- Author:
- Catherine Lloyd <c.lloyd@auckland.ac.nz>
- Date:
- 2010-05-25 22:37:27+12:00
- Desc:
- Added PubMed ID.
- Permanent Source URI:
- https://models.cellml.org/workspace/cui_kaandorp_2008/rawfile/6c850cb4b576ea5abcb5832719082cd980daad16/cui_kaandorp_2008.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : cui_2008.xml
CREATED : 12th May 2008
LAST MODIFIED : 12th May 2008
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Cui and Kaandorp's 2008 mathematical model of the calcium-calcineurin signalling network in cardiac myocytes.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="cui_2008" name="cui_2008">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling the calcium-calcineurin signalling network in cardiac myocytes</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in both PCEnv and COR to recreate the published results. The units have been checked and they are consistent.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: Understanding of processes in which calcium signaling is involved is of fundamental importance in systems biology and has many applications in medicine. In this paper we have studied the particular case of the complex calcium-calcineurin-MCIP-NFAT signaling network in cardiac myocytes, the understanding of which is critical for treatment of pathologic hypertrophy and heart failure. By including some most recent experimental findings, we constructed a computational model totally based on biochemical principles. The model can correctly predict the mutant (MCIP1-/-) behavior under different stress such as PO (pressure overload) and CaN* (activated calcineurin) overexpression.
</para>
<para>
In 2006, Shin <emphasis>et al.</emphasis> published a paper which modelled the dual role of MCIP in cardiac hypertrophy. In the study described here, Cui and Kaandorp have extended this model to include more recent and extensive experimental data. They used <ulink url="http://www.cellerator.org/">Cellerator</ulink>, an open source software, to automatically generate the equations, and the model was subsequently translated into CellML to facilitate future model exchange, reuse and implementation.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="cui_calcium_2008.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the Ca2+-calcineurin-MCIP-NFAT signalling networks in cardiac myocytes described by the model. Abbreviations: calmodulin (CaM); calcineurin (CaN); activated calcineurin (CaN*); nuclear factor of activated T-cells (NFAT); phosphorylated NFAT (NFATP); modulatory calcineurin-interacting protein (MCIP); phosphorylated MCIP on serine 112 (MCIPP); phosphorylated MCIP on both serine 112 and serine 108 (MCIPPP); big mitogen-activated protein kinase 1 (BMK1); glycogen synthase 3β (GSK3β); the complex formed by MCIP and calcineurin (Complex1); the complex formed by MCIPPP and 14-3-3 (Complex2); the complex formed by NFATP and 14-3-3 (Complex3); pressure overload (PO); hypertrophic stimuli (stress).</caption>
</informalfigure>
<para>
The original book chapter reference is cited below:
</para>
<para>
Simulating Complex Calcium-Calcineurin Signaling Network, Jiangjun Cui and Jaap A. Kaandorp, 2008,
<emphasis>Lecture Notes in Computer Science</emphasis>, 5013, 110-119, <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/16445978">PubMed ID: 16445978</ulink>.
</para>
</sect1>
</article>
</documentation>
<units name="minute">
<unit units="second" multiplier="60.0"/>
</units>
<units name="micromolar">
<unit units="mole" prefix="nano"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="flux">
<unit units="micromolar"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="minute" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="micromolar" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="fifth_order_rate_constant">
<unit units="micromolar" exponent="-4"/>
<unit units="minute" exponent="-1"/>
</units>
<component name="environment">
<variable units="minute" public_interface="out" name="time"/>
</component>
<!-- substrates : enzymes, reactants and products -->
<component name="BMK1" cmeta:id="BMK1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#BMK1">
<dc:title>BMK1</dc:title>
<dcterms:alternative>big mitogen-activated protein kinase 1</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="BMK1" initial_value="0.012"/>
<variable units="flux" public_interface="in" name="v10a"/>
<variable units="flux" public_interface="in" name="v10b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>BMK1</ci>
</apply>
<apply>
<minus/>
<ci>v10b</ci>
<ci>v10a</ci>
</apply>
</apply>
</math>
</component>
<component name="MRNA" cmeta:id="MRNA">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#MRNA">
<dc:title>MRNA</dc:title>
<dcterms:alternative>MCIP mRNA</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="MRNA" initial_value="3.33E-4"/>
<variable units="flux" public_interface="in" name="v18"/>
<variable units="flux" public_interface="in" name="v19"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MRNA</ci>
</apply>
<apply>
<minus/>
<ci>v19</ci>
<ci>v18</ci>
</apply>
</apply>
</math>
</component>
<component name="NFATc" cmeta:id="NFATc">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#NFATc">
<dc:title>NFATc</dc:title>
<dcterms:alternative>cytosolic NFAT</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="NFATc" initial_value="2E-5"/>
<variable units="flux" public_interface="in" name="v1"/>
<variable units="flux" public_interface="in" name="v14"/>
<variable units="flux" public_interface="in" name="v15"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATc</ci>
</apply>
<apply>
<minus/>
<ci>v14</ci>
<apply>
<plus/>
<ci>v1</ci>
<ci>v15</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="NFATn" cmeta:id="NFATn">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#NFATn">
<dc:title>NFATn</dc:title>
<dcterms:alternative>nuclear NFAT</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="NFATn" initial_value="4.99E-4"/>
<variable units="flux" public_interface="in" name="v1"/>
<variable units="flux" public_interface="in" name="v16"/>
<variable units="flux" public_interface="in" name="v17"/>
