Molecules


Descriptions of molecule types can be found in the Supplementary Text (model guide, File S3)

Lig1(aCD28,aCD28)

Lig1 aCD28 aCD28

Lig2(aCD28,aCD3)

Lig2 aCD28 aCD3

Lig3(aCD3,aCD3)

Lig3 aCD3 aCD3

TCR(epitope,Y149_D~0~P,Y171_G~0~P,Y111~0~P,Y123~0~P,fynbind,PRS_E,Y188_E~0~P,Y199_E~0~P)

TCR epitope Y149_D 0 P Y171_G 0 P Y111 0 P Y123 0 P fynbind PRS_E Y188_E 0 P Y199_E 0 P

CD28(epitope,PRS1,PRS2)

CD28 epitope PRS1 PRS2

LCK(SH2,SH3,Y192~0~P,Y424~0~P,Y505~0~P)

LCK SH2 SH3 Y192 0 P Y424 0 P Y505 0 P

ITK(SH3,SH2,PTK,Y512~0~P)

ITK SH3 SH2 PTK Y512 0 P

ZAP70(SH2,PTK,Y493~0~P)

ZAP70 SH2 PTK Y493 0 P

PTPN6(SH2,PTP,Y566~0~P)

PTPN6 SH2 PTP Y566 0 P

PAG1(Y163~0~P,Y317~0~P)

PAG1 Y163 0 P Y317 0 P

CSK(SH2)

CSK SH2

DOK1(Y449~0~P)

DOK1 Y449 0 P

DOK2(Y299~0~P)

DOK2 Y299 0 P

FYN(unique,PTK)

FYN unique PTK

NCK(SH3_1,SH3_3,SH2)

NCK SH3_1 SH3_3 SH2

WAS(PRS,Y291~0~P)

WAS PRS Y291 0 P

LAT(Y132~0~P,Y191~0~P)

LAT Y132 0 P Y191 0 P

PLCG1(SH2,SH3,Y783~0~P)

PLCG1 SH2 SH3 Y783 0 P

GRAP2(SH2,SH3)

GRAP2 SH2 SH3

LCP2(RxxK,Y113_Y128~0~P,PRS,Y145~0~P)

LCP2 RxxK Y113_Y128 0 P PRS Y145 0 P

Species


Seed species are used to initialize a simulation. Following each molecule is parameter that specifies copy number

Lig1(aCD28,aCD28)

Lig1 aCD28 aCD28

Lig2(aCD28,aCD3)

Lig2 aCD28 aCD3

Lig3(aCD3,aCD3)

Lig3 aCD3 aCD3

CD28(epitope,PRS1,PRS2)

CD28 epitope PRS1 PRS2

TCR(epitope,Y149_D~0,Y171_G~0,Y111~0,Y123~0,fynbind,PRS_E,Y188_E~0,Y199_E~0)

TCR epitope Y149_D 0 Y171_G 0 Y111 0 Y123 0 fynbind PRS_E Y188_E 0 Y199_E 0

LCK(SH2,SH3,Y192~0,Y424~0,Y505~0)

LCK SH2 SH3 Y192 0 Y424 0 Y505 0

ITK(SH3,SH2,PTK,Y512~0)

ITK SH3 SH2 PTK Y512 0

ZAP70(SH2,PTK,Y493~0)

ZAP70 SH2 PTK Y493 0

PAG1(Y163~0,Y317~0)

PAG1 Y163 0 Y317 0

CSK(SH2)

CSK SH2

DOK1(Y449~0)

DOK1 Y449 0

DOK2(Y299~0)

DOK2 Y299 0

FYN(unique,PTK)

FYN unique PTK

NCK(SH3_1,SH3_3,SH2)

NCK SH3_1 SH3_3 SH2

WAS(PRS,Y291~0)

WAS PRS Y291 0

LAT(Y132~0,Y191~0)

LAT Y132 0 Y191 0

PLCG1(SH2,SH3,Y783~0)

PLCG1 SH2 SH3 Y783 0

GRAP2(SH2,SH3)

GRAP2 SH2 SH3

To simulate PTPN6 knockdown, the copy number of PTPN6 was set to 0.

PTPN6(SH2,PTP,Y566~0)

PTPN6 SH2 PTP Y566 0

To simulate LCP2 knockdown, the copy number of LCP2 was set to 0.

LCP2(RxxK,Y113_Y128~0,PRS,Y145~0)

LCP2 RxxK Y113_Y128 0 PRS Y145 0

Observables


Beside each observable is noted the figure(s) in which the observable is plotted.

TCR_pY149_D TCR(Y149_D~P!?)

TCR ?epitope Y149_D ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR_pY171_G TCR(Y171_G~P!?)

TCR ?epitope Y149_D 0 ?P Y171_G ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR_pY111 TCR(Y111~P!?)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR_pY123 TCR(Y123~P!?)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR_pY188_E TCR(Y188_E~P!?)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E ?P Y199_E 0 ?P

TCR_pY199_E TCR(Y199_E~P!?)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E ?P

ZAP70_pY493 ZAP70(Y493~P!?)

ZAP70 ?SH2 ?PTK Y493 ?P

LCK_pY424 LCK(Y424~P!?)

LCK ?SH2 ?SH3 Y192 0 ?P Y424 ?P Y505 0 ?P

LCK_pY192 LCK(Y192~P!?)

LCK ?SH2 ?SH3 Y192 ?P Y424 0 ?P Y505 0 ?P

ITK_pY512 ITK(Y512~P!?)

ITK ?SH3 ?SH2 ?PTK Y512 ?P

PTPN6_pY566 PTPN6(Y566~P!?)

PTPN6 ?SH2 ?PTP Y566 ?P

WAS_pY291 WAS(Y291~P!?)

WAS ?PRS Y291 ?P

PAG1_pY163 PAG1(Y163~P!?)

PAG1 Y163 ?P Y317 0 ?P

DOK2_pY299 DOK2(Y299~P!?)

DOK2 Y299 ?P

DOK1_pY449 DOK1(Y449~P!?)

DOK1 Y449 ?P

PLCG1_pY783 PLCG1(Y783~P!?)

PLCG1 ?SH2 ?SH3 Y783 ?P

LAT_pY191 LAT(Y191~P!?)

LAT Y132 0 ?P Y191 ?P

LCK_pY505 LCK(Y505~P!?)

LCK ?SH2 ?SH3 Y192 0 ?P Y424 0 ?P Y505 ?P

NCK_TCR TCR(PRS_E!1).NCK(SH3_1!1)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind PRS_E Y188_E 0 ?P Y199_E 0 ?P NCK SH3_1 ?SH3_3 ?SH2

NCK_LCP2 LCP2(Y113_Y128~P!3).NCK(SH2!3)

LCP2 ?RxxK Y113_Y128 P ?PRS Y145 0 ?P NCK ?SH3_1 ?SH3_3 SH2

Reaction Rules


Rules are numbered to correspond to entries in Supplementary Text (model guide), where rules are annotated
Rule 1a

Lig1(aCD28,aCD28) + CD28(epitope) <-> Lig1(aCD28!1,aCD28).CD28(epitope!1)

Lig1 ⬇⬆aCD28 aCD28 ⬇⬆ CD28 ⬇⬆epitope ?PRS1 ?PRS2

Rule 1b

Lig1(aCD28!1,aCD28).CD28(epitope!1) + CD28(epitope) <-> Lig1(aCD28!1,aCD28!2).CD28(epitope!1).CD28(epitope!2)

Lig1 aCD28 ⬇⬆aCD28 CD28 epitope ?PRS1 ?PRS2 ⬇⬆ CD28 ⬇⬆epitope ?PRS1 ?PRS2

Rule 2a

Lig3(aCD3,aCD3) + TCR(epitope) <-> Lig3(aCD3!1,aCD3).TCR(epitope!1)

Lig3 ⬇⬆aCD3 aCD3 ⬇⬆ TCR ⬇⬆epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 2b

Lig3(aCD3!1,aCD3).TCR(epitope!1) + TCR(epitope) <-> Lig3(aCD3!1,aCD3!2).TCR(epitope!1).TCR(epitope!2)

Lig3 aCD3 ⬇⬆aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P ⬇⬆ TCR ⬇⬆epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 3a

Lig2(aCD28,aCD3) + CD28(epitope) <-> Lig2(aCD28!1,aCD3).CD28(epitope!1)

Lig2 ⬇⬆aCD28 aCD3 ⬇⬆ CD28 ⬇⬆epitope ?PRS1 ?PRS2

Rule 3b

Lig2(aCD28!1,aCD3).CD28(epitope!1) + TCR(epitope) <-> Lig2(aCD28!1,aCD3!2).CD28(epitope!1).TCR(epitope!2)

Lig2 aCD28 ⬇⬆aCD3 CD28 epitope ?PRS1 ?PRS2 ⬇⬆ TCR ⬇⬆epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 3c

Lig2(aCD28,aCD3) + TCR(epitope) <-> Lig2(aCD28,aCD3!1).TCR(epitope!1)

Lig2 aCD28 ⬇⬆aCD3 ⬇⬆ TCR ⬇⬆epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 3d

Lig2(aCD28,aCD3!1).TCR(epitope!1) + CD28(epitope) <-> Lig2(aCD28!2,aCD3!1).TCR(epitope!1).CD28(epitope!2)

Lig2 ⬇⬆aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P ⬇⬆ CD28 ⬇⬆epitope ?PRS1 ?PRS2

Rule 4

LCK(SH3) + CD28(PRS1) <-> LCK(SH3!1).CD28(PRS1!1)

LCK ?SH2 ⬇⬆SH3 Y192 0 ?P Y424 0 ?P Y505 0 ?P ⬇⬆ CD28 ?epitope ⬇⬆PRS1 ?PRS2

Rule 5

CD28(PRS2) + ITK(SH3) <-> CD28(PRS2!1).ITK(SH3!1)

CD28 ?epitope ?PRS1 ⬇⬆PRS2 ⬇⬆ ITK ⬇⬆SH3 ?SH2 ?PTK Y512 0 ?P

Rule 6

TCR(fynbind) + FYN(unique) <-> TCR(fynbind!1).FYN(unique!1)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ⬇⬆fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P ⬇⬆ FYN ⬇⬆unique ?PTK

Rule 7a

NCK(SH3_1) + TCR(Y188_E~0,PRS_E) <-> NCK(SH3_1!1).TCR(Y188_E~0,PRS_E!1)

NCK ⬇⬆SH3_1 ?SH3_3 ?SH2 ⬇⬆ TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ⬇⬆PRS_E Y188_E 0 Y199_E 0 ?P

Rule 7b

NCK(SH3_1!1).TCR(Y188_E~P,PRS_E!1) -> NCK(SH3_1) + TCR(Y188_E~P,PRS_E)

NCK ⬆SH3_1 ?SH3_3 ?SH2 ⬆ TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ⬆PRS_E Y188_E P Y199_E 0 ?P

Rule 8

TCR(Y111~P) + ZAP70(SH2) <-> TCR(Y111~P!1).ZAP70(SH2!1)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 ⬇⬆P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P ⬇⬆ ZAP70 ⬇⬆SH2 ?PTK Y493 0 ?P

Rule 9

TCR(Y123~P) + ZAP70(SH2) <-> TCR(Y123~P!1).ZAP70(SH2!1)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 ⬇⬆P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P ⬇⬆ ZAP70 ⬇⬆SH2 ?PTK Y493 0 ?P

Rule 10

TCR(Y199_E~P) + ZAP70(SH2) <-> TCR(Y199_E~P!1).ZAP70(SH2!1)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E ⬇⬆P ⬇⬆ ZAP70 ⬇⬆SH2 ?PTK Y493 0 ?P

Rule 11

TCR(Y188_E~P) + ZAP70(SH2) <-> TCR(Y188_E~P!1).ZAP70(SH2!1)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E ⬇⬆P Y199_E 0 ?P ⬇⬆ ZAP70 ⬇⬆SH2 ?PTK Y493 0 ?P

Rule 12

PTPN6(SH2) + TCR(Y149_D~P) <-> PTPN6(SH2!1).TCR(Y149_D~P!1)

PTPN6 ⬇⬆SH2 ?PTP Y566 0 ?P ⬇⬆ TCR ?epitope Y149_D ⬇⬆P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 13

PTPN6(SH2) + TCR(Y171_G~P) <-> PTPN6(SH2!1).TCR(Y171_G~P!1)

PTPN6 ⬇⬆SH2 ?PTP Y566 0 ?P ⬇⬆ TCR ?epitope Y149_D 0 ?P Y171_G ⬇⬆P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 14

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y188_E~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y188_E~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 P take all branches, once each, in any order⬇ Y199_E 0 ?P

Rule 15

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y199_E~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y199_E~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 P take all branches, once each, in any order⬇

Rule 16

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 P take all branches, once each, in any order⬇ Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 17

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 P take all branches, once each, in any order⬇ Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 18

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y111~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y111~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 P take all branches, once each, in any order⬇ Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 19

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y123~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y123~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 P take all branches, once each, in any order⬇ ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 20a

LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS1!4).LCK(SH3!4,Y424~0) -> LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS1!4).LCK(SH3!4,Y424~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 P CD28 epitope PRS1 ?PRS2 Lig1 aCD28 aCD28 CD28 epitope PRS1 ?PRS2 LCK ?SH2 SH3 Y192 0 ?P Y424 0 P take all branches, once each, in any order⬇ Y505 0 ?P

Rule 20b

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS1!4).LCK(SH3!4,Y424~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS1!4).LCK(SH3!4,Y424~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig1 aCD28 aCD28 CD28 epitope PRS1 ?PRS2 LCK ?SH2 SH3 Y192 0 ?P Y424 0 P take all branches, once each, in any order⬇ Y505 0 ?P

Rule 21a

LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS2!4).ITK(SH3!4,Y512~0) -> LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS2!4).ITK(SH3!4,Y512~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 P CD28 epitope PRS1 ?PRS2 Lig1 aCD28 aCD28 CD28 epitope ?PRS1 PRS2 ITK SH3 ?SH2 ?PTK Y512 0 P take all branches, once each, in any order⬇

Rule 21b

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS2!4).ITK(SH3!4,Y512~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig1(aCD28!2,aCD28!3).CD28(epitope!3,PRS2!4).ITK(SH3!4,Y512~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig1 aCD28 aCD28 CD28 epitope ?PRS1 PRS2 ITK SH3 ?SH2 ?PTK Y512 0 P take all branches, once each, in any order⬇

Rule 22a

TCR(epitope!3,Y111~P!1).ZAP70(Y493~0,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0) -> TCR(epitope!3,Y111~P!1).ZAP70(Y493~P,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0)

TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P ZAP70 SH2 ?PTK Y493 0 P take all branches, once each, in any order⬇ Lig2 aCD28 aCD3 CD28 epitope PRS1 ?PRS2 LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0

Rule 22b

TCR(epitope!3,Y123~P!1).ZAP70(Y493~0,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0) -> TCR(epitope!3,Y123~P!1).ZAP70(Y493~P,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0)

TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P ZAP70 SH2 ?PTK Y493 0 P take all branches, once each, in any order⬇ Lig2 aCD28 aCD3 CD28 epitope PRS1 ?PRS2 LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0

Rule 22c

TCR(epitope!3,Y188_E~P!1).ZAP70(Y493~0,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0) -> TCR(epitope!3,Y188_E~P!1).ZAP70(Y493~P,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0)

TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E P Y199_E 0 ?P ZAP70 SH2 ?PTK Y493 0 P take all branches, once each, in any order⬇ Lig2 aCD28 aCD3 CD28 epitope PRS1 ?PRS2 LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0

Rule 22d

TCR(epitope!3,Y199_E~P!1).ZAP70(Y493~0,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0) -> TCR(epitope!3,Y199_E~P!1).ZAP70(Y493~P,SH2!1).Lig2(aCD28!2,aCD3!3).CD28(epitope!2,PRS1!4).LCK(SH3!4,Y505~0)

TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E P ZAP70 SH2 ?PTK Y493 0 P take all branches, once each, in any order⬇ Lig2 aCD28 aCD3 CD28 epitope PRS1 ?PRS2 LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0

Rule 23a

LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~0) -> LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 P CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 0 P take all branches, once each, in any order⬇

Rule 23b

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 0 P take all branches, once each, in any order⬇

Rule 23c

LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~0) -> LCK(SH3!1,Y505~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 P CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 0 P take all branches, once each, in any order⬇

Rule 23d

LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~0) -> LCK(SH3!1,Y505~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~P)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 ?P Y505 0 CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 0 P take all branches, once each, in any order⬇

Rule 24a

LCK(SH2,Y192~0) + PTPN6(Y566~P) <-> LCK(SH2!1,Y192~0).PTPN6(Y566~P!1)

LCK ⬇⬆SH2 ?SH3 Y192 0 Y424 0 ?P Y505 0 ?P ⬇⬆ PTPN6 ?SH2 ?PTP Y566 ⬇⬆P

Rule 24b

LCK(SH2,Y192~P) + PTPN6(Y566~P) <-> LCK(SH2!1,Y192~P).PTPN6(Y566~P!1)

LCK ⬇⬆SH2 ?SH3 Y192 P Y424 0 ?P Y505 0 ?P ⬇⬆ PTPN6 ?SH2 ?PTP Y566 ⬇⬆P

Rule 25

PAG1(Y317~P) + CSK(SH2) <-> PAG1(Y317~P!1).CSK(SH2!1)

PAG1 Y163 0 ?P Y317 ⬇⬆P ⬇⬆ CSK ⬇⬆SH2

Rule 26

PAG1(Y163~P) + LCK(SH2) <-> PAG1(Y163~P!1).LCK(SH2!1)

PAG1 Y163 ⬇⬆P Y317 0 ?P ⬇⬆ LCK ⬇⬆SH2 ?SH3 Y192 0 ?P Y424 0 ?P Y505 0 ?P

Rule 27

PAG1(Y317~0,Y163~P!1).LCK(SH2!1) -> PAG1(Y317~P,Y163~P!1).LCK(SH2!1)

PAG1 Y163 P Y317 0 P take all branches, once each, in any order⬇ LCK SH2 ?SH3 Y192 0 ?P Y424 0 ?P Y505 0 ?P

Rule 28

PAG1(Y317~P!2,Y163~P!1).LCK(SH2!1,Y505~0).CSK(SH2!2) -> PAG1(Y317~P!2,Y163~P!1).LCK(SH2!1,Y505~P).CSK(SH2!2)

PAG1 Y163 P Y317 P LCK SH2 ?SH3 Y192 0 ?P Y424 0 ?P Y505 0 P take all branches, once each, in any order⬇ CSK SH2

Rule 29a

LCK(SH3!1,Y192~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~P!?) -> LCK(SH3!1,Y192~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~P!?)

LCK ?SH2 SH3 Y192 0 P take one or more branches, once each, in any order⬆ Y424 0 ?P Y505 0 ?P CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 ?P

Rule 29b

LCK(SH3!1,Y192~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~P!?) -> LCK(SH3!1,Y192~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~P!?)

LCK ?SH2 SH3 Y192 0 P take one or more branches, once each, in any order⬆ Y424 0 ?P Y505 0 ?P CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 ?P

Rule 30a

LCK(SH3!1,Y424~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~P!?) -> LCK(SH3!1,Y424~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y149_D~P!4).PTPN6(SH2!4,Y566~P!?)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 P take one or more branches, once each, in any order⬆ Y505 0 ?P CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 ?P

Rule 30b

LCK(SH3!1,Y424~P).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~P!?) -> LCK(SH3!1,Y424~0).CD28(PRS1!1,epitope!2).Lig2(aCD28!2,aCD3!3).TCR(epitope!3,Y171_G~P!4).PTPN6(SH2!4,Y566~P!?)

LCK ?SH2 SH3 Y192 0 ?P Y424 0 P take one or more branches, once each, in any order⬆ Y505 0 ?P CD28 epitope PRS1 ?PRS2 Lig2 aCD28 aCD3 TCR epitope Y149_D 0 ?P Y171_G P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P PTPN6 SH2 ?PTP Y566 ?P

Rule 30c

PTPN6(Y566~P!1).LCK(SH2!1,Y424~P) -> PTPN6(Y566~P!1).LCK(SH2!1,Y424~0)

PTPN6 ?SH2 ?PTP Y566 P LCK SH2 ?SH3 Y192 0 ?P Y424 0 P take one or more branches, once each, in any order⬆ Y505 0 ?P

Rule 31a

PAG1(Y163~P) + PTPN6(SH2!2,PTP).TCR(Y149_D~P!2) -> PAG1(Y163~P!1).PTPN6(SH2!2,PTP!1).TCR(Y149_D~P!2)

PAG1 Y163 ⬇P Y317 0 ?P ⬇ PTPN6 SH2 ⬇PTP Y566 0 ?P TCR ?epitope Y149_D P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 31b

PAG1(Y163~P) + PTPN6(SH2!2,PTP).TCR(Y171_G~P!2) -> PAG1(Y163~P!1).PTPN6(SH2!2,PTP!1).TCR(Y171_G~P!2)

PAG1 Y163 ⬇P Y317 0 ?P ⬇ PTPN6 SH2 ⬇PTP Y566 0 ?P TCR ?epitope Y149_D 0 ?P Y171_G P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 31c

PTPN6(PTP,SH2) + PAG1(Y163~P) -> PTPN6(PTP!1,SH2).PAG1(Y163~P!1)

PTPN6 SH2 ⬇PTP Y566 0 ?P ⬇ PAG1 Y163 ⬇P Y317 0 ?P

Rule 31d

PAG1(Y163~P!1).PTPN6(PTP!1) -> PAG1(Y163~P) + PTPN6(PTP)

PAG1 Y163 ⬆P Y317 0 ?P ⬆ PTPN6 ?SH2 ⬆PTP Y566 0 ?P

Rule 31e

PAG1(Y163~P!1).PTPN6(PTP!1,Y566~P!?) -> PAG1(Y163~0) + PTPN6(PTP,Y566~P!?)

PAG1 Y163 0 ⬆P take one or more branches, once each, in any order⬆ Y317 0 ?P ⬆ PTPN6 ?SH2 ⬆PTP Y566 ?P

Rule 32a

DOK1(Y449~P) + PTPN6(SH2!2,PTP).TCR(Y149_D~P!2) -> DOK1(Y449~P!1).PTPN6(SH2!2,PTP!1).TCR(Y149_D~P!2)

DOK1 Y449 ⬇P ⬇ PTPN6 SH2 ⬇PTP Y566 0 ?P TCR ?epitope Y149_D P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 32b

DOK1(Y449~P) + PTPN6(SH2!2,PTP).TCR(Y171_G~P!2) -> DOK1(Y449~P!1).PTPN6(SH2!2,PTP!1).TCR(Y171_G~P!2)

DOK1 Y449 ⬇P ⬇ PTPN6 SH2 ⬇PTP Y566 0 ?P TCR ?epitope Y149_D 0 ?P Y171_G P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 32c

DOK1(Y449~P!1).PTPN6(PTP!1) -> DOK1(Y449~P) + PTPN6(PTP)

DOK1 Y449 ⬆P ⬆ PTPN6 ?SH2 ⬆PTP Y566 0 ?P

Rule 32d

DOK1(Y449~P!1).PTPN6(PTP!1,Y566~P!?) -> DOK1(Y449~0) + PTPN6(PTP,Y566~P!?)

DOK1 Y449 0 ⬆P take one or more branches, once each, in any order⬆ ⬆ PTPN6 ?SH2 ⬆PTP Y566 ?P

Rule 33a

DOK2(Y299~P) + PTPN6(SH2!2,PTP).TCR(Y149_D~P!2) -> DOK2(Y299~P!1).PTPN6(SH2!2,PTP!1).TCR(Y149_D~P!2)

DOK2 Y299 ⬇P ⬇ PTPN6 SH2 ⬇PTP Y566 0 ?P TCR ?epitope Y149_D P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 33b

DOK2(Y299~P) + PTPN6(SH2!2,PTP).TCR(Y171_G~P!2) -> DOK2(Y299~P!1).PTPN6(SH2!2,PTP!1).TCR(Y171_G~P!2)

DOK2 Y299 ⬇P ⬇ PTPN6 SH2 ⬇PTP Y566 0 ?P TCR ?epitope Y149_D 0 ?P Y171_G P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

Rule 33c

DOK2(Y299~P!1).PTPN6(PTP!1) -> DOK2(Y299~P) + PTPN6(PTP)

DOK2 Y299 ⬆P ⬆ PTPN6 ?SH2 ⬆PTP Y566 0 ?P

Rule 33d

DOK2(Y299~P!1).PTPN6(PTP!1,Y566~P!?) -> DOK2(Y299~0) + PTPN6(PTP,Y566~P!?)

DOK2 Y299 0 ⬆P take one or more branches, once each, in any order⬆ ⬆ PTPN6 ?SH2 ⬆PTP Y566 ?P

Rule 34

WAS(PRS) + NCK(SH3_3) <-> WAS(PRS!1).NCK(SH3_3!1)

WAS ⬇⬆PRS Y291 0 ?P ⬇⬆ NCK ?SH3_1 ⬇⬆SH3_3 ?SH2

Rule 35a

TCR(epitope!3,fynbind!1).FYN(unique!1).Lig3(aCD3!2,aCD3!3).TCR(epitope!2,PRS_E!4).NCK(SH3_1!4,SH3_3!5).WAS(Y291~0,PRS!5) -> TCR(epitope!3,fynbind!1).FYN(unique!1).Lig3(aCD3!2,aCD3!3).TCR(epitope!2,PRS_E!4).NCK(SH3_1!4,SH3_3!5).WAS(Y291~P,PRS!5)

TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P FYN unique ?PTK Lig3 aCD3 aCD3 TCR epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind PRS_E Y188_E 0 ?P Y199_E 0 ?P NCK SH3_1 SH3_3 ?SH2 WAS PRS Y291 0 P take all branches, once each, in any order⬇

Rule 35b

LAT(Y191~P!1).GRAP2(SH2!1,SH3!2).LCP2(RxxK!2,Y113_Y128~P!3).NCK(SH2!3,SH3_3!4).WAS(PRS!4,Y291~0) + FYN(unique!+,PTK) -> LAT(Y191~P!1).GRAP2(SH2!1,SH3!2).LCP2(RxxK!2,Y113_Y128~P!3).NCK(SH2!3,SH3_3!4).WAS(PRS!4,Y291~0!5).FYN(unique!+,PTK!5)

LAT Y132 0 ?P Y191 P GRAP2 SH2 SH3 LCP2 RxxK Y113_Y128 P ?PRS Y145 0 ?P NCK ?SH3_1 SH3_3 SH2 WAS PRS Y291 ⬇0 ⬇ FYN unique ⬇PTK

Rule 35c

WAS(Y291~0!5).FYN(PTK!5) -> WAS(Y291~P) + FYN(PTK)

WAS ?PRS Y291 ⬆0 P take all branches, once each, in any order⬇ ⬆ FYN ?unique ⬆PTK

Rule 35d

WAS(Y291~0!1).FYN(PTK!1) -> WAS(Y291~0) + FYN(PTK)

WAS ?PRS Y291 ⬆0 ⬆ FYN ?unique ⬆PTK

Rule 36a

ZAP70(SH2!+,PTK) + LAT(Y132~0) -> ZAP70(SH2!+,PTK!1).LAT(Y132~0!1)

ZAP70 SH2 ⬇PTK Y493 0 ?P ⬇ LAT Y132 ⬇0 Y191 0 ?P

Rule 36b

ZAP70(PTK!1).LAT(Y132~0!1) -> ZAP70(PTK) + LAT(Y132~0)

ZAP70 ?SH2 ⬆PTK Y493 0 ?P ⬆ LAT Y132 ⬆0 Y191 0 ?P

Rule 36c

ZAP70(PTK!1,Y493~P).LAT(Y132~0!1) -> ZAP70(PTK,Y493~P) + LAT(Y132~P)

ZAP70 ?SH2 ⬆PTK Y493 P ⬆ LAT Y132 ⬆0 P take all branches, once each, in any order⬇ Y191 0 ?P

Rule 37a

ZAP70(SH2!+,PTK) + LAT(Y191~0) -> ZAP70(SH2!+,PTK!1).LAT(Y191~0!1)

ZAP70 SH2 ⬇PTK Y493 0 ?P ⬇ LAT Y132 0 ?P Y191 ⬇0

Rule 37b

ZAP70(PTK!1).LAT(Y191~0!1) -> ZAP70(PTK) + LAT(Y191~0)

ZAP70 ?SH2 ⬆PTK Y493 0 ?P ⬆ LAT Y132 0 ?P Y191 ⬆0

Rule 37c

ZAP70(PTK!1,Y493~P).LAT(Y191~0!1) -> ZAP70(PTK,Y493~P) + LAT(Y191~P)

ZAP70 ?SH2 ⬆PTK Y493 P ⬆ LAT Y132 0 ?P Y191 ⬆0 P take all branches, once each, in any order⬇

Rule 38

PLCG1(SH2) + LAT(Y132~P) <-> PLCG1(SH2!1).LAT(Y132~P!1)

PLCG1 ⬇⬆SH2 ?SH3 Y783 0 ?P ⬇⬆ LAT Y132 ⬇⬆P Y191 0 ?P

Rule 39

LAT(Y191~P) + GRAP2(SH2) <-> LAT(Y191~P!1).GRAP2(SH2!1)

LAT Y132 0 ?P Y191 ⬇⬆P ⬇⬆ GRAP2 ⬇⬆SH2 ?SH3

Rule 40

GRAP2(SH3) + LCP2(RxxK) <-> GRAP2(SH3!1).LCP2(RxxK!1)

GRAP2 ?SH2 ⬇⬆SH3 ⬇⬆ LCP2 ⬇⬆RxxK Y113_Y128 0 ?P ?PRS Y145 0 ?P

Rule 41

NCK(SH2) + LCP2(Y113_Y128~P) <-> NCK(SH2!1).LCP2(Y113_Y128~P!1)

NCK ?SH3_1 ?SH3_3 ⬇⬆SH2 ⬇⬆ LCP2 ?RxxK Y113_Y128 ⬇⬆P ?PRS Y145 0 ?P

Rule 42a

LAT(Y191~P!1).GRAP2(SH2!1,SH3!2).LCP2(RxxK!2,Y113_Y128~0) + ZAP70(SH2!+,PTK) -> LAT(Y191~P!1).GRAP2(SH2!1,SH3!2).LCP2(RxxK!2,Y113_Y128~0!3).ZAP70(SH2!+,PTK!3)

