The Septation Initiation Network (SIN) controls cytokinesis in fission yeast. This model uses CDK activity levels as control nodes to simutate SIN related events throughout different stages of the cell cycle. This model was optimized using single knock-out experiments and has made in silico predictions that have been validated in vivo, offering new insights into regulation of the SIN. Crowther Audrey audrey.crowther@huskers.unl.edu University of Nebraska-Lincoln 2016-07-21T18:05:02Z 2017-02-06T11:12:49Z

Septation initiation protein sid4/Casein kinase I family (serine/threonine-selective enzymes)

Gene: sid4

UniProt ID: O60187

Gene ID: 2540650

 2017-02-02T11:16:22Z

Protein Complex: Serine/threonine-protein kinase sid2/Maintenance of ploidy protein mob1

Gene: sid2/mob1

UniProt ID: Q09898/O94360

Gene ID: 2541599/2540845

 2017-02-01T19:04:48Z

This node represents low CDK levels during interphase.

Gene ID: 2539869/2540880

Cyclin-dependent kinase 1/G2/mitotic-specific cyclin cdc13

Gene: cdc2/cdc13

UniProt ID: P04551/P10815

 2016-07-29T09:48:10Z

Spindle pole body protein ppc89

Gene: ppc89

UniProt ID: Q10218

Gene ID: 2543554

 2017-02-02T13:19:13Z

Septation protein etd1

Gene: etd1

UniProt ID: Q9UTR4

Gene ID: 2543001

 2017-02-01T19:06:52Z

This node represents high CDK levels during early mitosis.

Cyclin-dependent kinase 1/G2/mitotic-specific cyclin cdc13

Gene: cdc2/cdc13

UniProt ID: P04551/P10815

Gene ID: 2539869/2540880

 2017-02-01T19:04:32Z

Ras-like protein 1

Gene: ras1

UniProt ID: P08647

Gene ID: 2542285

 2017-02-01T19:04:48Z

This node represents very low CDK activity during late mitosis.

Gene: cdc2/cdc13

Cyclin-dependent kinase 1/G2/mitotic-specific cyclin cdc13

UniProt ID: P04551/P10815

Gene ID: 2539869/2540880

 2016-07-29T09:52:28Z

Rho guanine nucleotide exchange factor scd1

Gene: scd1

UniProt ID: P40995

Gene ID: 2542337

 2016-07-21T19:34:16Z

Cell division control protein 42 homolog

Gene: cdc42

UniProt ID: Q01112

Gene ID: 2543027

 2016-07-21T19:45:16Z

Cell division control protein 16

Gene: cdc16

UniProt: P36618

Gene ID: 2542162

 2017-01-31T13:17:56Z

Dual specificity protein kinase pom1

Gene: pom1

UniProt ID: Q09690

Gene ID: 2541889

 2016-07-21T19:52:25Z

Serine/threonine-protein kinase nak1

Gene: nak1

UniProt ID: O75011 2

Gene ID: 2539963

 2017-02-01T19:04:32Z

Probable Rho-type GTPase-activating protein 4

Gene: rga4

UniProt ID: O74360

Gene ID: 2540593

 2016-07-21T19:52:25Z

Tyrosine-protein phosphatase CDC14 homolog

Gene:clp1

UniProt ID: Q9P7H1

Gene ID: 2542358

 2017-02-01T15:44:50Z

Probable E3 ubiquitin-protein ligase dma1

Gene: dma1

UniProt ID: Q10322

Gene ID: 2542409

 2017-02-02T13:33:53Z

Cell division control protein 7

Gene: cdc7

UniProt ID: P41892

Gene ID: 2540660

 2017-02-01T14:32:23Z

Serine/threonine-protein kinase shk1/pak1

Gene: shk1

UniProt ID: P50527

Gene ID: 2539997

 2016-07-21T19:52:25Z

Protein Complex: byr4/Cell division control protein 16

Gene: byr4/cdc16

UniProt IDs: Q10951/P36 618

Gene ID: 2541936/2542162

 2017-01-31T13:17:56Z

Serine/threonine-protein kinase sid2

Gene: sid2

UniProt ID: Q09898

Gene ID: 2541599

 2017-02-01T14:32:23Z

Rho guanine nucleotide exchange factor gef1

Gene: gef1

UniProt ID: Q09763

Gene ID: 2542635

 2016-07-21T19:52:25Z

Protein Complex: Cell division control protein 14/Serine/threonine-protein kinase sid1

Gene: cdc14/sid1

UniProt ID: P36589/O14305

Gene ID: 2540624/2542746

 2016-07-29T09:50:14Z

Septum-promoting GTP-binding protein 1

Gene: spg1

UniProt ID: P87027

Gene ID: 2542761

 2017-01-31T14:20:47Z

Serine/threonine-protein kinase orb6

Gene: orb6

UniProt ID: O13310

Gene ID: 2543441

 2016-07-21T19:52:25Z

byr4

Gene: byr4

UniProt ID: Q10951

Gene ID: 2541936

 2017-02-01T18:56:06Z

SIN-inhibitory phosphatase complex

 2017-02-01T18:57:32Z

Septation initiation network scaffold protein cdc11

Gene: cdc11

UniProt ID: O74473

Gene ID: 2539149

 2017-02-01T15:44:50Z

Gene: sid4

UniProt ID: O60187

Septation initiation protein sid4

Gene ID: 2540650

 2017-02-02T13:33:53Z

Mo25-like protein

Gene: pmo25

UniProt ID: Q9P7Q8

Gene ID: 2542388

 2016-07-21T19:09:47Z

G2-specific protein kinase fin1

Gene: fin1

UniProt ID: O13839

Gene ID: 2542237

 2016-09-19T18:57:52Z

Serine/threonine-protein kinase plo1

Gene: plo1

UniProt ID: P50528

Gene ID: 2541957

 2017-02-02T13:33:53Z

ras1 activates scd1.

ras1 binds to and activates scd1.

 S_24 1

scd1 activates cdc42.

gef1 activtes cdc42.

Rga4 inhibits cdc42.

scd1 is a guanine nucleotide exchange factor protein that targets Cdc42.

Rga4 is a GTPase-activating protein that targets cdc42.

Gef1p is a guanine nucleotide exchange factor protein that targets Cdc42p.

 S_19 1 S_9 1 S_2 1 S_9 1

fin1 inhibits cdc16.

fin1 is a suspected negative regulator for cdc16.

 S_30 1

pak1activates pom1.

pak1 phosphorylates pom1.

 S_15 1

pmo25 activates nak1.

sid2-mob1 with cdk-H activates nak1.

sid2 phosphorylates and activates nak1.

nak1 activity has been shown to be dependent on pmo25.

cdk1 indirectly activates nak1.

 S_4 1 S_18 1 S_28 1

pom1 inhibits Rga4.

pom1 activity leads to the exclusion of rga4 from the cell tips.

 S_7 1

cdk-0 activates flp1.

cdk-H inhibits flp1.

sid2-mob1 activates flp1.

sid2-mob1 indirectly activates flp1.

Cdk1 phosphorylates and inhibits the catalytic activity of flp1.

The drease in cdk1 activity during anaphase leads to the activation of flp1.

 S_29 1 S_18 1 S_4 1 S_18 1

sid4 with CK1 activates dma1.

CK1 associates stably with different SPB components, including sid4.

Dma1 localization to the SPB during meiosis is inferred to be depenent on scaffold protein sid4.

 S_27 1 S_1 1

spg1 with cdc7 activates cdc7.

cdc11 acts as an anchor for the septation initiation network components.

GTP-bound spg1 recruits cdc7.

 S_21 1 S_26 1

cdc42 activates pak1.

cdc42 disrupts the intramolecular interactions of pak1, preventing pak1 autoinhibition.

 S_3 1

byr4 and cd16 activates byr4-cdc16.

Proteins byr4 and cdc16 form a protein complex, referred to as byr4-cdc16 in this model.

Proteins byr4 and cdc16 form a protein complex, referred to as byr4-cdc16 in this model.

 S_23 1 S_5 1

cdc11 with cdc7 and SIP activates sid2.

cdc7 activates sid2.

cdc7 is required for sid2 localization to the SPB.

The N terminus of sid2 directs the positive interaction with cdc11.

SIP promotes cdc11 dephosphorylation.

 S_26 1 S_13 1 S_25 1 S_13 1

orb6 activates gef1.

orb6 localizes gef1 to the cell tips.

 S_22 1

cdc7 activates cdc14-sid1.

cdck-H inhibits cdc14-sid1.

cdc7 indirectly activates cdc14-sid1.

Supression of cdc2-cyclin activity promotes cdc14-sid1 association with the SPB.

 S_13 1

byr4-cdc16 inhibits spg1.

etd1 activates spg1.

cdc11 activates spg1.

byr4 and cdc16 form a two component GTPase-activating protein (GAP) that inhibits spg1.

Experimental results infer that cdc11 directly interacts with spg1.

etd1 causes hyperactivation of spg1 during late anaphase.

 S_26 1 S_16 1 S_14 1 S_16 1

pak1 activates orb6.

nak1 activates orb6.

pak1 is needed for the intracellular localization of orb6.

nak1 binds to orb6, leading to orb6 activation.

 S_15 1 S_8 1

cdc42 inhibits byr4.

cdk-H with plo1 inhibits byr4.

cdk-L activates byr4.

byr4 is activated by the co-regulation of SIN by cdk-L and GAP.

Cdk1-mediated phosphoregulation of Byr4 in concert with Plo1mediates Byr4 removal from metaphase SPBs.

cdc42 appears to inhibit inhibits byr4p based on the observation that scd1-null is more sensitive to very mild byr4OP.

Cdk1-mediated phosphoregulation of Byr4 in concert with Plo1mediates Byr4 removal from metaphase SPBs.

 S_6 1 S_18 1 S_31 1 S_3 1

cdk-H&ppc89 activates SIP.

cdk-0 inhibits SIP.

cdk-H and ppc89 is needed for the localisation of SIP.

cdk-H and ppc89 is needed for the localisation of SIP.

SIP dislocation from SPB is linked to cdc13 degradation.

 S_18 1 S_29 1 S_11 1

cdc7 activates cdc11.

cdc16 activates cdc11.

flp1 with sid4 activates cdc11.

sid4 activates cdc11.

cdc11 is a flp1 substrate.

cdc7 is required for the hyperphosphorylation of cdc11.

cdc16 activates cdc11 by interacting with the N-terminal 660 amino acids of cdc11.

sid4 is needed for the localization of cdc11 to the spindle pole body.

 S_5 1 S_10 1 S_27 1 S_13 1 S_27 1

ppc89 activates sid4.

ppc89 activates sid4 (inferred interaction).

 S_11 1

cdc7 activates pmo25.

cdc14-sid1 activates pmo25.

Localization of pmo25 at the SPBs is controlled by cdc7 and sid1.

Localization of pmo25 at the SPBs is controlled by cdc7 and sid1.

 S_13 1 S_20 1

cdk-H activates fin1.

cdk-H phosphorylates and activates fin1.

 S_18 1

sid4 activates plo1.

dma1 with sid4 inhibits plo1.

cdk-H activates plo1.

cdk-L inhibits plo1.

plo1 is activated downstream of mitosis-promoting factor.

dma1 ubiquitinates sid4, which in turn prevencts recruitment of plo1.

plo1 kinase is activated downstream of mitosis-promoting factor.

sid4 activates plo1 (inferred interaction).

 S_18 1 S_27 1 S_12 1 S_6 1 S_27 1 S_27 1 S_12 1