Molecules

SubstrateAttribute b˜1 indicates that an enzyme is bound to substrate and b˜0 indicates no enzyme is boundAttributes Y1, Y2, and Y3 each refer to individual ITAMs.Each ITAM can be unphosphorylated (Y˜U), phosphorylated on one tyrosine (Y˜P), or doubly phosphorylated (Y˜2P)

S(b~0~1,Y1~U~P~2P,Y2~U~P~2P,Y3~U~P~2P)

S b 0 1 Y1 U P 2P Y2 U P 2P Y3 U P 2P
Kinase

E(b)

E b
Phosphatase

F(b)

F b
ZAP-70

Z(b)

Z b

Species

S(b~0,Y1~U,Y2~U,Y3~U)

S b 0 Y1 U Y2 U Y3 U

E(b)

E b

F(b)

F b

Z(b)

Z b

Observables

Z(b!+)

Z b

S(b~?,Y1~U!?,Y2~U!?,Y3~U!?)

S b ? Y1 U Y2 U Y3 U

S(b~?,Y1~P!?,Y2~U!?,Y3~U!?)

S b ? Y1 P Y2 U Y3 U

S(b~?,Y1~2P!?,Y2~U!?,Y3~U!?)

S b ? Y1 2P Y2 U Y3 U

S(b~?,Y1~2P!?,Y2~P!?,Y3~U!?)

S b ? Y1 2P Y2 P Y3 U

S(b~?,Y1~2P!?,Y2~2P!?,Y3~U!?)

S b ? Y1 2P Y2 2P Y3 U

S(b~?,Y1~2P!?,Y2~2P!?,Y3~P!?)

S b ? Y1 2P Y2 2P Y3 P

S(b~?,Y1~2P!?,Y2~2P!?,Y3~2P!?)

S b ? Y1 2P Y2 2P Y3 2P

Reaction Rules

ITAM 1

E(b) + S(b~0,Y1~U,Y2~U,Y3~U) <-> E(b!1).S(b~1,Y1~U!1,Y2~U,Y3~U)

E 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 1 ⬆⬇U Y2 U Y3 U

E(b!1).S(b~1,Y1~U!1,Y2~U,Y3~U) -> E(b) + S(b~0,Y1~P,Y2~U,Y3~U)

E 1 b S b 0 1 take one or more branches, once each, in any order Y1 1 U P take all branches, once each, in any order Y2 U Y3 U

F(b) + S(b~0,Y1~P,Y2~U,Y3~U) <-> F(b!1).S(b~1,Y1~P!1,Y2~U,Y3~U)

F 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 1 ⬆⬇P Y2 U Y3 U

F(b!1).S(b~1,Y1~P!1,Y2~U,Y3~U) -> F(b) + S(b~0,Y1~U,Y2~U,Y3~U)

F 1 b S b 0 1 take one or more branches, once each, in any order Y1 U 1 P take one or more branches, once each, in any order Y2 U Y3 U

E(b) + S(b~0,Y1~P,Y2~U,Y3~U) <-> E(b!1).S(b~1,Y1~P!1,Y2~U,Y3~U)

E 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 1 ⬆⬇P Y2 U Y3 U

E(b!1).S(b~1,Y1~P!1,Y2~U,Y3~U) -> E(b) + S(b~0,Y1~2P,Y2~U,Y3~U)

E 1 b S b 0 1 take one or more branches, once each, in any order Y1 1 P 2P take all branches, once each, in any order Y2 U Y3 U

F(b) + S(b~0,Y1~2P,Y2~U,Y3~U) <-> F(b!1).S(b~1,Y1~2P!1,Y2~U,Y3~U)

F 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 1 ⬆⬇2P Y2 U Y3 U

F(b!1).S(b~1,Y1~2P!1,Y2~U,Y3~U) -> F(b) + S(b~0,Y1~P,Y2~U,Y3~U)

F 1 b S b 0 1 take one or more branches, once each, in any order Y1 P 1 2P take one or more branches, once each, in any order Y2 U Y3 U
ITAM 2

E(b) + S(b~0,Y2~U,Y1~2P,Y3~U) <-> E(b!1).S(b~1,Y2~U!1,Y1~2P,Y3~U)

E 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 1 ⬆⬇U Y3 U

E(b!1).S(b~1,Y2~U!1,Y1~2P,Y3~U) -> E(b) + S(b~0,Y2~P,Y1~2P,Y3~U)

E 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 1 U P take all branches, once each, in any order Y3 U

F(b) + S(b~0,Y2~P,Y1~2P,Y3~U) <-> F(b!1).S(b~1,Y2~P!1,Y1~2P,Y3~U)

F 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 1 ⬆⬇P Y3 U

F(b!1).S(b~1,Y2~P!1,Y1~2P,Y3~U) -> F(b) + S(b~0,Y2~U,Y1~2P,Y3~U)

F 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 U 1 P take one or more branches, once each, in any order Y3 U

E(b) + S(b~0,Y2~P,Y1~2P,Y3~U) <-> E(b!1).S(b~1,Y2~P!1,Y1~2P,Y3~U)

E 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 1 ⬆⬇P Y3 U

E(b!1).S(b~1,Y2~P!1,Y1~2P,Y3~U) -> E(b) + S(b~0,Y2~2P,Y1~2P,Y3~U)

E 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 1 P 2P take all branches, once each, in any order Y3 U

F(b) + S(b~0,Y2~2P,Y1~2P,Y3~U) <-> F(b!1).S(b~1,Y2~2P!1,Y1~2P,Y3~U)

F 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 1 ⬆⬇2P Y3 U

F(b!1).S(b~1,Y2~2P!1,Y1~2P,Y3~U) -> F(b) + S(b~0,Y2~P,Y1~2P,Y3~U)

F 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 P 1 2P take one or more branches, once each, in any order Y3 U
ITAM 3

E(b) + S(b~0,Y3~U,Y2~2P,Y1~2P) <-> E(b!1).S(b~1,Y3~U!1,Y2~2P,Y1~2P)

E 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 2P Y3 1 ⬆⬇U

E(b!1).S(b~1,Y3~U!1,Y2~2P,Y1~2P) -> E(b) + S(b~0,Y3~P,Y2~2P,Y1~2P)

E 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 2P Y3 1 U P take all branches, once each, in any order

F(b) + S(b~0,Y3~P,Y2~2P,Y1~2P) <-> F(b!1).S(b~1,Y3~P!1,Y2~2P,Y1~2P)

F 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 2P Y3 1 ⬆⬇P

F(b!1).S(b~1,Y3~P!1,Y2~2P,Y1~2P) -> F(b) + S(b~0,Y3~U,Y2~2P,Y1~2P)

F 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 2P Y3 U 1 P take one or more branches, once each, in any order

E(b) + S(b~0,Y3~P,Y2~2P,Y1~2P) <-> E(b!1).S(b~1,Y3~P!1,Y2~2P,Y1~2P)

E 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 2P Y3 1 ⬆⬇P

E(b!1).S(b~1,Y3~P!1,Y2~2P,Y1~2P) -> E(b) + S(b~0,Y3~2P,Y2~2P,Y1~2P)

E 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 2P Y3 1 P 2P take all branches, once each, in any order

F(b) + S(b~0,Y3~2P,Y2~2P,Y1~2P) <-> F(b!1).S(b~1,Y3~2P!1,Y2~2P,Y1~2P)

F 1 ⬆⬇b S b 0 1 take all branches, once each, in any order Y1 2P Y2 2P Y3 1 ⬆⬇2P

F(b!1).S(b~1,Y3~2P!1,Y2~2P,Y1~2P) -> F(b) + S(b~0,Y3~P,Y2~2P,Y1~2P)

F 1 b S b 0 1 take one or more branches, once each, in any order Y1 2P Y2 2P Y3 P 1 2P take one or more branches, once each, in any order
ZAP70 binding

Z(b) + S(Y1~2P) <-> Z(b!1).S(Y1~2P!1)

Z 1 ⬆⬇b S b 0 1 Y1 1 ⬆⬇2P Y2 U P 2P Y3 U P 2P

Z(b) + S(Y2~2P) <-> Z(b!1).S(Y2~2P!1)

Z 1 ⬆⬇b S b 0 1 Y1 U P 2P Y2 1 ⬆⬇2P Y3 U P 2P

Z(b) + S(Y3~2P) <-> Z(b!1).S(Y3~2P!1)

Z 1 ⬆⬇b S b 0 1 Y1 U P 2P Y2 U P 2P Y3 1 ⬆⬇2P