LAT Y132 0 ?P Y191 P GRAP2 SH2 SH3 LCP2 RxxK Y113_Y128 ⬇0 ?PRS Y145 0 ?P ⬇ ZAP70 SH2 ⬇PTK Y493 0 ?P

Rule 42b

ZAP70(PTK!1).LCP2(Y113_Y128~0!1) -> ZAP70(PTK) + LCP2(Y113_Y128~0)

ZAP70 ?SH2 ⬆PTK Y493 0 ?P ⬆ LCP2 ?RxxK Y113_Y128 ⬆0 ?PRS Y145 0 ?P

Rule 42c

LCP2(Y113_Y128~0!3).ZAP70(PTK!3,Y493~P) -> LCP2(Y113_Y128~P) + ZAP70(PTK,Y493~P)

LCP2 ?RxxK Y113_Y128 ⬆0 P take all branches, once each, in any order⬇ ?PRS Y145 0 ?P ⬆ ZAP70 ?SH2 ⬆PTK Y493 P

Rule 43

PLCG1(SH3) + LCP2(PRS) <-> PLCG1(SH3!1).LCP2(PRS!1)

PLCG1 ?SH2 ⬇⬆SH3 Y783 0 ?P ⬇⬆ LCP2 ?RxxK Y113_Y128 0 ?P ⬇⬆PRS Y145 0 ?P

Rule 44

LCP2(Y145~P) + ITK(SH2) <-> LCP2(Y145~P!1).ITK(SH2!1)

LCP2 ?RxxK Y113_Y128 0 ?P ?PRS Y145 ⬇⬆P ⬇⬆ ITK ?SH3 ⬇⬆SH2 ?PTK Y512 0 ?P

Rule 45a

LAT(Y191~P!1).GRAP2(SH2!1,SH3!2).LCP2(RxxK!2,Y145~0) + ZAP70(SH2!+,PTK) -> LAT(Y191~P!1).GRAP2(SH2!1,SH3!2).LCP2(RxxK!2,Y145~0!3).ZAP70(SH2!+,PTK!3)

LAT Y132 0 ?P Y191 P GRAP2 SH2 SH3 LCP2 RxxK Y113_Y128 0 ?P ?PRS Y145 ⬇0 ⬇ ZAP70 SH2 ⬇PTK Y493 0 ?P

Rule 45b

ZAP70(PTK!1).LCP2(Y145~0!1) -> ZAP70(PTK) + LCP2(Y145~0)

ZAP70 ?SH2 ⬆PTK Y493 0 ?P ⬆ LCP2 ?RxxK Y113_Y128 0 ?P ?PRS Y145 ⬆0

Rule 45c

LCP2(Y145~0!3).ZAP70(PTK!3,Y493~P) -> LCP2(Y145~P) + ZAP70(PTK,Y493~P)

LCP2 ?RxxK Y113_Y128 0 ?P ?PRS Y145 ⬆0 P take all branches, once each, in any order⬇ ⬆ ZAP70 ?SH2 ⬆PTK Y493 P

Rule 46

PLCG1(SH3!1,SH2!+,Y783~0).LCP2(PRS!1,Y145~P!2).ITK(SH2!2) -> PLCG1(SH3!1,SH2!+,Y783~P).LCP2(PRS!1,Y145~P!2).ITK(SH2!2)

PLCG1 SH2 SH3 Y783 0 P take all branches, once each, in any order⬇ LCP2 ?RxxK Y113_Y128 0 ?P PRS Y145 P ITK ?SH3 SH2 ?PTK Y512 0 ?P

The following rules account for phosphorylation and dephosphorylation in the basal state, and are not discussed in the model guide

TCR(Y149_D~0) -> TCR(Y149_D~P)

TCR ?epitope Y149_D 0 P take all branches, once each, in any order⬇ Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y149_D~P) -> TCR(Y149_D~0)

TCR ?epitope Y149_D 0 P take one or more branches, once each, in any order⬆ Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y171_G~0) -> TCR(Y171_G~P)

TCR ?epitope Y149_D 0 ?P Y171_G 0 P take all branches, once each, in any order⬇ Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y171_G~P) -> TCR(Y171_G~0)

TCR ?epitope Y149_D 0 ?P Y171_G 0 P take one or more branches, once each, in any order⬆ Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y111~0) -> TCR(Y111~P)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 P take all branches, once each, in any order⬇ Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y111~P) -> TCR(Y111~0)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 P take one or more branches, once each, in any order⬆ Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y123~0) -> TCR(Y123~P)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 P take all branches, once each, in any order⬇ ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y123~P) -> TCR(Y123~0)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 P take one or more branches, once each, in any order⬆ ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 ?P

TCR(Y199_E~0) -> TCR(Y199_E~P)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 P take all branches, once each, in any order⬇

TCR(Y199_E~P) -> TCR(Y199_E~0)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 ?P Y199_E 0 P take one or more branches, once each, in any order⬆

TCR(Y188_E~0) -> TCR(Y188_E~P)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 P take all branches, once each, in any order⬇ Y199_E 0 ?P

TCR(Y188_E~P) -> TCR(Y188_E~0)

TCR ?epitope Y149_D 0 ?P Y171_G 0 ?P Y111 0 ?P Y123 0 ?P ?fynbind ?PRS_E Y188_E 0 P take one or more branches, once each, in any order⬆ Y199_E 0 ?P

LCK(Y192~0) -> LCK(Y192~P)

LCK ?SH2 ?SH3 Y192 0 P take all branches, once each, in any order⬇ Y424 0 ?P Y505 0 ?P

LCK(Y192~P) -> LCK(Y192~0)

LCK ?SH2 ?SH3 Y192 0 P take one or more branches, once each, in any order⬆ Y424 0 ?P Y505 0 ?P

LCK(Y424~0) -> LCK(Y424~P)

LCK ?SH2 ?SH3 Y192 0 ?P Y424 0 P take all branches, once each, in any order⬇ Y505 0 ?P

LCK(Y424~P) -> LCK(Y424~0)

LCK ?SH2 ?SH3 Y192 0 ?P Y424 0 P take one or more branches, once each, in any order⬆ Y505 0 ?P

LCK(Y505~0) -> LCK(Y505~P)

LCK ?SH2 ?SH3 Y192 0 ?P Y424 0 ?P Y505 0 P take all branches, once each, in any order⬇

LCK(Y505~P) -> LCK(Y505~0)

LCK ?SH2 ?SH3 Y192 0 ?P Y424 0 ?P Y505 0 P take one or more branches, once each, in any order⬆

PTPN6(Y566~0) -> PTPN6(Y566~P)

PTPN6 ?SH2 ?PTP Y566 0 P take all branches, once each, in any order⬇

PTPN6(Y566~P) -> PTPN6(Y566~0)

PTPN6 ?SH2 ?PTP Y566 0 P take one or more branches, once each, in any order⬆

ZAP70(Y493~0) -> ZAP70(Y493~P)

ZAP70 ?SH2 ?PTK Y493 0 P take all branches, once each, in any order⬇

ZAP70(Y493~P) -> ZAP70(Y493~0)

ZAP70 ?SH2 ?PTK Y493 0 P take one or more branches, once each, in any order⬆

LAT(Y132~0) -> LAT(Y132~P)

LAT Y132 0 P take all branches, once each, in any order⬇ Y191 0 ?P

LAT(Y132~P) -> LAT(Y132~0)

LAT Y132 0 P take one or more branches, once each, in any order⬆ Y191 0 ?P

LAT(Y191~0) -> LAT(Y191~P)

LAT Y132 0 ?P Y191 0 P take all branches, once each, in any order⬇

LAT(Y191~P) -> LAT(Y191~0)

LAT Y132 0 ?P Y191 0 P take one or more branches, once each, in any order⬆

ITK(Y512~0) -> ITK(Y512~P)

ITK ?SH3 ?SH2 ?PTK Y512 0 P take all branches, once each, in any order⬇

ITK(Y512~P) -> ITK(Y512~0)

ITK ?SH3 ?SH2 ?PTK Y512 0 P take one or more branches, once each, in any order⬆

PLCG1(Y783~0) -> PLCG1(Y783~P)

PLCG1 ?SH2 ?SH3 Y783 0 P take all branches, once each, in any order⬇

PLCG1(Y783~P) -> PLCG1(Y783~0)

PLCG1 ?SH2 ?SH3 Y783 0 P take one or more branches, once each, in any order⬆

LCP2(Y113_Y128~0) -> LCP2(Y113_Y128~P)

LCP2 ?RxxK Y113_Y128 0 P take all branches, once each, in any order⬇ ?PRS Y145 0 ?P

LCP2(Y113_Y128~P) -> LCP2(Y113_Y128~0)

LCP2 ?RxxK Y113_Y128 0 P take one or more branches, once each, in any order⬆ ?PRS Y145 0 ?P

LCP2(Y145~0) -> LCP2(Y145~P)

LCP2 ?RxxK Y113_Y128 0 ?P ?PRS Y145 0 P take all branches, once each, in any order⬇

LCP2(Y145~P) -> LCP2(Y145~0)

LCP2 ?RxxK Y113_Y128 0 ?P ?PRS Y145 0 P take one or more branches, once each, in any order⬆

PAG1(Y163~0) -> PAG1(Y163~P)

PAG1 Y163 0 P take all branches, once each, in any order⬇ Y317 0 ?P

PAG1(Y163~P) -> PAG1(Y163~0)

PAG1 Y163 0 P take one or more branches, once each, in any order⬆ Y317 0 ?P

PAG1(Y317~0) -> PAG1(Y317~P)

PAG1 Y163 0 ?P Y317 0 P take all branches, once each, in any order⬇

PAG1(Y317~P) -> PAG1(Y317~0)

PAG1 Y163 0 ?P Y317 0 P take one or more branches, once each, in any order⬆

DOK1(Y449~0) -> DOK1(Y449~P)

DOK1 Y449 0 P take all branches, once each, in any order⬇

DOK1(Y449~P) -> DOK1(Y449~0)

DOK1 Y449 0 P take one or more branches, once each, in any order⬆

DOK2(Y299~0) -> DOK2(Y299~P)

DOK2 Y299 0 P take all branches, once each, in any order⬇

DOK2(Y299~P) -> DOK2(Y299~0)

DOK2 Y299 0 P take one or more branches, once each, in any order⬆

WAS(Y291~0) -> WAS(Y291~P)

WAS ?PRS Y291 0 P take all branches, once each, in any order⬇

WAS(Y291~P) -> WAS(Y291~0)

WAS ?PRS Y291 0 P take one or more branches, once each, in any order⬆