064203
reactant: 064239
reactant: 064227
fast: false
name: r2
modifier: 319402
reversible: true
modifier: 319427
type: Reaction
kinetic law: 064263
modifier: 319415
modifier: 319390
product: 064251
reactant: 064215

063387
stoichiometry: 1.0
species: 062212
type: SpeciesReference

062667
stoichiometry: 1.0
species: 062068
type: SpeciesReference

063411
stoichiometry: 1.0
species: 062128
type: SpeciesReference

063039
stoichiometry: 1.0
species: 062068
type: SpeciesReference

063963
stoichiometry: 1.0
species: 062068
type: SpeciesReference

063615
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062823
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062871
units: 061840
value: 3.3E-4
type: LocalParameter

062608
stoichiometry: 1.0
species: 062224
type: SpeciesReference

062715
reversible: true
kinetic law: 062763
type: Reaction
modifier: 318858
product: 062751
fast: false
name: r6
reactant: 062739
modifier: 318846
reactant: 062727

062284
constant: true
units: 061840
value: 6.13E-8
type: Parameter

063207
stoichiometry: 1.0
species: 062188
type: SpeciesReference

061900
exponent: -1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

062883
units: 061924
value: 0.5
type: LocalParameter

062080
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

062596
stoichiometry: 1.0
species: 062104
type: SpeciesReference

062056
constant: true
size: 1.0
spatial dimensions: 3.0
name: c0
type: Compartment

063087
units: 061840
value: 6.0E-4
type: LocalParameter

063975
stoichiometry: 1.0
species: 062212
type: SpeciesReference

063519
reversible: true
fast: false
modifier: 319113
modifier: 319125
product: 063567
reactant: 063531
type: Reaction
kinetic law: 063579
product: 063555
name: r20
reactant: 063543

063123
stoichiometry: 1.0
species: 062236
type: SpeciesReference

061960
exponent: 1.0
scale: 0
multipler: 0.001
kind: DIMENSIONLESS
type: SBMLUnit

064119
units: 061924
value: 0.5
type: LocalParameter

064143
stoichiometry: 1.0
species: 062152
type: SpeciesReference

062691
units: 061996
value: 5.0E-7
type: LocalParameter

062296
constant: false
units: 061924
value: NaN
type: Parameter

062835
stoichiometry: 1.0
species: 062104
type: SpeciesReference

063663
units: 061840
value: 8.3E-4
type: LocalParameter

063603
stoichiometry: 1.0
species: 062128
type: SpeciesReference

062248
constant: true
units: 061792
value: 0.00166112956810631
type: Parameter

064215
stoichiometry: 1.0
species: 062212
type: SpeciesReference

062703
units: 061996
value: 2.5E-6
type: LocalParameter

063375
reversible: true
fast: false
reactant: 063387
name: r1
reactant: 063399
type: Reaction
product: 063411
modifier: 319053
modifier: 319041
kinetic law: 063423

063951
reactant: 063963
name: r9
kinetic law: 064011
type: Reaction
reactant: 063975
product: 063987
modifier: 319306
product: 063999
fast: false
modifier: 319294
modifier: 319281
reversible: true

062344
constant: false
units: 061924
value: NaN
type: Parameter

063027
reversible: true
modifier: 318944
name: r16
type: Reaction
kinetic law: 063075
reactant: 063039
product: 063063
fast: false
reactant: 063051
modifier: 318932

062392
constant: true
units: 061924
value: 0.25
type: Parameter

063303
units: 061840
value: 0.00115
type: LocalParameter

063219
stoichiometry: 1.0
species: 062152
type: SpeciesReference

062631
units: 061840
value: 3.17E-5
type: LocalParameter

061912
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

062044
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

062895
reactant: 062919
modifier: 318895
product: 062931
modifier: 318908
reactant: 062907
kinetic law: 062955
name: r22
reversible: true
product: 062943
type: Reaction
fast: false

