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<body>Panther Pathway: P04392
The p53 pathway responds to stresses that can disrupt the fidelity of DNA replication and cell division. A stress signal is transmitted to the p53 protein by post-translational modifications. This results in the activation of the p53 protein as a transcription factor that initiates a program of cell cycle arrest, cellular senescence or apoptosis. The transcriptional network of p53-responsive genes produces proteins that interact with a large number of other signal transduction pathways in the cell and a number of positive and negative autoregulatory feedback loops act upon the p53 response.  This diagram illustrates 3 such negative feedback loops.
Medline=15838523
PMID: 15838523
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Synonym:  Synonym not specified
Accession:  G04681
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Accession:  P04536
Pathway Link:  P00033|P04496|Insulin/IGF pathway-protein kinase B signaling cascade*P04398|P04663|p53 pathway feedback loops 2*P00059|P01483|p53 pathway
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<species metaid="s8" id="s8" name="P73_Delta_N" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  P73DeltaN
Synonym:  Synonym not specified
Accession:  G04685
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>RNA</celldesigner:class>
<celldesigner:rnaReference>rn1</celldesigner:rnaReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s2" id="s2" name="P73_delta_N" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Delta Np73
Synonym:  Synonym not specified
Accession:  P04537
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>p2</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
<celldesigner:listOfCatalyzedReactions>
<celldesigner:catalyzed reaction="re32"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s3" id="s3" name="P73" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Tumor protein p73
Synonym:  p53-related protein p73
Accession:  G04686
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>GENE</celldesigner:class>
<celldesigner:geneReference>gn2</celldesigner:geneReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s9" id="s9" name="Mdm2" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Mdm2
Synonym:  Synonym not specified
Accession:  G04682
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>GENE</celldesigner:class>
<celldesigner:geneReference>gn3</celldesigner:geneReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s10" id="s10" name="Cop_minus_1" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Cop-1
Synonym:  Synonym not specified
Accession:  G04683
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>GENE</celldesigner:class>
<celldesigner:geneReference>gn4</celldesigner:geneReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s11" id="s11" name="Pirh_minus_1" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Pirh-2
Synonym:  Synonym not specified
Accession:  G04684
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>GENE</celldesigner:class>
<celldesigner:geneReference>gn5</celldesigner:geneReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s1" id="s1" name="P53" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  P53
Synonym:  Synonym not specified
Accession:  P04539
Pathway Link:  P00006|P00273|Apoptosis signaling pathway*P00033|P04497|Insulin/IGF pathway-protein kinase B signaling cascade*P04398|P04668|p53 pathway feedback loops 2*P00059|P01485|p53 pathway
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>p1</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
<celldesigner:listOfCatalyzedReactions>
<celldesigner:catalyzed reaction="re24"/>
<celldesigner:catalyzed reaction="re26"/>
<celldesigner:catalyzed reaction="re28"/>
<celldesigner:catalyzed reaction="re30"/>
<celldesigner:catalyzed reaction="re32"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s15" id="s15" name="Complex_br_(Cop_minus_1/P53)" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Long name not specified
Synonym:  Synonym not specified
Accession:  U05449
Heterodimer Member Info:  P53#PROTEIN#P53#P04539;Cop-1#PROTEIN#Constitutively photomorphogenic 1#P04540
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>Complex_br_(Cop_minus_1/P53)</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s16" id="s16" name="Complex_br_(Pirh_minus_1/P53)" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Long name not specified
Synonym:  Synonym not specified
Accession:  U05448
Heterodimer Member Info:  Pirh-1#PROTEIN#PMID: 11753569,15547185#P04538#Pirh2 is a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity. Pirh2 transcription is induced by p53|and its protein physically interacts with p53 and promotes ubiquitination and degradation of p53 independently of Mdm2.;P53#PROTEIN#P53#P04539
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>Complex_br_(Pirh_minus_1/P53)</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s17" id="s17" name="P53" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  P53
Synonym:  Synonym not specified
Accession:  P04539
Pathway Link:  P00006|P00273|Apoptosis signaling pathway*P00033|P04497|Insulin/IGF pathway-protein kinase B signaling cascade*P04398|P04668|p53 pathway feedback loops 2*P00059|P01485|p53 pathway
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>p1</celldesigner:proteinReference>
<celldesigner:state>
<celldesigner:listOfModifications>
<celldesigner:modification residue="rs1" state="ubiquitinated"/>
</celldesigner:listOfModifications>
</celldesigner:state>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s18" id="s18" name="a27_degraded" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  a27_degraded
Synonym:  Synonym not specified
Accession:  U05452
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>DEGRADED</celldesigner:class>
<celldesigner:name>a27_degraded</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s19" id="s19" name="a28_degraded" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  a28_degraded
Synonym:  Synonym not specified
Accession:  U05450
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>DEGRADED</celldesigner:class>
<celldesigner:name>a28_degraded</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s20" id="s20" name="a29_degraded" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  a29_degraded
Synonym:  Synonym not specified
Accession:  U05451
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>DEGRADED</celldesigner:class>
<celldesigner:name>a29_degraded</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s21" id="s21" name="Complex_br_(Mdm2/P53)" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Long name not specified
Synonym:  Synonym not specified
Accession:  U05447
Heterodimer Member Info:  Mdm2#PROTEIN#Mouse double minute 2#P04536;P53#PROTEIN#P53#P04539
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>Complex_br_(Mdm2/P53)</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s22" id="s22" name="Ub" compartment="default">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>
Long Name:  Ub
Synonym:  Synonym not specified
Accession:  S04838
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>SIMPLE_MOLECULE</celldesigner:class>
<celldesigner:name>Ub</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s26" id="s26" name="Mdm2" compartment="default" initialAmount="0">
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>RNA</celldesigner:class>
<celldesigner:rnaReference>rn2</celldesigner:rnaReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s27" id="s27" name="Cop-1" compartment="default" initialAmount="0">
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>RNA</celldesigner:class>
<celldesigner:rnaReference>rn3</celldesigner:rnaReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s28" id="s28" name="Pirh-1" compartment="default" initialAmount="0">
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>RNA</celldesigner:class>
<celldesigner:rnaReference>rn4</celldesigner:rnaReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s29" id="s29" name="P53 responsive genes" compartment="default" initialAmount="0">
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>RNA</celldesigner:class>
<celldesigner:rnaReference>rn5</celldesigner:rnaReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
</listOfSpecies>
<listOfReactions>
<reaction metaid="re14" id="re14" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>HETERODIMER_ASSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s1" alias="a1">
<celldesigner:linkAnchor position="S"/>
</celldesigner:baseReactant>
<celldesigner:baseReactant species="s6" alias="a7"/>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s15" alias="a25">
<celldesigner:linkAnchor position="N"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection arm="0" index="0" value="unknown"/>
<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="0" num1="0" num2="0" tShapeIndex="0">0.031047551943362173,0.6885633543268295</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00011" species="s1">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a1</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00012" species="s6">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a7</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00013" species="s15">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a25</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re15" id="re15" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>HETERODIMER_ASSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s1" alias="a1">
<celldesigner:linkAnchor position="ESE"/>
</celldesigner:baseReactant>
<celldesigner:baseReactant species="s7" alias="a8">
<celldesigner:linkAnchor position="W"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s16" alias="a26">
<celldesigner:linkAnchor position="N"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection arm="0" index="0" value="unknown"/>
<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="0" num1="0" num2="0" tShapeIndex="0">0.2612932514880333,0.5245068576267524</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00014" species="s1">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a1</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00015" species="s7">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a8</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00016" species="s16">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a26</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re17" id="re17" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>DISSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s15" alias="a25">
<celldesigner:linkAnchor position="S"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s6" alias="a31"/>
<celldesigner:baseProduct species="s17" alias="a28">
<celldesigner:linkAnchor position="N"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:listOfReactantLinks>
<celldesigner:reactantLink reactant="s22" alias="a41" targetLineIndex="-1,0">
<celldesigner:line width="1.0" color="ff000000" type="Curve"/>
</celldesigner:reactantLink>
</celldesigner:listOfReactantLinks>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection arm="0" index="0" value="unknown"/>
<celldesigner:lineDirection arm="0" index="1" value="unknown"/>
<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="1" num1="0" num2="0" tShapeIndex="0">0.5779791788594153,8.744705234322581E-4 0.008341672673838119,0.677658663500921</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00017" species="s15">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a25</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00018" species="s22">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a41</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00019" species="s6">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a31</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00020" species="s17">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a28</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re18" id="re18" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>DISSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s16" alias="a26">
<celldesigner:linkAnchor position="S"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s7" alias="a32"/>
<celldesigner:baseProduct species="s17" alias="a29">
<celldesigner:linkAnchor position="N"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:listOfReactantLinks>
<celldesigner:reactantLink reactant="s22" alias="a40" targetLineIndex="-1,0">
<celldesigner:line width="1.0" color="ff000000" type="Curve"/>
</celldesigner:reactantLink>
</celldesigner:listOfReactantLinks>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection arm="0" index="0" value="unknown"/>
<celldesigner:lineDirection arm="0" index="1" value="unknown"/>
<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="1" num1="0" num2="0" tShapeIndex="0">0.5124533447373345,9.520159404932116E-4 0.0010792904737915165,0.6807244466682967</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00021" species="s16">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a26</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00022" species="s22">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a40</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00023" species="s7">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a32</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00024" species="s17">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a29</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re19" id="re19" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>STATE_TRANSITION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s17" alias="a27">
<celldesigner:linkAnchor position="S"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s18" alias="a33">
<celldesigner:linkAnchor position="N"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct" rectangleIndex="0">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
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<annotation>
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</annotation>
</speciesReference>
</listOfReactants>
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<annotation>
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</annotation>
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</reaction>
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<annotation>
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<celldesigner:reactionType>STATE_TRANSITION</celldesigner:reactionType>
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</celldesigner:baseProducts>
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</celldesigner:listOfLineDirection>
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<celldesigner:line width="1.0" color="ff000000"/>
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</annotation>
<listOfReactants>
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<annotation>
<celldesigner:extension>
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</annotation>
</speciesReference>
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<listOfProducts>
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<annotation>
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</annotation>
</speciesReference>
</listOfProducts>
</reaction>
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<annotation>
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<celldesigner:reactionType>HETERODIMER_ASSOCIATION</celldesigner:reactionType>
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</annotation>
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</annotation>
</speciesReference>
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<annotation>
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</annotation>
</speciesReference>
</listOfProducts>
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<reaction metaid="re23" id="re23" reversible="false">
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</celldesigner:baseReactant>
</celldesigner:baseReactants>
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<celldesigner:line width="1.0" color="ff000000"/>
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</annotation>
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</annotation>
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</annotation>
</speciesReference>
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</annotation>
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</annotation>
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<reaction metaid="re24" id="re24" reversible="false">
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</annotation>
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<annotation>
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</annotation>
</modifierSpeciesReference>
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</annotation>
<listOfReactants>
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</speciesReference>
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</annotation>
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<celldesigner:listOfLineDirection>
<celldesigner:lineDirection index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:modification>
<celldesigner:modification type="PHYSICAL_STIMULATION" modifiers="s1" aliases="a1" targetLineIndex="-1,0">
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:linkTarget species="s1" alias="a1">
<celldesigner:linkAnchor position="SSW"/>
</celldesigner:linkTarget>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:modification>
<celldesigner:modification type="PHYSICAL_STIMULATION" modifiers="s2" aliases="a2" targetLineIndex="-1,0">
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection index="0" value="horizontal"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:linkTarget species="s2" alias="a2">
<celldesigner:linkAnchor position="WNW"/>
</celldesigner:linkTarget>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:modification>
</celldesigner:listOfModification>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00063" species="s4">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a5</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00064" species="s29">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa33</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
<listOfModifiers>
<modifierSpeciesReference metaid="CDMT00065" species="s1">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a1</celldesigner:alias>
</celldesigner:extension>
</annotation>
</modifierSpeciesReference>
<modifierSpeciesReference metaid="CDMT00066" species="s2">
<annotation>
<celldesigner:extension>
<celldesigner:alias>a2</celldesigner:alias>
</celldesigner:extension>
</annotation>
</modifierSpeciesReference>
</listOfModifiers>
</reaction>
</listOfReactions>
</model>
</sbml>

