BIOMD0000000009
type: SBMLModel
species: 506692
species: 506712
reaction: 506812
name: Huang1996 - MAPK ultrasens
rule: metai0051
rule: met100050
is described by: http://identifiers.org/pubmed/8816754
reaction: 506853
species: 506772
modified:
  W3 CDTF: Thu May 16 15:40:49 BST 2013
species: 506432
compartment: 506358
area units: area
parameter: metaid_0011050
curated: true
reaction: 507013
reaction: 506893
reaction: 506993
reaction: 506973
species: 506732
notes: Huang1996 - MAPK ultrasens Ultrasensitivity in the mitogen-activated protein kinase cascade. This model is described in the article: Ultrasensitivity in the mitogen-activated protein kinase cascade. Huang CY, Ferrell JE Jr Proc. Natl. Acad. Sci. U.S.A. 1996:93(19):10078-83 Abstract: The mitogen-activated protein kinase (MAPK) cascade is a highly conserved series of three protein kinases implicated in diverse biological processes. Here we demonstrate that the cascade arrangement has unexpected consequences for the dynamics of MAPK signaling. We solved the rate equations for the cascade numerically and found that MAPK is predicted to behave like a highly cooperative enzyme, even though it was not assumed that any of the enzymes in the cascade were regulated cooperatively. Measurements of MAPK activation in Xenopus oocyte extracts confirmed this prediction. The stimulus/response curve of the MAPK was found to be as steep as that of a cooperative enzyme with a Hill coefficient of 4-5, well in excess of that of the classical allosteric protein hemoglobin. The shape of the MAPK stimulus/ response curve may make the cascade particularly appropriate for mediating processes like mitogenesis, cell fate induction, and oocyte maturation, where a cell switches from one discrete state to another. The species K_PP_norm, KKK_P_norm and KK_PP_norm are the relative concentrations of the active MAPK, MAPKK and MAPKKK, that is the double, or single resp. phophorylated forms divided by the total concentrations of each kinase. For MAPK additionally the also active MAPK divided by the maximal concentration of active MAPK is given by rel_K_PP_max. The parameter K_PP_norm_max, the maximal ratio of active MapK, has to be calculated for each change of parameters. This model is hosted on BioModels Database and identified by: BIOMD0000000009 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To th…
species: 506792
species: 506452
reaction: 507053
reaction: 507033
species: metaid_0000049
species: metaid_0000048
creator:
  ORG:
    orgname: University of Vienna
  n:
    given: Rainer
    family: Machne
species: 506512
species: 506392
reaction: 507173
species: 506612
species: 506572
reaction: 507153
species: 506472
species: 506412
species: 506372
rule: metaid_0000050
reaction: 506873
length unit: length
is version of: GO:0000165
species: 506632
species: 506592
reaction: 506913
species: 506492
reaction: 506833
species: 506552
time units: metaid_0000018
species: metaid_0100049
reaction: 507133
reaction: 507113
rule: metaid_0000052
reaction: 507093
species: 506532
species: 506652
reaction: 507073
reaction: 506953
reaction: 506933
reaction: 507193
volume units: volume
created:
  W3 CDTF: Thu Feb 10 23:39:30 GMT 2005
occurs in: http://identifiers.org/taxonomy/8355
species: 506752
is: MODEL6615048798
is homolog to: REACT 634
species: metaid_0000047
substance units: metaid_0000046
species: 506672
units def: metaid_0000046

506692
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name: PP-MAPKK_MAPK
has part: Q05116
constant: false
in compartment: 506358
initial concentration: 0.0

506358
type: Compartment
constant: true
size: 4.0E-12
spatial dimensions: 3.0

506712
type: Species
boundary condition: false
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has only substance units: false
in compartment: 506358
name: PP-MAPKK_P-MAPK
initial concentration: 0.0
initial amount: NaN
has part: Q05116

506812
type: Reaction
kinetic law: 396531
name: binding of MAPKKK activator
reactant: 396507
is homolog to: REACT 996
product: 396519
fast: false
reversible: true
is version of: GO:0031435
reactant: 396495

815887
type: LocalParameter
value: 150.0

815886
type: LocalParameter
value: 1000.0

396507
type: SpeciesReference
stoichiometry: 1.0
species: 506372

506372
type: Species
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constant: false
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name: MAPKKK activator

396519
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506612
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name: activ_MAPKKK
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396495
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species: 506412

