Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.2.1.114 - mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC3.2.1.114
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
The enzyme, found in plants and animals, participates in the processing of N-glycans in the Golgi apparatus. It removes two mannosyl residues, one linked by alpha1,3 linkage, and the other linked by alpha1,6 linkage, both of which are removed by the same catalytic site. The enzyme is sensitive to swainsonine.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
mannosidase ii, jack bean alpha-mannosidase, man2a1, alpha-mannosidase iix, dgmii, manii, alpha-mii, drosophila gmii, alpha-d-mannosidase ii, afams1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alpha-1,3-mannosidase
-
-
alpha-D-mannosidase II
-
-
-
-
alpha-mannosidase II
alpha-mannosidase III
-
-
-
-
alpha-mannosidase IIx
-
homolog to alpha-mannosidase II with different substrate specificity
alpha1-3,6-mannosidase
-
-
-
-
Bt3991
-
-
class II alpha-D-mannosidase
-
-
exo-1,3-1,6-alpha-mannosidase
-
-
-
-
GlcNAc transferase I-dependent alpha1,3[alpha1,6]mannosidase
-
-
-
-
Golgi alpha-mannosidase II
Golgi mannosidase IIx
-
close homolog to Golgi mannosidase II with different substrate specificity
human type II alpha-mannosidase
-
-
Man II
-
-
-
-
MAN IIx
-
-
-
-
ManII
-
-
ManIII
-
-
-
-
mannosidase II
-
-
-
-
mannosidase, exo-1,3-1,6-alpha-
-
-
-
-
mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase
-
-
-
-
neutral alpha-mannosidase
-
-
additional information
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis
-
-
hydrolysis of O-glycosyl bond
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
(1->3)-(1->6)-mannosyl-oligosaccharide alpha-D-mannohydrolase (configuration-retaining)
The enzyme, found in plants and animals, participates in the processing of N-glycans in the Golgi apparatus. It removes two mannosyl residues, one linked by alpha1,3 linkage, and the other linked by alpha1,6 linkage, both of which are removed by the same catalytic site. The enzyme is sensitive to swainsonine.
CAS REGISTRY NUMBER
COMMENTARY hide
349553-33-9
alpha-mannosidase III
82047-77-6
alpha-mannosidase II
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(Man)9GlcNAc + H2O
(Man)5GlcNAc + D-mannose
show the reaction diagram
-
hydrolysis to (Man)5GlcNAc in the presence of Fe2+, Co2+, and Mn2+. Without activating cations the main reaction product is (Man)8GlcNAc
-
-
?
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
2 alpha-D-mannopyranose
show the reaction diagram
-
Bt3991 displays particularly high activity against alpha-1,3-mannobiose
-
-
?
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
4-methyl-umbelliferyl-alpha-D-mannopyranoside + H2O
4-methyl-umbelliferone + alpha-D-mannopyranose
show the reaction diagram
-
30 min, 37°C
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
4-nitrophenyl alpha-D-mannopyranoside + H2O
4-nitrophenol + alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn + H2O
D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn + alpha-D-mannose
show the reaction diagram
-
i.e. glycopeptide III, derived from ovalbumin, no hydrolysis of the innermost alpha-1,6-linked or the alpha-1,2-linked mannose
i.e. glycopeptide II
?
GlcNAcMan5GlcNAc2 + H2O
?
show the reaction diagram
-
-
-
-
?
Man5GlcNAc2 + H2O
Man3GlcNAc2 + 2 alpha-D-mannopyranose
show the reaction diagram
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
ovalbumin + H2O
?
show the reaction diagram
-
-
-
-
?
yeast mannan + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
Man5GlcNAc2 + H2O
Man3GlcNAc2 + 2 alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase IIx, M6Gn2 is the primary target in vivo, integral part of N-glycan biosynthesis
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase II, biosynthesis of N-glycans
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
-
Fe2+
-
is more activated by Fe2+ than Co2+
Mn2+
-
-
additional information
-
no effect with Zn2+, Ca2+, and Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-allyl-ester-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-benzylamino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-allyl ester benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-benzylamino)cyclopentane
-
-
(1R,6R,7R,8S)-7,8-dihydroxy-5-thia-1-thioniabicyclo[4.3.0]nonane chloride
-
synthetic inhibitor, selective and potent inhibition at 1 mM, 97% inhibition of the activity of the liver lysosomal fraction at pH 4.0, 100% at pH 6.5
(2R,3R,4S)-2-[[((1R)-2-hydroxy-1-[4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl]ethyl)amino] methyl]pyrrolidine-3,4-diol
-
inhibits the proliferation of primary cells and cell lines of different origins, irrespective of Bcl-2 expression levels, inducing a G2/Mcell cycle arrest and by modification of genes involved in cell cycle progression and survival, IC50 in vivo and cytotoxic effects in different cell lines, overview
(2R,3R,4S)-2[([(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]amino)-methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-1-[1,1'-biphenyl]-4-yl-2-hydroxyethyl)amino]-methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-2-hydroxy-1-(4-(phenylmethoxy)phenyl)ethyl)amino]methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-2-hydroxy-1-[4-(2-thienyl)phenyl]ethyl)-amino]methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-2-hydroxy-1-[4-(prop-2-enyloxy)phenyl]-ethyl)amino]methyl] pyrrolidine-3,4-diol
-
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
(2S,3R,4S)-2-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]pyrrolidine-3,4-diol
-
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
competitve inhibitor
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxy-1-methylpyrrolidin-2-one
-
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxypyrrolidin-2-one
-
-
(RS)-2-phenylethyl alpha-D-mannopyranosyl sulfoxide
-
-
1,4-Dideoxy-1,4-imino-D-mannitol
-
-
1-deoxymannojirimycin
-
61% inhibition of the activity of the liver lysosomal fraction at pH 4.0, 37% at pH 6.5, at 1 mM
2-phenylethyl alpha-D-mannopyranosyl sulfone
-
-
8,8a-di-epi-swainsonine
-
-
8a-epi-swainsonine
-
-
benzyl alpha-D-mannopyranosyl sulfone
-
-
Cu2+
-
completely inhibits
mannostatin
-
-
Mannostatin A
-
-
meso-aminocyclopentitretrol
-
-
swainsonine
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
no effect with EDTA
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
-
pH 7.0, 37°C, Bt3991
0.55 - 1.065
4-methylumbelliferyl-alpha-D-mannopyranoside
2.7
4-nitrophenyl alpha-D-mannopyranoside
-
pH 7.0, 37°C, Bt3991
0.2
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn
-
i.e. glycopeptide III
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.67
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
-
pH 7.0, 37°C, Bt3991
0.0025
4-nitrophenyl alpha-D-mannopyranoside
-
pH 7.0, 37°C, Bt3991
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.52
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
-
pH 7.0, 37°C, Bt3991
0.0009
4-nitrophenyl alpha-D-mannopyranoside
-
pH 7.0, 37°C, Bt3991
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00322
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-allyl ester benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.00051
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.00091
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.00053
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.00052
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.00088
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-benzylamino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.0044
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-allyl ester benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.0076
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.0081
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.006
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.0066
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.01
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-benzylamino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
0.0233 - 0.0415
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
0.00055 - 0.0032
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
0.75
1-deoxymannojirimycin
-
pH 5.5, liver lysosomal fraction
0.02
8,8a-di-epi-swainsonine
-
liver lysosomal fraction
0.75
8a-epi-swainsonine
-
liver lysosomal fraction
0.00021
mannostatin
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
50
meso-aminocyclopentitretrol
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.025 - 0.05
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
0.075 - 0.2
(2S,3R,4S)-2-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]pyrrolidine-3,4-diol
0.0005 - 0.002
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
0.05 - 0.35
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
0.00075 - 0.075
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxy-1-methylpyrrolidin-2-one
0.075 - 0.75
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxypyrrolidin-2-one
2.5
(RS)-2-phenylethyl alpha-D-mannopyranosyl sulfoxide
Homo sapiens
-
in 50 mM sodium acetate buffer pH 5.8, at 37°C
1.5
2-phenylethyl alpha-D-mannopyranosyl sulfone
Homo sapiens
-
in 50 mM sodium acetate buffer pH 5.8, at 37°C
2
benzyl alpha-D-mannopyranosyl sulfone
Homo sapiens
-
in 50 mM sodium acetate buffer pH 5.8, at 37°C
0.00013
Mannostatin A
Homo sapiens
-
in 50 mM sodium acetate buffer pH 5.8, at 37°C
0.000005 - 0.00005
swainsonine
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
optimal pH is between 6.25 and 6.75
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.25 - 8
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
granularly distributed
Manually annotated by BRENDA team
additional information
-
absent from the endoplasmic reticulum, lysosomes, and autophagosomes
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MA2A1_HUMAN
1144
1
131141
Swiss-Prot
Secretory Pathway (Reliability: 2)
MA2A2_HUMAN
1150
1
130539
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
112000
-
4 * 112000, SDS-PAGE
468000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
-
4 * 112000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
phosphoprotein
-
phosphate is present as serine phosphate
additional information
-
study of posttanslational modifications, sulfate is attached to N-linked oligosaccharide, no proteolytic modification
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R60Q/R73N/L79S/E81S
-
beta1,4-N-acetylglucosaminyltransferase III-ManII mutant with amino acid substitutions in the localization domain of ManII, is expressed in similar amounts as beta1,4-N-acetylglucosaminyltransferase III-ManII, yields antibody glycovariants featuring substantially reduced proportions of bisected non-fucosylated oligosaccharides compared to the non-mutated beta1,4-N-acetylglucosaminyltransferase III-ManII
R73N/L79S/E81S
-
beta1,4-N-acetylglucosaminyltransferase III-ManII mutant with amino acid substitutions in the localization domain of ManII, is expressed in similar amounts as beta1,4-N-acetylglucosaminyltransferase III-ManII, yields antibody glycovariants featuring substantially reduced proportions of bisected non-fucosylated oligosaccharides compared to the non-mutated beta1,4-N-acetylglucosaminyltransferase III-ManII
additional information
-
the mutant gene MAN2A1 from strain Lec36 harbors a point mutation in the active site in one allele and an in-frame deletion of 12 nucleotides in the other allele, compared to parent HEK293T cells, which alters the glycosylation pattern. Expression of the wild-type but not the mutant MAN2A1 alleles in Lec36 cells restores processing of the 19A reporter glycoprotein to complex-type glycosylation, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate fractionation of recombinant enzyme followed by two cobalt chelating chromatography steps
-
partial
-
recombinant protein A fusion of alpha-mannosidase II and IIx, expressed in COS cells
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
alpha-mannosidase II and IIx, expression in COS cells as protein A fusion, overexpression of alpha-mannosidase IIx in CHO-K1 cells
-
expressed in Drosophila melanogaster
-
expressed in HEK293 cells
-
gene MAN2A1 from mutant strain Lec36 and wild-type gene, DNA and amino acid sequence determination and analysis. Wild-type and mutant enzyme expression analysis, overview
-
Golgi mannosidase II gene is located on chromosome 5q21, Golgi mannosidase IIx on chromosome 15q25
-
isolation of partial cDNA clones, gene is located on chromosome 5
-
preparation of expression construct containing 6 x His and tobacco etch virus protease recognition sites in the N-terminus of NAM and integrated into the Pichia pastoris chromosome under inducible alcohol oxygenase promoter. CHO-K1 cells transfected with pNAM-EGFP
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
-
the Lec36 cell line will be useful for expressing therapeutic glycoproteins with hybrid-type glycans and as a sensitive host for detecting mutations in human MAN2A1 causing type II congenital dyserythropoietic anemia
medicine
pharmacology
-
the enzyme is a pharmaceutical target for the design of inhibitors with anti-cancer activity. The QSAR models with the fragmented QM-DFT descriptors may find a useful application in structure-based drug design where pure empirical and forcefield methods reach their limits and where quantum mechanics effects are critical for ligand-receptor interactions. The optimized models will apply in lead optimization processes for alpha-mannosidase II drug developments
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chandrasekaran, E.V.; Savila, M.; Nixon, D.; Mendicino, J.
Purification and properties of alpha-D-mannose:beta-1,2-N-acetylglucosaminyl-transferases and alpha-D-mannosidases from human adenocarcinoma
Cancer Res.
44
4059-4068
1984
Homo sapiens
Manually annotated by BRENDA team
Moremen, K.W.; Touster, O.
Biosynthesis and modification of Golgi mannosidase II in HeLa and 3T3 cells
J. Biol. Chem.
260
6654-6662
1985
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Moremen, K.W.; Robbins, P.W.
Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans
J. Cell Biol.
115
1521-1534
1991
Homo sapiens, Mus musculus (P27046), Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Moremen, K.W.
Golgi alpha-mannosidase II deficiency in vertebrate systems: implications for asparagine-linked oligosaccharide processing in mammals
Biochim. Biophys. Acta
1573
225-235
2002
Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Oh-Eda, M.; Nakagawa, H.; Akama, T.O.; Lowitz, K.; Misago, M.; Moremen, K.W.; Fukuda, M.N.
Overexpression of the Golgi-localized enzyme alpha-mannosidase IIx in Chinese hamster ovary cells results in the conversion of hexamannosyl-N-acetylchitobiose to tetramannosyl-N-acetylchitobiose in the N-glycan-processing pathway
Eur. J. Biochem.
268
1280-1288
2001
Homo sapiens
Manually annotated by BRENDA team
Li, B.; Kawatkar, S.P.; George, S.; Strachan, H.; Woods, R.J.; Siriwardena, A.; Moremen, K.W.; Boons, G.J.
Inhibition of Golgi mannosidase II with mannostatin A analogues: synthesis, biological evaluation, and structure-activity relationship studies
Chembiochem
5
1220-1227
2004
Homo sapiens
Manually annotated by BRENDA team
Siriwardena, A.; Strachan, H.; El-Daher, S.; Way, G.; Winchester, B.; Glushka, J.; Moremen, K.; Boons, G.
Potent and selective inhibition of class II alpha-D-mannosidase activity by a bicyclic sulfonium salt
ChemBioChem
6
845-848
2005
Homo sapiens
Manually annotated by BRENDA team
Ferrara, C.; Bruenker, P.; Suter, T.; Moser, S.; Puentener, U.; Umana, P.
Modulation of therapeutic antibody effector functions by glycosylation engineering: influence of Golgi enzyme localization domain and co-expression of heterologous beta1,4-N-acetylglucosaminyltransferase III and Golgi alpha-mannosidase II
Biotechnol. Bioeng.
93
851-861
2006
Homo sapiens
Manually annotated by BRENDA team
Crispin, M.; Aricescu, A.R.; Chang, V.T.; Jones, E.Y.; Stuart, D.I.; Dwek, R.A.; Davis, S.J.; Harvey, D.J.
Disruption of alpha-mannosidase processing induces non-canonical hybrid-type glycosylation
FEBS Lett.
581
1963-1968
2007
Homo sapiens
Manually annotated by BRENDA team
Kuokkanen, E.; Smith, W.; Maekinen, M.; Tuominen, H.; Puhka, M.; Jokitalo, E.; Duvet, S.; Berg, T.; Heikinheimo, P.
Characterization and subcellular localization of human neutral class II alpha-mannosidase cytosolic enzymes/free oligosaccharides/glycosidehydrolase family 38/M2C1/N-glycosylation
Glycobiology
17
1084-1093
2007
Homo sapiens
Manually annotated by BRENDA team
Fiaux, H.; Kuntz, D.A.; Hoffman, D.; Janzer, R.C.; Gerber-Lemaire, S.; Rose, D.R.; Juillerat-Jeanneret, L.
Functionalized pyrrolidine inhibitors of human type II alpha-mannosidases as anti-cancer agents: optimizing the fit to the active site
Bioorg. Med. Chem.
16
7337-7346
2008
Canavalia ensiformis, Drosophila melanogaster, Drosophila melanogaster (Q24451), Homo sapiens
Manually annotated by BRENDA team
Bello, C.; Cea, M.; Bello, G.D.; Garuti, A.; Rocco, I.; Cirmena, G.; Moran, E.; Nahimana, A.; Duchosal, M.A.; Fruscione, F.; Pronzato, P.; Grossi, F.; Patrone, F.; Ballestrero, A.; Dupuis, M.; Sordat, B.; Nencioni, A.; Vogel, P.
Novel 2-[(benzylamino)methyl]pyrrolidine-3,4-diol derivatives as alpha-mannosidase inhibitors and with antitumor activities against hematological and solid malignancies
Bioorg. Med. Chem.
18
3320-3334
2010
Homo sapiens
Manually annotated by BRENDA team
Crispin, M.; Chang, V.T.; Harvey, D.J.; Dwek, R.A.; Evans, E.J.; Stuart, D.I.; Jones, E.Y.; Lord, J.M.; Spooner, R.A.; Davis, S.J.
A human embryonic kidney 293T cell line mutated at the Golgi alpha-mannosidase II locus
J. Biol. Chem.
284
21684-21695
2009
Homo sapiens
Manually annotated by BRENDA team
Zhu, Y.; Suits, M.D.; Thompson, A.J.; Chavan, S.; Dinev, Z.; Dumon, C.; Smith, N.; Moremen, K.W.; Xiang, Y.; Siriwardena, A.; Williams, S.J.; Gilbert, H.J.; Davies, G.J.
Mechanistic insights into a Ca2+-dependent family of alpha-mannosidases in a human gut symbiont
Nat. Chem. Biol.
6
125-132
2010
Homo sapiens
Manually annotated by BRENDA team
Polakova, M.; Sestak, S.; Lattova, E.; Petrus, L.; Mucha, J.; Tvaroska, I.; Kona, J.
alpha-D-mannose derivatives as models designed for selective inhibition of Golgi alpha-mannosidase II
Eur. J. Med. Chem.
46
944-952
2011
Homo sapiens
Manually annotated by BRENDA team
Cheng, T.; Chan, T.; Tsou, E.; Chang, S.; Yun, W.; Yang, P.; Wu, Y.; Cheng, W.
From natural product-inspired pyrrolidine scaffolds to the development of new human Golgi alpha-mannosidase II inhibitors
Chemistry
8
2600-2604
2013
Homo sapiens
-
Manually annotated by BRENDA team
Bobovska, A.; Tvaro?ka, I.; Kona, J.
Using DFT methodology for more reliable predictive models Design of inhibitors of Golgi alpha-mannosidase II
J. Mol. Graph. Model.
66
47-57
2016
Homo sapiens
Manually annotated by BRENDA team