BRENDA - Enzyme Database show
show all sequences of 3.6.5.6

Alpha-crystallin expression affects microtubule assembly and prevents their aggregation

Xi, J.H.; Bai, F.; McGaha, R.; Andley, U.P.; FASEB J. 20, 846-857 (2006)

Data extracted from this reference:

Inhibitors
Inhibitors
Commentary
Organism
Structure
tubulin
unassembled tubulin denatures relatively easily, and the denatured tubulin can inhibit the assembly itself
Mus musculus
Molecular Weight [Da]
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
49800
-
theoretical molecular mass, beta tubulin
Bos taurus
49800
-
theoretical molecular mass, beta tubulin
Mus musculus
50000
-
alpha-beta tubulin
Bos taurus
50000
-
determined by SDS-PAGE and immunoblot analysis
Mus musculus
50130
-
theoretical molecular mass, alpha tubulin
Bos taurus
50130
-
theoretical molecular mass, alpha tubulin
Mus musculus
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
GTP + H2O
Mus musculus
-
GDP + phosphate
-
-
ir
GTP + H2O
Bos taurus
-
GDP + phosphate
-
-
ir
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Bos taurus
-
-
-
Mus musculus
-
-
-
Purification (Commentary)
Commentary
Organism
microtubules are prepared from freshly isolated lens epithelial fractions from mice
Mus musculus
Source Tissue
Source Tissue
Commentary
Organism
Textmining
brain
-
Bos taurus
-
lens
lens epithelial cell
Mus musculus
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
GTP + H2O
-
686631
Mus musculus
GDP + phosphate
-
-
-
ir
GTP + H2O
-
686631
Bos taurus
GDP + phosphate
-
-
-
ir
Subunits
Subunits
Commentary
Organism
heterodimer
-
Bos taurus
heterodimer
-
Mus musculus
More
elongated microtubule protofilaments form at 37°C in the presence of GTP and later close into hollow cylindrical polymers
Mus musculus
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
elongated microtubule protofilaments form at 37°C in the presence of GTP and later close into hollow cylindrical polymers
Mus musculus
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.0077
-
GTP
in the presence of alphaA-crystallin
Bos taurus
0.008
-
GTP
in the presence of alphaB-crystallin
Bos taurus
0.0083
-
GTP
-
Bos taurus
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
6.8
-
assembly of microtubules
Mus musculus
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
tubulin
unassembled tubulin denatures relatively easily, and the denatured tubulin can inhibit the assembly itself
Mus musculus
Molecular Weight [Da] (protein specific)
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
49800
-
theoretical molecular mass, beta tubulin
Bos taurus
49800
-
theoretical molecular mass, beta tubulin
Mus musculus
50000
-
alpha-beta tubulin
Bos taurus
50000
-
determined by SDS-PAGE and immunoblot analysis
Mus musculus
50130
-
theoretical molecular mass, alpha tubulin
Bos taurus
50130
-
theoretical molecular mass, alpha tubulin
Mus musculus
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
GTP + H2O
Mus musculus
-
GDP + phosphate
-
-
ir
GTP + H2O
Bos taurus
-
GDP + phosphate
-
-
ir
Purification (Commentary) (protein specific)
Commentary
Organism
microtubules are prepared from freshly isolated lens epithelial fractions from mice
Mus musculus
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
brain
-
Bos taurus
-
lens
lens epithelial cell
Mus musculus
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
GTP + H2O
-
686631
Mus musculus
GDP + phosphate
-
-
-
ir
GTP + H2O
-
686631
Bos taurus
GDP + phosphate
-
-
-
ir
Subunits (protein specific)
Subunits
Commentary
Organism
heterodimer
-
Bos taurus
heterodimer
-
Mus musculus
More
elongated microtubule protofilaments form at 37°C in the presence of GTP and later close into hollow cylindrical polymers
Mus musculus
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
elongated microtubule protofilaments form at 37°C in the presence of GTP and later close into hollow cylindrical polymers
Mus musculus
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.0077
-
GTP
in the presence of alphaA-crystallin
Bos taurus
0.008
-
GTP
in the presence of alphaB-crystallin
Bos taurus
0.0083
-
GTP
-
Bos taurus
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
6.8
-
assembly of microtubules
Mus musculus
Other publictions for EC 3.6.5.6
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
733717
Geyer
A mutation uncouples the tubul ...
Saccharomyces cerevisiae
eLife
4
e10113
2015
-
-
1
-
3
-
-
-
1
1
-
1
-
1
-
-
1
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
3
-
-
-
-
-
1
1
-
1
-
-
-
1
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
3
3
-
-
-
733983
Modi
FtsZDr, a tubulin homologue in ...
Deinococcus radiodurans
Int. J. Biochem. Cell Biol.
50
38-46
2014
1
-
1
-
-
-
1
1
-
5
-
2
-
2
-
-
1
-
-
-
1
-
4
-
1
-
-
-
1
-
-
-
-
-
-
1
-
1
-
-
-
-
-
1
-
1
-
5
-
2
-
-
-
1
-
-
1
-
4
-
1
-
-
-
1
-
-
-
-
2
2
-
-
-
733253
Nakajima
Enhancement of tubulin polymer ...
Sus scrofa
Biochem. Biophys. Res. Commun.
425
225-229
2012
-
-
-
-
-
-
3
-
2
1
-
1
-
1
-
-
-
-
-
2
-
-
2
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
2
1
-
1
-
-
-
-
-
2
-
-
2
-
1
-
-
-
1
-
-
-
-
2
2
-
-
-
698103
Inoue
New model for assembly dynamic ...
Escherichia coli
Genes Cells
14
435-444
2009
-
-
1
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
698984
Cormier
The PN2-3 domain of centrosoma ...
Ovis aries
J. Biol. Chem.
284
6909-6917
2009
-
-
1
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
699587
Mendieta
Structural and functional mode ...
Methanocaldococcus jannaschii
J. Mol. Biol.
390
17-25
2009
-
-
-
-
-
-
-
-
-
3
-
-
-
1
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
685385
Layden
Structural model of a complex ...
Ovis aries
Biochim. Biophys. Acta
1783
964-973
2008
1
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
1
-
-
1
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
1
-
1
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
685083
Wang
Insight into the GTPase activi ...
Bos taurus
Biochemistry
46
10595-10602
2007
2
-
-
-
-
-
2
-
-
-
-
1
-
1
-
-
1
-
-
1
-
1
1
1
1
-
-
7
1
-
-
-
-
-
-
2
-
-
-
-
-
-
-
2
-
-
-
-
-
1
-
-
-
1
-
1
-
1
1
1
1
-
-
7
1
-
-
-
-
-
-
-
-
-
686670
Srivastava
Rotenone inhibits mammalian ce ...
Capra hircus
FEBS J.
274
4788-4801
2007
-
-
-
-
-
-
1
-
-
-
-
1
-
1
-
-
1
-
-
1
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
1
-
1
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
687396
Tang
Iteron-binding ORF157 and FtsZ ...
Bacillus thuringiensis
J. Bacteriol.
189
8053-8058
2007
-
-
1
-
-
-
-
-
-
1
1
1
-
4
-
-
1
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
1
1
1
-
-
-
1
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
667729
Buey
The nucleotide switch of tubul ...
Bos taurus, Rattus norvegicus
Biochemistry
45
5933-5938
2006
-
-
-
-
-
-
-
-
-
-
-
2
-
2
-
-
-
-
-
2
-
-
4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
2
-
-
4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
668356
Nogales
Structural mechanisms underlyi ...
Prosthecobacter sp.
Curr. Opin. Struct. Biol.
16
221-229
2006
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
686631
Xi
Alpha-crystallin expression af ...
Bos taurus, Mus musculus
FASEB J.
20
846-857
2006
-
-
-
-
-
-
1
-
-
-
6
2
-
2
-
-
1
-
-
2
-
-
2
3
1
-
-
3
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
6
2
-
-
-
1
-
2
-
-
2
3
1
-
-
3
1
-
-
-
-
-
-
-
-
-
686645
Gupta
Dietary antioxidant curcumin i ...
Capra hircus
FEBS J.
273
5320-5332
2006
-
-
-
-
-
-
1
-
-
-
-
1
-
1
-
-
1
-
-
1
2
-
1
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
1
-
1
2
-
1
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
687534
Thakur
GTPase activity of mycobacteri ...
Escherichia coli, Mycobacterium tuberculosis
J. Biol. Chem.
281
40107-40113
2006
-
-
2
-
-
-
1
2
-
-
-
2
-
5
-
2
2
-
-
-
-
-
2
2
2
-
-
-
-
-
-
-
-
1
-
-
-
2
-
-
-
-
-
1
-
2
-
-
-
2
-
-
2
2
-
-
-
-
2
2
2
-
-
-
-
-
-
1
-
-
-
-
-
-
669575
Sontag
In vitro assembly and GTP hydr ...
Prosthecobacter sp.
J. Cell Biol.
169
233-238
2005
-
-
1
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
669786
Banerjee
Sulfonamide drugs binding to t ...
Capra hircus
J. Med. Chem.
48
547-555
2005
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
656124
Brannstrom
Molecular dissection of GTP ex ...
Homo sapiens
J. Biol. Chem.
278
16651-16657
2003
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
1
-
-
-
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
654625
Gupta
Perturbation of microtubule po ...
Capra hircus
Biochemistry
41
13029-13038
2002
1
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
654590
Dougherty
Mutation in the beta-tubulin s ...
Saccharomyces cerevisiae
Biochemistry
40
15725-15732
2001
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
656756
Anders
Dominant-lethal alpha-tubulin ...
Saccharomyces cerevisiae
Mol. Biol. Cell
12
3973-3986
2001
1
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644210
Tian
Tubulin folding cofactors as G ...
Bos taurus, Gallus gallus, Mus musculus
J. Biol. Chem.
274
24054-24058
1999
1
-
-
-
-
-
-
-
1
-
-
3
-
3
-
-
2
-
-
2
-
-
3
2
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
-
-
3
-
-
-
2
-
2
-
-
3
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644211
Roychowdhury
G Protein alpha subunits activ ...
Bos taurus, Ovis aries
J. Biol. Chem.
274
13485-13490
1999
-
-
-
-
-
-
-
-
-
-
-
2
-
2
-
-
1
-
-
1
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
1
-
1
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644209
Banerjee
Differential effects of colchi ...
Bos taurus
Biochem. Biophys. Res. Commun.
231
698-700
1997
1
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
1
-
-
1
-
1
1
1
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
1
-
1
-
1
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644206
Mejillano
Studies on the nocodazole-indu ...
Bos taurus
Arch. Biochem. Biophys.
336
130-138
1996
2
-
-
-
-
-
2
-
-
1
-
1
-
1
-
-
1
-
-
1
-
1
5
1
1
1
-
-
1
-
-
-
-
-
-
2
-
-
-
-
-
-
-
2
-
-
-
1
-
1
-
-
-
1
-
1
-
1
5
1
1
1
-
-
1
-
-
-
-
-
-
-
-
-
644207
Soto
Calcium and gadolinium ions st ...
Gallus gallus
Biochemistry
35
6337-6344
1996
-
-
-
-
-
-
-
-
-
3
-
1
-
1
-
-
1
-
-
1
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
1
-
-
-
1
-
1
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644208
Best
The ras-related GTPase Rac1 bi ...
Rattus norvegicus
J. Biol. Chem.
271
3756-3762
1996
2
-
1
-
-
-
-
-
1
-
1
1
-
1
-
-
1
-
-
4
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
2
-
1
-
-
-
-
-
-
-
-
1
-
1
1
-
-
-
1
-
4
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644205
Sage
Site directed mutagenesis of p ...
Bos taurus, Gallus gallus, Saccharomyces cerevisiae
Biochemistry
34
7409-7419
1995
-
-
1
-
-
-
-
-
-
-
-
3
-
4
-
-
1
-
-
2
-
-
3
3
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
1
-
2
-
-
3
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644202
Roychowdhury
Tubulin-G protein association ...
Bos taurus, Gallus gallus
Biochemistry
33
9800-9805
1994
-
-
-
-
-
-
-
-
-
-
-
2
-
2
-
-
1
-
-
2
-
-
2
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
1
-
2
-
-
2
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644203
Perez-Ramirez
The colchicine-induced GTPase ...
Bos taurus
Biochemistry
33
6253-6261
1994
7
-
-
-
-
-
-
6
-
1
2
1
-
1
-
-
1
-
-
1
1
-
1
1
1
-
-
1
-
-
1
-
-
-
-
7
-
-
-
-
-
-
-
-
-
6
-
1
2
1
-
-
-
1
-
1
1
-
1
1
1
-
-
1
-
-
1
-
-
-
-
-
-
-
644204
Perez-Ramirez
Cosolvent modulation of the tu ...
Bos taurus
Biochemistry
33
6262-6267
1994
2
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
1
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
1
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644201
Burns
-
Kinetics of GTP hydrolysis dur ...
Gallus gallus
Biochem. J.
277
239-243
1991
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644200
Caplow
Mechanism of the microtubule G ...
Bos taurus, Sus scrofa
J. Biol. Chem.
265
8935-8941
1990
-
-
-
-
-
-
2
-
-
-
5
2
-
2
-
-
2
-
-
2
-
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
5
2
-
-
-
2
-
2
-
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644199
Monasterio
Inhibition of tubulin self-ass ...
Bos taurus
Biochemistry
26
6091-6099
1987
1
-
-
-
-
-
3
2
-
-
1
1
-
1
-
-
1
-
-
1
-
-
2
1
-
-
-
1
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
3
-
2
-
-
1
1
-
-
-
1
-
1
-
-
2
1
-
-
-
1
-
-
-
-
-
-
-
-
-
-