506412
type: Species
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constant: false
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initial concentration: 0.003
initial amount: NaN
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name: MAPKKK

506853
type: Reaction
kinetic law: 396627
product: 396615
reactant: 396603
reactant: 396591
is version of: GO:0031435
fast: false
reversible: true
name: binding of MAPKKK inactivator

815890
type: LocalParameter
value: 150.0

815889
type: LocalParameter
value: 1000.0

396615
type: SpeciesReference
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506632
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constant: false
boundary condition: false
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initial concentration: 0.0
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name: inact_P-MAPKKK

396603
type: SpeciesReference
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species: 506392

506392
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.0E-4
initial amount: NaN
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name: MAPKKK inactivator

396591
type: SpeciesReference
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506432
type: Species
is version of: P12965
constant: false
boundary condition: false
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initial amount: NaN
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name: P-MAPKKK

506772
type: Species
boundary condition: false
initial concentration: 0.0
initial amount: NaN
has only substance units: false
has part: Q90W58
in compartment: 506358
constant: false
has part: P26696
name: MAPK-Pase_PP-MAPK

metaid_0011050
type: Parameter
notes: the maximal value of K_PP_norm at a stimulation conc. of 10.
constant: true
value: 0.900049

507013
type: Reaction
kinetic law: 397013
product: 397001
reactant: 396989
reactant: 396977
is version of: GO:0031434
fast: false
reversible: true
name: binding MAPKK-Pase and PP-MAPKK

815904
type: LocalParameter
value: 150.0

815903
type: LocalParameter
value: 1000.0

397001
type: SpeciesReference
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506732
type: Species
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name: MAPKK-Pase_PP-MAPKK

396989
type: SpeciesReference
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species: 506592

506592
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.0E-4
initial amount: NaN
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name: MAPKK-Pase

396977
type: SpeciesReference
stoichiometry: 1.0
species: 506492

506492
type: Species
is version of: Q05116
constant: false
boundary condition: false
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initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: PP-MAPKK

506893
type: Reaction
product: 396712
is homolog to: REACT 143
kinetic law: 396724
is version of: GO:0031435
reactant: 396699
fast: false
is version of: GO:0031434
reactant: 396687
reversible: true
name: binding P-MAPKKK and MAPKK

396712
type: SpeciesReference
stoichiometry: 1.0
species: 506652

506652
type: Species
initial concentration: 0.0
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boundary condition: false
initial amount: NaN
in compartment: 506358
constant: false
name: P-MAPKKK_MAPKK
has part: Q05116
has only substance units: false

815893
type: LocalParameter
value: 150.0

815892
type: LocalParameter
value: 1000.0

396699
type: SpeciesReference
stoichiometry: 1.0
species: 506432

396687
type: SpeciesReference
stoichiometry: 1.0
species: 506452

506452
type: Species
is version of: Q05116
constant: false
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initial concentration: 1.2
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in compartment: 506358
name: MAPKK

506993
type: Reaction
is version of: http://identifiers.org/ec-code/2.7.11.25
reactant: 396928
fast: false
is version of: GO:0006468
is version of: GO:0004709
kinetic law: 396965
is version of: GO:0000186
product: 396940
is homolog to: REACT 614
product: 396952
name: phosphorylation of P-MAPKK
reversible: false

396928
type: SpeciesReference
stoichiometry: 1.0
species: 506672

506672
type: Species
name: P-MAPKKK_P-MAPKK
constant: false
boundary condition: false
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initial amount: NaN
has part: Q05116
initial concentration: 0.0
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in compartment: 506358

815902
type: LocalParameter
value: 150.0

396940
type: SpeciesReference
stoichiometry: 1.0
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396952
type: SpeciesReference
stoichiometry: 1.0
species: 506432

506973
type: Reaction
product: 396904
fast: false
reversible: true
reactant: 396892
name: binding P-MAPKKK and P-MAPKK
reactant: 396880
is version of: GO:0031434
kinetic law: 396916
is version of: GO:0031435
is homolog to: REACT 143

396904
type: SpeciesReference
stoichiometry: 1.0
species: 506672

396892
type: SpeciesReference
stoichiometry: 1.0
species: 506432

396880
type: SpeciesReference
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species: 506472

506472
type: Species
is version of: Q05116
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: P-MAPKK

815901
type: LocalParameter
value: 150.0

815899
type: LocalParameter
value: 1000.0

506792
type: Species
has only substance units: false
initial amount: NaN
boundary condition: false
name: MAPK-Pase_P-MAPK
has part: P26696
in compartment: 506358
constant: false
initial concentration: 0.0
has part: Q90W58

507053
type: Reaction
reactant: 397073
reactant: 397085
fast: false
name: binding MAPK and PP-MAPKK
is version of: GO:0031434
kinetic law: 397109
has version: REACT 495
product: 397097
is version of: GO:0051019
reversible: true
has version: REACT 1780

397073
type: SpeciesReference
stoichiometry: 1.0
species: 506512

506512
type: Species
is version of: P26696
constant: false
boundary condition: false
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initial concentration: 1.2
initial amount: NaN
in compartment: 506358
name: MAPK

397085
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species: 506492

815907
type: LocalParameter
value: 150.0

815906
type: LocalParameter
value: 1000.0

397097
type: SpeciesReference
stoichiometry: 1.0
species: 506692

507033
type: Reaction
is version of: GO:0051389
name: dephosphorylation of PP-MAPKK
product: 397037
reversible: false
kinetic law: 397061
fast: false
product: 397049
is version of: http://identifiers.org/ec-code/3.1.3.16
is version of: GO:0006470
reactant: 397025

397037
type: SpeciesReference
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species: 506472

815905
type: LocalParameter
value: 150.0

397049
type: SpeciesReference
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species: 506592

397025
type: SpeciesReference
stoichiometry: 1.0
species: 506732

metaid_0000049
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
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name: KKK_P_norm

metaid_0000048
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 506358
name: KK_PP_norm

507173
type: Reaction
kinetic law: 397400
product: 397388
reactant: 397376
reactant: 397363
is version of: GO:0051019
fast: false
reversible: true
name: binding MAPK-Pase and PP-MAPK

815918
type: LocalParameter
value: 150.0

815916
type: LocalParameter
value: 1000.0

397388
type: SpeciesReference
stoichiometry: 1.0
species: 506772

397376
type: SpeciesReference
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species: 506572

506572
type: Species
is: Q90W58
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 506358
name: MAPK-Pase

397363
type: SpeciesReference
stoichiometry: 1.0
species: 506552

506552
type: Species
is version of: P26696
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 506358
name: PP-MAPK

507153
type: Reaction
is version of: GO:0000187
has version: REACT 136
reactant: 397315
is version of: GO:0004708
name: phosphorylation of P-MAPK
fast: false
is version of: http://identifiers.org/ec-code/2.7.12.2
product: 397339
reversible: false
is version of: GO:0006468
product: 397327
has version: REACT 2247
kinetic law: 397351

397315
type: SpeciesReference
stoichiometry: 1.0
species: 506712

397339
type: SpeciesReference
stoichiometry: 1.0
species: 506552

397327
type: SpeciesReference
stoichiometry: 1.0
species: 506492

815914
type: LocalParameter
value: 150.0

506873
type: Reaction
is version of: http://identifiers.org/ec-code/3.1.3.16
is version of: GO:0006470
reactant: 396639
reversible: false
is version of: GO:0051390
fast: false
name: MAPKKK inactivation
kinetic law: 396675
product: 396651
product: 396663

396639
type: SpeciesReference
stoichiometry: 1.0
species: 506632

815891
type: LocalParameter
value: 150.0

396651
type: SpeciesReference
stoichiometry: 1.0
species: 506392

396663
type: SpeciesReference
stoichiometry: 1.0
species: 506412

506913
type: Reaction
is version of: GO:0006468
is version of: GO:0004709
is version of: http://identifiers.org/ec-code/2.7.11.25
is homolog to: REACT 614
product: 396760
reactant: 396736
name: phosphorylation of MAPKK
fast: false
product: 396748
reversible: false
kinetic law: 396772

396760
type: SpeciesReference
stoichiometry: 1.0
species: 506432

396736
type: SpeciesReference
stoichiometry: 1.0
species: 506652

396748
type: SpeciesReference
stoichiometry: 1.0
species: 506472

815894
type: LocalParameter
value: 150.0

506833
type: Reaction
is version of: http://identifiers.org/ec-code/2.7.11.1
reversible: false
product: 396555
is version of: GO:0000185
product: 396567
is version of: GO:0008349
fast: false
is homolog to: REACT 525
reactant: 396543
name: MAPKKK activation
kinetic law: 396579

396555
type: SpeciesReference
stoichiometry: 1.0
species: 506372

396567
type: SpeciesReference
stoichiometry: 1.0
species: 506432

396543
type: SpeciesReference
stoichiometry: 1.0
species: 506612

815888
type: LocalParameter
value: 150.0

metaid_0100049
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 506358
name: relative maximal K_PP

507133
type: Reaction
has version: REACT 495
is version of: GO:0051019
reactant: 397266
kinetic law: 397303
reversible: true
name: binding PP-MAPKK and P-MAPK
is version of: GO:0031434
product: 397291
reactant: 397278
fast: false
has version: REACT 1780

397266
type: SpeciesReference
stoichiometry: 1.0
species: 506532

506532
type: Species
is version of: P26696
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has only substance units: false
initial concentration: 0.0
initial amount: NaN
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name: P-MAPK

815913
type: LocalParameter
value: 150.0

815912
type: LocalParameter
value: 1000.0

397291
type: SpeciesReference
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species: 506712

397278
type: SpeciesReference
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species: 506492

507113
type: Reaction
reactant: 397218
product: 397230
reversible: false
fast: false
kinetic law: 397254
is version of: http://identifiers.org/ec-code/3.1.3.16
is version of: GO:0006470
product: 397242
name: dephosphorylation of P-MAPK

397218
type: SpeciesReference
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species: 506792

397230
type: SpeciesReference
stoichiometry: 1.0
species: 506512

815911
type: LocalParameter
value: 150.0

397242
type: SpeciesReference
stoichiometry: 1.0
species: 506572

507093
type: Reaction
kinetic law: 397206
product: 397194
reactant: 397182
reactant: 397170
is version of: GO:0051019
fast: false
reversible: true
name: binding MAPK-Pase and P-MAPK

815910
type: LocalParameter
value: 150.0

815909
type: LocalParameter
value: 1000.0

397194
type: SpeciesReference
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species: 506792

397182
type: SpeciesReference
stoichiometry: 1.0
species: 506572

397170
type: SpeciesReference
stoichiometry: 1.0
species: 506532

507073
type: Reaction
reversible: false
name: phosphorylation of MAPK
is version of: GO:0004708
is version of: http://identifiers.org/ec-code/2.7.12.2
reactant: 397121
has version: REACT 2247
fast: false
is version of: GO:0006468
kinetic law: 397158
product: 397145
has version: REACT 136
product: 397133

397121
type: SpeciesReference
stoichiometry: 1.0
species: 506692

815908
type: LocalParameter
value: 150.0

397145
type: SpeciesReference
stoichiometry: 1.0
species: 506492

397133
type: SpeciesReference
stoichiometry: 1.0
species: 506532

506953
type: Reaction
name: dephosphorylation of P-MAPKK
product: 396856
fast: false
is version of: GO:0006470
reversible: false
reactant: 396832
product: 396844
kinetic law: 396868
is version of: http://identifiers.org/ec-code/3.1.3.16

396856
type: SpeciesReference
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species: 506592

396832
type: SpeciesReference
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species: 506752

506752
type: Species
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initial concentration: 0.0
initial amount: NaN
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name: MAPKK-Pase_P-MAPKK

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type: SpeciesReference
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species: 506452

815897
type: LocalParameter
value: 150.0

506933
type: Reaction
kinetic law: 396820
product: 396808
reactant: 396796
reactant: 396784
is version of: GO:0031434
fast: false
reversible: true
name: binding MAPKK-Pase and P-MAPKK

815896
type: LocalParameter
value: 150.0

815895
type: LocalParameter
value: 1000.0

396808
type: SpeciesReference
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species: 506752

396796
type: SpeciesReference
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species: 506592

396784
type: SpeciesReference
stoichiometry: 1.0
species: 506472

507193
type: Reaction
reversible: false
product: 397436
product: 397424
name: dephosphorylation of PP-MAPK
kinetic law: 397448
is version of: http://identifiers.org/ec-code/3.1.3.16
reactant: 397412
is version of: GO:0006470
is version of: GO:0000188
fast: false

397436
type: SpeciesReference
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397424
type: SpeciesReference
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species: 506532

815919
type: LocalParameter
value: 150.0

397412
type: SpeciesReference
stoichiometry: 1.0
species: 506772

metaid_0000047
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 506358
name: K_PP_norm

metaid_0000046
type: SBMLUnitsDef
unit: 396483
name: micromole

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type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE