yamada1
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000093). Biomodels notes: "NCBS Curation Comments This model shows the control mechanism of Jak-Stat pathway, here SOCS1 (Suppressor of cytokine signaling-I) was identified as the negative regulator of Jak and STAT signal transduction pathway. Note: There are a few ambiguities in the paper like initial concentration of IFN and some reactions were missing in the paper that were employed for obtaining the results. The graphs are almost similar to the graphs as shown in the paper but still some ambiguities regarding the concentration are there. Thanks to Dr Satoshi Yamada for clarifying some of those ambiguities and providing the values used in simulations. Biomodels Curation Comments The model reproduces Fig 2 (A,C,E,G,I,K,M) of the paper. The set of equations present in the paper are inadequate to reproduce the figures mentioned . The model appears to have been fine tuned after correspondence between the curators at NCBS and the authors. There is however a slight discrepancy between the simulation results and the plots in the paper. The model was tested on MathSBML." JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.
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Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.
| Name | Definition | |
|---|---|---|
| — | 1e-09 mole | |
| — | 1e-09 mole litre^(-1.0) second^(-1.0) | |
| — | 1.0 second^(-1.0) | |
| — | 1000000000.0 mole^(-1.0) litre second^(-1.0) | |
| — | 1e-09 mole litre^(-1.0) |
| Id | Name | Spatial dimensions | Size | |
|---|---|---|---|---|
| cytoplasm | cytoplasm | 3.0 | 1.0 | |
| nucleus | nucleus | 3.0 | 1.0 |
| Id | Name | Initial quantity | Compartment | Fixed | |
|---|---|---|---|---|---|
| IFN | IFN | 10.0 | cytoplasm (cytoplasm) | ✔ | |
| IFNR | IFNR | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ | Interferon-Receptor-JAK complex | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2 | IFNRJ dimer | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star | Activated IFNRJ complex | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_SHP2 | IFNRJ2_star_SHP2 | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_SHP2_SOCS1 | IFNRJ2_star_SHP2_SOCS1 | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_SHP2_SOCS1_STAT1c | IFNRJ2_star_SHP2_SOCS1_STAT1c | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_SHP2_STAT1c | IFNRJ2_star_SHP2_STAT1c | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_SOCS1 | IFNRJ2_star_SOCS1 | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_SOCS1_STAT1c | IFNRJ2_star_SOCS1_STAT1c | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_STAT1c | IFNRJ2_star_STAT1c | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| IFNRJ2_star_STAT1c_star | IFNRJ2_star_STAT1c_star | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| JAK | JAK | 10.0 | cytoplasm (cytoplasm) | ✘ | |
| PPN | PPN | 60.0 | nucleus (nucleus) | ✘ | |
| PPX | PPX | 50.0 | cytoplasm (cytoplasm) | ✘ | |
| R | Receptor | 10.0 | cytoplasm (cytoplasm) | ✘ | |
| RJ | Receptor JAK complex | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| SHP2 | SHP2 | 100.0 | cytoplasm (cytoplasm) | ✘ | |
| SOCS1 | SOCS1 | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| STAT1c | STAT1c | 1000.0 | cytoplasm (cytoplasm) | ✘ | |
| STAT1c_STAT1c_star | STAT1c_STAT1c_star | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| STAT1c_star | STAT1c_star | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| STAT1c_star_PPX | STAT1c_star_PPX | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| STAT1c_star_STAT1c_star | STAT1c_star_STAT1c_star | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| STAT1c_star_STAT1c_star_PPX | STAT1c_star_STAT1c_star_PPX | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| STAT1n | STAT1n | 0.0 | nucleus (nucleus) | ✘ | |
| STAT1n_STAT1n_star | STAT1n_STAT1n_star | 0.0 | nucleus (nucleus) | ✘ | |
| STAT1n_star | STAT1n_star | 0.0 | nucleus (nucleus) | ✘ | |
| STAT1n_star_PPN | STAT1n_star_PPN | 0.0 | nucleus (nucleus) | ✘ | |
| STAT1n_star_STAT1n_star | STAT1n_star_STAT1n_star | 0.0 | nucleus (nucleus) | ✘ | |
| STAT1n_star_STAT1n_star_PPN | STAT1n_star_STAT1n_star_PPN | 0.0 | nucleus (nucleus) | ✘ | |
| mRNAc | mRNAc | 0.0 | cytoplasm (cytoplasm) | ✘ | |
| mRNAn | mRNAn | 0.0 | nucleus (nucleus) | ✘ |
Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.
| Definition |
|---|
| Id | Name | Objective coefficient | Reaction Equation and Kinetic Law | Flux bounds | |
|---|---|---|---|---|---|
| v1 | Receptor-JAK Binding | JAK + R > RJ cytoplasm * (kf * R * JAK - kb * RJ) | |||
| v10 | IFNJR2 dephosphorylation | IFNRJ2_star_SHP2 > SHP2 + IFNRJ2 cytoplasm * kf * IFNRJ2_star_SHP2 | |||
| v11 | Phosphorylated STAT1c-PPX binding | STAT1c_star + PPX > STAT1c_star_PPX cytoplasm * (kf * PPX * STAT1c_star - kb * STAT1c_star_PPX) | |||
| v12 | STAT1c dephosphorylation | STAT1c_star_PPX > STAT1c + PPX cytoplasm * kf * STAT1c_star_PPX | |||
| v13 | PPX binding | STAT1c_star_STAT1c_star + PPX > STAT1c_star_STAT1c_star_PPX cytoplasm * (kf * PPX * STAT1c_star_STAT1c_star - kb * STAT1c_star_STAT1c_star_PPX) | |||
| v14 | STAT1c dimer dephosphorylation | STAT1c_star_STAT1c_star_PPX > STAT1c_STAT1c_star + PPX cytoplasm * kf * STAT1c_star_STAT1c_star_PPX | |||
| v15 | STAT1c-phosphorylated STAT1c binding | STAT1c_star + STAT1c > STAT1c_STAT1c_star cytoplasm * (kf * STAT1c * STAT1c_star - kb * STAT1c_STAT1c_star) | |||
| v16 | STAT1c-nuclear transport | STAT1c_star_STAT1c_star > STAT1n_star_STAT1n_star cytoplasm * kf * STAT1c_star_STAT1c_star | |||
| v17 | Phosphorylated STAT1n dimerization | {2.0}STAT1n_star > STAT1n_star_STAT1n_star nucleus * (kf * STAT1n_star * STAT1n_star - kb * STAT1n_star_STAT1n_star) | |||
| v18 | PPN binding | STAT1n_star + PPN > STAT1n_star_PPN nucleus * (kf * PPN * STAT1n_star - kb * STAT1n_star_PPN) | |||
| v19 | STAT1n dephosphorylation | STAT1n_star_PPN > STAT1n + PPN nucleus * kf * STAT1n_star_PPN | |||
| v2 | Interferon-Receptor Binding | RJ + IFN > IFNRJ cytoplasm * (kf * IFN * RJ - kb * IFNRJ) | |||
| v20 | PPN binding | STAT1n_star_STAT1n_star + PPN > STAT1n_star_STAT1n_star_PPN nucleus * (kf * PPN * STAT1n_star_STAT1n_star - kb * STAT1n_star_STAT1n_star_PPN) | |||
| v21 | STAT1n dephosphorylation | STAT1n_star_STAT1n_star_PPN > STAT1n_STAT1n_star + PPN nucleus * kf * STAT1n_star_STAT1n_star_PPN | |||
| v22 | STAT1n-phosphorylated STAT1n dimerization | STAT1n_star + STAT1n > STAT1n_STAT1n_star nucleus * (kf * STAT1n * STAT1n_star - kb * STAT1n_STAT1n_star) | |||
| v23 | STAT1n transport to cytoplasm | STAT1n > STAT1c nucleus * kf * STAT1n | |||
| v24 | Transcription | ∅ > mRNAn nucleus * ka * STAT1n_star_STAT1n_star / (kb + STAT1n_star_STAT1n_star) | |||
| v25 | mRNA transport to cytoplasm | mRNAn > mRNAc nucleus * kf * mRNAn | |||
| v26 | SOCS1 synthesis | ∅ > SOCS1 cytoplasm * kf * mRNAc | |||
| v27 | mRNAc degradation | mRNAc > ∅ cytoplasm * kf * mRNAc | |||
| v28 | SOCS1 degradation | SOCS1 > ∅ cytoplasm * kf * SOCS1 | |||
| v29 | phosphorylated IFNRJ2-SOCS1 binding | IFNRJ2_star + SOCS1 > IFNRJ2_star_SOCS1 cytoplasm * (kf * SOCS1 * IFNRJ2_star - kb * IFNRJ2_star_SOCS1) | |||
| v3 | IFN-Receptor complex dimerization | {2.0}IFNRJ > IFNRJ2 cytoplasm * (kf * IFNRJ * IFNRJ - kb * IFNRJ2) | |||
| v30 | STAT1c binding | IFNRJ2_star_SOCS1 + STAT1c > IFNRJ2_star_SOCS1_STAT1c cytoplasm * (kf * STAT1c * IFNRJ2_star_SOCS1 - kb * IFNRJ2_star_SOCS1_STAT1c) | |||
| v31 | SHP2 binding | IFNRJ2_star_SOCS1_STAT1c + SHP2 > IFNRJ2_star_SHP2_SOCS1_STAT1c cytoplasm * (kf * SHP2 * IFNRJ2_star_SOCS1_STAT1c - kb * IFNRJ2_star_SHP2_SOCS1_STAT1c) | |||
| v32 | IFNRJ2 dephosphorylation | IFNRJ2_star_SHP2_SOCS1_STAT1c > IFNRJ2 + SOCS1 + STAT1c + SHP2 cytoplasm * kf * IFNRJ2_star_SHP2_SOCS1_STAT1c | |||
| v33 | SOCS1 unbinding | IFNRJ2_star_SHP2_SOCS1_STAT1c > IFNRJ2_star_SHP2_STAT1c cytoplasm * kf * IFNRJ2_star_SHP2_SOCS1_STAT1c | |||
| v34 | SHP2 binding | IFNRJ2_star_SOCS1 + SHP2 > IFNRJ2_star_SHP2_SOCS1 cytoplasm * (kf * SHP2 * IFNRJ2_star_SOCS1 - kb * IFNRJ2_star_SHP2_SOCS1) | |||
| v35 | STAT1c binding | IFNRJ2_star_SHP2_SOCS1 + STAT1c > IFNRJ2_star_SHP2_SOCS1_STAT1c cytoplasm * (kf * STAT1c * IFNRJ2_star_SHP2_SOCS1 - kb * IFNRJ2_star_SHP2_SOCS1_STAT1c) | |||
| v36 | SHP2 binding | IFNRJ2_star_STAT1c + SHP2 > IFNRJ2_star_SHP2_STAT1c cytoplasm * (kf * SHP2 * IFNRJ2_star_STAT1c - kb * IFNRJ2_star_SHP2_STAT1c) | |||
| v37 | — | IFNRJ2_star_SHP2_STAT1c > STAT1c + SHP2 + IFNRJ2 cytoplasm * kf * IFNRJ2_star_SHP2_STAT1c | |||
| v38 | SOCS1 unbinding | IFNRJ2_star_SOCS1_STAT1c > IFNRJ2_star_STAT1c cytoplasm * kf * IFNRJ2_star_SOCS1_STAT1c | |||
| v39 | SOCS1 unbinding | IFNRJ2_star_SHP2_SOCS1 > IFNRJ2_star_SHP2 cytoplasm * kf * IFNRJ2_star_SHP2_SOCS1 | |||
| v4 | INF-Receptor complex activation | IFNRJ2 > IFNRJ2_star cytoplasm * kf * IFNRJ2 | |||
| v40 | IFNRJ2 dephosphorylation | IFNRJ2_star_SHP2_SOCS1 > SHP2 + IFNRJ2 + SOCS1 cytoplasm * kf * IFNRJ2_star_SHP2_SOCS1 | |||
| v41 | SOCS1 unbinding | IFNRJ2_star_SOCS1 > IFNRJ2_star cytoplasm * kf * IFNRJ2_star_SOCS1 | |||
| v42 | SOCS1 binding | IFNRJ2_star_STAT1c + SOCS1 > IFNRJ2_star_SOCS1_STAT1c cytoplasm * (kf * SOCS1 * IFNRJ2_star_STAT1c - kb * IFNRJ2_star_SOCS1_STAT1c) | |||
| v43 | SOCS1 binding | IFNRJ2_star_SHP2 + SOCS1 > IFNRJ2_star_SHP2_SOCS1 cytoplasm * (kf * SOCS1 * IFNRJ2_star_SHP2 - kb * IFNRJ2_star_SHP2_SOCS1) | |||
| v44 | SOCS1 binding | IFNRJ2_star_SHP2_STAT1c + SOCS1 > IFNRJ2_star_SHP2_SOCS1_STAT1c cytoplasm * (kf * SOCS1 * IFNRJ2_star_SHP2_STAT1c - kb * IFNRJ2_star_SHP2_SOCS1_STAT1c) | |||
| v45 | Interferon-receptor binding | R + IFN > IFNR cytoplasm * (kf * IFN * R - kb * IFNR) | |||
| v46 | IFNR-JAK binding | JAK + IFNR > IFNRJ cytoplasm * (kf * IFNR * JAK - kb * IFNRJ) | |||
| v5 | Activated INFRJ2-STAT1c binding | IFNRJ2_star + STAT1c > IFNRJ2_star_STAT1c cytoplasm * (kf * STAT1c * IFNRJ2_star - kb * IFNRJ2_star_STAT1c) | |||
| v6 | STAT1c activation | IFNRJ2_star_STAT1c > STAT1c_star + IFNRJ2_star cytoplasm * kf * IFNRJ2_star_STAT1c | |||
| v7 | Activated IFNRJ2-STAT1c binding | STAT1c_star + IFNRJ2_star > IFNRJ2_star_STAT1c_star cytoplasm * (kf * IFNRJ2_star * STAT1c_star - kb * IFNRJ2_star_STAT1c_star) | |||
| v8 | Activated STAT1c dimerization | {2.0}STAT1c_star > STAT1c_star_STAT1c_star cytoplasm * (kf * STAT1c_star * STAT1c_star - kb * STAT1c_star_STAT1c_star) | |||
| v9 | SHP2 binding | SHP2 + IFNRJ2_star > IFNRJ2_star_SHP2 cytoplasm * (kf * IFNRJ2_star * SHP2 - kb * IFNRJ2_star_SHP2) |
| Id | Value |
|---|
| Id | Value | Reaction | |
|---|---|---|---|
| kf | 0.1 nM_inv_sec_inv | v1 (Receptor-JAK Binding) | |
| kb | 0.05 sec_inv | v1 (Receptor-JAK Binding) | |
| kf | 0.02 nM_inv_sec_inv | v2 (Interferon-Receptor Binding) | |
| kb | 0.02 sec_inv | v2 (Interferon-Receptor Binding) | |
| kf | 0.04 nM_inv_sec_inv | v3 (IFN-Receptor complex dimerization) | |
| kb | 0.2 sec_inv | v3 (IFN-Receptor complex dimerization) | |
| kf | 0.005 sec_inv | v4 (INF-Receptor complex activation) | |
| kf | 0.008 nM_inv_sec_inv | v5 (Activated INFRJ2-STAT1c binding) | |
| kb | 0.8 sec_inv | v5 (Activated INFRJ2-STAT1c binding) | |
| kf | 0.4 sec_inv | v6 (STAT1c activation) | |
| kf | 0.005 nM_inv_sec_inv | v7 (Activated IFNRJ2-STAT1c binding) | |
| kb | 0.5 sec_inv | v7 (Activated IFNRJ2-STAT1c binding) | |
| kf | 0.02 nM_inv_sec_inv | v8 (Activated STAT1c dimerization) | |
| kb | 0.1 sec_inv | v8 (Activated STAT1c dimerization) | |
| kf | 0.001 nM_inv_sec_inv | v9 (SHP2 binding) | |
| kb | 0.2 sec_inv | v9 (SHP2 binding) | |
| kf | 0.003 sec_inv | v10 (IFNJR2 dephosphorylation) | |
| kf | 0.001 nM_inv_sec_inv | v11 (Phosphorylated STAT1c-PPX binding) | |
| kb | 0.2 sec_inv | v11 (Phosphorylated STAT1c-PPX binding) | |
| kf | 0.003 sec_inv | v12 (STAT1c dephosphorylation) | |
| kf | 0.001 nM_inv_sec_inv | v13 (PPX binding) | |
| kb | 0.2 sec_inv | v13 (PPX binding) | |
| kf | 0.003 sec_inv | v14 (STAT1c dimer dephosphorylation) | |
| kf | 2e-07 nM_inv_sec_inv | v15 (STAT1c-phosphorylated STAT1c binding) | |
| kb | 0.2 sec_inv | v15 (STAT1c-phosphorylated STAT1c binding) | |
| kf | 0.005 sec_inv | v16 (STAT1c-nuclear transport) | |
| kf | 0.02 nM_inv_sec_inv | v17 (Phosphorylated STAT1n dimerization) | |
| kb | 0.1 sec_inv | v17 (Phosphorylated STAT1n dimerization) | |
| kf | 0.001 nM_inv_sec_inv | v18 (PPN binding) | |
| kb | 0.2 sec_inv | v18 (PPN binding) | |
| kf | 0.005 sec_inv | v19 (STAT1n dephosphorylation) | |
| kf | 0.001 nM_inv_sec_inv | v20 (PPN binding) | |
| kb | 0.2 sec_inv | v20 (PPN binding) | |
| kf | 0.005 sec_inv | v21 (STAT1n dephosphorylation) | |
| kf | 2e-07 nM_inv_sec_inv | v22 (STAT1n-phosphorylated STAT1n dimerization) | |
| kb | 0.2 sec_inv | v22 (STAT1n-phosphorylated STAT1n dimerization) | |
| kf | 0.05 sec_inv | v23 (STAT1n transport to cytoplasm) | |
| ka | 0.01 nM_per_second | v24 (Transcription) | |
| kb | 400.0 nM | v24 (Transcription) | |
| kf | 0.001 sec_inv | v25 (mRNA transport to cytoplasm) | |
| kf | 0.01 sec_inv | v26 (SOCS1 synthesis) | |
| kf | 0.0005 sec_inv | v27 (mRNAc degradation) | |
| kf | 0.0005 sec_inv | v28 (SOCS1 degradation) | |
| kf | 0.02 nM_inv_sec_inv | v29 (phosphorylated IFNRJ2-SOCS1 binding) | |
| kb | 0.1 sec_inv | v29 (phosphorylated IFNRJ2-SOCS1 binding) | |
| kf | 0.008 nM_inv_sec_inv | v30 (STAT1c binding) | |
| kb | 0.8 sec_inv | v30 (STAT1c binding) | |
| kf | 0.001 nM_inv_sec_inv | v31 (SHP2 binding) | |
| kb | 0.2 sec_inv | v31 (SHP2 binding) | |
| kf | 0.003 sec_inv | v32 (IFNRJ2 dephosphorylation) | |
| kf | 0.0005 sec_inv | v33 (SOCS1 unbinding) | |
| kf | 0.001 nM_inv_sec_inv | v34 (SHP2 binding) | |
| kb | 0.2 sec_inv | v34 (SHP2 binding) | |
| kf | 0.008 nM_inv_sec_inv | v35 (STAT1c binding) | |
| kb | 0.8 sec_inv | v35 (STAT1c binding) | |
| kf | 0.001 nM_inv_sec_inv | v36 (SHP2 binding) | |
| kb | 0.2 sec_inv | v36 (SHP2 binding) | |
| kf | 0.003 sec_inv | v37 | |
| kf | 0.0005 sec_inv | v38 (SOCS1 unbinding) | |
| kf | 0.0005 sec_inv | v39 (SOCS1 unbinding) | |
| kf | 0.003 sec_inv | v40 (IFNRJ2 dephosphorylation) | |
| kf | 0.0005 sec_inv | v41 (SOCS1 unbinding) | |
| kf | 0.02 nM_inv_sec_inv | v42 (SOCS1 binding) | |
| kb | 0.1 sec_inv | v42 (SOCS1 binding) | |
| kf | 0.02 nM_inv_sec_inv | v43 (SOCS1 binding) | |
| kb | 0.1 sec_inv | v43 (SOCS1 binding) | |
| kf | 0.02 nM_inv_sec_inv | v44 (SOCS1 binding) | |
| kb | 0.1 sec_inv | v44 (SOCS1 binding) | |
| kf | 0.02 nM_inv_sec_inv | v45 (Interferon-receptor binding) | |
| kb | 0.02 sec_inv | v45 (Interferon-receptor binding) | |
| kf | 0.1 nM_inv_sec_inv | v46 (IFNR-JAK binding) | |
| kb | 0.05 sec_inv | v46 (IFNR-JAK binding) |
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| Definition |
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| Definition |
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| Trigger | Assignments |
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