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BIOMD0000000074 - Leloup2003_CircClock_DD_REV-ERBalpha

 

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Reference Publication
Publication ID: 12775757
Leloup JC, Goldbeter A.
Toward a detailed computational model for the mammalian circadian clock.
Proc. Natl. Acad. Sci. U.S.A. 2003 Jun; 100(12): 7051-7056
Unité de Chronobiologie Théorique, Faculté des Sciences, Université Libre de Bruxelles, Campus Plaine, C. P. 231, B-1050 Brussels, Belgium.  [more]
Model
Original Model: BIOMD0000000074.origin
Submitter: Enuo He
Submission ID: MODEL1272626224
Submission Date: 01 Nov 2006 15:13:11 UTC
Last Modification Date: 25 Feb 2015 13:01:01 UTC
Creation Date: 19 Oct 2006 10:21:38 UTC
Encoders:  Enuo He
set #1
bqbiol:hasTaxon Taxonomy Mammalia
set #2
bqmodel:isDerivedFrom BioModels Database Leloup1999_CircClock
set #3
bqbiol:isVersionOf Gene Ontology regulation of circadian rhythm
bqbiol:hasVersion KEGG Pathway Circadian rhythm - Homo sapiens (human)
Notes

This is model in continous darkness (DD) described in the article Toward a detailed computational model for the mammalian circadian clock

This model features the full interlocked negative and positive regulation of Per,Cry,Bmal and REV-ERBalpha. The model exhibits robust oscillations quite independent of the initial conditions for teh parameters given. Each species is assigned zero as initial value, and the graph started at time=120h.

Simulation results could be reproduced using Copasi 4.0.19(development) and roadRunner online.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.
For more information see the terms of use.
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Model
Publication ID: 12775757 Submission Date: 01 Nov 2006 15:13:11 UTC Last Modification Date: 25 Feb 2015 13:01:01 UTC Creation Date: 19 Oct 2006 10:21:38 UTC
Mathematical expressions
Reactions
Mb synthesized Mb translated into protein Mb nonspecific degradation Bc phosphorylation
Bc transfered from cytosolic to nuclear Mc translated into protein Mc nonspecific degradation Cc phosphorylation
Ccp specific degradation Mp synthesis Mp translated into protein Pcp specific degradation
Pc phospholation Cc and Pc produce PCc PCc phospholation PCcp specific degradation
PCc transfered into nuclear PCnp nonspecific degradation Bcp nonspecific degradation Bnp nonspecific degradation
Mc synthesis PCn phospholation Mp nonspecific degradation Per_Cry and Clock_Bmal form inactive complex
Mb specific degradation Mc specific degradation Mp specific degradation Pc nonspecific degradation
Cc nonspecific degradation Pcp nonspecific degradation Ccp nonspecific degradation PCcp nonspecific degradation
PCc nonspecific degradation PCnp specific degradation Bc nonspecific degradation Bcp specific degradation
Bn phospholation Bnp specific degradation In nonspecific degration In specific degradation
Bn nonspecific degradation Bcp dephospholation Bnp dephospholation Ccp dephospholation
Pcp dephospholation PCnp dephospholation PCn nonspecific degradation PCcp dephospholation
Mr synthesized Mr nonspecific degradation Mr specific degradation Mr translated into protein
Rc transfered into nuclear Rc specific degradation Rc nonspecific degradation Rn specific degradation
Rn nonspecific degradation      
Physical entities
Compartments Species
cell Mb Bc Bcp
Bn Cc Mc
Ccp Mp Pc
Pcp PCc PCcp
PCn Bnp PCnp
In Mr Rc
Rn    
Reactions (57)
 
 Mb synthesized  → [Mb];   {Rn}
 
 Mb translated into protein  → [Bc];   {Mb}
 
 Mb nonspecific degradation [Mb] → ;  
 
 Bc phosphorylation [Bc] → [Bcp];  
 
 Bc transfered from cytosolic to nuclear [Bc] ↔ [Bn];  
 
 Mc translated into protein  → [Cc];   {Mc}
 
 Mc nonspecific degradation [Mc] → ;  
 
 Cc phosphorylation [Cc] → [Ccp];  
 
 Ccp specific degradation [Ccp] → ;  
 
 Mp synthesis  → [Mp];   {Bn}
 
 Mp translated into protein  → [Pc];   {Mp}
 
 Pcp specific degradation [Pcp] → ;  
 
 Pc phospholation [Pc] → [Pcp];  
 
 Cc and Pc produce PCc [Cc] + [Pc] ↔ [PCc];  
 
 PCc phospholation [PCc] → [PCcp];  
 
 PCcp specific degradation [PCcp] → ;  
 
 PCc transfered into nuclear [PCc] ↔ [PCn];  
 
 PCnp nonspecific degradation [PCnp] → ;  
 
 Bcp nonspecific degradation [Bcp] → ;  
 
 Bnp nonspecific degradation [Bnp] → ;  
 
 Mc synthesis  → [Mc];   {Bn}
 
 PCn phospholation [PCn] → [PCnp];  
 
 Mp nonspecific degradation [Mp] → ;  
 
 Per_Cry and Clock_Bmal form inactive complex [PCn] + [Bn] ↔ [In];  
 
 Mb specific degradation [Mb] → ;  
 
 Mc specific degradation [Mc] → ;  
 
 Mp specific degradation [Mp] → ;  
 
 Pc nonspecific degradation [Pc] → ;  
 
 Cc nonspecific degradation [Cc] → ;  
 
 Pcp nonspecific degradation [Pcp] → ;  
 
 Ccp nonspecific degradation [Ccp] → ;  
 
 PCcp nonspecific degradation [PCcp] → ;  
 
 PCc nonspecific degradation [PCc] → ;  
 
 PCnp specific degradation [PCnp] → ;  
 
 Bc nonspecific degradation [Bc] → ;  
 
 Bcp specific degradation [Bcp] → ;  
 
 Bn phospholation [Bn] → [Bnp];  
 
 Bnp specific degradation [Bnp] → ;  
 
 In nonspecific degration [In] → ;  
 
 In specific degradation [In] → ;  
 
 Bn nonspecific degradation [Bn] → ;  
 
 Bcp dephospholation [Bcp] → [Bc];  
 
 Bnp dephospholation [Bnp] → [Bn];  
 
 Ccp dephospholation [Ccp] → [Cc];  
 
 Pcp dephospholation [Pcp] → [Pc];  
 
 PCnp dephospholation [PCnp] → [PCn];  
 
 PCn nonspecific degradation [PCn] → ;  
 
 PCcp dephospholation [PCcp] → [PCc];  
 
 Mr synthesized  → [Mr];   {Bn}
 
 Mr nonspecific degradation [Mr] → ;  
 
 Mr specific degradation [Mr] → ;  
 
 Mr translated into protein  → [Rc];   {Mr}
 
 Rc transfered into nuclear [Rc] ↔ [Rn];  
 
 Rc specific degradation [Rc] → ;  
 
 Rc nonspecific degradation [Rc] → ;  
 
 Rn specific degradation [Rn] → ;  
 
 Rn nonspecific degradation [Rn] → ;  
 
Functions (4)
 
 Activation of gene lambda(Vs, B, n, K, Vs*B^n/(K^n+B^n))
 
 Michaelis-Menten (irreversible) lambda(V, substrate, Km, V*substrate/(Km+substrate))
 
 mRNA translated into protein lambda(k, mRNA, k*mRNA)
 
 Inhibition of gene lambda(vsb, K, m, Bn, vsb*K^m/(K^m+Bn^m))
 
 cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 Mb
Compartment: cell
Initial concentration: 0.0
 
 Bc
Compartment: cell
Initial concentration: 0.0
 
 Bcp
Compartment: cell
Initial concentration: 0.0
 
 Bn
Compartment: cell
Initial concentration: 0.0
 
 Cc
Compartment: cell
Initial concentration: 0.0
 
 Mc
Compartment: cell
Initial concentration: 0.0
 
 Ccp
Compartment: cell
Initial concentration: 0.0
 
 Mp
Compartment: cell
Initial concentration: 0.0
 
 Pc
Compartment: cell
Initial concentration: 0.0
 
 Pcp
Compartment: cell
Initial concentration: 0.0
 
 PCc
Compartment: cell
Initial concentration: 0.0
 
 PCcp
Compartment: cell
Initial concentration: 0.0
 
 PCn
Compartment: cell
Initial concentration: 0.0
 
 Bnp
Compartment: cell
Initial concentration: 0.0
 
 PCnp
Compartment: cell
Initial concentration: 0.0
 
   In
Compartment: cell
Initial concentration: 0.0
 
 Mr
Compartment: cell
Initial concentration: 0.0
 
 Rc
Compartment: cell
Initial concentration: 0.0
 
 Rn
Compartment: cell
Initial concentration: 0.0
 
Mb synthesized (3)
 
   vsb
Value: 1.8
Constant
 
   Kib
Value: 1.0
Constant
 
   m
Value: 2.0
Constant
 
Mb translated into protein (1)
 
   ksb
Value: 0.32
Constant
 
Mb nonspecific degradation (1)
 
   kdmb
Value: 0.02
Constant
 
Bc phosphorylation (2)
 
   V1b
Value: 1.4
Constant
 
   Kp
Value: 1.006
Constant
 
Bc transfered from cytosolic to nuclear (2)
 
   k5
Value: 0.8
Constant
 
   k6
Value: 0.4
Constant
 
Mc translated into protein (1)
 
   ksc
Value: 3.2
Constant
 
Mc nonspecific degradation (1)
 
   kdmc
Value: 0.02
Constant
 
Cc phosphorylation (2)
 
   V1c
Value: 1.2
Constant
 
   Kp
Value: 1.006
Constant
 
Ccp specific degradation (2)
 
   vdcc
Value: 1.4
Constant
 
   Kd
Value: 0.3
Constant
 
Mp synthesis (3)
 
   vsp
Value: 2.4
Constant
 
   n
Value: 2.0
Constant
 
   Kap
Value: 0.6
Constant
 
Mp translated into protein (1)
 
   ksp
Value: 1.2
Constant
 
Pcp specific degradation (2)
 
   vdpc
Value: 3.4
Constant
 
   Kd
Value: 0.3
Constant
 
Pc phospholation (2)
 
   V1p
Value: 9.6
Constant
 
   Kp
Value: 1.006
Constant
 
Cc and Pc produce PCc (2)
 
   k3
Value: 0.8
Constant
 
   k4
Value: 0.4
Constant
 
PCc phospholation (2)
 
   V1pc
Value: 2.4
Constant
 
   Kp
Value: 1.006
Constant
 
PCcp specific degradation (2)
 
   vdpcc
Value: 1.4
Constant
 
   Kd
Value: 0.3
Constant
 
PCc transfered into nuclear (2)
 
   k1
Value: 0.8
Constant
 
   k2
Value: 0.4
Constant
 
PCnp nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Bcp nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Bnp nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Mc synthesis (3)
 
   vsc
Value: 2.2
Constant
 
   n
Value: 2.0
Constant
 
   Kac
Value: 0.6
Constant
 
PCn phospholation (2)
 
   V3pc
Value: 2.4
Constant
 
   Kp
Value: 1.006
Constant
 
Mp nonspecific degradation (1)
 
   kdmp
Value: 0.02
Constant
 
Per_Cry and Clock_Bmal form inactive complex (2)
 
   k7
Value: 1.0
Constant
 
   k8
Value: 0.2
Constant
 
Mb specific degradation (2)
 
   vmb
Value: 1.3
Constant
 
   Kmb
Value: 0.4
Constant
 
Mc specific degradation (2)
 
   vmc
Value: 2.0
Constant
 
   Kmc
Value: 0.4
Constant
 
Mp specific degradation (2)
 
   vmp
Value: 2.2
Constant
 
   Kmp
Value: 0.3
Constant
 
Pc nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Cc nonspecific degradation (1)
 
   kdnc
Value: 0.02
Constant
 
Pcp nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Ccp nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
PCcp nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
PCc nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
PCnp specific degradation (2)
 
   vdpcn
Value: 1.4
Constant
 
   Kd
Value: 0.3
Constant
 
Bc nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Bcp specific degradation (2)
 
   vdbc
Value: 3.0
Constant
 
   Kd
Value: 0.3
Constant
 
Bn phospholation (2)
 
   V3b
Value: 1.4
Constant
 
   Kp
Value: 1.006
Constant
 
Bnp specific degradation (2)
 
   vdbn
Value: 3.0
Constant
 
   Kd
Value: 0.3
Constant
 
In nonspecific degration (1)
 
   kdn
Value: 0.02
Constant
 
In specific degradation (2)
 
   vdin
Value: 1.6
Constant
 
   Kd
Value: 0.3
Constant
 
Bn nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Bcp dephospholation (2)
 
   V2b
Value: 0.2
Constant
 
   Kdp
Value: 0.1
Constant
 
Bnp dephospholation (2)
 
   V4b
Value: 0.4
Constant
 
   Kdp
Value: 0.1
Constant
 
Ccp dephospholation (2)
 
   V2c
Value: 0.2
Constant
 
   Kdp
Value: 0.1
Constant
 
Pcp dephospholation (2)
 
   V2p
Value: 0.6
Constant
 
   Kdp
Value: 0.1
Constant
 
PCnp dephospholation (2)
 
   V4pc
Value: 0.2
Constant
 
   Kdp
Value: 0.1
Constant
 
PCn nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
PCcp dephospholation (2)
 
   V2pc
Value: 0.2
Constant
 
   Kdp
Value: 0.1
Constant
 
Mr synthesized (3)
 
   vsr
Value: 1.6
Constant
 
   n
Value: 2.0
Constant
 
   Kar
Value: 0.6
Constant
 
Mr nonspecific degradation (1)
 
   kdmr
Value: 0.02
Constant
 
Mr specific degradation (2)
 
   vmr
Value: 1.6
Constant
 
   Kmr
Value: 0.4
Constant
 
Mr translated into protein (1)
 
   ksr
Value: 1.7
Constant
 
Rc transfered into nuclear (2)
 
   k9
Value: 0.8
Constant
 
   k10
Value: 0.4
Constant
 
Rc specific degradation (2)
 
   vdrc
Value: 4.4
Constant
 
   Kd
Value: 0.3
Constant
 
Rc nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Rn specific degradation (2)
 
   vdrn
Value: 0.8
Constant
 
   Kd
Value: 0.3
Constant
 
Rn nonspecific degradation (1)
 
   kdn
Value: 0.02
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000074

Curator's comment: (updated: 28 Nov 2006 10:27:39 GMT)

Supporting figure 8a obtained in RoadRunner.

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