<variable units="flux" public_interface="in" name="v18"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATn</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v1</ci>
<ci>v16</ci>
</apply>
<apply>
<plus/>
<ci>v17</ci>
<ci>v18</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="NFATpc" cmeta:id="NFATpc">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#NFATpc">
<dc:title>NFATpc</dc:title>
<dcterms:alternative>cytosolic NFATp</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="NFATpc" initial_value="4.94E-3"/>
<variable units="flux" public_interface="in" name="v2"/>
<variable units="flux" public_interface="in" name="v9"/>
<variable units="flux" public_interface="in" name="v14"/>
<variable units="flux" public_interface="in" name="v15"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATpc</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v2</ci>
<ci>v15</ci>
</apply>
<apply>
<plus/>
<ci>v9</ci>
<ci>v14</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="NFATpn" cmeta:id="NFATpn">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#NFATpn">
<dc:title>NFATpn</dc:title>
<dcterms:alternative>nuclear NFATp</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="NFATpn" initial_value="8.01E-5"/>
<variable units="flux" public_interface="in" name="v2"/>
<variable units="flux" public_interface="in" name="v16"/>
<variable units="flux" public_interface="in" name="v17"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATpn</ci>
</apply>
<apply>
<minus/>
<ci>v17</ci>
<apply>
<plus/>
<ci>v2</ci>
<ci>v16</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="GSK3betac" cmeta:id="GSK3betac">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#GSK3betac">
<dc:title>GSK3betac</dc:title>
<dcterms:alternative>cytosolic glycogen synthase 3-beta</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="GSK3betac" initial_value="0.17"/>
<variable units="flux" public_interface="in" name="v3"/>
<variable units="flux" public_interface="in" name="v12a"/>
<variable units="flux" public_interface="in" name="v12b"/>
<variable units="flux" public_interface="in" name="v15a"/>
<variable units="flux" public_interface="in" name="v15b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>GSK3betac</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v12b</ci>
<ci>v15b</ci>
</apply>
<apply>
<plus/>
<ci>v3</ci>
<ci>v12a</ci>
<ci>v15a</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="GSK3betan" cmeta:id="GSK3betan">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#GSK3betan">
<dc:title>GSK3betan</dc:title>
<dcterms:alternative>nuclear glycogen synthase 3-beta</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="GSK3betan" initial_value="0.339"/>
<variable units="flux" public_interface="in" name="v3"/>
<variable units="flux" public_interface="in" name="v17a"/>
<variable units="flux" public_interface="in" name="v17b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>GSK3betan</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v3</ci>
<ci>v17b</ci>
</apply>
<ci>v17a</ci>
</apply>
</apply>
</math>
</component>
<component name="CaNc" cmeta:id="CaNc">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#CaNc">
<dc:title>CaNc</dc:title>
<dcterms:alternative>cytosolic inactive calcineurin</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="CaNc" initial_value="0.91"/>
<variable units="flux" public_interface="in" name="v6"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>CaNc</ci>
</apply>
<apply>
<minus/>
<ci>v6</ci>
</apply>
</apply>
</math>
</component>
<component name="CaNc_star" cmeta:id="CaNc_star">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#CaNc_star">
<dc:title>CaNc_star</dc:title>
<dcterms:alternative>cytosolic activated calcineurin</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="CaNc_star" initial_value="0.0275"/>
<variable units="flux" public_interface="in" name="v4"/>
<variable units="flux" public_interface="in" name="v6"/>
<variable units="flux" public_interface="in" name="v7"/>
<variable units="flux" public_interface="in" name="v11a"/>
<variable units="flux" public_interface="in" name="v11b"/>
<variable units="flux" public_interface="in" name="v13a"/>
<variable units="flux" public_interface="in" name="v13b"/>
<variable units="flux" public_interface="in" name="v14a"/>
<variable units="flux" public_interface="in" name="v14b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>CaNc_star</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v6</ci>
<ci>v11b</ci>
<ci>v13b</ci>
<ci>v14b</ci>
</apply>
<apply>
<plus/>
<ci>v4</ci>
<ci>v7</ci>
<ci>v11a</ci>
<ci>v13a</ci>
<ci>v14a</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="CaNn_star" cmeta:id="CaNn_star">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#CaNn_star">
<dc:title>CaNn_star</dc:title>
<dcterms:alternative>nuclear activated calcineurin</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="CaNn_star" initial_value="0.0568"/>
<variable units="flux" public_interface="in" name="v4"/>
<variable units="flux" public_interface="in" name="v16a"/>
<variable units="flux" public_interface="in" name="v16b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>CaNn_star</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v4</ci>
<ci>v16b</ci>
</apply>
<ci>v16a</ci>
</apply>
</apply>
</math>
</component>
<component name="CaNn" cmeta:id="CaNn">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#CaNn">
<dc:title>CaNn</dc:title>
<dcterms:alternative>nuclear inactive calcineurin</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="CaNn" initial_value="0.0057"/>
<variable units="flux" public_interface="in" name="v6"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>CaNn</ci>
</apply>
<apply>
<minus/>
<ci>v6</ci>
</apply>
</apply>
</math>
</component>
<component name="CaM" cmeta:id="CaM">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#CaM">
<dc:title>CaM</dc:title>
<dcterms:alternative>calmodulin</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="CaM" initial_value="25.2"/>
<variable units="flux" public_interface="in" name="v5"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>CaM</ci>
</apply>
<apply>
<minus/>
<ci>v5</ci>
</apply>
</apply>
</math>
</component>
<component name="CaMCa" cmeta:id="CaMCa">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#CaMCa">
<dc:title>CaMCa</dc:title>
<dcterms:alternative>calcium-calmodulin complex</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="CaMCa" initial_value="7.88E-7"/>
<variable units="flux" public_interface="in" name="v5"/>
<variable units="flux" public_interface="in" name="v6"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>CaMCa</ci>
</apply>
<apply>
<minus/>
<ci>v5</ci>
<ci>v6</ci>
</apply>
</apply>
</math>
</component>
<component name="MCIP" cmeta:id="MCIP">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#MCIP">
<dc:title>MCIP</dc:title>
<dcterms:alternative>modulatory calcineurin-interacting protein</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="MCIP" initial_value="2.15E-4"/>
<variable units="flux" public_interface="in" name="v7"/>
<variable units="flux" public_interface="in" name="v10"/>
<variable units="flux" public_interface="in" name="v11"/>
<variable units="flux" public_interface="in" name="v19"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MCIP</ci>
</apply>
<apply>
<minus/>
<ci>v11</ci>
<apply>
<plus/>
<ci>v7</ci>
<ci>v10</ci>
<ci>v19</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="MCIPp" cmeta:id="MCIPp">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#MCIPp">
<dc:title>MCIPp</dc:title>
<dcterms:alternative>phosphorylated MCIP on serine 112</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="MCIPp" initial_value="7.76E-3"/>
<variable units="flux" public_interface="in" name="v10"/>
<variable units="flux" public_interface="in" name="v11"/>
<variable units="flux" public_interface="in" name="v12"/>
<variable units="flux" public_interface="in" name="v13"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MCIPp</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v10</ci>
<ci>v13</ci>
</apply>
<apply>
<plus/>
<ci>v11</ci>
<ci>v12</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="MCIPpp" cmeta:id="MCIPpp">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#MCIPpp">
<dc:title>MCIPpp</dc:title>
<dcterms:alternative>phosphorylated MCIP on both serine 112 and serine 108</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="MCIPpp" initial_value="0.0798"/>
<variable units="flux" public_interface="in" name="v8"/>
<variable units="flux" public_interface="in" name="v12"/>
<variable units="flux" public_interface="in" name="v13"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MCIPpp</ci>
</apply>
<apply>
<minus/>
<ci>v12</ci>
<apply>
<plus/>
<ci>v8</ci>
<ci>v13</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Comp1" cmeta:id="Comp1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#Comp1">
<dc:title>Comp1</dc:title>
<dcterms:alternative>complex formed by MCIP and calcineurin</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Comp1" initial_value="5.21E-3"/>
<variable units="flux" public_interface="in" name="v7"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Comp1</ci>
</apply>
<ci>v7</ci>
</apply>
</math>
</component>
<component name="Comp2" cmeta:id="Comp2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#Comp2">
<dc:title>Comp2</dc:title>
<dcterms:alternative>complex formed by MCIPPP and 14-3-3</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Comp2" initial_value="0.283"/>
<variable units="flux" public_interface="in" name="v8"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Comp2</ci>
</apply>
<ci>v8</ci>
</apply>
</math>
</component>
<component name="Comp3" cmeta:id="Comp3">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#Comp3">
<dc:title>Comp3</dc:title>
<dcterms:alternative>complex formed by NFATP and 14-3-3</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Comp3" initial_value="0.014"/>
<variable units="flux" public_interface="in" name="v9"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Comp3</ci>
</apply>
<ci>v9</ci>
</apply>
</math>
</component>
<component name="P1433" cmeta:id="P1433">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#P1433">
<dc:title>P1433</dc:title>
<dcterms:alternative>14-3-3 protein</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="P1433" initial_value="0.708"/>
<variable units="flux" public_interface="in" name="v8"/>
<variable units="flux" public_interface="in" name="v9"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P1433</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>v8</ci>
<ci>v9</ci>
</apply>
</apply>
</apply>
</math>
</component>
<!-- reactants-enzyme complexes -->
<component name="MCIP_BMK1">
<variable units="micromolar" public_interface="out" name="MCIP_BMK1" initial_value="2.14E-5"/>
<variable units="flux" public_interface="in" name="v10a"/>
<variable units="flux" public_interface="in" name="v10b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MCIP_BMK1</ci>
</apply>
<apply>
<minus/>
<ci>v10a</ci>
<ci>v10b</ci>
</apply>
</apply>
</math>
</component>
<component name="MCIPp_CaNc_star">
<variable units="micromolar" public_interface="out" name="MCIPp_CaNc_star" initial_value="1.07E-4"/>
<variable units="flux" public_interface="in" name="v11a"/>
<variable units="flux" public_interface="in" name="v11b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MCIPp_CaNc_star</ci>
</apply>
<apply>
<minus/>
<ci>v11a</ci>
<ci>v11b</ci>
</apply>
</apply>
</math>
</component>
<component name="MCIPp_GSK3betac">
<variable units="micromolar" public_interface="out" name="MCIPp_GSK3betac" initial_value="1.1E-3"/>
<variable units="flux" public_interface="in" name="v12a"/>
<variable units="flux" public_interface="in" name="v12b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MCIPp_GSK3betac</ci>
</apply>
<apply>
<minus/>
<ci>v12a</ci>
<ci>v12b</ci>
</apply>
</apply>
</math>
</component>
<component name="MCIPpp_CaNc_star">
<variable units="micromolar" public_interface="out" name="MCIPpp_CaNc_star" initial_value="1.1E-3"/>
<variable units="flux" public_interface="in" name="v13a"/>
<variable units="flux" public_interface="in" name="v13b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MCIPpp_CaNc_star</ci>
</apply>
<apply>
<minus/>
<ci>v13a</ci>
<ci>v13b</ci>
</apply>
</apply>
</math>
</component>
<component name="NFATpc_CaNc_star">
<variable units="micromolar" public_interface="out" name="NFATpc_CaNc_star" initial_value="8.15E-5"/>
<variable units="flux" public_interface="in" name="v14a"/>
<variable units="flux" public_interface="in" name="v14b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATpc_CaNc_star</ci>
</apply>
<apply>
<minus/>
<ci>v14a</ci>
<ci>v14b</ci>
</apply>
</apply>
</math>
</component>
<component name="NFATc_GSK3betac">
<variable units="micromolar" public_interface="out" name="NFATc_GSK3betac" initial_value="1.36E-6"/>
<variable units="flux" public_interface="in" name="v15a"/>
<variable units="flux" public_interface="in" name="v15b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATc_GSK3betac</ci>
</apply>
<apply>
<minus/>
<ci>v15a</ci>
<ci>v15b</ci>
</apply>
</apply>
</math>
</component>
<component name="NFATpn_CaNn_star">
<variable units="micromolar" public_interface="out" name="NFATpn_CaNn_star" initial_value="2.27E-6"/>
<variable units="flux" public_interface="in" name="v16a"/>
<variable units="flux" public_interface="in" name="v16b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATpn_CaNn_star</ci>
</apply>
<apply>
<minus/>
<ci>v16a</ci>
<ci>v16b</ci>
</apply>
</apply>
</math>
</component>
<component name="NFATn_GSK3betan">
<variable units="micromolar" public_interface="out" name="NFATn_GSK3betan" initial_value="8.46E-5"/>
<variable units="flux" public_interface="in" name="v17a"/>
<variable units="flux" public_interface="in" name="v17b"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NFATn_GSK3betan</ci>
</apply>
<apply>
<minus/>
<ci>v17a</ci>
<ci>v17b</ci>
</apply>
</apply>
</math>
</component>
<!-- Simple Irreversible Reactions -->
<component name="v1">
<variable units="flux" public_interface="out" name="v1"/>
<variable units="micromolar" public_interface="in" name="NFATc"/>
<variable units="first_order_rate_constant" public_interface="in" name="k29"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v1 </ci>
<apply>
<times/>
<ci> k29 </ci>
<ci> NFATc </ci>
</apply>
</apply>
</math>
</component>
<component name="v2">
<variable units="flux" public_interface="out" name="v2"/>
<variable units="micromolar" public_interface="in" name="NFATpn"/>
<variable units="first_order_rate_constant" public_interface="in" name="k30"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v2 </ci>
<apply>
<times/>
<ci> k30 </ci>
<ci> NFATpn </ci>
</apply>
</apply>
</math>
</component>
<!-- Simple Reversible Reactions -->
<component name="v3">
<variable units="flux" public_interface="out" name="v3"/>
<variable units="micromolar" public_interface="in" name="GSK3betac"/>
<variable units="micromolar" public_interface="in" name="GSK3betan"/>
<variable units="first_order_rate_constant" public_interface="in" name="k31"/>
<variable units="first_order_rate_constant" public_interface="in" name="k32"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v3 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k31 </ci>
<ci> GSK3betac </ci>
</apply>
<apply>
<times/>
<ci> k32 </ci>
<ci> GSK3betan </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v4">
<variable units="flux" public_interface="out" name="v4"/>
<variable units="micromolar" public_interface="in" name="CaNc_star"/>
<variable units="micromolar" public_interface="in" name="CaNn_star"/>
<variable units="first_order_rate_constant" public_interface="in" name="k33"/>
<variable units="first_order_rate_constant" public_interface="in" name="k34"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v4 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k33 </ci>
<ci> CaNc_star </ci>
</apply>
<apply>
<times/>
<ci> k34 </ci>
<ci> CaNn_star </ci>
</apply>
</apply>
</apply>
</math>
</component>
<!-- Reversible Binding Reactions -->
<component name="v5">
<variable units="flux" public_interface="out" name="v5"/>
<variable units="micromolar" public_interface="in" name="CaM"/>
<variable units="micromolar" public_interface="in" name="Ca"/>
<variable units="micromolar" public_interface="in" name="CaMCa"/>
<variable units="fifth_order_rate_constant" public_interface="in" name="k1"/>
<variable units="first_order_rate_constant" public_interface="in" name="k2"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v5 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k1 </ci>
<ci> CaM </ci>
<apply>
<power/>
<ci> Ca </ci>
<cn cellml:units="dimensionless"> 4 </cn>
</apply>
</apply>
<apply>
<times/>
<ci> k2 </ci>
<ci> CaMCa </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v6">
<variable units="flux" public_interface="out" name="v6"/>
<variable units="micromolar" public_interface="in" name="CaNc"/>
<variable units="micromolar" public_interface="in" name="CaNc_star"/>
<variable units="micromolar" public_interface="in" name="CaMCa"/>
<variable units="second_order_rate_constant" public_interface="in" name="k3"/>
<variable units="first_order_rate_constant" public_interface="in" name="k4"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v6 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> CaMCa </ci>
<ci> CaNc </ci>
</apply>
<apply>
<times/>
<ci> k4 </ci>
<ci> CaNc_star </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v7">
<variable units="flux" public_interface="out" name="v7"/>
<variable units="micromolar" public_interface="in" name="MCIP"/>
<variable units="micromolar" public_interface="in" name="CaNc_star"/>
<variable units="micromolar" public_interface="in" name="Comp1"/>
<variable units="second_order_rate_constant" public_interface="in" name="k5"/>
<variable units="first_order_rate_constant" public_interface="in" name="k6"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v7 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k5 </ci>
<ci> CaNc_star </ci>
<ci> MCIP </ci>
</apply>
<apply>
<times/>
<ci> k6 </ci>
<ci> Comp1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v8">
<variable units="flux" public_interface="out" name="v8"/>
<variable units="micromolar" public_interface="in" name="MCIPpp"/>
<variable units="micromolar" public_interface="in" name="P1433"/>
<variable units="micromolar" public_interface="in" name="Comp2"/>
<variable units="second_order_rate_constant" public_interface="in" name="k19"/>
<variable units="first_order_rate_constant" public_interface="in" name="k20"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v8 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k19 </ci>
<ci> P1433 </ci>
<ci> MCIPpp </ci>
</apply>
<apply>
<times/>
<ci> k20 </ci>
<ci> Comp2 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v9">
<variable units="flux" public_interface="out" name="v9"/>
<variable units="micromolar" public_interface="in" name="NFATpc"/>
<variable units="micromolar" public_interface="in" name="P1433"/>
<variable units="micromolar" public_interface="in" name="Comp3"/>
<variable units="second_order_rate_constant" public_interface="in" name="k27"/>
<variable units="first_order_rate_constant" public_interface="in" name="k28"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v9 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k27 </ci>
<ci> NFATpc </ci>
<ci> P1433 </ci>
</apply>
<apply>
<times/>
<ci> k28 </ci>
<ci> Comp3 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<!-- Catalytic Binding Reactions -->
<component name="v10">
<variable units="flux" public_interface="out" name="v10"/>
<variable units="flux" public_interface="out" name="v10a"/>
<variable units="flux" public_interface="out" name="v10b"/>
<variable units="micromolar" public_interface="in" name="BMK1"/>
<variable units="micromolar" public_interface="in" name="MCIP_BMK1"/>
<variable units="micromolar" public_interface="in" name="MCIP"/>
<variable units="second_order_rate_constant" public_interface="in" name="k7"/>
<variable units="first_order_rate_constant" public_interface="in" name="k8"/>
<variable units="first_order_rate_constant" public_interface="in" name="k9"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v10a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k7 </ci>
<ci> MCIP </ci>
<ci> BMK1 </ci>
</apply>
<apply>
<times/>
<ci> k8 </ci>
<ci> MCIP_BMK1 </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v10b </ci>
<apply>
<times/>
<ci> k9 </ci>
<ci> MCIP_BMK1 </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v10 </ci>
<apply>
<plus/>
<ci> v10a </ci>
<ci> v10b </ci>
</apply>
</apply>
</math>
</component>
<component name="v11">
<variable units="flux" public_interface="out" name="v11"/>
<variable units="flux" public_interface="out" name="v11a"/>
<variable units="flux" public_interface="out" name="v11b"/>
<variable units="micromolar" public_interface="in" name="MCIPp_CaNc_star"/>
<variable units="micromolar" public_interface="in" name="CaNc_star"/>
<variable units="micromolar" public_interface="in" name="MCIPp"/>
<variable units="second_order_rate_constant" public_interface="in" name="k10"/>
<variable units="first_order_rate_constant" public_interface="in" name="k11"/>
<variable units="first_order_rate_constant" public_interface="in" name="k12"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v11a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k10 </ci>
<ci> MCIPp </ci>
<ci> CaNc_star </ci>
</apply>
<apply>
<times/>
<ci> k11 </ci>
<ci> MCIPp_CaNc_star </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v11b </ci>
<apply>
<times/>
<ci> k12 </ci>
<ci> MCIPp_CaNc_star </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v11 </ci>
<apply>
<plus/>
<ci> v11a </ci>
<ci> v11b </ci>
</apply>
</apply>
</math>
</component>
<component name="v12">
<variable units="flux" public_interface="out" name="v12"/>
<variable units="flux" public_interface="out" name="v12a"/>
<variable units="flux" public_interface="out" name="v12b"/>
<variable units="micromolar" public_interface="in" name="MCIPp_GSK3betac"/>
<variable units="micromolar" public_interface="in" name="GSK3betac"/>
<variable units="micromolar" public_interface="in" name="MCIPp"/>
<variable units="second_order_rate_constant" public_interface="in" name="k13"/>
<variable units="first_order_rate_constant" public_interface="in" name="k14"/>
<variable units="first_order_rate_constant" public_interface="in" name="k15"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v12a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k13 </ci>
<ci> MCIPp </ci>
<ci> GSK3betac </ci>
</apply>
<apply>
<times/>
<ci> k14 </ci>
<ci> MCIPp_GSK3betac </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v12b </ci>
<apply>
<times/>
<ci> k15 </ci>
<ci> MCIPp_GSK3betac </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v12 </ci>
<apply>
<plus/>
<ci> v12a </ci>
<ci> v12b </ci>
</apply>
</apply>
</math>
</component>
<component name="v13">
<variable units="flux" public_interface="out" name="v13"/>
<variable units="flux" public_interface="out" name="v13a"/>
<variable units="flux" public_interface="out" name="v13b"/>
<variable units="micromolar" public_interface="in" name="MCIPpp_CaNc_star"/>
<variable units="micromolar" public_interface="in" name="CaNc_star"/>
<variable units="micromolar" public_interface="in" name="MCIPpp"/>
<variable units="second_order_rate_constant" public_interface="in" name="k16"/>
<variable units="first_order_rate_constant" public_interface="in" name="k17"/>
<variable units="first_order_rate_constant" public_interface="in" name="k18"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v13a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k16 </ci>
<ci> MCIPpp </ci>
<ci> CaNc_star </ci>
</apply>
<apply>
<times/>
<ci> k17 </ci>
<ci> MCIPpp_CaNc_star </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v13b </ci>
<apply>
<times/>
<ci> k18 </ci>
<ci> MCIPpp_CaNc_star </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v13 </ci>
<apply>
<plus/>
<ci> v13a </ci>
<ci> v13b </ci>
</apply>
</apply>
</math>
</component>
<component name="v14">
<variable units="flux" public_interface="out" name="v14"/>
<variable units="flux" public_interface="out" name="v14a"/>
<variable units="flux" public_interface="out" name="v14b"/>
<variable units="micromolar" public_interface="in" name="NFATpc_CaNc_star"/>
<variable units="micromolar" public_interface="in" name="CaNc_star"/>
<variable units="micromolar" public_interface="in" name="NFATpc"/>
<variable units="second_order_rate_constant" public_interface="in" name="k21"/>
<variable units="first_order_rate_constant" public_interface="in" name="k22"/>
<variable units="first_order_rate_constant" public_interface="in" name="k23"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v14a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k21 </ci>
<ci> NFATpc </ci>
<ci> CaNc_star </ci>
</apply>
<apply>
<times/>
<ci> k22 </ci>
<ci> NFATpc_CaNc_star </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v14b </ci>
<apply>
<times/>
<ci> k23 </ci>
<ci> NFATpc_CaNc_star </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v14 </ci>
<apply>
<plus/>
<ci> v14a </ci>
<ci> v14b </ci>
</apply>
</apply>
</math>
</component>
<component name="v15">
<variable units="flux" public_interface="out" name="v15"/>
<variable units="flux" public_interface="out" name="v15a"/>
<variable units="flux" public_interface="out" name="v15b"/>
<variable units="micromolar" public_interface="in" name="NFATc_GSK3betac"/>
<variable units="micromolar" public_interface="in" name="GSK3betac"/>
<variable units="micromolar" public_interface="in" name="NFATc"/>
<variable units="second_order_rate_constant" public_interface="in" name="k24"/>
<variable units="first_order_rate_constant" public_interface="in" name="k25"/>
<variable units="first_order_rate_constant" public_interface="in" name="k26"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v15a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k24 </ci>
<ci> NFATc </ci>
<ci> GSK3betac </ci>
</apply>
<apply>
<times/>
<ci> k25 </ci>
<ci> NFATc_GSK3betac </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v15b </ci>
<apply>
<times/>
<ci> k26 </ci>
<ci> NFATc_GSK3betac </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v15 </ci>
<apply>
<plus/>
<ci> v15a </ci>
<ci> v15b </ci>
</apply>
</apply>
</math>
</component>
<component name="v16">
<variable units="flux" public_interface="out" name="v16"/>
<variable units="flux" public_interface="out" name="v16a"/>
<variable units="flux" public_interface="out" name="v16b"/>
<variable units="micromolar" public_interface="in" name="NFATpn_CaNn_star"/>
<variable units="micromolar" public_interface="in" name="CaNn_star"/>
<variable units="micromolar" public_interface="in" name="NFATpn"/>
<variable units="second_order_rate_constant" public_interface="in" name="k35"/>
<variable units="first_order_rate_constant" public_interface="in" name="k36"/>
<variable units="first_order_rate_constant" public_interface="in" name="k37"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v16a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k35 </ci>
<ci> NFATpn </ci>
<ci> CaNn_star </ci>
</apply>
<apply>
<times/>
<ci> k36 </ci>
<ci> NFATpn_CaNn_star </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v16b </ci>
<apply>
<times/>
<ci> k37 </ci>
<ci> NFATpn_CaNn_star </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v16 </ci>
<apply>
<plus/>
<ci> v16a </ci>
<ci> v16b </ci>
</apply>
</apply>
</math>
</component>
<component name="v17">
<variable units="flux" public_interface="out" name="v17"/>
<variable units="flux" public_interface="out" name="v17a"/>
<variable units="flux" public_interface="out" name="v17b"/>
<variable units="micromolar" public_interface="in" name="NFATn_GSK3betan"/>
<variable units="micromolar" public_interface="in" name="GSK3betan"/>
<variable units="micromolar" public_interface="in" name="NFATn"/>
<variable units="second_order_rate_constant" public_interface="in" name="k38"/>
<variable units="first_order_rate_constant" public_interface="in" name="k39"/>
<variable units="first_order_rate_constant" public_interface="in" name="k40"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v17a </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k38 </ci>
<ci> NFATn </ci>
<ci> GSK3betan </ci>
</apply>
<apply>
<times/>
<ci> k39 </ci>
<ci> NFATn_GSK3betan </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> v17b </ci>
<apply>
<times/>
<ci> k40 </ci>
<ci> NFATn_GSK3betan </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> v17 </ci>
<apply>
<plus/>
<ci> v17a </ci>
<ci> v17b </ci>
</apply>
</apply>
</math>
</component>
<!-- transcription control process of MCIP by NFAT -->
<component name="v18">
<variable units="flux" public_interface="out" name="v18"/>
<variable units="micromolar" public_interface="in" name="NFATn"/>
<variable units="micromolar" public_interface="in" name="MRNA"/>
<variable units="first_order_rate_constant" public_interface="in" name="k41"/>
<variable units="first_order_rate_constant" public_interface="in" name="k42"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v18 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k41 </ci>
<ci> NFATn </ci>
</apply>
<apply>
<times/>
<ci> k42 </ci>
<ci> MRNA </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v19">
<variable units="flux" public_interface="out" name="v19"/>
<variable units="minute" public_interface="in" name="t_half"/>
<variable units="micromolar" public_interface="in" name="MRNA"/>
<variable units="micromolar" public_interface="in" name="MCIP"/>
<variable units="first_order_rate_constant" public_interface="in" name="k43"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> v19 </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> k43 </ci>
<ci> MRNA </ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<ln/>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> t_half </ci>
</apply>
<ci> MCIP </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="model_parameters">
<variable units="fifth_order_rate_constant" public_interface="out" name="k1" initial_value="5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k2" initial_value="100"/>
<variable units="second_order_rate_constant" public_interface="out" name="k3" initial_value="2760"/>
<variable units="first_order_rate_constant" public_interface="out" name="k4" initial_value="0.072"/>
<variable units="second_order_rate_constant" public_interface="out" name="k5" initial_value="50"/>
<variable units="first_order_rate_constant" public_interface="out" name="k6" initial_value="0.0567"/>
<variable units="second_order_rate_constant" public_interface="out" name="k7" initial_value="5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k8" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k9" initial_value="0.5"/>
<variable units="second_order_rate_constant" public_interface="out" name="k10" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k11" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k12" initial_value="0.1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k13" initial_value="0.5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k14" initial_value="0.5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k15" initial_value="0.1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k16" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k17" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k18" initial_value="0.1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k19" initial_value="0.5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k20" initial_value="0.1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k21" initial_value="0.15"/>
<variable units="first_order_rate_constant" public_interface="out" name="k22" initial_value="0.15"/>
<variable units="first_order_rate_constant" public_interface="out" name="k23" initial_value="0.15"/>
<variable units="second_order_rate_constant" public_interface="out" name="k24" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k25" initial_value="0.15"/>
<variable units="first_order_rate_constant" public_interface="out" name="k26" initial_value="0.1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k27" initial_value="0.4"/>
<variable units="first_order_rate_constant" public_interface="out" name="k28" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k29" initial_value="0.4"/>
<variable units="first_order_rate_constant" public_interface="out" name="k30" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k31" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k32" initial_value="0.05"/>
<variable units="first_order_rate_constant" public_interface="out" name="k33" initial_value="0.114"/>
<variable units="first_order_rate_constant" public_interface="out" name="k34" initial_value="0.0552"/>
<variable units="second_order_rate_constant" public_interface="out" name="k35" initial_value="0.15"/>
<variable units="first_order_rate_constant" public_interface="out" name="k36" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k37" initial_value="0.2"/>
<variable units="second_order_rate_constant" public_interface="out" name="k38" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k39" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k40" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="k41" initial_value="0.02"/>
<variable units="first_order_rate_constant" public_interface="out" name="k42" initial_value="0.03"/>
<variable units="first_order_rate_constant" public_interface="out" name="k43" initial_value="0.03"/>
<variable units="minute" public_interface="out" name="t_half" initial_value="15"/>
<variable units="micromolar" public_interface="out" name="Ca" initial_value="0.2"/>
</component>
<connection>
<map_components component_2="environment" component_1="BMK1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MRNA"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATc"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATn"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATpc"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATpn"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="GSK3betac"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="GSK3betan"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="CaNc"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="CaNn"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="CaNc_star"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="CaNn_star"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="CaM"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="CaMCa"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MCIP"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MCIPp"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MCIPpp"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Comp1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Comp2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Comp3"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="P1433"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MCIP_BMK1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MCIPp_CaNc_star"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MCIPp_GSK3betac"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="MCIPpp_CaNc_star"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATpc_CaNc_star"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATc_GSK3betac"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATpn_CaNn_star"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="NFATn_GSK3betan"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="BMK1" component_1="v10"/>
<map_variables variable_2="v10a" variable_1="v10a"/>
<map_variables variable_2="v10b" variable_1="v10b"/>
<map_variables variable_2="BMK1" variable_1="BMK1"/>
</connection>
<connection>
<map_components component_2="MRNA" component_1="v18"/>
<map_variables variable_2="v18" variable_1="v18"/>
<map_variables variable_2="MRNA" variable_1="MRNA"/>
</connection>
<connection>
<map_components component_2="MRNA" component_1="v19"/>
<map_variables variable_2="v19" variable_1="v19"/>
<map_variables variable_2="MRNA" variable_1="MRNA"/>
</connection>
<connection>
<map_components component_2="NFATc" component_1="v1"/>
<map_variables variable_2="v1" variable_1="v1"/>
<map_variables variable_2="NFATc" variable_1="NFATc"/>
</connection>
<connection>
<map_components component_2="NFATc" component_1="v14"/>
<map_variables variable_2="v14" variable_1="v14"/>
</connection>
<connection>
<map_components component_2="NFATc" component_1="v15"/>
<map_variables variable_2="v15" variable_1="v15"/>
<map_variables variable_2="NFATc" variable_1="NFATc"/>
</connection>
<connection>
<map_components component_2="NFATn" component_1="v1"/>
<map_variables variable_2="v1" variable_1="v1"/>
</connection>
<connection>
<map_components component_2="NFATn" component_1="v16"/>
<map_variables variable_2="v16" variable_1="v16"/>
</connection>
<connection>
<map_components component_2="NFATn" component_1="v17"/>
<map_variables variable_2="v17" variable_1="v17"/>
<map_variables variable_2="NFATn" variable_1="NFATn"/>
</connection>
<connection>
<map_components component_2="NFATn" component_1="v18"/>
<map_variables variable_2="v18" variable_1="v18"/>
<map_variables variable_2="NFATn" variable_1="NFATn"/>
</connection>
<connection>
<map_components component_2="NFATpc" component_1="v2"/>
<map_variables variable_2="v2" variable_1="v2"/>
</connection>
<connection>
<map_components component_2="NFATpc" component_1="v9"/>
<map_variables variable_2="v9" variable_1="v9"/>
<map_variables variable_2="NFATpc" variable_1="NFATpc"/>
</connection>
<connection>
<map_components component_2="NFATpc" component_1="v14"/>
<map_variables variable_2="v14" variable_1="v14"/>
<map_variables variable_2="NFATpc" variable_1="NFATpc"/>
</connection>
<connection>
<map_components component_2="NFATpc" component_1="v15"/>
<map_variables variable_2="v15" variable_1="v15"/>
</connection>
<connection>
<map_components component_2="NFATpn" component_1="v2"/>
<map_variables variable_2="v2" variable_1="v2"/>
<map_variables variable_2="NFATpn" variable_1="NFATpn"/>
</connection>
<connection>
<map_components component_2="NFATpn" component_1="v16"/>
<map_variables variable_2="v16" variable_1="v16"/>
<map_variables variable_2="NFATpn" variable_1="NFATpn"/>
</connection>
<connection>
<map_components component_2="NFATpn" component_1="v17"/>
<map_variables variable_2="v17" variable_1="v17"/>
</connection>
<connection>
<map_components component_2="GSK3betac" component_1="v3"/>
<map_variables variable_2="v3" variable_1="v3"/>
<map_variables variable_2="GSK3betac" variable_1="GSK3betac"/>
</connection>
<connection>
<map_components component_2="GSK3betac" component_1="v12"/>
<map_variables variable_2="v12a" variable_1="v12a"/>
<map_variables variable_2="v12b" variable_1="v12b"/>
<map_variables variable_2="GSK3betac" variable_1="GSK3betac"/>
</connection>
<connection>
<map_components component_2="GSK3betac" component_1="v15"/>
<map_variables variable_2="v15a" variable_1="v15a"/>
<map_variables variable_2="v15b" variable_1="v15b"/>
<map_variables variable_2="GSK3betac" variable_1="GSK3betac"/>
</connection>
<connection>
<map_components component_2="GSK3betan" component_1="v3"/>
<map_variables variable_2="v3" variable_1="v3"/>
<map_variables variable_2="GSK3betan" variable_1="GSK3betan"/>
</connection>
<connection>
<map_components component_2="GSK3betan" component_1="v17"/>
<map_variables variable_2="v17a" variable_1="v17a"/>
<map_variables variable_2="v17b" variable_1="v17b"/>
<map_variables variable_2="GSK3betan" variable_1="GSK3betan"/>
</connection>
<connection>
<map_components component_2="CaNc" component_1="v6"/>
<map_variables variable_2="v6" variable_1="v6"/>
<map_variables variable_2="CaNc" variable_1="CaNc"/>
</connection>
<connection>
<map_components component_2="CaNc_star" component_1="v4"/>
<map_variables variable_2="v4" variable_1="v4"/>
<map_variables variable_2="CaNc_star" variable_1="CaNc_star"/>
</connection>
<connection>
<map_components component_2="CaNc_star" component_1="v6"/>
<map_variables variable_2="v6" variable_1="v6"/>
<map_variables variable_2="CaNc_star" variable_1="CaNc_star"/>
</connection>
<connection>
<map_components component_2="CaNc_star" component_1="v7"/>
<map_variables variable_2="v7" variable_1="v7"/>
<map_variables variable_2="CaNc_star" variable_1="CaNc_star"/>
</connection>
<connection>
<map_components component_2="CaNc_star" component_1="v11"/>
<map_variables variable_2="v11a" variable_1="v11a"/>
<map_variables variable_2="v11b" variable_1="v11b"/>
<map_variables variable_2="CaNc_star" variable_1="CaNc_star"/>
</connection>
<connection>
<map_components component_2="CaNc_star" component_1="v13"/>
<map_variables variable_2="v13a" variable_1="v13a"/>
<map_variables variable_2="v13b" variable_1="v13b"/>
<map_variables variable_2="CaNc_star" variable_1="CaNc_star"/>
</connection>
<connection>
<map_components component_2="CaNc_star" component_1="v14"/>
<map_variables variable_2="v14a" variable_1="v14a"/>
<map_variables variable_2="v14b" variable_1="v14b"/>
<map_variables variable_2="CaNc_star" variable_1="CaNc_star"/>
</connection>
<connection>
<map_components component_2="CaNn_star" component_1="v4"/>
<map_variables variable_2="v4" variable_1="v4"/>
<map_variables variable_2="CaNn_star" variable_1="CaNn_star"/>
</connection>
<connection>
<map_components component_2="CaNn_star" component_1="v16"/>
<map_variables variable_2="v16a" variable_1="v16a"/>
<map_variables variable_2="v16b" variable_1="v16b"/>
<map_variables variable_2="CaNn_star" variable_1="CaNn_star"/>
</connection>
<connection>
<map_components component_2="CaNn" component_1="v6"/>
<map_variables variable_2="v6" variable_1="v6"/>
</connection>
<connection>
<map_components component_2="CaM" component_1="v5"/>
<map_variables variable_2="v5" variable_1="v5"/>
<map_variables variable_2="CaM" variable_1="CaM"/>
</connection>
<connection>
<map_components component_2="CaMCa" component_1="v5"/>
<map_variables variable_2="v5" variable_1="v5"/>
<map_variables variable_2="CaMCa" variable_1="CaMCa"/>
</connection>
<connection>
<map_components component_2="CaMCa" component_1="v6"/>
<map_variables variable_2="v6" variable_1="v6"/>
<map_variables variable_2="CaMCa" variable_1="CaMCa"/>
</connection>
<connection>
<map_components component_2="MCIP" component_1="v7"/>
<map_variables variable_2="v7" variable_1="v7"/>
<map_variables variable_2="MCIP" variable_1="MCIP"/>
</connection>
<connection>
<map_components component_2="MCIP" component_1="v10"/>
<map_variables variable_2="v10" variable_1="v10"/>
<map_variables variable_2="MCIP" variable_1="MCIP"/>
</connection>
<connection>
<map_components component_2="MCIP" component_1="v11"/>
<map_variables variable_2="v11" variable_1="v11"/>
</connection>
<connection>
<map_components component_2="MCIP" component_1="v19"/>
<map_variables variable_2="v19" variable_1="v19"/>
<map_variables variable_2="MCIP" variable_1="MCIP"/>
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