Information on EC 2.3.1.78 - heparan-alpha-glucosaminide N-acetyltransferase

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The expected taxonomic range for this enzyme is: Euarchontoglires

EC NUMBER
COMMENTARY
2.3.1.78
-
RECOMMENDED NAME
GeneOntology No.
heparan-alpha-glucosaminide N-acetyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
acetyl-CoA + heparan sulfate alpha-D-glucosaminide = CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
-
-
-
acetyl-CoA + heparan sulfate alpha-D-glucosaminide = CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
di-iso ping-pong mechanism
-
acetyl-CoA + heparan sulfate alpha-D-glucosaminide = CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
transmembranal reaction mechanism
-
acetyl-CoA + heparan sulfate alpha-D-glucosaminide = CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
di-iso ping-pong mechanism; transmembranal reaction mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
Acyl group transfer
-
-
PATHWAY
KEGG Link
MetaCyc Link
Glycosaminoglycan degradation
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:heparan-alpha-D-glucosaminide N-acetyltransferase
Brings about the acetylation of glucosamine groups of heparan sulfate and heparin from which the sulfate has been removed. Also acts on heparin. Not identical with EC 2.3.1.3 glucosamine N-acetyltransferase or EC 2.3.1.4 glucosamine-phosphate N-acetyltransferase.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
acetyl-CoA:alpha-glucosaminide N-acetyltransferase
-
-
-
-
acetyl-coenzyme A-alpha-glucosaminide N-acetyltransferase
-
-
-
-
acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase
Q3UDW8
-
acetyl-coenzyme:alpha-D-2-amino-glucosamine transferase
-
-
acetyltransferase, alpha-glucosaminide
-
-
-
-
acetyl–coenzyme A:alpha-glucosaminide N-acetyltransferase
Q68CP4
-
GNAT
-
-
heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase
-
-
heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase
-
-
TMEM76
Q68CP4
-
transmembrane protein 76
Q68CP4
-
transmembrane protein 76
Q3UDW8
-
CAS REGISTRY NUMBER
COMMENTARY
79955-83-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
isoform 2
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 4-methylumbelliferyl beta-D-glucosaminide
?
show the reaction diagram
-
substrate activity assay
-
-
?
acetyl-CoA + 4-methylumbelliferyl-alpha-D-glucosaminide
CoA + 4-methylumbelliferyl-N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
-
-
?
acetyl-CoA + 4-methylumbelliferyl-alpha-D-glucosaminide
CoA + 4-methylumbelliferyl-N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q68CP4
-
-
-
?
acetyl-CoA + 4-methylumbelliferyl-alpha-D-glucosaminide
CoA + 4-methylumbelliferyl-N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
-
-
-
?
acetyl-CoA + 4-methylumbelliferyl-alpha-D-glucosaminide
CoA + 4-methylumbelliferyl-N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q3UDW8
-
-
-
?
acetyl-CoA + 4-methylumbelliferyl-beta-D-glucosaminide
CoA + 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide
show the reaction diagram
-
-
-
?
acetyl-CoA + beta-D-glucosamine
CoA + N-acetyl-beta-D-glucosamine
show the reaction diagram
-
-
-
?
acetyl-CoA + beta-D-glucosamine
CoA + N-acetyl-beta-D-glucosamine
show the reaction diagram
-
-
-
?
acetyl-CoA + glucosamine-L-iduronic acid-D-glucosamine
?
show the reaction diagram
-
reduced with NaBH4
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
-
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
-
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q68CP4
-
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q3UDW8
-
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
brings about the acetylation of glucosamine groups of heparan sulfate and heparin from which the sulfate has been removed
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
brings about the acetylation of glucosamine groups of heparan sulfate and heparin from which the sulfate has been removed
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
brings about the acetylation of glucosamine groups of heparan sulfate and heparin from which the sulfate has been removed
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
brings about the acetylation of glucosamine groups of heparan sulfate and heparin from which the sulfate has been removed
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
brings about the acetylation of glucosamine groups of heparan sulfate and heparin from which the sulfate has been removed
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
initial step in heparan sulfate degradation
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q68CP4
mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal storage disorder caused by the inherited deficiency of the lysosomal membrane enzyme acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase, which leads to impaired degradation of heparan sulfate. Structural protein that transports the activated acetyl residues across the cell membrane
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q3UDW8
mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal storage disorder caused by the inherited deficiency of the lysosomal membrane enzyme acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase, which leads to impaired degradation of heparan sulfate. Structural protein that transports the activated acetyl residues across the cell membrane
-
-
?
acetyl-CoA + heparin alpha-D-glucosaminide
CoA + heparin N-acetyl-D-glucosamine
show the reaction diagram
-
also acetylates di- and tetrasaccharide fragments of heparin
-
-
?
acetyl-CoA + phosphatidylethanolamine
CoA + N-acetylphosphatidylethanolamine
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme deficiency leads to Sanfilippo syndrome type C, i.e. mucopolysaccharidosis III C
-
-
-
additional information
?
-
-
enzyme is acetylated at the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate
-
-
-
additional information
?
-
-
enzyme deficiency causes mucopolysaccharidosis type IIIC
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
-
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
-
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-
initial step in heparan sulfate degradation
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q68CP4
mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal storage disorder caused by the inherited deficiency of the lysosomal membrane enzyme acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase, which leads to impaired degradation of heparan sulfate. Structural protein that transports the activated acetyl residues across the cell membrane
-
-
?
acetyl-CoA + heparan sulfate alpha-D-glucosaminide
CoA + heparan sulfate N-acetyl-alpha-D-glucosaminide
show the reaction diagram
-, Q3UDW8
mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal storage disorder caused by the inherited deficiency of the lysosomal membrane enzyme acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase, which leads to impaired degradation of heparan sulfate. Structural protein that transports the activated acetyl residues across the cell membrane
-
-
?
additional information
?
-
-
enzyme deficiency leads to Sanfilippo syndrome type C, i.e. mucopolysaccharidosis III C
-
-
-
additional information
?
-
-
enzyme is acetylated at the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate
-
-
-
additional information
?
-
-
enzyme deficiency causes mucopolysaccharidosis type IIIC
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
membrane-bound enzyme is insensitive, solubilized enzyme is inactivated
alpha-D-glucosamine 6-phosphate
-
weak
alpha-methyl-D-glucose
-
weak
cellobiose
-
weak
coenzyme A
-
noncompetitive
coenzyme A
-
noncompetitive
D-glucosamine
-
competitive inhibitor
desulfo-CoA
-
competitive against acetyl-CoA
diethyl dicarbonate
-
reversible by incubation with hydroxylamine, binds a histidine residue at the active site
dithiothreitol
-
solubilized protein
Hg2+
-
complete inhibition
N-acetyl-alpha-D-glucosamine
-
-
N-acetyl-beta-D-glucosamine
-
noncompetitive against acetyl-CoA
N-acetyl-beta-D-glucosamine
-
-
N-acetyl-beta-D-glucosamine
-
competitive against glucosamine; noncompetitive against acetyl-CoA
N-bromosuccinimide
-
binds a histidine residue at the active site
N-laurylsarcosine
-
1%
p-chloromercuribenzoate
-
binding site is not the active site
p-chloromercuribenzoate
-
-
Zwittergent
-
1%
-
additional information
-
iodoacetamide and N-ethylmaleimide are not inhibitory
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
methyl methanethiolsulfonate
-
activates the membrane-bound enzyme 1.5fold
taurodeoxycholate
-
2 to 3fold increase of activity
Triton X-100
-
2 to 3fold increase of activity
Triton X-100
-
1.5 to 2.5fold stimulation at 0.25% w/v
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0025
-
acetyl-CoA
-
pH 7.0
0.054
-
acetyl-CoA
-
pH 5.0
0.55
-
acetyl-CoA
-
-
0.29
0.3
alpha-D-glucosamine
-
-
0.003
-
beta-D-glucosamine
-
pH 7.0
0.37
-
beta-D-glucosamine
-
pH 5.0
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.032
-
coenzyme A
-
versus acetyl-CoA
0.082
-
coenzyme A
-
versus beta-D-glucosamine
3
7
coenzyme A
-
-
3
-
coenzyme A
-
versus acetyl-CoA
7
-
coenzyme A
-
versus N-acetyl-alpha-D-glucosamine
0.21
-
desulfo-CoA
-
versus beta-D-glucosamine
0.22
-
desulfo-CoA
-
versus acetyl-CoA
15
17
N-acetyl-alpha-D-glucosamine
-
-
15
-
N-acetyl-alpha-D-glucosamine
-
versus glusosamine, no detergents added
16.5
-
N-acetyl-alpha-D-glucosamine
-
versus acetyl-CoA, no detergents added
3.8
-
N-acetyl-beta-D-glucosamine
-
versus acetyl-CoA
5.6
-