061852
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

063675
units: 061924
value: 0.5
type: LocalParameter

064155
stoichiometry: 1.0
species: 062224
type: SpeciesReference

061756
exponent: 1.0
scale: 0
multipler: 1.0E-21
kind: MOLE
type: SBMLUnit

063111
stoichiometry: 1.0
species: 062200
type: SpeciesReference

063927
stoichiometry: 1.0
species: 062116
type: SpeciesReference

062332
constant: true
units: 061948
value: 0.32
type: Parameter

063987
stoichiometry: 1.0
species: 062080
type: SpeciesReference

062380
constant: false
units: 061864
value: NaN
type: Parameter

062943
stoichiometry: 1.0
species: 062140
type: SpeciesReference

064227
stoichiometry: 1.0
species: 062224
type: SpeciesReference

063363
units: 061996
value: 1.7E-5
type: LocalParameter

063435
kinetic law: 063495
name: r10
modifier: 319065
reversible: true
reactant: 063471
reactant: 063459
fast: false
reactant: 063447
modifier: 319089
product: 063483
type: Reaction
modifier: 319077
modifier: 319101

062643
units: 061924
value: 0.5
type: LocalParameter

063015
units: 061840
value: 0.0015
type: LocalParameter

062356
constant: false
units: 061924
value: NaN
type: Parameter

063783
stoichiometry: 1.0
species: 062104
type: SpeciesReference

063267
stoichiometry: 1.0
species: 062200
type: SpeciesReference

062847
stoichiometry: 1.0
species: 062176
type: SpeciesReference

063171
modifier: 319004
type: Reaction
modifier: 318992
kinetic law: 063231
modifier: 319017
reactant: 063183
name: r3
reactant: 063207
fast: false
product: 063219
reactant: 063195
modifier: 318980
reversible: true

063999
stoichiometry: 1.0
species: 062104
type: SpeciesReference

063687
kinetic law: 063723
modifier: 319173
modifier: 319161
product: 063711
reactant: 063699
fast: false
reversible: true
name: r19
type: Reaction

062104
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

062452
constant: false
units: 061864
value: NaN
type: Parameter

062919
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062032
exponent: 1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

063063
stoichiometry: 1.0
species: 062116
type: SpeciesReference

062931
stoichiometry: 1.0
species: 062116
type: SpeciesReference

063471
stoichiometry: 1.0
species: 062188
type: SpeciesReference

063759
stoichiometry: 1.0
species: 062188
type: SpeciesReference

064239
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062655
kinetic law: 062679
product: 062667
fast: false
reversible: true
name: r11
type: Reaction

063351
units: 061996
value: 2.0E-5
type: LocalParameter

062368
constant: false
units: 061924
value: 0.0
type: Parameter

063771
stoichiometry: 1.0
species: 062116
type: SpeciesReference

064131
reversible: true
modifier: 319354
reactant: 064143
name: r5
type: Reaction
modifier: 319378
product: 064179
kinetic law: 064191
reactant: 064167
reactant: 064155
modifier: 319366
modifier: 319342
fast: false

063699
stoichiometry: 1.0
species: 062116
type: SpeciesReference

062140
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

061876
exponent: 1.0
scale: 0
multipler: 1000.0
kind: DIMENSIONLESS
type: SBMLUnit

063507
units: 061840
value: 2.23E-6
type: LocalParameter

062020
exponent: -3.0
scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

062092
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

062440
constant: true
units: 061948
value: 0.46
type: Parameter

062428
constant: true
units: 061996
value: 5.5E-5
type: Parameter

063051
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062907
stoichiometry: 1.0
species: 062092
type: SpeciesReference

062560
stoichiometry: 1.0
species: 062092
type: SpeciesReference

062464
constant: false
units: 061864
value: NaN
type: Parameter

061684
exponent: 3.0
scale: 0
multipler: 1.0E-6
kind: METRE
type: SBMLUnit

062188
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

063807
units: 061840
value: 1.12E-5
type: LocalParameter

062416
constant: true
units: 061948
value: 0.0085
type: Parameter

063183
stoichiometry: 1.0
species: 062212
type: SpeciesReference

061936
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

064035
reversible: true
product: 064071
modifier: 319330
product: 064083
reactant: 064059
name: r13
kinetic law: 064095
reactant: 064047
type: Reaction
modifier: 319318
fast: false

062008
exponent: 1.0
scale: 0
multipler: 0.001
kind: DIMENSIONLESS
type: SBMLUnit

064071
stoichiometry: 1.0
species: 062224
type: SpeciesReference

063843
stoichiometry: 1.0
species: 062140
type: SpeciesReference

062128
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

062212
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

063747
stoichiometry: 1.0
species: 062080
type: SpeciesReference

064275
units: 061840
value: 1.7E-6
type: LocalParameter

063459
stoichiometry: 1.0
species: 062224
type: SpeciesReference

063243
units: 061840
value: 3.2E-7
type: LocalParameter

062799
fast: false
product: 062847
modifier: 318870
product: 062835
reactant: 062811
reactant: 062823
type: Reaction
reversible: true
name: r14
modifier: 318883
kinetic law: 062859

063543
stoichiometry: 1.0
species: 062188
type: SpeciesReference

061816
exponent: -1.0
scale: 0
multipler: 1.0
kind: ITEM
type: SBMLUnit

062272
constant: true
units: 061864
value: 8.33
type: Parameter

063831
reactant: 063867
reactant: 063843
reactant: 063855
name: r4
modifier: 319209
modifier: 319245
modifier: 319233
product: 063879
modifier: 319221
reversible: true
fast: false
type: Reaction
kinetic law: 063891

063003
units: 061996
value: 0.00166666666666667
type: LocalParameter

062404
constant: true
units: 061924
value: 0.01
type: Parameter

061780
exponent: 2.0
scale: 0
multipler: 1.0E-6
kind: METRE
type: SBMLUnit

062176
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 60.2
initial amount: NaN
in compartment: 062056
type: Species

062116
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

063855
stoichiometry: 1.0
species: 062176
type: SpeciesReference

062200
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

063531
stoichiometry: 1.0
species: 062080
type: SpeciesReference

063195
stoichiometry: 1.0
species: 062176
type: SpeciesReference

064023
units: 061840
value: 2.57E-8
type: LocalParameter

064083
stoichiometry: 1.0
species: 062104
type: SpeciesReference

MODEL1204040000
units def: 061948
rule: 062476
reaction: 063435
volume units: 061672
parameter: 062404
parameter: 062332
units def: 061792
parameter: 062416
parameter: 062260
units def: 061924
units def: 061672
type: SBMLModel
reaction: 062548
reaction: 063255
species: 062152
parameter: 062272
reaction: 063315
reaction: 063951
reaction: 064131
species: 062200
species: 062068
notes: This model is from the article: Positive roles for negative regulators in the mating response of yeast. Houser JR, Ford E, Nagiec MJ, Errede B, Elston TC. Mol Syst Biol 2012 June 5;8:586 22669614 , Abstract: All cells must detect and respond to changes in their environment, often through changes in gene expression. The yeast pheromone pathway has been extensively characterized, and is an ideal system for studying transcriptional regulation. Here we combine computational and experimental approaches to study transcriptional regulation mediated by Ste12, the key transcription factor in the pheromone response. Our mathematical model is able to explain multiple counterintuitive experimental results and led to several novel findings. First, we found that the transcriptional repressors Dig1 and Dig2 positively affect transcription by stabilizing Ste12. This stabilization through protein-protein interactions creates a large pool of Ste12 that is rapidly activated following pheromone stimulation. Second, we found that protein degradation follows saturating kinetics, explaining the long half-life of Ste12 in mutants expressing elevated amounts of Ste12. Finally, our model reveals a novel mechanism for robust perfect adaptation through protein-protein interactions that enhance complex stability. This mechanism allows the transcriptional response to act on a shorter time scale than upstream pathway activity.
parameter: 062320
units def: 061864
reaction: 062799
species: 062116
time units: 291235
reaction: 062655
units def: 061744
parameter: 062296
parameter: 062428
reaction: 062967
rule: 062536
reaction: 063519
species: 062104
parameter: 062380
parameter: 062308
units def: 061768
substance units: 061648
parameter: 062392
rule: 062524
reaction: 063903
rule: 062500
reaction: 064203
species: 062176
reaction: 063591
reaction: 063735
parameter: 062248
length unit: length
reaction: 062715
species: 062224
parameter: 062464
reaction: 063375
reaction: 063171
species: 062080
units def: 061648
units def: 061840
units def: 061996
compartment: 062056
reaction: 064035
species: 062164
reaction: 063831
area units: 061696
species: 062140
parameter: 062344
reaction: 062895
species: 062212
species: 062092
units def: 061720
parameter: 062440
rule: 062488
reaction: 063099
name: Houser2012_pheromone_Ste12
parameter: 062356
curated: false
species: 062188
parameter: 062452
parameter: 062368
species: 062236
rule: 062512

061888
exponent: 3.0
scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

061828
exponent: 1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

063159
units: 061840
value: 1.3E-4
type: LocalParameter

063735
reversible: true
product: 063771
kinetic law: 063795
reactant: 063747
modifier: 319197
type: Reaction
fast: false
product: 063783
reactant: 063759
name: r17
modifier: 319185

063447
stoichiometry: 1.0
species: 062080
type: SpeciesReference

063255
kinetic law: 063279
modifier: 319029
product: 063267
fast: false
reversible: true
name: r7
type: Reaction

063591
product: 063639
fast: false
reactant: 063603
reactant: 063615
reversible: true
modifier: 319137
kinetic law: 063651
modifier: 319149
product: 063627
name: r12
type: Reaction

062260
constant: true
units: 061840
value: 0.0578
type: Parameter

062967
kinetic law: 062991
modifier: 318920
product: 062979
fast: false
reversible: true
name: r21
type: Reaction

063915
stoichiometry: 1.0
species: 062104
type: SpeciesReference

061732
exponent: 1.0
scale: 0
multipler: 1.0
kind: ITEM
type: SBMLUnit

064107
units: 061840
value: 7.4E-4
type: LocalParameter

061984
exponent: 1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

064059
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062308
constant: true
units: 061948
value: 0.0061
type: Parameter

064167
stoichiometry: 1.0
species: 062188
type: SpeciesReference

063867
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062584
stoichiometry: 1.0
species: 062116
type: SpeciesReference

062164
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

061660
exponent: 1.0
scale: 0
multipler: 1.0
kind: ITEM
type: SBMLUnit

063315
kinetic law: 063339
product: 063327
fast: false
reversible: true
name: r0
type: Reaction

062979
stoichiometry: 1.0
species: 062188
type: SpeciesReference

063291
units: 061996
value: 1.0
type: LocalParameter

062236
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

064251
stoichiometry: 1.0
species: 062140
type: SpeciesReference

061708
exponent: 2.0
scale: 0
multipler: 1.0E-6
kind: METRE
type: SBMLUnit

062811
stoichiometry: 1.0
species: 062152
type: SpeciesReference

063639
stoichiometry: 1.0
species: 062104
type: SpeciesReference

062739
stoichiometry: 1.0
species: 062188
type: SpeciesReference

063567
stoichiometry: 1.0
species: 062212
type: SpeciesReference

063147
units: 061840
value: 1.0E-4
type: LocalParameter

062775
units: 061840
value: 0.0037
type: LocalParameter

062751
stoichiometry: 1.0
species: 062104
type: SpeciesReference

062320
constant: true
units: 061948
value: 0.5
type: Parameter

063879
stoichiometry: 1.0
species: 062164
type: SpeciesReference

064179
stoichiometry: 1.0
species: 062164
type: SpeciesReference

063903
kinetic law: 063939
modifier: 319269
modifier: 319257
product: 063927
reactant: 063915
fast: false
reversible: true
name: r15
type: Reaction

064047
stoichiometry: 1.0
species: 062140
type: SpeciesReference

061972
exponent: -3.0
scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

063099
kinetic law: 063135
modifier: 318968
modifier: 318956
product: 063123
reactant: 063111
fast: false
reversible: true
name: r8
type: Reaction

062068
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

063819
units: 061924
value: 0.5
type: LocalParameter

062572
stoichiometry: 1.0
species: 062188
type: SpeciesReference

062152
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 0.0
initial amount: NaN
in compartment: 062056
type: Species

063327
stoichiometry: 1.0
species: 062212
type: SpeciesReference

063483
stoichiometry: 1.0
species: 062092
type: SpeciesReference

063627
stoichiometry: 1.0
species: 062104
type: SpeciesReference

061804
exponent: 1.0
scale: 0
multipler: 1.0E-21
kind: DIMENSIONLESS
type: SBMLUnit

063555
stoichiometry: 1.0
species: 062116
type: SpeciesReference

062727
stoichiometry: 1.0
species: 062212
type: SpeciesReference

062787
units: 061924
value: 0.5
type: LocalParameter

063399
stoichiometry: 1.0
species: 062212
type: SpeciesReference

062224
constant: false
boundary condition: false
has only substance units: false
substance units: 061720
initial concentration: 150.5
initial amount: NaN
in compartment: 062056
type: Species

062548
product: 062596
modifier: 318834
product: 062608
fast: false
type: Reaction
reversible: true
kinetic law: 062620
reactant: 062560
name: r18
modifier: 318822
reactant: 062572
product: 062584

063711
stoichiometry: 1.0
species: 062104
type: SpeciesReference