wild type enzyme, the mutant polypeptides are retained in the endoplasmic reticulum, most probably due to the misfolding of the mutant polypeptide
-
infantile neuronal ceroid lipofuscinosis is a lysosomal storage disease
-
enzyme is recognized by the mannose 6-phosphate receptor and routed to the lysosome
-
the glycoslated enzyme is recognized by the mannose 6-phosphate receptor and routed to the lysosome
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
first case of infantile neuronal ceroid lipofuscinosis in 37 month old Japanese boy diagnosed by enzyme activity deficiency of palmitoyl-protein thioesterase, displaying symptoms of severe deterioration beginning in his 14th month
malfunction
PPT1 deficient cells are partially resistant to tumor necrosis factor-induced cell death (57-75% cell viability versus 15-30% for control fibroblasts), tumor necrosis factor-initiated proteolytic cleavage of caspase-8, Bid and caspase-3, as well as cytochrome c release is strongly attenuated. Activation of p42/p44 mitogen-activated protein kinase and of transcription factor NF-kappaB by tumor necrosis factor, and induction of cell death by staurosporine or chemotherapeutic drugs in infantile neuronal ceroid lipofuscinosis cells are unaffected by PPT1 deficiency
physiological function
role of PPT1 and, likely, protein depalmitoylation in the regulation of tumor necrosis factor-induced apoptosis. PPT1 is involved in cell death triggered by death receptors but not receptor-independent cytotoxic agents. Expression of PPT1 cDNA in infantile neuronal ceroid lipofuscinosis cells restores the tumor necrosis factor sensitivity
physiological function
-
when injected intravenously into PPT1-deficient mice, the clearance of recombinant PPT1 from plasma is rapid, with a half-life of 10 min. Most of the injected dose is distributed to the kidney and liver and potentially corrective levels are also observed in heart, lung and spleen. Brain uptake is minimal. The enzyme is largely mannose 6-phosphorylated and takes up rapidly by PPT1-deficient immortalized lymphoblasts derived from infantile neuronal ceroid lipofuscinosis patients
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). LYPA1_HUMAN
230
0
24670
Swiss-Prot
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
heterogenous glycosylation is the major cause of multiple bands observed in SDS-PAGE
glycoprotein
three potential asparagine-linked glycosylation sites are found near the carboxyl terminus of the protein at positions 199, 214, and 234. Glycosylation of the amino acid 234 demonstrated experimentally
glycoprotein
-
N-glycosylation at Asn232, Asn197, and Asn212, essential for activity
glycoprotein
N-glycosylation of N197 and N232, but not N212, is essential for enzyme activity and intracellular transport. Deglycosylation of overexpressed PPT1 produced in neurons and fibroblasts demonstrates differentially modified PPT1 in different cell types
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme with and without bound palmitate, sitting drop vapor diffusion method, 12 mg/ml enzyme in 20 mM HEPES, pH 7.0, plus 150 mM NaCl, plus reservoir solution, containing 55% PEG 400, 100 mM Bis-Tris, pH 6.5, in a ratio 3:2, equilibrated against a250fold excess, X-ray multiwave length anomalous diffraction phasing for structure determinationand analysis, 2.25 A resolution
-
purified recombinant PPT2 15 mg/ml, sitting drop vapour diffusion method, 4°C, with equal volume of precipitant solution conataining 2 M ammonium sulfate, 100 mM sodium cacodylate, pH 5.5-6.5, 8% methyl pentanediol, X-ray diffraction structure determination and analysis at 2.7 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C6S
the activity of the non-palmitoylatable mutant significantly surpasses that of the wild type enzyme by more than 42% in the cell lysate and 25% in the cell medium
D79G
E184K
-
naturally occurring mutation, recombinant enzyme is nearly inactive showing an activity below 2% of the wild-type activity, mutation is associated with the infantile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
F84del
-
natural deletion mutation in gene ppt1, leading to enzyme deficiency and infantile progressive neurological defects
G118D
-
natural mutation in gene ppt1, leading to enzyme deficiency and infantile progressive neurological defects
G250V
-
naturally occurring mutation, recombinant enzyme shows 5.9% of the wild-type activity, mutation is associated with the juvenile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
G42E
-
naturally occurring mutation, recombinant enzyme is nearly inactive showing an activity below 2% of the wild-type activity, mutation is associated with the infantile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
H39Q
-
naturally occurring mutation, recombinant enzyme is nearly inactive showing an activity below 2% of the wild-type activity, mutation is associated with the infantile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
L219Q
-
naturally occurring mutation, mutation is associated with the late onset form of infantile neuronal ceroid lipofuscinosis, the mutant enzymes shows minor altered intracellular localization in transfected cells and are localized in the presynaptic space and neuronal shaft, about 10fold reduced activity
N197Q
-
site-directed mutagenesis, mutation of a glycosylation site, slightly reduced activity
N197Q/N212Q
-
site-directed mutagenesis, mutation of glycosylation sites, slightly reduced activity, mutant shows 10% of the wild-type expression level
N197Q/N212Q/N232Q
-
site-directed mutagenesis, mutation of all glycosylation sites, inactive mutant
N197Q/N232Q
-
site-directed mutagenesis, mutation of glycosylation sites, reduced activity
N212Q
-
site-directed mutagenesis, mutation of a glycosylation site, slightly reduced activity
N212Q/N232Q
-
site-directed mutagenesis, mutation of glycosylation sites, highly reduced activity
N232Q
-
site-directed mutagenesis, mutation of a glycosylation site, slightly reduced activity
Q177E
Q291X
-
natural mutation in gene ppt1, leading to enzyme deficiency and infantile progressive neurological defects
R122W
-
naturally occurring mutation, recombinant enzyme is nearly inactive showing an activity below 2% of the wild-type activity, mutation is associated with the infantile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor, accumulation of the recombinant mutant enzyme in the endoplamic reticulum due to decreased degradation turnover
R164X
-
natural mutation in gene ppt1, leading to enzyme deficiency and infantile progressive neurological defects
S234A
mutation shows 1-5% of normal activity. Partial localization to lysosomes, although a major proportion is retained in the endoplasmic reticulum
T75P
V181M
Y109D
-
naturally occurring mutation, recombinant enzyme is nearly inactive showing an activity below 2% of the wild-type activity, mutation is associated with an unclassified form of neuronal ceroid lipofuscinosis
Y247H
-
naturally occurring mutation, recombinant enzyme is nearly inactive showing an activity below 2% of the wild-type activity, mutation is associated with an unclassified form of neuronal ceroid lipofuscinosis
additional information
D79G
-
naturally occurring mutation, recombinant enzyme shows 32.8% of the wild-type activity, mutation is associated with the juvenile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
Q177E
-
natural missense mutation in gene ppt1, leading to enzyme deficiency and progressive neurological defects, late-infantile phenotype
Q177E
-
naturally occurring mutation, recombinant enzyme shows 7.3% of the wild-type activity, mutation is associated with the late infantile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
T75P
-
natural mutation in gene ppt1, leading to enzyme deficiency and infantile progressive neurological defects
T75P
-
naturally occurring mutation, mutation is associated with the late onset form of infantile neuronal ceroid lipofuscinosis, the mutant enzymes shows minor altered intracellular localization in transfected cells and are localized in the presynaptic space and neuronal shaft, about 10fold reduced activity
T75P
-
naturally occurring mutation, recombinant enzyme shows 6.8% of the wild-type activity, mutation is associated with the juvenile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
V181M
-
natural mutation in gene ppt1, leading to enzyme deficiency and infantile progressive neurological defects
V181M
-
naturally occurring mutation, recombinant enzyme is nearly inactive showing an activity below 2% of the wild-type activity, mutation is associated with the infantile form of neuronal ceroid lipofuscinosis, no binding of mannose 6-phosphate receptor
additional information
-
naturally occurring mutations delPhe84 and insCys45, mutation is associated with the late onset form of infantile neuronal ceroid lipofuscinosis, the mutant enzymes shows severely altered intracellular localization in transfected cells and are targeted to the endoplasmic reticulum, about 10fold reduced activity
additional information
-
residues involved in ligand binding differ between PPT1 and PPT2, exchange by site-directed mutagenesis and functional analysis, overview
additional information
-
several naturally occurring mutations of alleles 1 and 2 from enzyme deficient patients shows reduced activity compred with the wild-type, overview
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant PPT2 from overexpressing insect cells, recombinant PPT2 mutant from COS cells
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
GST-fusion protein expressed in Escherichia coli BL21, expressed in HEK-293 cell
expression of the enzyme in Caco-2 cells, orientation to the basolateral side, also after endocytosis of the recombinant enzyme into Caco-2 cells
-
expression of wild-type and enzymes with naturally occurring mutations in COS cells as His-tagged enzyme, and in Sf9 cells, the latter via baculovirus infection
-
fragment corresponding to the entire coding region of PPT1 amplified from pCMV5-hPPT1, and cloned into XhoI sites in the polylinker region of expression vector pMSXND1, overexpressed in CHO cells. PPT1 injected intravenously into PPT1-deficient mice
-
gene ppt, DNA sequence determnation and analysis, identification of 8 natural mutations of different origins leading to enzyme deficiency
-
overexpression of PPT2 in an insect-baculovirus expression system, secretion of the recombinant enzyme to the culture medium, expression of mutant PPT2 in COS cells, subcloning in Escherichia coli XL1-blue
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
in vitro enzyme assay that can be readily used for the clinical diagnosis of both infantile neuronal ceroid lipofuscinosis patients and carrier
medicine
-
palmitoyl protein thioesterase 1, expressed in the human saliva is a reliable and non-invasive source for the diagnosis of infantile neuronal ceroid lipofuscinosis
medicine
-
enzyme may be useful as an adjunct to central nervous system-directed therapies and may be used as a starting point for modifications designed to improve brain delivery
medicine
-
if patients are diagnosed with any type of mental and/or physical retardation accompanied by strong and severe visual impairment, then the case physician may consider the possibility of infantile neuronal ceroid lipofuscinosis and conduct an examination of PPT activity level
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Cho, S.; Dawson, G.
Enzymatic and molecular biological analysis of palmitoyl protein thioesterase deficiency in infantile neuronal ceroid lipofuscinosis
J. Neurochem.
71
323-329
1998
Homo sapiens
Hellsten, E.; Vesa, J.; Olkkonen, V.M.; Jalanko, A.; Peltonen, L.
Human palmitoyl protein thioesterase: evidence for lysosomal targeting of the enzyme and disturbed cellular routing in infantile neuronal ceroid lipofuscinosis
EMBO J.
15
5240-5245
1996
Homo sapiens
Vesa, J.; Hellsten, E.; Verkruyse, L.A.; Camp, L.A.; Rapola, J.; Santavuori, P.; Hofmann, S.L.; Peltonen, L.
Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis
Nature
376
584-587
1995
Homo sapiens
Schriner, J.E.; Yi, W.; Hofmann, S.L.
cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis
Genomics
34
317-4322
1996
Homo sapiens (P50897), Homo sapiens
Verkruyse, L.A.; Hofmann, S.L.
Lysosomal targeting of palmitoyl-protein thioesterase
J. Biol. Chem.
271
15831-15836
1996
Homo sapiens
Lu, J.Y.; Verkruyse, L.A.; Hofmann, S.L.
Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase
Proc. Natl. Acad. Sci. USA
93
10046-10050
1996
Homo sapiens
Meng, L.; Sin, N.; Crews, C.M.
The antiproliferative agent didemnin B uncompetitively inhibits palmitoyl protein thioesterase
Biochemistry
37
10488-10492
1998
Homo sapiens
Lu, J.Y.; Verkruyse, L.A.; Hofmann, S.L.
The effects of lysosomotropic agents on normal and INCL cells provide further evidence for the lysosomal nature of palmitoyl-protein thioesterase function
Biochim. Biophys. Acta
1583
35-44
2002
Homo sapiens
Lukacs, Z.; Santavuori, P.; Keil, A.; Steinfeld, R.; Kohlschutter, A.
Rapid and simple assay for the determination of tripeptidyl peptidase and palmitoyl protein thioesterase activities in dried blood spots
Clin. Chem.
49
509-512
2003
Homo sapiens
Das, A.K.; Lu, J.Y.; Hofmann, S.L.
Biochemical analysis of mutations in palmitoyl-protein thioesterase causing infantile and late-onset forms of neuronal ceroid lipofuscinosis
Hum. Mol. Genet.
10
1431-1439
2001
Homo sapiens
Lehtovirta, M.; Kyttala, A.; Eskelinen, E.L.; Hess, M.; Heinonen, O.; Jalanko, A.
Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL)
Hum. Mol. Genet.
10
69-75
2001
Homo sapiens, Mus musculus
Waliany, S.; Das, A.K.; Gaben, A.; Wisniewski, K.E.; Hofmann, S.L.
Identification of three novel mutations of the palmitoyl-protein thioesterase-1 (PPT1) gene in children with neuronal ceroid-lipofuscinosis
Hum. Mutat.
15
206-207
2000
Homo sapiens
Salonen, T.; Jarvela, I.; Peltonen, L.; Jalanko, A.
Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1)
Hum. Mutat.
15
273-279
2000
Homo sapiens
Calero, G.; Gupta, P.; Nonato, M.C.; Tandel, S.; Biehl, E.R.; Hofmann, S.L.; Clardy, J.
The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2
J. Biol. Chem.
278
37957-37964
2003
Homo sapiens
Salonen, T.; Heinonen-Kopra, O.; Vesa, J.; Jalanko, A.
Neuronal trafficking of palmitoyl protein thioesterase provides an excellent model to study the effects of different mutations which cause infantile neuronal ceroid lipofuscinocis
Mol. Cell. Neurosci.
18
131-140
2001
Homo sapiens
Bellizzi, J.J., 3rd; Widom, J.; Kemp, C.; Lu, J.Y.; Das, A.K.; Hofmann, S.L.; Clardy, J.
The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis
Proc. Natl. Acad. Sci. USA
97
4573-4578
2000
Homo sapiens
Kohan, R.; Noher de Halac, I.; Anzolini, V.T.; Cismondi, A.; Oller Ramirez, A.M.; Capra, A.P.; Dodelson de Kremer, R.
Palmitoyl protein thioesterase 1 (PPT1) and tripeptidyl peptidase-I (TPP-I) are expressed in the human saliva. A reliable and non-invasive source for the diagnosis of infantile (CLN1) and late infantile (CLN2) neuronal ceroid lipofuscinoses
Clin. Biochem.
38
492-494
2005
Homo sapiens
Lyly, A.; von Schantz, C.; Salonen, T.; Kopra, O.; Saarela, J.; Jauhiainen, M.; Kyttaelae, A.; Jalanko, A.
Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1) - distinct characteristics in neurons
BMC Cell Biol.
8
22
2007
Homo sapiens (P50897)
Kim, S.J.; Zhang, Z.; Sarkar, C.; Tsai, P.C.; Lee, Y.C.; Dye, L.; Mukherjee, A.B.
Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice
J. Clin. Invest.
118
3075-3086
2008
Homo sapiens, Mus musculus
Hirano, T.; Kishi, M.; Sugimoto, H.; Taguchi, R.; Obinata, H.; Ohshima, N.; Tatei, K.; Izumi, T.
Thioesterase activity and subcellular localization of acylprotein thioesterase 1/lysophospholipase 1
Biochim. Biophys. Acta
1791
797-805
2009
Homo sapiens (O75608), Homo sapiens
Tardy, C.; Sabourdy, F.; Garcia, V.; Jalanko, A.; Therville, N.; Levade, T.; Andrieu-Abadie, N.
Palmitoyl protein thioesterase 1 modulates tumor necrosis factor alpha-induced apoptosis
Biochim. Biophys. Acta
1793
1250-1258
2009
Homo sapiens (P50897), Homo sapiens, Mus musculus
Takano, K.; Shimono, M.; Shiota, N.; Kato, A.; Tomioka, S.; Oka, A.; Ohno, K.; Sathou, H.
Infantile neuronal ceroid lipofuscinosis: The first reported case in Japan diagnosed by palmitoyl-protein thioesterase enzyme activity deficiency
Brain Dev.
30
370-373
2008
Homo sapiens
Lu, J.Y.; Hu, J.; Hofmann, S.L.
Human recombinant palmitoyl-protein thioesterase-1 (PPT1) for preclinical evaluation of enzyme replacement therapy for infantile neuronal ceroid lipofuscinosis
Mol. Genet. Metab.
99
374-378
2010
Homo sapiens
Spinelli, M.; Fusco, S.; Grassi, C.
Nutrient-dependent changes of protein palmitoylation Impact on nuclear enzymes and regulation of gene expression
Int. J. Mol. Sci.
19
E3820
2018
Homo sapiens
-
Scifo, E.; Szwajda, A.; Soliymani, R.; Pezzini, F.; Bianchi, M.; Dapkunas, A.; Debski, J.; Uusi-Rauva, K.; Dadlez, M.; Gingras, A.C.; Tyynelae, J.; Simonati, A.; Jalanko, A.; Baumann, M.H.; Lalowski, M.
Proteomic analysis of the palmitoyl protein thioesterase 1 interactome in SH-SY5Y human neuroblastoma cells
J. Proteomics
123
42-53
2015
Homo sapiens (P50897), Homo sapiens
Shyng, C.; Macauley, S.L.; Dearborn, J.T.; Sands, M.S.
Widespread expression of a membrane-tethered version of the soluble lysosomal enzyme palmitoyl protein thioesterase-1
JIMD Rep.
36
85-92
2017
Homo sapiens
EXTERNAL LINKS (specific for EC-Number 3.1.2.22)
Transporter Classification Database (TCDB): 4.C.3.2.1, 8.A.161.1.1
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