N-acetyl-beta-D-glucosamine
-
versus glucosamine
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000017
-
-
leukocyte, substrate 4-methylumbelliferyl-alpha-D-glucosaminide + acetyl-CoA
0.000022
-
-
leukocyte, substrate 4-methylumbelliferyl-beta-D-glucosaminide + acetyl-CoA
0.000058
-
-
fibroblast, substrate 4-methylumbelliferyl-beta-D-glucosaminide + acetyl-CoA
0.000059
-
-
fibroblast, substrate 4-methylumbelliferyl-alpha-D-glucosaminide + acetyl-CoA
0.000673
-
-
lysosomal fraction
0.34
-
-
-
5.351
-
-
-
additional information
-
-
-
additional information
-
-
Sanfilippo syndrome type C patients in comparison
additional information
-
-
mutant A489E, relative activity 23.1%, wild-type 100%; mutant A615T, relative activity 54.9%, wild-type 100%; mutant C76F, relative activity 15.4%, wild-type 100%; mutant D562V, relative activity 22.0%, wild-type 100%; mutant E471K, relative activity 19.8%, wild-type 100%; mutant G262R, relative activity 17.6%, wild-type 100%; mutant G424S, relative activity 18.7%, wild-type 100%; mutant K523Q, relative activity 96.7%, wild-type 100%; mutant L137P, relative activity 17.6%, wild-type 100%; mutant M482K, relative activity 24.2%, wild-type 100%; mutant N273K, relative activity 18.7%, wild-type 100%; mutant P237Q, relative activity 108.8%, wild-type 100%; mutant P283L, relative activity 20.9%, wild-type 100%; mutant P571L, relative activity 22.0%, wild-type 100%; mutant R344C, relative activity 12.1%, wild-type 100%; mutant R344H, relative activity 14.3%, wild-type 100%; mutant S518F, relative activity 30.8%, wild-type 100%; mutant S539C, relative activity 27.5%, wild-type 100%; mutant S541L, relative activity 23.1%, wild-type 100%; mutant V481L, relative activity 114.3%, wild-type 100%; mutant W403C, relative activity 17.6%, wild-type 100%
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
-
-
about
5.5
-
-
above, broad maximum
5.7
-
-
-
5.7
-
-
actvity assay
6.5
8
-
mono-and disaccharide substrates
6.5
-
-
tetrasaccharide substrate
7
-
-
assay at
additional information
-
-
transmembrane transfer
additional information
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
5.5
-
pH 5.0: about 30% of activity maximum, pH 5.5: maximum activity above
5
7
-
half-maximal activity at pH 5.0 and pH 7.0
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
actvity assay
45
-
-
membrane-bound form
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
chromatofocusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
from primary skin fibroblasts, wild-type SF4528 and KD8, and MPS IIIC mutants thereof
Manually annotated by BRENDA team
-
deficiency on leukocytes from patients with Sanfillippo syndrome type C
Manually annotated by BRENDA team
-
deficiency on fibroblasts from patients with Sanfillippo syndrome type C
Manually annotated by BRENDA team
-
the enzyme is present in the lysosomal membranes purified from the normal human skin fibroblasts, but absent in those from the skin fibroblasts of patients with mucopolysaccharidosis IIIC
Manually annotated by BRENDA team
additional information
-
immortalization of cell lines, the cells retain the mucopolysaccharidosis type IIIC phenotype, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
transmembrane enzyme
Manually annotated by BRENDA team
-
lysosomal transmembrane protein
Manually annotated by BRENDA team
-
membrane bound, about one fourth of the activity
Manually annotated by BRENDA team
-
enzyme is acetylated at the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
enzyme is acetylated at the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate; integral membrane protein
Manually annotated by BRENDA team
Q68CP4
enzyme is synthesized as a catalytically inactive 77-kDa precursor that is transported to the lysosomes via an adaptor protein-mediated pathway that involves conserved tyrosine- and dileucine-based lysosomal targeting signals in its C-terminal cytoplasmic domain with a contribution from a dileucine-based signal in the N-terminal cytoplasmic loop. In the lysosome, the precursor is cleaved into a 29-kDa N-terminal alpha-chain and a 48-kDa C-terminal beta-chain, and assembled into active 440-kDa oligomers. The subunits are held together by disulfide bonds between at least two cysteine residues, Cys123 and Cys434, in the lysosomal luminal loops of the enzyme
Manually annotated by BRENDA team
-
membrane-bound, greater part of activity is recovered in microsomes
-
Manually annotated by BRENDA team
additional information
-
enzyme is associated to detergent-resistent microdomains of lysosomal membrane
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
67000
-
-
all missense mutants have a smaller molecular mass of ca. 67 kDa, determined by SDS-PAGE and Western blot analysis
77000
-
-
the four polymorphisms, mutant P237Q, V481L, K523Q and A615T, determined by SDS-PAGE and Western blot analysis; wild-type enzyme, determined by SDS-PAGE and Western blot analysis
240000
-
-
gel filtration
260000
-
Q68CP4
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oligomer
Q68CP4
x * 48000, SDS-PAGE of mature protein
?
-
x * 120000, SDS-PAGE
additional information
-
two major bands are detected by SDS-PAGE, 12000 Da (catalytic subunit) and 145000 Da
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
Q68CP4
enzyme is synthesized as a catalytically inactive 77-kDa precursor that is transported to the lysosomes via an adaptor protein-mediated pathway that involves conserved tyrosine- and dileucine-based lysosomal targeting signals in its C-terminal cytoplasmic domain with a contribution from a dileucine-based signal in the N-terminal cytoplasmic loop. In the lysosome, the precursor is cleaved into a 29-kDa N-terminal alpha-chain and a 48-kDa C-terminal beta-chain, and assembled into active 440-kDa oligomers. The subunits are held together by disulfide bonds between at least two cysteine residues, Cys123 and Cys434, in the lysosomal luminal loops of the enzyme. Proteolytic cleavage may allow the nucleophile residue, His269, in the active site to access the substrate acetyl-CoA in the cytoplasm, for further transfer of the acetyl group to the terminal glucosamine on heparan sulfate
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
5 min, solubilized enzyme, 50% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
solubilized enzyme, not stable
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70°C, membrane-bound enzyme, 12 months stable
-
4°C, solubilized enzyme, 25% loss of activity after 7 days
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partial
-
partially, preparation of lysosomal membranes
-
purified from transfected COS-7 cells by ion-exchange chromatography on a Mono Q HR 5/5 column
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cytogenetic analysis of skin fibroblast cell lines derived from enzyme-deficient mutant parent cell line and immortalized cell lines
-
into the pCTAP vector
-
-
-, Q3UDW8
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A489E
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
A615T
-
mutant represents a rare polymorphism which has no effect on the activity, processing and targeting of the enzyme
C123S
Q68CP4
mutation within the lysosomal luminal loops, complete loss of activity. Mutants does not undergo intralysosomal maturation and does not form the mature oligomer
C151S
Q68CP4
mutation within the lysosomal luminal loops, complete loss of activity. Mutants does not undergo intralysosomal maturation
C305S
Q68CP4
mutation within the predicted cytosolic luminal loops, no loss of activity
C308S
Q68CP4
mutation within the predicted cytosolic luminal loops, no loss of activity
C374S
Q68CP4
mutation within the predicted cytosolic luminal loops, no loss of activity
C434S
Q68CP4
mutation within the lysosomal luminal loops, complete loss of activity. Mutants does not undergo intralysosomal maturation and does not form the mature oligomer
C76F
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
C76F
Q68CP4
mutation within the lysosomal luminal loops, complete loss of activity. Mutants does not undergo intralysosomal maturation
C79S
Q68CP4
mutation within the lysosomal luminal loops, complete loss of activity. Mutants does not undergo intralysosomal maturation
D562V
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
E471K
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
