<?xml version="1.0"?>
<!-- FILE :Ras_cascade.xml
CREATED : 30th October 2002
LAST MODIFIED : 5th April 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Vojtek and Der's 1998 analysis of a Ras signalling pathway.
CHANGES:
05/04/2003 - AAC - Changed the model name so the model loads in the database
easier.
-->
<model name="Ras_cascade_1998" cmeta:id="Ras_cascade" xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
<!--
The following RDF block contains metadata that applies to this document
as a whole, as indicated by the empty about attribute on the
<rdf:Description> element.
-->
<rdf:Description rdf:about="">
<!--
The Model Builder Metadata. The Dublin Core "creator" element is used
to indicate the person who translated the model into CellML.
-->
<dc:creator rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Lloyd</vCard:Family>
<vCard:Given>Catherine</vCard:Given>
<vCard:Other>May</vCard:Other>
</vCard:N>
<vCard:EMAIL rdf:parseType="Resource">
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet" />
</vCard:EMAIL>
<vCard:ORG rdf:parseType="Resource">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</vCard:ORG>
</dc:creator>
<!--
The Creation Date metadata. This is the date on which the model
was translated into CellML.
-->
<dcterms:created rdf:parseType="Resource">
<dcterms:W3CDTF>2002-10-30</dcterms:W3CDTF>
</dcterms:created>
<!--
The Modification History metadata. This lists the changes that have been
made to the document, who made the changes, and when they were made.
-->
<cmeta:modification rdf:parseType="Resource">
<rdf:value>
Changed the model name so the model loads in the database easier.
</rdf:value>
<cmeta:modifier rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Cuellar</vCard:Family>
<vCard:Given>Autumn</vCard:Given>
<vCard:Other>A</vCard:Other>
</vCard:N>
</cmeta:modifier>
<dcterms:modified rdf:parseType="Resource">
<dcterms:W3CDTF>2003-04-05</dcterms:W3CDTF>
</dcterms:modified>
</cmeta:modification>
<!-- The Publisher metadata. -->
<dc:publisher>
The University of Auckland, Bioengineering Institute
</dc:publisher>
</rdf:Description>
<!--
The following metadata refers to the model itself, as indicated by the
reference to the ID "Ras_cascade", which is declared on the
<model> element.
-->
<rdf:Description rdf:about="#Ras_cascade">
<!-- A human readable name for the model. -->
<dc:title>
Vojtek and Der's 1998 analysis of a Ras signalling pathway.
</dc:title>
<!-- A comment regarding the model. -->
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
This is the CellML descripition of Vojtek and Der's 1998 analysis of a
Ras signalling pathway.
</rdf:value>
<!-- The creator of the comment. -->
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<!-- Keyword(s) -->
<bqs:reference rdf:parseType="Resource">
<dc:subject rdf:parseType="Resource">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>signal transduction</rdf:value>
</dc:subject>
</bqs:reference>
<!--
The CellML Metadata Specification recommends that bibliographic metadata
is used to provide information about the original model reference. The
"identifier" attribute on the "BibliographicReference" class provides an
elegant way to identify a cited reference using a database identifier
such as Pubmed. All associated data such as author, journal title,
date, etc can be looked up on the database.
-->
<bqs:reference rdf:parseType="Resource">
<bqs:Pubmed_id>9685325</bqs:Pubmed_id>
<bqs:JournalArticle rdf:parseType="Resource">
<dc:creator>
<rdf:Seq>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Vojtek</vCard:Family>
<vCard:Given>Anne</vCard:Given>
<vCard:Other>B</vCard:Other>
</vCard:N>
</bqs:Person>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Der</vCard:Family>
<vCard:Given>Channing</vCard:Given>
<vCard:Other>J</vCard:Other>
</vCard:N>
</bqs:Person>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>
Increasing Complexity of the Ras Signaling Pathway
</dc:title>
<dcterms:issued rdf:parseType="Resource">
<dcterms:W3CDTF>1998-08-07</dcterms:W3CDTF>
</dcterms:issued>
<bqs:Journal rdf:parseType="Resource">
<dc:title>The Journal of Biological Chemistry</dc:title>
</bqs:Journal>
<bqs:volume>273</bqs:volume>
<bqs:first_page>19925</bqs:first_page>
<bqs:last_page>19928</bqs:last_page>
</bqs:JournalArticle>
</bqs:reference>
</rdf:Description>
</rdf:RDF>
<!--
Below, we define some additional units for association with variables and
constants within the model. The identifiers are fairly self-explanatory.
-->
<units name="micromolar">
<unit prefix="micro" units="mole" />
<unit units="litre" exponent="-1" />
</units>
<units name="flux">
<unit units="micromolar" exponent="1" />
<unit units="second" exponent="-1" />
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1" />
</units>
<units name="second_order_rate_constant">
<unit units="micromolar" exponent="-1" />
<unit units="second" exponent="-1" />
</units>
<units name="third_order_rate_constant">
<unit units="micromolar" exponent="-2" />
<unit units="second" exponent="-1" />
</units>
<!--
The "environment" component is used to declare variables that are used by
all or most of the other components, in this case just "time".
-->
<component name="environment">
<variable name="time" public_interface="out" units="second" />
</component>
<!--
The following components describe all the reactants, products, enzymes,
activators and inhibitors involved in the reactions.
-->
<component name="TRK" cmeta:id="TRK">
<variable name="TRK" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_TRK_rxn0" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>TRK</ci>
</apply>
<ci>delta_TRK_rxn0</ci>
</apply>
</math>
</component>
<component name="EGF" cmeta:id="EGF">
<variable name="EGF" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_EGF_rxn0" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>EGF</ci>
</apply>
<ci>delta_EGF_rxn0</ci>
</apply>
</math>
</component>
<component name="EGF_TRK_complex" cmeta:id="EGF_TRK_complex">
<variable name="EGF_TRK_complex" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_EGF_TRK_complex_rxn0" public_interface="in" units="flux" />
<variable name="delta_EGF_TRK_complex_rxn1" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>EGF_TRK_complex</ci>
</apply>
<apply>
<plus />
<ci>delta_EGF_TRK_complex_rxn0</ci>
<ci>delta_EGF_TRK_complex_rxn1</ci>
</apply>
</apply>
</math>
</component>
<component name="Phosphate" cmeta:id="Phosphate">
<variable name="Phosphate" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Phosphate_rxn1" public_interface="in" units="flux" />
<variable name="delta_Phosphate_rxn6" public_interface="in" units="flux" />
<variable name="delta_Phosphate_rxn7" public_interface="in" units="flux" />
<variable name="delta_Phosphate_rxn8" public_interface="in" units="flux" />
<variable name="delta_Phosphate_rxn9" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Phosphate</ci>
</apply>
<apply>
<plus />
<ci>delta_Phosphate_rxn1</ci>
<ci>delta_Phosphate_rxn6</ci>
<ci>delta_Phosphate_rxn7</ci>
<ci>delta_Phosphate_rxn8</ci>
<ci>delta_Phosphate_rxn9</ci>
</apply>
</apply>
</math>
</component>
<component name="Phosphorylated_receptor_complex" cmeta:id="Phosphorylated_receptor_complex">
<variable name="Phosphorylated_receptor_complex" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Phosphorylated_receptor_complex_rxn1" public_interface="in" units="flux" />
<variable name="delta_Phosphorylated_receptor_complex_rxn2" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Phosphorylated_receptor_complex</ci>
</apply>
<apply>
<plus />
<ci>delta_Phosphorylated_receptor_complex_rxn1</ci>
<ci>delta_Phosphorylated_receptor_complex_rxn2</ci>
</apply>
</apply>
</math>
</component>
<component name="GRB2" cmeta:id="GRB2">
<variable name="GRB2" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_GRB2_rxn2" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>GRB2</ci>
</apply>
<ci>delta_GRB2_rxn2</ci>
</apply>
</math>
</component>
<component name="SOS" cmeta:id="SOS">
<variable name="SOS" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_SOS_rxn2" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>SOS</ci>
</apply>
<ci>delta_SOS_rxn2</ci>
</apply>
</math>
</component>
<component name="Ras_GDP" cmeta:id="Ras_GDP">
<variable name="Ras_GDP" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Ras_GDP_rxn3" public_interface="in" units="flux" />
<variable name="delta_Ras_GDP_rxn4" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Ras_GDP</ci>
</apply>
<apply>
<plus />
<ci>delta_Ras_GDP_rxn3</ci>
<ci>delta_Ras_GDP_rxn4</ci>
</apply>
</apply>
</math>
</component>
<component name="active_receptor_complex" cmeta:id="active_receptor_complex">
<variable name="active_receptor_complex" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_active_receptor_complex_rxn2" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>active_receptor_complex</ci>
</apply>
<ci>delta_active_receptor_complex_rxn2</ci>
</apply>
</math>
</component>
<component name="Ras_GTP" cmeta:id="Ras_GTP">
<variable name="Ras_GTP" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Ras_GTP_rxn4" public_interface="in" units="flux" />
<variable name="delta_Ras_GTP_rxn3" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Ras_GTP</ci>
</apply>
<apply>
<plus />
<ci>delta_Ras_GTP_rxn4</ci>
<ci>delta_Ras_GTP_rxn3</ci>
</apply>
</apply>
</math>
</component>
<component name="GAP" cmeta:id="GAP">
<variable name="GAP" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="time" public_interface="in" units="second" />
</component>
<component name="inactive_Raf" cmeta:id="inactive_Raf">
<variable name="inactive_Raf" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_inactive_Raf_rxn5" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>inactive_Raf</ci>
</apply>
<ci>delta_inactive_Raf_rxn5</ci>
</apply>
</math>
</component>
<component name="active_Raf" cmeta:id="active_Raf">
<variable name="active_Raf" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_active_Raf_rxn5" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>active_Raf</ci>
</apply>
<ci>delta_active_Raf_rxn5</ci>
</apply>
</math>
</component>
<component name="inactive_MEK" cmeta:id="inactive_MEK">
<variable name="inactive_MEK" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_inactive_MEK_rxn6" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>inactive_MEK</ci>
</apply>
<ci>delta_inactive_MEK_rxn6</ci>
</apply>
</math>
</component>
<component name="active_MEK" cmeta:id="active_MEK">
<variable name="active_MEK" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_active_MEK_rxn6" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>active_MEK</ci>
</apply>
<ci>delta_active_MEK_rxn6</ci>
</apply>
</math>
</component>
<component name="inactive_ERK" cmeta:id="inactive_ERK">
<variable name="inactive_ERK" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_inactive_ERK_rxn7" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>inactive_ERK</ci>
</apply>
<ci>delta_inactive_ERK_rxn7</ci>
</apply>
</math>
</component>
<component name="active_ERK_i" cmeta:id="active_ERK_i">
<variable name="active_ERK_i" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_active_ERK_i_rxn7" public_interface="in" units="flux" />
<variable name="delta_active_ERK_i_rxn10" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>active_ERK_i</ci>
</apply>
<apply>
<plus />
<ci>delta_active_ERK_i_rxn7</ci>
<ci>delta_active_ERK_i_rxn10</ci>
</apply>
</apply>
</math>
</component>
<component name="inactive_Mnk" cmeta:id="inactive_Mnk">
<variable name="inactive_Mnk" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_inactive_Mnk_rxn8" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>inactive_Mnk</ci>
</apply>
<ci>delta_inactive_Mnk_rxn8</ci>
</apply>
</math>
</component>
<component name="active_Mnk" cmeta:id="active_Mnk">
<variable name="active_Mnk" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_active_Mnk_rxn8" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>active_Mnk</ci>
</apply>
<ci>delta_active_Mnk_rxn8</ci>
</apply>
</math>
</component>
<component name="active_ERK_n" cmeta:id="active_ERK_n">
<variable name="active_ERK_n" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_active_ERK_n_rxn10" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply></