Information on EC 3.2.1.113 - mannosyl-oligosaccharide 1,2-alpha-mannosidase and Organism(s) Homo sapiens

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.2.1.113
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RECOMMENDED NAME
GeneOntology No.
mannosyl-oligosaccharide 1,2-alpha-mannosidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of the terminal (1->2)-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide Man9(GlcNAc)2
show the reaction diagram
structure and function of enzyme from subgroups 1 to 3, overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of O-glycosyl bond
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
protein N-glycosylation processing phase (plants and animals)
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N-Glycan biosynthesis
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Various types of N-glycan biosynthesis
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
2-alpha-mannosyl-oligosaccharide alpha-D-mannohydrolase
Involved in the synthesis of glycoproteins.
CAS REGISTRY NUMBER
COMMENTARY hide
9068-25-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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endoplasmic reticulum mannosidase I knockdown does not affect binding of an endoplasmic reticulum-associated degradation substrate glycoprotein to EDEM1
metabolism
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part of N-glycan pathway
physiological function
-
endoplasmic reticulum mannosidase I activity is not required for association of H2a with EDEM1
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
2 alpha-D-mannose
show the reaction diagram
-
-
-
-
?
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + H2O
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + D-mannose
show the reaction diagram
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-
-
-
?
alpha1-antitrypsin null (Hong Kong) + H2O
? + D-mannose
show the reaction diagram
-
-
-
-
?
alpha1-antitrypsin null + H2O
? + D-mannose
show the reaction diagram
-
-
-
-
?
alpha1-antitrypsin null + H2O
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + D-mannose
show the reaction diagram
-
-
-
-
?
alpha1-antitrypsin null + H2O
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + D-mannose
show the reaction diagram
-
-
-
-
?
alpha1-antitrypsin null + H2O
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + D-mannose
show the reaction diagram
-
-
-
-
?
alpha1-antitrypsin null + H2O
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + D-mannose
show the reaction diagram
-
-
-
-
?
alpha1-antitrypsin null + H2O
alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + D-mannose
show the reaction diagram
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overexpression of each Golgi alpha1,2-mannosidase enhances alpha1-antitrypsin null degradation and trimming of its N-glycans to alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose
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-
?
Glcalpha(1-3)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-6)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Glcalpha(1-3)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-3)[Manalpha(1-6)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + D-mannose
show the reaction diagram
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-
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Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-6)[Manalpha(1-2)Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-6)[Manalpha(1-2)Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-6)[Manalpha(1-2)Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-6)[Manalpha(1-2)Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-2)Manalpha(1-3)[Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 3 alpha-D-mannose
show the reaction diagram
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-
-
-
?
Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-6)[Manalpha(1-2)Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-3)[Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 4 alpha-D-mannose
show the reaction diagram
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-
-
-
?
Manalpha(1-2)Manalpha(1-3)Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc + 2 H2O
(Man)5GlcNAc + 2 D-mannose
show the reaction diagram
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-
-
-
?
Manalpha(1-2)Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc + 4 H2O
(Man)5GlcNAc + 4 D-mannose
show the reaction diagram
Manalpha(1-2)Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
(Man)6(GlcNAc)2 + D-mannose
show the reaction diagram
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i.e. (Man)9(GlcNAc)2
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-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
(Man)5(GlcNAc)2-Asn + D-mannose
show the reaction diagram
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i.e. GPIV
major product formed, 3.5 mol mannose/mol GP IV per h, i.e. GPI
?
Manalpha(1->2)Manalpha(1->2)Manalpha(1->3)[Manalpha(1->2)Manalpha(1->6)[Manalpha(1->2)Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + H2O
Manalpha(1->2)Manalpha(1->3)[Manalpha(1->2)Manalpha(1->6)[Manalpha(1->2)Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + D-mannose
show the reaction diagram
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-
-
?
Manalpha(1->2)Manalpha(1->3)[Manalpha(1->2)Manalpha(1->6)[Manalpha(1->2)Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + H2O
Manalpha(1->3)[Manalpha(1->2)Manalpha(1->6)[Manalpha(1->2)Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + D-mannose
show the reaction diagram
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-
-
?
Manalpha(1->3)[Manalpha(1->2)Manalpha(1->6)[Manalpha(1->2)Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + H2O
Manalpha(1->3)[Manalpha(1->6)[Manalpha(1->2)Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + D-mannose
show the reaction diagram
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-
-
?
Manalpha(1->3)[Manalpha(1->6)[Manalpha(1->2)Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + H2O
Manalpha(1->3)[Manalpha(1->6)[Manalpha(1->3)]Manalpha(1->6)]Manbeta(1->4)GlcNAcbeta(1->4)GlcNAcbeta-2-pyridylamine + D-mannose
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + H2O
alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,3)-[alpha-D-mannopyranosyl-(1,2)-alpha-D-mannopyranosyl-(1,6)]-alpha-D-mannopyranosyl-(1,6)]-beta-D-mannopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1,4)-2-(acetylamino)-2-deoxy-beta-D-glucopyranose + D-mannose
show the reaction diagram
-
-
-
-
?
alpha1-antitrypsin null + H2O
? + D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-2)Manalpha(1-3)Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc + 2 H2O
(Man)5GlcNAc + 2 D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-2)Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc + 4 H2O
(Man)5GlcNAc + 4 D-mannose
show the reaction diagram
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function of enzyme from subgroup 1 to 3
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-
?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
the activity of isoform ManIC is 94% in the presence of 15 mM Zn2+ and 50% in the presence of 1.5 mM Zn2+ compared with that of the original solution
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-deoxymannojirimycin
brefeldin A
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known inhibitor of vesicle transport, ablated intracellular turnover of the radiolabeled molecules. Plus digestion with potato acid phosphatase implies that phosphorylation of ER mannosidase I is responsible for the altered electrophoretic mobility
Chloroquine
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lysosomotrophic amine capable of raising the pH of acidic intracellular compartments, added to the medium with weak inhibition
EDTA
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Ca2+ restores
EGTA
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complete loss of acvtivity at 0.1 mM, Ca2+ restores
kifunensine
lactacystin
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irreversible inhibitor of multicatalytic proteasomes, only a minor effect on the disappearance of radiolabeled human ER mannosidase I
leupeptin
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lysosomal protease inhibitor, intracellular turnover of pulse-radiolabeled recombinant human ER mannosidase I is substantially inhibited
swainsonine
isoform ManIC shows 86% activity at 0.5 mM swainsonine
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.015 - 0.51
Manalpha(1-2)Manalpha(1-3)Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc
0.068 - 0.26
Manalpha(1-2)Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.03 - 3.7
Manalpha(1-2)Manalpha(1-3)Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc
0.000026 - 3.7
Manalpha(1-2)Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manalpha(1-6)Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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modeling studies, molecular basis of difference in specificity, distinction of subgroup 1 and 2
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.3
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mutant enzyme E330Q
6 - 6.5
isoform ManIC
6.5 - 7
isoform ManIA2
6.5
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mutant enzyme T688A, R461A and R461L
6.6
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mutant enzyme E330Q/E599Q and D463N/E599Q
6.7
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mutant enzyme E599Q
6.9
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mutant enzyme H524A
7.1
-
wild-type enzyme
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35
isoform ManIC
40
isoform ManIA2
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
subgroup 2 enzymes
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
58000
x * 58000, SDS-PAGE; x * 58000, SDS-PAGE
71000
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x * 71000, deduced from gene sequence, type-II transmembrane protein
79000
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Western blotting of cell lysates, transiently expressed recombinant human ER mannosidase I is absent from mock transfected cells but detected as a single immunoreactive 79 kDa band following transient expression
82000
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SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
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three potential N-glycosylation sites, one of which is used
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
co-complex with an uncleaved thiodisaccharide substrate analog, hanging drop vapor diffusion method
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docking studies
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in complex with kifunensine
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 6
isoform ManIC is stable (more than 75% activity) in the pH range of 5.5-6.0 at 37°C for 90 min
715684
6.5 - 8
isoform ManIA2 is stable (more than 75% activity) in the pH range of 6.5-8.0 at 37°C for 90 min
715684
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 30
isoform ManIA2 shows more than 75% activity at 30°C in the presence of Ca2+, and more than 75% activity at 20°C in the absence of Ca2+
40
isoform ManIC shows more than 75% activity at 40°C in the absence and presence of Ca2+
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ER degradation-enhancing-mannosidase-like protein
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
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Talon Co2+ affinity resin column chromatography; Talon Co2+ affinity resin column chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli JM109 (DE3) cells; expressed in Escherichia coli JM109 (DE3) cells
expressed in Pichia pastoris
-
overexpressed in HEK-293 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
homozygosity for the minor A allele rs4567(A), but not rs4567(G), suppresses ERManI translation under endoplasmic reticulum stress conditions
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increased expression after anti-CD3 stimulation; T cell receptor signaling enhances mRNA levels of MIa,b,c
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D463N/E599Q
-
pH-optimum is 6.6 compared to 7.1 for wild-type enzyme, kcat/Km is 8.3fold lower than wild-type value
E220Q
-
the mutant contains a conserved acidic amino acid mutation that abolishes alpha1,2-mannosidase enzyme activity
E330Q/E599Q
-
pH-optimum is 6.6 compared to 7.1 for wild-type enzyme, kcat/Km is 340000fold lower than wild-type value
H524A
-
pH-optimum is 6.9 compared to 7.1 for wild-type enzyme, kcat/Km is 28.3fold lower than wild-type value
R334A
-
mutant enzyme is not detected in the culture medium, kcat/Km is 28.3fold lower than wild-type value
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
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development of anti-cancer therapies