G262R
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
G424S
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
H269A
Q68CP4
complete loss of enzymic activity, intralysosomal processing is retained
H451A
Q68CP4
complete loss of enzymic activity, no processing observed
H605A
Q68CP4
complete loss of enzymic activity, no processing observed
K523Q
-
mutant represents a rare polymorphism which has no effect on the activity, processing and targeting of the enzyme
L137P
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
L208A/I209A
Q68CP4
mutation in a predicted dileucine targeting motif, mutant displays both lysosomal and plasma membrane localization
N273K
-
missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
P237Q
-
mutant represents a rare polymorphism which has no effect on the activity, processing and targeting of the enzyme
P283L
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
P571L
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
R344C
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
R344H
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
S518F
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
S539C
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
S541L
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
V481L
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mutant represents a rare polymorphism which has no effect on the activity, processing and targeting of the enzyme
W403C
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
M482K
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missense mutant, mutation causes misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum
additional information
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c.1030C>T, missense mutation, predicted effect on protein, p.R344C; c.1-1925_118+296del, mutation, 2339-bp deletion including exon 1; c.1209G>T, missense mutation, predicted effect on protein, p.W403C; c.1250+1G>A, splicing site mutation, intron 12; c.1250+2T>C, splicing site mutation, intron 12; c.1271dupG, mutation, predicted effect on protein, p.I425HfsX45; c.1411G>A, missense mutation, predicted effect on protein, p.E471K; c.1441G>T, polymorphism, predicted effect on protein, p.V481L; c.1457G>A, missense mutation, predicted effect on protein, p.G486E; c.1466C>A, missense mutation, predicted effect on protein, p.A489E; c.1516C>T, nonsense mutation, predicted effect on protein, p.R506X, premature termination codon; c.1542+4dupA, splicing site mutation, intron 15; c.1553C>T, missense mutation, predicted effect on protein, p.S518F; c.1622C>T, missense mutation, predicted effect on protein, p.S541L; c.1674C>G, nonsense mutation, predicted effect on protein, p.Y558X, premature termination codon; c.1843G>A, polymorphism, predicted effect on protein, p.A615T; c.410T>C, missense mutation, predicted effect on protein, p.L137P; c.493+1G>A, splicing site mutation, intron 4; c.641delG, mutation, predicted effect on protein, p.Gly214AspfsX62; c.739delA, mutation, predicted effect on protein, p.R247GfsX29; c.744-2A>G, splicing site mutation, intron 7; c.848C>T, missense mutation, predicted effect on protein, p.P283L; c.852-1G>A, splicing site mutation, intron 9; c.887C>A, nonsense mutation, predicted effect on protein, p.S296X, premature termination codon
additional information
Q68CP4
deletion of 12 residues at the C terminus of the enzyme, del624-635, leads to localization of the protein to the plasma membrane, in contrast to the lysosomal localization of wild-type enzyme. Mutant protein does not show maturation and has no enzymic activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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overview, design and synthesis of substrate and internal standard conjugates as substrates in enzyme assay for confirmation of enzyme deficiency using a combination of affinity chromatography and electrospray ionization mass spectrometry
medicine
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mucopolysaccharidosis type IIIC or Sanfilippo syndrome type C is an autosomal recessive disorder caused by deficiency of heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase