Supplemental Table 6

Parent or Parent or Parent Child Child Lowest Mean Median Patient Patient Patient Parent Child Child Path Patient 1 Patient 1 Patient 2 Patient 2 Patient 2 Patient 3 PathwayName PathwayID Pathway in Pathway in Pathway in Level Pathway Pathway Patient 1 Gene List Patient 2 Gene List Patient 3 Gene List 1 2 3 PathwayID PathwayID Pathway in Length Uniprot List Targetome Uniprot List Targetome Uniprot List Targetome PathwayID PathwayID PathwayID Pathway Score Score PathwayID Unique R-HSA- R-HSA- Acetylation NA NA 1 FALSE NA FALSE FALSE FALSE 2 TRUE 1 1 NA NA NA NA NA NA P18440 NAT1,AAC1 NA 156582 156580 Butyrophilin (BTN) R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 12 TRUE 1.41666667 1 Q8WVV5 BTN2A2,BT2.2,BTF2 NA NA NA NA NA NA NA family interactions 8851680 1280218

Carboxyterminal post-translational R-HSA- R-HSA- Q3ZCM7,Q8 2 1 1 FALSE NA FALSE FALSE FALSE 38 TRUE 2.71052632 1 TUBB8,TTLL11,C9orf20 NA Q8IUZ0 LRRC49 NA Q5VU57 AGBL4,CCP6 NA modifications of 8955332 597592 NHH1 tubulin P11168,P14 SLC2A2,GLUT2,SLC2A4, Cellular hexose R-HSA- R-HSA- NA 1 3 FALSE NA FALSE FALSE FALSE 22 TRUE 1.86363636 1 NA NA NA A0PJK1 SLC5A10,SGLT5 NA 672,Q9NY6 GLUT4,SLC2A8,GLUT8,G NA transport 189200 425407 4 LUTX1 Chondroitin sulfate R-HSA- R-HSA- CSGALNACT2,CHGN2,G 1 NA NA FALSE NA FALSE FALSE FALSE 20 TRUE 5 1 Q8N6G5 NA NA NA NA NA NA NA biosynthesis 2022870 1793185 ALNACT2,PRO0082

Cytosolic iron- R-HSA- R-HSA- P18074,P53 ERCC2,XPD,XPDC,NUBP1 sulfur cluster NA NA 2 FALSE NA FALSE FALSE FALSE 13 TRUE 6.15384615 1 NA NA NA NA NA NA NA 2564830 1430728 384 ,NBP,NBP1 assembly Cytosolic R-HSA- R-HSA- R-HSA- SULT1B1,ST1B2,SULT1B sulfonation of NA NA 1 FALSE FALSE FALSE FALSE 24 TRUE 1.875 1 NA NA NA NA NA NA O43704 NA 156584 156580 174362 2 small molecules Estrogen R-HSA- R-HSA- CYP19A1,ARO1,CYAR,CY 1 NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 1.83333333 1 P11511 NA NA NA NA C9JRZ8 AKR1B15 NA biosynthesis 193144 196071 P19 Gap junction R-HSA- R-HSA- R-HSA- P36383,Q8 1 NA 2 FALSE FALSE FALSE FALSE 19 TRUE 1.78947368 1 Q3ZCM7 TUBB8 NA NA NA NA GJC1,GJA7,GJD3,GJA11 NA assembly 190861 190828 190827 N144 Gap junction R-HSA- R-HSA- R-HSA- P36383,Q8 1 NA 2 FALSE FALSE FALSE FALSE 19 TRUE 1.78947368 1 Q3ZCM7 TUBB8 NA NA NA NA GJC1,GJA7,GJD3,GJA11 NA assembly 190861 190828 190704 N144 Gap junction R-HSA- R-HSA- R-HSA- P36383,Q8 1 NA 2 FALSE FALSE FALSE FALSE 19 TRUE 1.78947368 1 Q3ZCM7 TUBB8 NA NA NA NA GJC1,GJA7,GJD3,GJA11 NA assembly 190861 190828 190872 N144 R-HSA- R-HSA- R-HSA- Glucuronidation 1 NA NA FALSE FALSE FALSE FALSE 24 TRUE 1.41666667 1 P35504 UGT1A5,GNT1,UGT1 NA NA NA NA NA NA NA 156588 156580 173599 R-HSA- R-HSA- HCN channels NA NA 1 FALSE NA FALSE FALSE FALSE 4 TRUE 1 1 NA NA NA NA NA NA Q9Y3Q4 HCN4 NA 1296061 1296071 IL-6-type cytokine R-HSA- R-HSA- receptor ligand 1 NA NA FALSE NA FALSE FALSE FALSE 17 TRUE 6 1 P42702 LIFR NA NA NA NA NA NA NA 6788467 6783589 interactions Interaction With R-HSA- R-HSA- ADAM30,UNQ2509/PRO 1 NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 1.7 1 Q9UKF2 NA NA NA NA Q9UKJ8 ADAM21 NA The Zona Pellucida 1300644 1187000 5997

Intracellular R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 3 TRUE 1.33333333 1 NA NA NA NA NA NA Q9NPG2 NGB NA oxygen transport 8981607 382551 P19013,P78 KRT4,CYK4,KRT85,KRTH O43790,Q8 KRT86,KRTHB6,KRT73,K KRTAP4- R-HSA- R-HSA- R-HSA- 386,Q02487 B5,DSC2,CDHF2,DSC3,KR Keratinization 4 1 5 FALSE TRUE TRUE TRUE 217 TRUE 1.60829493 1 6Y46,Q9945 6IRS3,KB36,KRT6IRS3,K NA Q9BYQ5 6,KAP4.15,KRTAP4- NA NA 6805567 1266738 6809371 ,Q86Y46,Q9 T73,K6IRS3,KB36,KRT6I 6,Q99959 RT12,PKP2 15,KRTAP4.15,KRTAP4.6 9569 RS3,PKP4 Miscellaneous R-HSA- R-HSA- transport and NA NA 1 FALSE NA FALSE FALSE FALSE 24 TRUE 1.375 1 NA NA NA NA NA NA Q7RTP0 NIPA1,SPG6 NA 5223345 382551 binding events Mitochondrial R-HSA- R-HSA- Q5JPH6,Q96 EARS2,KIAA1970,MARS tRNA 2 1 NA FALSE NA FALSE FALSE FALSE 21 TRUE 1.28571429 1 NA Q9NP81 SARS2,SARSM NA NA NA NA 379726 379724 GW9 2 aminoacylation Q15700,Q6 O14490,Q1 DLGAP1,DAP1,GKAP,GRI Neurexins and R-HSA- R-HSA- DLG2,SYT10,NRXN3,KIA 4 NA 3 FALSE NA FALSE FALSE FALSE 57 TRUE 3.66666667 1 XYQ8,Q9HD NA NA NA NA 2879,Q9NS N2A,NMDAR2A,HOMER NA neuroligins 6794361 6794362 A0743,C14orf60 B5,Q9Y4C0 C5 3 Phenylalanine and R-HSA- R-HSA- tyrosine NA NA 1 FALSE NA FALSE FALSE FALSE 11 TRUE 1.45454545 1 NA NA NA NA NA NA Q16773 KYAT1,CCBL1 NA 71182 6788656 catabolism Post-translational modification: R-HSA- R-HSA- R-HSA- LY6G6C,C6orf24,G6C,NG NA NA 1 FALSE TRUE TRUE TRUE 94 TRUE 1.60638298 1 NA NA NA NA NA NA O95867 NA synthesis of GPI- 163125 597592 162710 24,UNQ1947/PRO4430 anchored proteins Post-translational modification: R-HSA- R-HSA- R-HSA- LY6G6C,C6orf24,G6C,NG NA NA 1 FALSE FALSE FALSE TRUE 94 TRUE 1.60638298 1 NA NA NA NA NA NA O95867 NA synthesis of GPI- 163125 597592 162791 24,UNQ1947/PRO4430 anchored proteins Post-translational modification: R-HSA- R-HSA- R-HSA- LY6G6C,C6orf24,G6C,NG NA NA 1 FALSE FALSE FALSE TRUE 94 TRUE 1.60638298 1 NA NA NA NA NA NA O95867 NA synthesis of GPI- 163125 597592 162699 24,UNQ1947/PRO4430 anchored proteins PTK6 Regulates R-HSA- R-HSA- Proteins Involved NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 3.6 1 NA NA NA NA NA NA O75525 KHDRBS3,SALP,SLM2 NA 8849468 8848021 in RNA Processing R-HSA- R-HSA- Purine salvage 1 NA 1 FALSE NA FALSE FALSE FALSE 13 TRUE 1.53846154 1 P23109 AMPD1 NA NA NA NA Q6DHV7 ADAL NA 74217 8956321 R-HSA- R-HSA- SDK interactions NA NA 1 FALSE NA FALSE FALSE FALSE 2 TRUE 1 1 NA NA NA NA NA NA Q58EX2 SDK2,KIAA1514 NA 373756 421270 Sphingolipid de R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 44 TRUE 1.34090909 1 P48448 ALDH3B2,ALDH8 NA NA NA NA NA NA NA novo biosynthesis 1660661 428157 Striated Muscle R-HSA- R-HSA- P35609,Q00 ACTN2,MYBPC1,MYBPC NA NA 2 FALSE NA FALSE FALSE FALSE 34 TRUE 1.70588235 1 NA NA NA NA NA NA NA Contraction 390522 397014 872 S Synthesis of R-HSA- R-HSA- pyrophosphates in NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 1.4 1 NA NA NA NA NA NA Q13572 ITPK1 NA 1855167 1483249 the cytosol TET1,2,3 and TDG R-HSA- R-HSA- Q13569,Q6 TDG,TET2,KIAA1546,Nbl NA NA 2 FALSE NA FALSE FALSE FALSE 4 TRUE 2.25 1 NA NA NA NA NA NA NA demethylate DNA 5221030 212165 N021 a00191 tRNA modification R-HSA- R-HSA- R-HSA- Q7Z6V5,Q8I ADAT2,DEADC1,TRMT44 in the nucleus and 2 NA NA FALSE FALSE FALSE FALSE 43 TRUE 1.34883721 1 NA NA NA NA NA NA NA 6782315 72306 6782861 YL2 ,C4orf23,METTL19 cytosol

Tryptophan R-HSA- R-HSA- P48775,Q16 NA NA 2 FALSE NA FALSE FALSE FALSE 14 TRUE 1.92857143 1 NA NA NA NA NA NA TDO2,TDO,KYAT1,CCBL1 NA catabolism 71240 6788656 773 Vitamin B1 R-HSA- R-HSA- (thiamin) NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 1 1 NA NA NA NA NA NA Q9BZV2 SLC19A3 NA 196819 196849 metabolism

O95259,Q8 Voltage gated KCNH1,EAG,EAG1,KCNH R-HSA- R-HSA- O43525,P22 NCM2,Q8TD Potassium 2 NA 5 FALSE NA FALSE FALSE FALSE 43 TRUE 1.53488372 1 KCNQ3,KCNA4,KCNA4L NA NA NA NA 5,EAG2,KCNG4,KCNG3,K NA 1296072 1296071 459 N1,Q9H3M0 channels CNF1,KCNQ5 ,Q9NR82

R-HSA- R-HSA- Q8NE62,Q8 CHDH,SLC44A1,CD92,CD Choline catabolism 2 NA NA FALSE NA FALSE FALSE FALSE 6 TRUE 1.83333333 1.5 NA NA NA NA NA NA NA 6798163 71291 WWI5 W92,CTL1 LGI-ADAM R-HSA- R-HSA- LGI3,LGIL4,UNQ8190/P 1 NA 1 FALSE NA FALSE FALSE FALSE 14 TRUE 4.28571429 1.5 Q8N145 NA NA NA NA Q9P0K1 ADAM22,MDC2 NA interactions 5682910 1266738 RO23199 Receptor-type R-HSA- R-HSA- O94991,P23 SLITRK5,KIAA0918,LRRC tyrosine-protein 1 NA 2 FALSE NA FALSE FALSE FALSE 20 TRUE 3.15 1.5 P23468 PTPRD NA NA NA NA NA 388844 6794362 468 11,PTPRD phosphatases R-HSA- R-HSA- O14641,Q9 Signaling by Hippo NA NA 2 FALSE NA FALSE FALSE FALSE 20 TRUE 6 1.5 NA NA NA NA NA NA DVL2,AMOTL2,KIAA0989 NA 2028269 162582 Y2J4 ABC transporters R-HSA- R-HSA- in lipid 1 NA NA TRUE NA FALSE TRUE TRUE 18 TRUE 3.27777778 2 Q8IUA7 ABCA9 NA NA NA NA NA NA NA 1369062 382556 homeostasis P55285,Q12 CDH6,CDH17,CDH24,CDH Adherens junctions R-HSA- R-HSA- R-HSA- Q9ULB4,Q9 3 NA 2 FALSE FALSE FALSE FALSE 31 TRUE 3.03225806 2 864,Q86UP 11L,UNQ2834/PRO3400 NA NA NA NA CDH9,CDH7,CDH7L1 NA interactions 418990 421270 420597 ULB5 0 9 Amino acid P49448,Q16 synthesis and R-HSA- R-HSA- R-HSA- GLUD2,GLUDP1,KYAT1,C NA NA 3 FALSE FALSE FALSE FALSE 34 TRUE 2 2 NA NA NA NA NA NA 773,Q9Y3Q NA interconversion 70614 71291 977347 CBL1,NAALAD2 0 (transamination)

ASB14,MGRN1,KIAA054 PSME3,PSMD2,TRAP2,T P61289,Q13 A6NK59,O6 4,RNF156,PSMA1,HC2,N RIP12,KIAA0045,ULF,HU Antigen 200,Q14669 0291,P2578 U,PROS30,PSC2,UBE2D1 WE1,KIAA0312,KIAA157 processing: ,Q7Z6Z7,Q8 R-HSA- R-HSA- 6,P51668,Q ,SFT,UBC5A,UBCH5,UBC 8,UREB1,HSPC272,UBR1 Ubiquitination & 7 1 9 FALSE NA FALSE FALSE FALSE 309 TRUE 17.4854369 2 PSMA1 Q9UJX4 ANAPC5,APC5 NA IWV7,Q8TB PSMD2 983168 983169 5GLZ8,Q6U H5A,HERC4,KIAA1593,LR ,LNX1,LNX,PDZRN2,UNQ Proteasome B1,Q96PU5, WE0,Q9Y29 SAM1,TAL,UNQ6496/PR 574/PRO1136,NEDD4L,K degradation Q9H765,Q9 7 O21356,BTRC,BTRCP,FB IAA0439,NEDL3,ASB8,PP UH77 W1A,FBXW1A 14212,KLHL3,KIAA1129

BBSome-mediated R-HSA- R-HSA- cargo-targeting to NA NA 1 FALSE NA FALSE FALSE FALSE 23 TRUE 4.08695652 2 NA NA NA NA NA NA P50991 CCT4,CCTD,SRB NA 5620922 5620920 cilium

Cation-coupled R-HSA- R-HSA- Chloride NA NA 1 TRUE NA FALSE TRUE TRUE 7 TRUE 2 2 NA NA NA NA NA NA Q13621 SLC12A1,NKCC2 NA 426117 425393 cotransporters

Cell-extracellular R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE FALSE 16 TRUE 4.375 2 Q14315 FLNC,ABPL,FLN2 NA NA NA NA NA NA NA matrix interactions 446353 446728 446388

Cell-extracellular R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE FALSE 16 TRUE 4.375 2 Q14315 FLNC,ABPL,FLN2 NA NA NA NA NA NA NA matrix interactions 446353 446728 446343

Citric acid cycle R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 22 TRUE 1.90909091 2 P50213 IDH3A NA NA NA NA NA NA NA (TCA cycle) 71403 71406 Class C/3 (Metabotropic R-HSA- R-HSA- GRM7,GPRC1G,MGLUR NA 1 1 FALSE NA FALSE FALSE FALSE 40 TRUE 2.325 2 NA NA NA Q9NYW7 TAS2R1 NA Q14831 NA glutamate/phero 420499 500792 7 mone receptors) Coenzyme A R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 8 TRUE 2 2 NA NA NA NA NA NA Q9NVE7 PANK4 NA biosynthesis 196783 199220 Complex I R-HSA- R-HSA- Q16718,Q9 NDUFA5,NDUFB9,LYRM NA NA 2 TRUE NA FALSE TRUE TRUE 55 TRUE 2.47272727 2 NA NA NA NA NA NA NA biogenesis 6799198 611105 Y6M9 3,UQOR22 Conjugation of R-HSA- R-HSA- GLYAT,ACGNAT,CAT,GA benzoate with NA 1 NA FALSE NA FALSE FALSE FALSE 6 TRUE 2.16666667 2 NA NA NA Q6IB77 NA NA NA NA 177135 159424 T glycine Conjugation of R-HSA- R-HSA- GLYAT,ACGNAT,CAT,GA salicylate with NA 1 NA FALSE NA FALSE FALSE FALSE 8 TRUE 1.75 2 NA NA NA Q6IB77 NA NA NA NA 177128 159424 T glycine Creatine R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 10 TRUE 3.6 2 P50440 GATM,AGAT NA NA NA NA NA NA NA metabolism 71288 351202 R-HSA- R-HSA- HSPA9,GRP75,HSPA9B, Cristae formation NA 1 NA FALSE NA FALSE FALSE FALSE 31 TRUE 2.16129032 2 NA NA NA P38646 NA NA NA NA 8949613 1592230 mt-HSP70 R-HSA- R-HSA- R-HSA- Digestion NA NA 1 FALSE FALSE FALSE TRUE 22 TRUE 2.22727273 2 NA NA NA NA NA NA O00625 PIR NA 8935690 8963743 192456 R-HSA- R-HSA- R-HSA- Digestion NA NA 1 FALSE TRUE TRUE TRUE 22 TRUE 2.22727273 2 NA NA NA NA NA NA O00625 PIR NA 8935690 8963743 189085 Digestion of R-HSA- R-HSA- dietary NA NA 1 TRUE NA FALSE TRUE TRUE 10 TRUE 2.2 2 NA NA NA NA NA NA P14410 SI NA 189085 8935690 carbohydrate Electric Transmission R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 1.8 2 NA NA NA NA NA NA P36383 GJC1,GJA7 NA Across Gap 112303 112307 Junctions Fatty acyl-CoA R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 37 TRUE 2.59459459 2 NA NA NA NA NA NA P49327 FASN,FAS NA biosynthesis 75105 8978868 75876 P19013,P78 O43790,P22 KRT4,CYK4,KRT85,KRTH KRT86,KRTHB6,TGM1,K 386,Q02487 Formation of the R-HSA- R-HSA- 735,Q86Y46 B5,DSC2,CDHF2,DSC3,LI 5 NA 6 TRUE NA FALSE TRUE TRUE 75 TRUE 2.74666667 2 TG,KRT73,K6IRS3,KB36, NA NA NA NA ,Q5W064,Q NA cornified envelope 6809371 6805567 ,Q99456,Q9 PJ,LIPL1,KRT73,K6IRS3,K KRT6IRS3,KRT12,PKP2 86Y46,Q995 9959 B36,KRT6IRS3,PKP4 69 Formation of the R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 8 TRUE 2 2 NA NA NA NA NA NA Q9NQ94 A1CF,ACF,ASP NA Editosome 75094 72200 Fructose R-HSA- R-HSA- P05062,P50 NA NA 2 FALSE NA FALSE FALSE FALSE 5 TRUE 2.4 2 NA NA NA NA NA NA ALDOB,ALDB,KHK NA catabolism 70350 5652084 053 P27815,P35 PDE4A,DPDE2,GRK3,AD G alpha (s) R-HSA- R-HSA- R-HSA- P12272,P23 PTHLH,PTHRP,FSHR,LGR 626,Q08493 RBK2,BARK2,PDE4C,DPD 3 1 5 FALSE FALSE FALSE FALSE 575 TRUE 3.70086957 2 NA Q08462 ADCY2,KIAA1060 NA NA signalling events 418555 388396 381753 945,P34947 1,GRK5,GPRK5 ,Q96RI8,Q9 E1,TAAR6,TA4,TAR4,TR Y233 AR4,PDE10A R-HSA- R-HSA- P07205,P35 PGK2,PGKB,PCK1,PEPCK Gluconeogenesis 2 NA 1 FALSE NA FALSE FALSE FALSE 34 TRUE 2.32352941 2 NA NA NA NA P05062 ALDOB,ALDB NA 70263 70326 558 1 Glycerophospholipi R-HSA- R-HSA- ENPP6,UNQ1889/PRO4 1 NA NA TRUE NA FALSE TRUE TRUE 7 TRUE 2 2 Q6UWR7 NA NA NA NA NA NA NA d catabolism 6814848 1483255 334 Glycogen R-HSA- R-HSA- breakdown NA NA 1 FALSE NA FALSE FALSE FALSE 16 TRUE 6 2 NA NA NA NA NA NA P06737 PYGL NA 70221 8982491 (glycogenolysis) Glyoxylate metabolism and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE FALSE 31 TRUE 2.5483871 2 NA NA NA NA NA NA Q9NR77 PXMP2,PMP22 NA glycine 389661 71291 6783984 degradation

KDM4B,JHDM3B,JMJD2 B,KIAA0876,HIST1H4A,H 4/A,H4FA;,HIST1H4B,H4 /I,H4FI;,HIST1H4C,H4/G, H4FG;,HIST1H4D,H4/B,H 4FB;,HIST1H4E,H4/J,H4F J;,HIST1H4F,H4/C,H4FC;, HIST1H4H,H4/H,H4FH;,H HDMs O94953,P62 R-HSA- R-HSA- IST1H4I,H4/M,H4FM;,HI demethylate 4 NA 1 TRUE NA FALSE TRUE TRUE 27 TRUE 6.7037037 2 805,Q6ZMT NA NA NA NA Q6NYC1 JMJD6,KIAA0585,PTDSR NA 3214842 3247509 ST1H4J,H4/E,H4FE;,HIST histones 4,Q9UGL1 1H4K,H4/D,H4FD;,HIST1 H4L,H4/K,H4FK;,HIST2H4 A,H4/N,H4F2,H4FN,HIST 2H4;,HIST2H4B,H4/O,H4 FO;,HIST4H4,KDM7A,JH DM1D,KDM7,KIAA1718, KDM5B,JARID1B,PLU1,R BBP2H1

R-HSA- R-HSA- Heme degradation NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 2 2 NA NA NA NA NA NA P53004 BLVRA,BLVR,BVR NA 189483 189445 Hyaluronan uptake R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 2.83333333 2 NA NA NA NA NA NA Q12891 HYAL2,LUCA2 NA and degradation 2160916 2142845

Intraflagellar R-HSA- R-HSA- Q86WT1,Q9 TTC30A,IFT140,KIAA059 2 NA NA TRUE NA FALSE TRUE TRUE 41 TRUE 3.65853659 2 NA NA NA NA NA NA NA transport 5620924 5617833 6RY7 0,WDTC2 Metabolism of R-HSA- R-HSA- Angiotensinogen 1 NA 1 FALSE NA FALSE FALSE FALSE 17 TRUE 3.05882353 2 P15088 CPA3 NA NA NA NA P15088 CPA3 NA 2022377 2980736 to Angiotensins Mitochondrial R-HSA- R-HSA- R-HSA- calcium ion NA NA 1 FALSE TRUE TRUE TRUE 23 TRUE 2.60869565 2 NA NA NA NA NA NA P57103 SLC8A3,NCX3 NA 8949215 382551 8949664 transport Mitochondrial R-HSA- R-HSA- HSPA9,GRP75,HSPA9B, NA 1 1 FALSE NA FALSE FALSE FALSE 65 TRUE 1.92307692 2 NA NA NA P38646 NA P62072 TIMM10,TIM10 NA protein import 1268020 9609507 mt-HSP70 mRNA Editing: C R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 8 TRUE 2 2 NA NA NA NA NA NA Q9NQ94 A1CF,ACF,ASP NA to U Conversion 72200 75072 75094

ASB14,PSMA1,HC2,NU,P A6NK59,P25 UBXN7,KIAA0794,UBXD ROS30,PSC2,UBE2D1,SF O94888,P61 786,P51668, 7,PSME3,PSMD2,TRAP2, T,UBC5A,UBCH5,UBCH5 289,Q13200 R-HSA- R-HSA- Q13619,Q5 COPS5,CSN5,JAB1,ASB8, Neddylation 8 1 7 FALSE NA FALSE FALSE FALSE 235 TRUE 21.3276596 2 A,CUL4A,DCAF8,H326,W PSMA1 Q8N5D0 WDTC1,KIAA1037 NA ,Q92905,Q9 PSMD2 8951664 597592 TAQ9,Q96B PP14212,DTL,CDT2,CDW DR42A,ANKRD9,COMM H765,Q9NZJ M1,Q9P000, 1,DCAF2,L2DTL,RAMP,KL D9,HSPC166,BTRC,BTRC 0,Q9UH77 Q9Y297 HL3,KIAA1129 P,FBW1A,FBXW1A

Nicotinamide R-HSA- R-HSA- Q460N5,Q6 PARP14,BAL2,KIAA1268, NA NA 2 FALSE NA FALSE FALSE FALSE 19 TRUE 4 2 NA NA NA NA NA NA NA salvaging 197264 196807 XQN6 NAPRT,FHIP,NAPRT1 Organic anion R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 5 TRUE 2 2 Q9NSA0 SLC22A11,OAT4 NA NA NA NA NA NA NA transport 561048 549132 Passive transport R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 13 TRUE 1.69230769 2 NA NA NA NA NA NA P55087 AQP4 NA by Aquaporins 432047 445717 Phase 4 - resting R-HSA- R-HSA- KCNK17,TALK2,TASK4,U membrane NA NA 1 FALSE NA FALSE FALSE FALSE 19 TRUE 2.63157895 2 NA NA NA NA NA NA Q96T54 NA 5576886 5576891 NQ5816/PRO19634 potential PIWI-interacting R-HSA- R-HSA- O60522,Q9 RNA (piRNA) NA NA 2 FALSE NA FALSE FALSE FALSE 29 TRUE 23.1034483 2 NA NA NA NA NA NA TDRD6,MOV10L1 NA 5601884 211000 BXT6 biogenesis Processing of R-HSA- R-HSA- Q9UQ90,Q9 SPG7,CAR,CMAR,PGN,A NA NA 2 TRUE NA FALSE TRUE TRUE 16 TRUE 2.4375 2 NA NA NA NA NA NA NA SMDT1 8949664 8949215 Y4W6 FG3L2 Protein R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 17 TRUE 8.17647059 2 NA NA NA NA NA NA P55072 VCP NA methylation 8876725 597592 RAB R-HSA- R-HSA- P20336,Q14 geranylgeranylatio NA NA 2 FALSE NA FALSE FALSE FALSE 65 TRUE 3.09230769 2 NA NA NA NA NA NA RAB3A,RAB39A,RAB39 NA 8873719 597592 964 n Regulation of gene expression in endocrine- R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 1.6 2 NA NA NA NA NA NA Q01101 INSM1,IA1 NA committed 210746 186712 (NEUROG3+) progenitor cells NDUFA5,COX18,OXA1L2 Q16718,Q8 Respiratory R-HSA- R-HSA- R-HSA- ,TACO1,CCDC44,PRO047 NA NA 4 FALSE TRUE TRUE TRUE 101 TRUE 2.51485149 2 NA NA NA NA NA NA N8Q8,Q9BS NA electron transport 611105 163200 6799198 7,NDUFB9,LYRM3,UQO H4,Q9Y6M9 R22 Retrograde P11717,Q14 IGF2R,MPRI,COG2,LDLC, transport at the R-HSA- R-HSA- NA NA 4 FALSE NA FALSE FALSE FALSE 49 TRUE 3.14285714 2 NA NA NA NA NA NA 746,Q8N1B VPS52,SACM2L,USP6NL, NA Trans-Golgi- 6811440 6811442 4,Q92738 KIAA0019 Network O75691,P46 UTP20,DRIM,RPS9,TBL3, rRNA modification R-HSA- R-HSA- 781,Q12788 SAZD,NAT10,ALP,KIAA1 in the nucleus and NA NA 5 FALSE NA FALSE FALSE FALSE 62 TRUE 3.61290323 2 NA NA NA NA NA NA NA 6790901 8868773 ,Q9H0A0,Q9 709,NOP58,NOL5,NOP5, cytosol Y2X3 HSPC120 Small interfering R-HSA- R-HSA- DICER1,DICER,HERNA,KI RNA (siRNA) NA NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 9.22222222 2 NA NA NA NA NA NA Q9UPY3 NA 426486 211000 AA0928 biogenesis Smooth Muscle R-HSA- R-HSA- MYLK,MLCK,MLCK1,MYL 1 NA NA FALSE NA FALSE FALSE FALSE 35 TRUE 6.71428571 2 Q15746 MYLK NA NA NA NA NA NA Contraction 445355 397014 K1 CLCN7,TRDN,ANO6,TME P51798,Q13 M16F,NEDD4L,KIAA0439 Stimuli-sensing R-HSA- R-HSA- R-HSA- P51793,P51 CLCN4,CLCN7,WNK3,KIA 061,Q4KMQ 3 NA 5 FALSE TRUE TRUE TRUE 102 TRUE 11.372549 2 NA NA NA NA ,NEDL3,WNK2,KIAA1760 NA channels 2672351 983712 3295583 798,Q9BYP7 A1566,PRKWNK3 2,Q96PU5,Q ,PRKWNK2,SDCCAG43,P 9Y3S1 /OKcl.13 Synthesis of R-HSA- R-HSA- glycosylphosphatid NA NA 1 TRUE NA FALSE TRUE TRUE 18 TRUE 2.16666667 2 NA NA NA NA NA NA Q9H3S5 PIGM NA 162710 163125 ylinositol (GPI) Synthesis of very R-HSA- R-HSA- ACSBG1,BGM,KIAA0631 long-chain fatty NA NA 1 TRUE NA FALSE TRUE TRUE 24 TRUE 2.75 2 NA NA NA NA NA NA Q96GR2 NA 75876 75105 ,LPD acyl-CoAs R-HSA- R-HSA- TBC/RABGAPs 1 NA 1 FALSE NA FALSE FALSE FALSE 45 TRUE 3.06666667 2 P49815 TSC2,TSC4 NA NA NA NA Q8IV04 TBC1D10C NA 8854214 9007101 Terminal pathway R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 8 TRUE 2.875 2 NA NA NA NA NA NA P10643 C7 NA of complement 166665 166658 The fatty acid R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 5 TRUE 2 2 P55916 UCP3,SLC25A9 NA NA NA NA NA NA NA cycling model 167826 166187 The proton R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 5 TRUE 2 2 P55916 UCP3,SLC25A9 NA NA NA NA NA NA NA buffering model 167827 166187 TNFs bind their TNFSF13B,BAFF,BLYS,T R-HSA- R-HSA- physiological 1 NA 1 TRUE NA FALSE TRUE TRUE 29 TRUE 2.5862069 2 Q07011 TNFRSF9,CD137,ILA NA NA NA NA Q9Y275 ALL1,TNFSF20,ZTNF4,U NA 5669034 5668541 receptors NQ401/PRO738 Transport of fatty R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 8 TRUE 2.25 2 Q6P1M0 SLC27A4,ACSVL4,FATP4 NA NA NA NA NA NA NA acids 804914 425397 Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 427652 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 427975 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 427601 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 425986 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 428643 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 425381 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 352230 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 428559 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 425561 acids/oligopeptide s Transport of inorganic cations/anions and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 106 TRUE 3.40566038 2 NA NA NA NA NA NA O00341 SLC1A7,EAAT5 NA amino 425393 425407 426117 acids/oligopeptide s Transport of nucleosides and free purine and R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 7 TRUE 2 2 NA NA NA NA NA NA Q99808 SLC29A1,ENT1 NA pyrimidine bases 83936 425397 across the plasma membrane AGMO,TMEM195,MOG Triglyceride R-HSA- R-HSA- Q6ZNB7,Q8 2 NA NA FALSE NA FALSE FALSE FALSE 14 TRUE 3.14285714 2 AT3,DC7,DGAT2L7,UNQ NA NA NA NA NA NA NA biosynthesis 75109 8979227 6VF5 9383/PRO34208 Triglyceride R-HSA- R-HSA- P22612,P41 PRKACG,PNPLA4,DXS12 2 NA NA FALSE NA FALSE FALSE FALSE 24 TRUE 7.66666667 2 NA NA NA NA NA NA NA catabolism 163560 8979227 247 83E,GS2 tRNA modification R-HSA- R-HSA- in the NA NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 2 2 NA NA NA NA NA NA Q9Y2Z2 MTO1,CGI-02 NA 6787450 72306 mitochondrion TWIK-related alkaline pH R-HSA- R-HSA- KCNK17,TALK2,TASK4,U NA NA 1 FALSE NA FALSE FALSE FALSE 2 TRUE 2 2 NA NA NA NA NA NA Q96T54 NA activated K+ 1299361 1296346 NQ5816/PRO19634 channel (TALK) R-HSA- R-HSA- Urea cycle NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 2.2 2 NA NA NA NA NA NA P31327 CPS1 NA 70635 351202 Vitamin B5 R-HSA- R-HSA- R-HSA- (pantothenate) 1 NA 1 FALSE TRUE TRUE TRUE 17 TRUE 2.52941176 2 Q13822 ENPP2,ATX,PDNP2 NA NA NA NA P49327 FASN,FAS NA 199220 196849 196783 metabolism

Caspase activation via Dependence R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 10 TRUE 4.4 2.5 P43146 DCC,IGDCC1 NA NA NA NA NA NA NA Receptors in the 418889 5357769 absence of ligand

R-HSA- R-HSA- Ethanol oxidation 1 NA 1 TRUE NA FALSE TRUE TRUE 12 TRUE 3.16666667 2.5 P07327 ADH1A,ADH1 NA NA NA NA P08319 ADH4 NA 71384 211945 Interleukin-20 R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 26 TRUE 10.8076923 2.5 P42229 STAT5A,STAT5 NA NA NA NA NA NA NA family signaling 8854691 449147 Intestinal hexose R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 4 TRUE 3 2.5 NA NA NA NA NA NA P11168 SLC2A2,GLUT2 NA absorption 8981373 8963676 SLCO1C1,OATP14,OATP Transport of R-HSA- R-HSA- Q9NYB5,Q9 1C1,OATPF,SLC21A14,SL NA NA 2 FALSE NA FALSE FALSE FALSE 12 TRUE 4.08333333 2.5 NA NA NA NA NA NA NA organic anions 879518 425397 Y6L6 CO1B1,LST1,OATP1B1,O ATP2,OATPC,SLC21A6 Abacavir R-HSA- R-HSA- P07327,P35 ADH1A,ADH1,PCK1,PEPC 2 NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 3 3 NA NA NA NA Q6DHV7 ADAL NA metabolism 2161541 2161522 558 K1 Activation of Ca- R-HSA- R-HSA- permeable Kainate NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 11.1 3 NA NA NA NA NA NA P39086 GRIK1,GLUR5 NA 451308 451306 Receptor Activation of Na- R-HSA- R-HSA- permeable kainate NA NA 1 FALSE NA FALSE FALSE FALSE 2 TRUE 3 3 NA NA NA NA NA NA P39086 GRIK1,GLUR5 NA 451307 451306 receptors Aflatoxin R-HSA- R-HSA- activation and NA 1 NA FALSE NA FALSE FALSE FALSE 20 TRUE 3.5 3 NA NA NA P16444 DPEP1,MDP,RDP NA NA NA NA 5423646 211859 detoxification Amino acid SLC38A4,ATA3,NAT3,SN transport across R-HSA- R-HSA- Q969I6,Q99 NA NA 2 TRUE NA FALSE TRUE TRUE 33 TRUE 3.3030303 3 NA NA NA NA NA NA AT4,SLC38A3,G17,NAT1, NA the plasma 352230 425393 624 SN1,SNAT3 membrane SEMG1,SEMG,BPI,REG3 P04279,P17 G,PAP1B,UNQ429/PRO1 Antimicrobial R-HSA- R-HSA- R-HSA- P17213,Q06 BPI,REG3A,HIP,PAP,PAP 2 NA 4 FALSE FALSE FALSE FALSE 95 TRUE 3.36842105 3 NA NA NA NA 213,Q6UW1 62,BPIFB1,C20orf114,LP NA peptides 6803157 168249 6803544 141 1 5,Q8TDL5 LUNC1,UNQ706/PRO13 57 SEMG1,SEMG,BPI,REG3 P04279,P17 G,PAP1B,UNQ429/PRO1 Antimicrobial R-HSA- R-HSA- R-HSA- P17213,Q06 BPI,REG3A,HIP,PAP,PAP 2 NA 4 FALSE FALSE FALSE FALSE 95 TRUE 3.36842105 3 NA NA NA NA 213,Q6UW1 62,BPIFB1,C20orf114,LP NA peptides 6803157 168249 1461973 141 1 5,Q8TDL5 LUNC1,UNQ706/PRO13 57 SEMG1,SEMG,BPI,REG3 P04279,P17 G,PAP1B,UNQ429/PRO1 Antimicrobial R-HSA- R-HSA- R-HSA- P17213,Q06 BPI,REG3A,HIP,PAP,PAP 2 NA 4 FALSE FALSE FALSE FALSE 95 TRUE 3.36842105 3 NA NA NA NA 213,Q6UW1 62,BPIFB1,C20orf114,LP NA peptides 6803157 168249 6799990 141 1 5,Q8TDL5 LUNC1,UNQ706/PRO13 57 Association of TriC/CCT with P04637,P50 TP53,P53,CCT4,CCTD,SR R-HSA- R-HSA- target proteins 1 1 4 FALSE NA FALSE FALSE FALSE 39 TRUE 6.35897436 3 P04637 TP53,P53 NA P04637 TP53,P53 NA 991,Q92526 B,CCT6B,CCT7,CCTH,NIP NA 390471 390466 during ,Q99832 7-1 biosynthesis Biotin transport R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 11 TRUE 3.72727273 3 NA NA NA NA NA NA O00763 ACACB,ACC2,ACCB NA and metabolism 196780 196849 CDO in R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 29 TRUE 8.31034483 3 Q4KMG0 CDON,CDO NA NA NA NA P15923 TCF3,BHLHB21,E2A,ITF1 NA myogenesis 375170 525793 CNOT3,KIAA0691,LENG2 CNOT1,CDC39,KIAA1007 Deadenylation of R-HSA- R-HSA- O75175,P38 A5YKK6,O95 2 1 2 FALSE NA FALSE FALSE FALSE 25 TRUE 4.72 3 ,NOT3,EIF4A3,DDX48,KI NA Q92600 CNOT9,RCD1,RQCD1 NA ,NOT1,AD- NA mRNA 429947 429914 919 628 AA0111 005,CNOT4,NOT4 ADAMTSL3,KIAA1233,A P82987,Q8 DAMTSL1,ADAMTSR1,C Defective B3GALTL N6G6,Q9C0I R-HSA- R-HSA- P82987,Q8T ADAMTSL3,KIAA1233,A 9orf94,UNQ528/PRO10 causes Peters-plus 2 1 6 FALSE NA FALSE FALSE FALSE 37 TRUE 3.86486486 3 NA Q9P2N4 ADAMTS9,KIAA1312 NA 4,Q9P2N4,Q NA 5083635 3906995 E60 DAMTS18,ADAMTS21 71,THSD7B,KIAA1679,A syndrome (PpS) 9UKP4,Q9U DAMTS9,KIAA1312,ADA KP5 MTS7,ADAMTS6 Dissolution of R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 13 TRUE 3.53846154 3 NA NA NA NA NA NA P07093 SERPINE2,PI7,PN1 NA Fibrin Clot 75205 109582 Q04759,Q1 PRKCQ,PRKCT,TRPC3,TR Effects of PIP2 R-HSA- R-HSA- R-HSA- 1 NA 4 TRUE FALSE TRUE TRUE 27 TRUE 7.11111111 3 Q14643 ITPR1,INSP3R1 NA NA NA NA 3507,Q9Y21 P3,TRPC6,TRP6,DGKB,D PRKCQ hydrolysis 114508 416476 426048 0,Q9Y6T7 AGK2,KIAA0718 Q04759,Q1 PRKCQ,PRKCT,TRPC3,TR Effects of PIP2 R-HSA- R-HSA- R-HSA- 1 NA 4 FALSE FALSE FALSE TRUE 27 TRUE 7.11111111 3 Q14643 ITPR1,INSP3R1 NA NA NA NA 3507,Q9Y21 P3,TRPC6,TRP6,DGKB,D PRKCQ hydrolysis 114508 76002 426048 0,Q9Y6T7 AGK2,KIAA0718 Fanconi Anemia R-HSA- R-HSA- Q0VG06,Q8 FAAP100,C17orf70,ATRI 1 1 2 FALSE NA FALSE FALSE FALSE 38 TRUE 26.4473684 3 Q8IYD8 FANCM,KIAA1596 NA Q13535 ATR,FRP1 NA NA Pathway 6783310 73894 WXE1 P,AGS1 GABA A receptor R-HSA- R-HSA- P14867,P47 1 NA 2 TRUE NA FALSE TRUE TRUE 13 TRUE 3.23076923 3 P47870 GABRB2 NA NA NA NA GABRA1,GABRA2 NA activation 977441 977443 869 Gamma carboxylation, hypusine R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE TRUE 39 TRUE 4.33333333 3 Q9HA64 FN3KRP NA NA NA NA NA NA NA formation and 163841 597592 204626 arylsulfatase activation Gamma carboxylation, hypusine R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE TRUE 39 TRUE 4.33333333 3 Q9HA64 FN3KRP NA NA NA NA NA NA NA formation and 163841 597592 5358493 arylsulfatase activation Gamma carboxylation, hypusine R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE TRUE 39 TRUE 4.33333333 3 Q9HA64 FN3KRP NA NA NA NA NA NA NA formation and 163841 597592 159854 arylsulfatase activation Gamma carboxylation, hypusine R-HSA- R-HSA- R-HSA- 1 NA NA FALSE TRUE TRUE TRUE 39 TRUE 4.33333333 3 Q9HA64 FN3KRP NA NA NA NA NA NA NA formation and 163841 597592 1663150 arylsulfatase activation Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483213 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1482798 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483076 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483171 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483101 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483191 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1482788 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1482883 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483152 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1482801 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1482839 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483115 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483148 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483196 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1482925 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483166 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1483226 Glycerophospholipi R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 129 TRUE 3.88372093 3 NA NA NA NA NA NA O75131 CPNE3,CPN3,KIAA0636 NA d biosynthesis 1483206 1483257 1482922 B4GALNT1,GALGT,SIAT Glycosphingolipid R-HSA- R-HSA- P15848,Q9B ARSB,ESYT1,FAM62A,KI Q00973,Q9 2 NA 2 FALSE NA FALSE FALSE FALSE 46 TRUE 2.67391304 3 NA NA NA NA 2,ARSG,KIAA1001,UNQ8 NA metabolism 1660662 428157 SJ8 AA0747,MBC2 6EG1 39/PRO1777 Highly calcium permeable R-HSA- R-HSA- nicotinic 1 NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 3.55555556 3 P17787 CHRNB2 NA NA NA NA Q05901 CHRNB3 NA 629597 622323 acetylcholine receptors Highly calcium permeable postsynaptic R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 11 TRUE 3.27272727 3 P17787 CHRNB2 NA NA NA NA Q05901 CHRNB3 NA nicotinic 629594 622327 acetylcholine receptors Hormone ligand- R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 13 TRUE 4.76923077 3 P23945 FSHR,LGR1 NA NA NA NA NA NA NA binding receptors 375281 373076 HuR (ELAVL1) R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA binds and NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 11.6 3 NA NA NA NA NA NA P35658 NA 450520 450531 0023 stabilizes mRNA Hydroxycarboxylic R-HSA- R-HSA- HCAR1,GPR104,GPR81, acid-binding NA 1 NA FALSE NA FALSE FALSE FALSE 3 TRUE 3 3 NA NA NA Q9BXC0 NA NA NA NA 3296197 373076 HCA1,FKSG80 receptors Inactivation, METAP2,MNPEP,P67EIF recovery and R-HSA- R-HSA- P50579,Q02 2,GUCY2D,CORD6,GUC1 regulation of the 1 1 3 FALSE NA FALSE FALSE FALSE 33 TRUE 8.6969697 3 Q15835 GRK1,RHOK GRK1 Q15835 GRK1,RHOK GRK1 PRKCQ 2514859 2514856 846,Q04759 A4,GUC2D,RETGC,RETG phototransduction C1,PRKCQ,PRKCT cascade O15020,P16 SPTBN2,KIAA0302,SCA5, O43525,P32 KCNQ3,L1CAM,CAML1, Interaction 157,P35498, ANK1,ANK,SCN1A,NAC1, R-HSA- R-HSA- 004,P35498, MIC5,SCN1A,NAC1,SCN1 Q9NY46,Q9 SCN3A,KIAA1356,NAC3, between L1 and 6 2 7 TRUE NA FALSE TRUE TRUE 29 TRUE 4.68965517 3 NA NA P35499,Q01 SCN1,SCN4A,SCN7A,SC NA 445095 373760 P35499,Q01 ,SCN4A,SCN7A,SCN6A,S Y5Y9 SCN10A Ankyrins 118,Q9UI33 N6A,SCN11A,SCN12A,S 118,Q15858 CN9A,NENA ,Q9UQD0 NS2,SCN8A,MED

P01891,P01 892,P04439, P05534,P10 314,P10316, P13746,P16 188,P16189, Interferon R-HSA- R-HSA- R-HSA- IFIT2,CIG- P16190,P18 alpha/beta 1 NA 1 FALSE FALSE FALSE FALSE 69 TRUE 7.26086957 3 P09913 NA NA NA NA HLA-A,HLAA NA 909733 913531 912694 42,G10P2,IFI54,ISG54 462,P30443, signaling P30447,P30 450,P30453, P30455,P30 456,P30457, P30459,P30 512,Q09160

Ion transport by P- R-HSA- R-HSA- O14983,P16 ATP2A1,ATP2A2,ATP2B, 3 NA 1 FALSE NA FALSE FALSE FALSE 55 TRUE 5.25454545 3 NA NA NA NA P54707 ATP12A,ATP1AL1 NA type ATPases 936837 983712 615,Q8TF62 ATP8B4,KIAA1939

Lectin pathway of R-HSA- R-HSA- R-HSA- COLEC11,UNQ596/PRO1 complement NA NA 1 FALSE FALSE FALSE FALSE 8 TRUE 3 3 NA NA NA NA NA NA Q9BWP8 NA 166662 166786 2855086 182 activation Lysosphingolipid R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 14 TRUE 3 3 NA NA NA NA NA NA Q9H1C0 LPAR5,GPR92,GPR93 NA and LPA receptors 419408 373076 Metal ion SLC R-HSA- R-HSA- R-HSA- HEPH,KIAA0698,UNQ25 NA NA 1 TRUE FALSE TRUE TRUE 26 TRUE 3.19230769 3 NA NA NA NA NA NA Q9BQS7 NA transporters 425410 425366 435354 62/PRO6242

Misspliced LRP5 mutants have R-HSA- R-HSA- enhanced beta- NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 3.83333333 3 NA NA NA NA NA NA Q8NCW0 KREMEN2,KRM2 NA 5339717 4791275 catenin-dependent signaling

MRPL2,CGI- Mitochondrial Q5T653,Q9 R-HSA- R-HSA- 22,MRPL37,RPML2,HSPC MRPL19,KIAA0104,MRP translation 3 NA 1 FALSE NA FALSE FALSE FALSE 91 TRUE 3.12087912 3 BZE1,Q9N NA NA NA NA P49406 NA 5389840 5368287 235,AURKAIP1,AIP,AKIP, L15 elongation WT8 MRPS38 MRPL2,CGI- Mitochondrial Q5T653,Q9 R-HSA- R-HSA- 22,MRPL37,RPML2,HSPC MRPL19,KIAA0104,MRP translation 3 NA 1 FALSE NA FALSE FALSE FALSE 91 TRUE 3.12087912 3 BZE1,Q9N NA NA NA NA P49406 NA 5368286 5368287 235,AURKAIP1,AIP,AKIP, L15 initiation WT8 MRPS38 MRPL2,CGI- Mitochondrial Q5T653,Q9 R-HSA- R-HSA- 22,MRPL37,RPML2,HSPC P49406,Q9 MRPL19,KIAA0104,MRP translation 3 NA 2 FALSE NA FALSE FALSE FALSE 91 TRUE 3.12087912 3 BZE1,Q9N NA NA NA NA NA 5419276 5368287 235,AURKAIP1,AIP,AKIP, UGC7 L15,MTRF1L,MTRF1A termination WT8 MRPS38 SNRNP200,ASCC3L1,HEL O75643,P52 IC2,KIAA0788,RBM5,H37 O75533,P38 SF3B1,SAP155,EIF4A3,D 756,Q05519 ,LUCA15,SRSF11,SFRS1 mRNA Splicing - R-HSA- R-HSA- 919,Q00839 DX48,KIAA0111,HNRNP ,Q10570,Q8 5 1 8 FALSE NA FALSE FALSE FALSE 180 TRUE 7.69444444 3 NA Q9UNP9 PPIE,CYP33 NA 1,CPSF1,CPSF160,CPSF7, NA Major Pathway 72163 72172 ,Q15366,Q8 U,C1orf199,HNRPU,SAF N684,Q994 CDC5L,KIAA0432,PCDC5 6XP3 A,U21.1,PCBP2,DDX42 59,Q9UHX1, RP,PUF60,FIR,ROBPI,SIA Q9UKF6 HBP1,CPSF3,CPSF73 Negative regulation of TCF- R-HSA- R-HSA- dependent NA NA 1 TRUE NA FALSE TRUE TRUE 15 TRUE 4.2 3 NA NA NA NA NA NA Q8NCW0 KREMEN2,KRM2 NA 3772470 201681 signaling by WNT ligand antagonists

O75131,O9 4804,P0100 CPNE3,CPN3,KIAA0636,S 9,P02766,P0 TK10,LOK,SERPINA1,AA 6396,P0673 T,PI,PRO0684,PRO2209, QSOX1,QSCN6,UNQ252 7,P11717,P1 TTR,PALB,GSN,PYGL,IGF O00391,O9 0/PRO6013,AP2A2,ADT 7213,P1792 2R,MPRI,BPI,CR1,C3BR, 4973,P0976 AB,CLAPA2,HIP9,HYPJ,KI 7,P20336,P3 RAB3A,HLA- 9,P15848,P1 AA0899,FGR,SRC2,ARSB 0453,P3045 P41218,Q7L MNDA,CYFIP1,KIAA0068 A,HLAA,CHI3L1,CD97,VC Neutrophil R-HSA- R-HSA- 7213,P5157 ,BPI,P2RX1,P2X1,NBEAL 9,P36222,P4 STK10,PSM 11 4 24 FALSE NA FALSE FALSE FALSE 479 TRUE 7.11273486 3 FGR 576,Q9UNP ,PPIE,CYP33,PA2G4,EBP NA P,PTPRJ,DEP1,PSMD2,TR degranulation 6798695 168249 5,Q6ZNJ1,Q 2,KIAA0540,UNQ253/PR 8960,P5507 D2 9,Q9UQ80 1 AP2,MVP,LRP,ANO6,TM 8TF62,Q926 O290,ATP8B4,KIAA1939, 2,Q12913,Q EM16F,NAPRT,FHIP,NAP 08,Q9P000, DOCK2,KIAA0209,COMM 13200,Q147 RT1,HUWE1,KIAA0312,K Q9Y336 D9,HSPC166,SIGLEC9,U 64,Q4KMQ2 IAA1578,UREB1,HSPC27 NQ668/PRO1302 ,Q6XQN6,Q 2,TBC1D10C,PTPRN2,KIA 7Z6Z7,Q8IV A0387,VAT1,ADGRE3,E 04,Q92932, MR3,UNQ683/PRO1562 Q99536,Q9 BY15

RASGRF2,GRF2,MCF2L, O14827,O1 KIAA0362,OST,PREX1,KI NRAGE signals R-HSA- R-HSA- 5068,Q8TC 1 NA 5 FALSE NA FALSE FALSE FALSE 59 TRUE 7.33898305 3 Q92888 ARHGEF1 NA NA NA NA AA1415,ARHGEF2,KIAA0 NA death through JNK 193648 204998 U6,Q92974, 651,LFP40,AATF,CHE1,D Q9NY61 ED,HSPC277 ADAMTSL3,KIAA1233,A P82987,Q8 O-glycosylation of DAMTSL1,ADAMTSR1,C N6G6,Q9C0I TSR domain- R-HSA- R-HSA- P82987,Q8T ADAMTSL3,KIAA1233,A 9orf94,UNQ528/PRO10 2 1 6 TRUE NA FALSE TRUE TRUE 39 TRUE 3.76923077 3 NA Q9P2N4 ADAMTS9,KIAA1312 NA 4,Q9P2N4,Q NA containing 5173214 5173105 E60 DAMTS18,ADAMTS21 71,THSD7B,KIAA1679,A 9UKP4,Q9U proteins DAMTS9,KIAA1312,ADA KP5 MTS7,ADAMTS6 O-linked R-HSA- R-HSA- R-HSA- Q14118,Q8 DAG1,POMGNT1,MGAT 1 NA 2 FALSE TRUE TRUE TRUE 115 TRUE 3.88695652 3 Q9Y6A1 POMT1 NA NA NA NA NA glycosylation 5173105 597592 913709 WZA1 1.2,UNQ746/PRO1475 O-linked R-HSA- R-HSA- R-HSA- Q14118,Q8 DAG1,POMGNT1,MGAT 1 NA 2 FALSE TRUE TRUE TRUE 115 TRUE 3.88695652 3 Q9Y6A1 POMT1 NA NA NA NA NA glycosylation 5173105 597592 5173214 WZA1 1.2,UNQ746/PRO1475 O-linked R-HSA- R-HSA- R-HSA- B3GNT3,B3GALT8,TME Q49A17,Q6I GALNTL6,GALNT17,WB glycosylation of 1 NA 3 TRUE FALSE TRUE TRUE 66 TRUE 4.25757576 3 Q9Y2A9 NA NA NA NA NA 913709 5173105 977068 M3,UNQ637/PRO1266 S24,Q8IXK2 SCR17,GALNT12 mucins OAS antiviral R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 3.4 3 NA NA NA NA NA NA O95786 DDX58 NA response 8983711 1169410 UBE2D1,SFT,UBC5A,UB Peroxisomal R-HSA- R-HSA- R-HSA- P51668,Q93 USP9X,DFFRX,FAM,USP 2 NA 1 FALSE FALSE FALSE FALSE 63 TRUE 16.6190476 3 CH5,UBCH5A,USP9X,DFF NA NA NA NA Q93008 NA protein import 9033241 9609507 9033500 008 9 RX,FAM,USP9

SCN1A,NAC1,SCN1,SCN SCN1A,NAC1,SCN1,SCN P35498,P35 P35498,P35 4A,FGF12,FGF12B,FHF1 4A,SCN7A,SCN6A,CACN 499,P61328, Phase 0 - rapid R-HSA- R-HSA- 499,Q01118 Q9NY46,Q9 SCN3A,KIAA1356,NAC3, ,SCN7A,SCN6A,CACNA1 5 2 7 FALSE NA FALSE FALSE FALSE 44 TRUE 5.97727273 3 A1C,CACH2,CACN2,CACN NA NA Q01118,Q0 NA depolarisation 5576892 5576891 ,Q13936,Q1 Y5Y9 SCN10A D,CACH3,CACN4,CACNL1 L1A1,CCHL1A1,SCN9A,N 1668,Q9UI3 5858 A2,CCHL1A2,SCN11A,SC ENA 3,Q9UQD0 N12A,SNS2,SCN8A,MED

Phase 2 - plateau R-HSA- R-HSA- CACNA1C,CACH2,CACN2, CACNA1D,CACH3,CACN4 1 NA 1 FALSE NA FALSE FALSE FALSE 27 TRUE 4.25925926 3 Q13936 NA NA NA NA Q01668 NA phase 5576893 5576891 CACNL1A1,CCHL1A1 ,CACNL1A2,CCHL1A2 Pyruvate R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE FALSE 31 TRUE 3.87096774 3 P00338 LDHA,PIG19 NA NA NA NA NA NA NA metabolism 70268 71406 204174 P20336,P31 RAB3A,AKT2,RAB39A,R RAB GEFs P48553,Q9H TRAPPC10,EHOC1,TME R-HSA- R-HSA- 751,Q14964 AB39,DENND1C,FAM31 exchange GTP for 3 1 5 FALSE NA FALSE FALSE FALSE 90 TRUE 4.28888889 3 2M9,Q9Y24 M1,RAB3GAP2,KIAA083 NA O95248 SBF1,MTMR5 NA AKT2 8876198 9007101 ,Q8IV53,Q9 C,ALS2,ALS2CR6,KIAA15 GDP on RABs 3 9,AKT3,PKBG 6Q42 63

Recycling of bile R-HSA- R-HSA- SLCO1B1,LST1,OATP1B1 1 NA 1 FALSE NA FALSE FALSE FALSE 16 TRUE 7.375 3 O95342 ABCB11,BSEP NA NA NA NA Q9Y6L6 NA acids and salts 159418 194068 ,OATP2,OATPC,SLC21A6

Reelin signalling R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 11.4 3 NA NA NA NA NA NA P78509 RELN NA pathway 8866376 422475 Regulation of gene P11168,Q14 SLC2A2,GLUT2,HNF4G, R-HSA- R-HSA- R-HSA- expression in beta 1 NA 4 FALSE TRUE TRUE TRUE 21 TRUE 8.52380952 3 P20823 HNF1A,TCF1 NA NA NA NA 541,Q8HWS NR2A2,RFX6,RFXDC1,FO NA 210745 186712 211163 cells 3,Q9Y261 XA2,HNF3B,TCF3B

RASGRF2,GRF2,MCF2L, KIAA0362,OST,SRGAP3, O14559,O9 ARHGAP33,SNX26,TCGA O14827,O1 ARHGAP14,KIAA0411,KI 4844,P4233 P,RHOBTB1,KIAA0740,A 5068,O4329 R-HSA- R-HSA- SRGAP1,ARHGAP13,KIA AA1156,MEGAP,SRGAP Rho GTPase cycle 6 1 7 FALSE NA FALSE FALSE FALSE 141 TRUE 4.39716312 3 1,Q14CB8,Q RHGAP25,KIAA0053,AR NA Q7Z6B7 NA 5,Q7Z6B7,Q NA 194840 194315 A1304 2,SRGAP1,ARHGAP13,KI 7Z5H3,Q928 HGAP19,ARHGAP22,RH 8IXI2,Q8TC AA1304,RHOT1,ARHT1,P 88 OGAP2,ARHGEF1 U6,Q92974 REX1,KIAA1415,ARHGEF 2,KIAA0651,LFP40 RNA polymerase II R-HSA- R-HSA- Q96AH0,Q9 NABP1,OBFC2A,SSB2,IN transcribes snRNA NA NA 2 FALSE NA FALSE FALSE FALSE 81 TRUE 14.0493827 3 NA NA NA NA NA NA NA 6807505 73857 6HW7 TS4,MSTP093 genes R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB Signaling by BMP 1 NA NA FALSE NA FALSE FALSE FALSE 28 TRUE 5.39285714 3 P51668 NA NA NA NA NA NA NA 201451 9006936 CH5,UBCH5A Synthesis of active UBE2D1,SFT,UBC5A,UB ubiquitin: roles of R-HSA- R-HSA- P51668,Q93 USP9X,DFFRX,FAM,USP 2 NA 1 FALSE NA FALSE FALSE FALSE 30 TRUE 32.0666667 3 CH5,UBCH5A,USP9X,DFF NA NA NA NA Q93008 NA E1 and E2 8866652 8852135 008 9 RX,FAM,USP9 enzymes Synthesis of IP2, R-HSA- R-HSA- IP, and Ins in the NA NA 1 FALSE NA FALSE FALSE FALSE 14 TRUE 3 3 NA NA NA NA NA NA Q96PE3 INPP4A NA 1855183 1483249 cytosol SLC44A4,C6orf29,CTL4,N R-HSA- R-HSA- Q53GD3,Q8 G22,TPPT1,UNQ441/PR P28329,Q8 Synthesis of PC 2 NA 2 TRUE NA FALSE TRUE TRUE 28 TRUE 4.64285714 3 NA NA NA NA CHAT,SLC44A5,CTL5 NA 1483191 1483206 WWI5 O874,SLC44A1,CD92,CD NCS7 W92,CTL1 Synthesis of PIPs R-HSA- R-HSA- at the ER NA 1 NA TRUE NA FALSE TRUE TRUE 5 TRUE 3.8 3 NA NA NA O95248 SBF1,MTMR5 NA NA NA NA 1483248 1483255 membrane Synthesis of UDP- R-HSA- R-HSA- N-acetyl- NA NA 1 FALSE NA FALSE FALSE FALSE 8 TRUE 3.25 3 NA NA NA NA NA NA Q9Y303 AMDHD2,CGI-14 NA 446210 446219 glucosamine The activation of R-HSA- R-HSA- ARSG,KIAA1001,UNQ83 1 NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 3.23076923 3 P15848 ARSB NA NA NA NA Q96EG1 NA arylsulfatases 1663150 163841 9/PRO1777 TNF receptor superfamily TNFSF13B,BAFF,BLYS,T (TNFSF) members R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 17 TRUE 5.64705882 3 NA NA NA NA NA NA Q9Y275 ALL1,TNFSF20,ZTNF4,U NA mediating non- 5676594 5668541 NQ401/PRO738 canonical NF-kB pathway Toxicity of R-HSA- R-HSA- botulinum toxin NA NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 3.88888889 3 NA NA NA NA NA NA Q496J9 SV2C,KIAA1054 NA 5250968 168799 type A (BoNT/A)

TP53 regulates transcription of CNOT1,CDC39,KIAA1007 additional cell R-HSA- R-HSA- O75175,P04 CNOT3,KIAA0691,LENG2 P04637,Q92 TP53,P53,CNOT9,RCD1, A5YKK6,O95 ,NOT1,AD- cycle genes whose 2 2 3 FALSE NA FALSE FALSE FALSE 21 TRUE 5.80952381 3 NA NA NA 6804115 6791312 637 ,NOT3,TP53,P53 600 RQCD1 628,P04637 005,CNOT4,NOT4,TP53, exact role in the P53 p53 pathway remain uncertain

Transport of bile SLC14A2,HUT2,UT2,SLC salts and organic Q15849,Q5 44A4,C6orf29,CTL4,NG2 R-HSA- R-HSA- R-HSA- acids, metal ions 3 NA 1 FALSE FALSE FALSE TRUE 86 TRUE 3.41860465 3 3GD3,Q8W 2,TPPT1,UNQ441/PRO8 NA NA NA NA Q8NCS7 SLC44A5,CTL5 NA 425366 425407 429593 and amine WI5 74,SLC44A1,CD92,CDW9 compounds 2,CTL1 Transport of bile SLC14A2,HUT2,UT2,SLC salts and organic Q15849,Q5 44A4,C6orf29,CTL4,NG2 R-HSA- R-HSA- R-HSA- acids, metal ions 3 NA 1 FALSE FALSE FALSE TRUE 86 TRUE 3.41860465 3 3GD3,Q8W 2,TPPT1,UNQ441/PRO8 NA NA NA NA Q8NCS7 SLC44A5,CTL5 NA 425366 425407 433692 and amine WI5 74,SLC44A1,CD92,CDW9 compounds 2,CTL1 Transport of bile SLC14A2,HUT2,UT2,SLC salts and organic Q15849,Q5 44A4,C6orf29,CTL4,NG2 R-HSA- R-HSA- R-HSA- acids, metal ions 3 NA 1 FALSE FALSE FALSE TRUE 86 TRUE 3.41860465 3 3GD3,Q8W 2,TPPT1,UNQ441/PRO8 NA NA NA NA Q8NCS7 SLC44A5,CTL5 NA 425366 425407 444411 and amine WI5 74,SLC44A1,CD92,CDW9 compounds 2,CTL1 Transport of bile SLC14A2,HUT2,UT2,SLC salts and organic Q15849,Q5 44A4,C6orf29,CTL4,NG2 R-HSA- R-HSA- R-HSA- acids, metal ions 3 NA 1 FALSE FALSE FALSE TRUE 86 TRUE 3.41860465 3 3GD3,Q8W 2,TPPT1,UNQ441/PRO8 NA NA NA NA Q8NCS7 SLC44A5,CTL5 NA 425366 425407 549132 and amine WI5 74,SLC44A1,CD92,CDW9 compounds 2,CTL1 Transport of bile SLC14A2,HUT2,UT2,SLC salts and organic Q15849,Q5 44A4,C6orf29,CTL4,NG2 R-HSA- R-HSA- R-HSA- acids, metal ions 3 NA 1 FALSE FALSE FALSE TRUE 86 TRUE 3.41860465 3 3GD3,Q8W 2,TPPT1,UNQ441/PRO8 NA NA NA NA Q8NCS7 SLC44A5,CTL5 NA 425366 425407 433137 and amine WI5 74,SLC44A1,CD92,CDW9 compounds 2,CTL1 Transport of bile SLC14A2,HUT2,UT2,SLC salts and organic Q15849,Q5 44A4,C6orf29,CTL4,NG2 R-HSA- R-HSA- R-HSA- acids, metal ions 3 NA 1 FALSE TRUE TRUE TRUE 86 TRUE 3.41860465 3 3GD3,Q8W 2,TPPT1,UNQ441/PRO8 NA NA NA NA Q8NCS7 SLC44A5,CTL5 NA 425366 425407 425410 and amine WI5 74,SLC44A1,CD92,CDW9 compounds 2,CTL1 Transport of bile SLC14A2,HUT2,UT2,SLC salts and organic Q15849,Q5 44A4,C6orf29,CTL4,NG2 R-HSA- R-HSA- R-HSA- acids, metal ions 3 NA 1 FALSE TRUE TRUE TRUE 86 TRUE 3.41860465 3 3GD3,Q8W 2,TPPT1,UNQ441/PRO8 NA NA NA NA Q8NCS7 SLC44A5,CTL5 NA 425366 425407 442660 and amine WI5 74,SLC44A1,CD92,CDW9 compounds 2,CTL1 Q13507,Q9 TRPC3,TRP3,TRPV6,ECA R-HSA- R-HSA- O75762,Q9 TRPA1,ANKTM1,TRPC5, H1D0,Q9HC C2,TRPM3,KIAA1616,LT TRP channels 2 NA 5 TRUE NA FALSE TRUE TRUE 25 TRUE 4.28 3 NA NA NA NA NA 3295583 2672351 UL62 TRP5 F6,Q9UBN4 RPC3,TRPC4,TRPC6,TRP ,Q9Y210 6 DNAJB11,EDJ,ERJ3,HDJ9 XBP1(S) activates R-HSA- R-HSA- Q93075,Q9 TATDN2,KIAA0218,SEC6 1 NA 2 FALSE NA FALSE FALSE FALSE 59 TRUE 5.28813559 3 Q9UBS4 ,PSEC0121,UNQ537/PR NA NA NA NA NA chaperone genes 381038 381070 H9S3 1A2 O1080 Zinc influx into R-HSA- R-HSA- SLC39A14,KIAA0062,ZIP cells by the SLC39 NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 3 3 NA NA NA NA NA NA Q15043 NA 442380 435354 14 gene family ATP sensitive R-HSA- R-HSA- Potassium 1 NA NA FALSE NA FALSE FALSE FALSE 4 TRUE 3.5 3.5 O60706 ABCC9,SUR2 NA NA NA NA NA NA NA 1296025 1296065 channels Molecules R-HSA- R-HSA- P53708,Q8 P15502,P35 associated with 2 1 3 TRUE NA FALSE TRUE TRUE 30 TRUE 6.6 3.5 ITGA8,LTBP4 NA P02751 FN1,FN NA ELN,FBN1,FBN,LTBP1 NA 2129379 1566948 N2S1 555,Q14766 elastic fibres Other interleukin R-HSA- R-HSA- PTPRZ1,HTPZP2,PTPRZ,P 1 NA 1 FALSE NA FALSE FALSE FALSE 26 TRUE 7.19230769 3.5 P23471 NA NA NA NA Q15833 STXBP2,UNC18B NA signaling 449836 449147 TPRZ2,PTPZ Reactions specific to the complex N- R-HSA- R-HSA- O43529,P49 CHST10,MAN2A2,MANA NA NA 2 FALSE NA FALSE FALSE FALSE 10 TRUE 5.1 3.5 NA NA NA NA NA NA NA glycan synthesis 975578 975576 641 2X pathway Toxicity of R-HSA- R-HSA- botulinum toxin NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 6.16666667 3.5 NA NA NA NA NA NA Q496J9 SV2C,KIAA1054 NA 5250955 168799 type D (BoNT/D) Toxicity of R-HSA- R-HSA- botulinum toxin NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 6.16666667 3.5 NA NA NA NA NA NA Q496J9 SV2C,KIAA1054 NA 5250981 168799 type F (BoNT/F) Amine ligand- R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 43 TRUE 4.46511628 4 NA NA NA NA NA NA Q96RI8 TAAR6,TA4,TAR4,TRAR4 NA binding receptors 375280 373076 390650 Amine ligand- R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 4.46511628 4 NA NA NA NA NA NA Q96RI8 TAAR6,TA4,TAR4,TRAR4 NA binding receptors 375280 373076 390696 Amine ligand- R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 4.46511628 4 NA NA NA NA NA NA Q96RI8 TAAR6,TA4,TAR4,TRAR4 NA binding receptors 375280 373076 390648 Amine ligand- R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 43 TRUE 4.46511628 4 NA NA NA NA NA NA Q96RI8 TAAR6,TA4,TAR4,TRAR4 NA binding receptors 375280 373076 390651 Amine ligand- R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 4.46511628 4 NA NA NA NA NA NA Q96RI8 TAAR6,TA4,TAR4,TRAR4 NA binding receptors 375280 373076 390666 Asparagine N- R-HSA- R-HSA- R-HSA- P07911,P46 linked NA NA 2 FALSE FALSE FALSE TRUE 286 TRUE 8.28671329 4 NA NA NA NA NA NA UMOD,STT3A,ITM1,TMC NA 446203 597592 948021 977 glycosylation Asparagine N- R-HSA- R-HSA- R-HSA- P07911,P46 linked NA NA 2 FALSE TRUE TRUE TRUE 286 TRUE 8.28671329 4 NA NA NA NA NA NA UMOD,STT3A,ITM1,TMC NA 446203 597592 532668 977 glycosylation Asparagine N- R-HSA- R-HSA- R-HSA- P07911,P46 linked NA NA 2 FALSE FALSE FALSE TRUE 286 TRUE 8.28671329 4 NA NA NA NA NA NA UMOD,STT3A,ITM1,TMC NA 446203 597592 446193 977 glycosylation R-HSA- R-HSA- cGMP effects 1 NA 1 TRUE NA FALSE TRUE TRUE 18 TRUE 6.16666667 4 Q14643 ITPR1,INSP3R1 NA NA NA NA Q9Y233 PDE10A NA 418457 392154 Cholesterol R-HSA- R-HSA- biosynthesis via NA NA 1 FALSE NA FALSE FALSE FALSE 4 TRUE 4 4 NA NA NA NA NA NA O75845 SC5D,SC5DL NA 6807047 191273 desmosterol Cholesterol R-HSA- R-HSA- biosynthesis via NA NA 1 FALSE NA FALSE FALSE FALSE 4 TRUE 4 4 NA NA NA NA NA NA O75845 SC5D,SC5DL NA 6807062 191273 lathosterol Chromatin R-HSA- R-HSA- R-HSA- SMARCA4,BAF190A,BR modifying NA NA 1 FALSE TRUE TRUE TRUE 241 TRUE 9.82572614 4 NA NA NA NA NA NA P51532 NA 3247509 4839726 3214815 G1,SNF2B,SNF2L4 enzymes Chromatin R-HSA- R-HSA- R-HSA- SMARCA4,BAF190A,BR modifying NA NA 1 FALSE TRUE TRUE TRUE 241 TRUE 9.82572614 4 NA NA NA NA NA NA P51532 NA 3247509 4839726 3214842 G1,SNF2B,SNF2L4 enzymes Chromatin R-HSA- R-HSA- R-HSA- SMARCA4,BAF190A,BR modifying NA NA 1 FALSE TRUE TRUE TRUE 241 TRUE 9.82572614 4 NA NA NA NA NA NA P51532 NA 3247509 4839726 3214847 G1,SNF2B,SNF2L4 enzymes Chromatin R-HSA- R-HSA- R-HSA- SMARCA4,BAF190A,BR modifying NA NA 1 FALSE TRUE TRUE TRUE 241 TRUE 9.82572614 4 NA NA NA NA NA NA P51532 NA 3247509 4839726 3214841 G1,SNF2B,SNF2L4 enzymes Chromatin R-HSA- R-HSA- R-HSA- SMARCA4,BAF190A,BR modifying NA NA 1 FALSE TRUE TRUE TRUE 241 TRUE 9.82572614 4 NA NA NA NA NA NA P51532 NA 3247509 4839726 3214858 G1,SNF2B,SNF2L4 enzymes R-HSA- R-HSA- R-HSA- Cilium Assembly 1 NA NA FALSE TRUE TRUE TRUE 187 TRUE 7.26737968 4 Q3ZCM7 TUBB8 NA NA NA NA NA NA NA 5617833 1852241 5620912 R-HSA- R-HSA- R-HSA- Cilium Assembly 1 NA NA FALSE TRUE TRUE TRUE 187 TRUE 7.26737968 4 Q3ZCM7 TUBB8 NA NA NA NA NA NA NA 5617833 1852241 5620924 R-HSA- R-HSA- R-HSA- Cilium Assembly 1 NA NA FALSE FALSE FALSE TRUE 187 TRUE 7.26737968 4 Q3ZCM7 TUBB8 NA NA NA NA NA NA NA 5617833 1852241 5620920 FZD9,FZD3,CD97,ADGRE Class B/2 (Secretin R-HSA- R-HSA- R-HSA- P12272,Q13 PTHLH,PTHRP,PTCH1,PT O00144,P48 2 NA 3 FALSE FALSE FALSE FALSE 94 TRUE 8.74468085 4 NA NA NA NA 3,EMR3,UNQ683/PRO1 NA family receptors) 373080 500792 419812 635 CH 960,Q9BY15 562 FZD9,FZD3,CD97,ADGRE Class B/2 (Secretin R-HSA- R-HSA- R-HSA- P12272,Q13 PTHLH,PTHRP,PTCH1,PT O00144,P48 2 NA 3 FALSE FALSE FALSE FALSE 94 TRUE 8.74468085 4 NA NA NA NA 3,EMR3,UNQ683/PRO1 NA family receptors) 373080 500792 420092 635 CH 960,Q9BY15 562 Cobalamin (Cbl, vitamin B12) R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 21 TRUE 3.23809524 4 NA NA NA NA NA NA P33527 ABCC1,MRP,MRP1 NA transport and 196741 196849 metabolism KIF18B,ARFGAP2,ZNF28 COPI-dependent Q86Y91,Q8 R-HSA- R-HSA- 9,Nbla10535,KIF16B,C20 Golgi-to-ER 1 NA 4 FALSE NA FALSE FALSE FALSE 83 TRUE 4.95180723 4 Q3ZCM7 TUBB8 NA NA NA NA N6H7,Q96L NA 6811434 8856688 orf23,KIAA1590,SNX23,C retrograde traffic 93,Q9Y678 OPG1,COPG CRMPs in Sema3A R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 16 TRUE 7.5 4 NA NA NA NA NA NA P07332 FES,FPS FES signaling 399956 373755 COL4A1,COL4A4,PXDN,K Crosslinking of R-HSA- R-HSA- P02462,P53 3 NA 1 TRUE NA FALSE TRUE TRUE 10 TRUE 4.6 4 IAA0230,MG50,PRG2,VP NA NA NA NA P02462 COL4A1 NA collagen fibrils 2243919 2022090 420,Q92626 O,VPO1 Defective CSF2RA causes pulmonary surfactant R-HSA- R-HSA- SFTPA1,COLEC4,PSAP,SF 1 NA NA FALSE NA FALSE FALSE FALSE 8 TRUE 4.625 4 Q8IWL2 NA NA NA NA NA NA NA metabolism 5688890 5687613 TP1,SFTPA,SFTPA1B dysfunction 4 (SMDP4) Defective CSF2RB causes pulmonary surfactant R-HSA- R-HSA- SFTPA1,COLEC4,PSAP,SF 1 NA NA FALSE NA FALSE FALSE FALSE 8 TRUE 4.625 4 Q8IWL2 NA NA NA NA NA NA NA metabolism 5688849 5687613 TP1,SFTPA,SFTPA1B dysfunction 5 (SMDP5) Displacement of R-HSA- R-HSA- O95243,Q1 DNA glycosylase NA NA 2 FALSE NA FALSE FALSE FALSE 9 TRUE 5.11111111 4 NA NA NA NA NA NA MBD4,MED1,TDG NA 110357 73933 3569 by APEX1 Elastic fibre R-HSA- R-HSA- R-HSA- P15502,P35 NA NA 2 TRUE TRUE TRUE TRUE 41 TRUE 6.31707317 4 NA NA NA NA NA NA ELN,FBN1,FBN NA formation 1566948 1474244 2129379 555 Elevation of Q13507,Q9 R-HSA- R-HSA- P51575,Q14 P2RX1,P2X1,ITPR1,INSP TRPC3,TRP3,P2RX4,TRP cytosolic Ca2+ 2 NA 3 FALSE NA FALSE FALSE FALSE 16 TRUE 7.6875 4 NA NA NA NA 9571,Q9Y21 NA 139853 418360 643 3R1 C6,TRP6 levels 0 R-HSA- R-HSA- EPHB2,DRT,EPHT3,EPTH Ephrin signaling 1 NA NA TRUE NA FALSE TRUE TRUE 19 TRUE 15 4 P29323 EPHB2 NA NA NA NA NA NA 3928664 2682334 3,ERK,HEK5,TYRO5

Factors involved in P04637,P22 TP53,P53,PRKACG,DOCK megakaryocyte R-HSA- R-HSA- R-HSA- P04637,Q13 TP53,P53,ITPK1,DOCK4,K 4 1 3 FALSE TRUE TRUE TRUE 139 TRUE 7.35971223 4 612,Q8IZD9, 3,KIAA0299,MOCA,DOCK NA P04637 TP53,P53 NA NA development and 983231 109582 983189 572,Q8N1I0 IAA0716 Q92608 2,KIAA0209 platelet production

Formation of Senescence- R-HSA- R-HSA- Associated 1 1 1 TRUE NA FALSE TRUE TRUE 17 TRUE 7.88235294 4 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA 2559584 2559586 Heterochromatin Foci (SAHF) A5PLK6,P08 RGSL1,RGSL,RGSL2,CHR Q08462,Q9 ADCY2,KIAA1060,HCAR1 172,P08908, M2,HTR1A,ADRB2RL1,A G alpha (i) R-HSA- R-HSA- R-HSA- NA 3 6 FALSE FALSE FALSE FALSE 395 TRUE 8.14683544 4 NA NA NA BXC0,Q9NY ,GPR104,GPR81,HCA1,F NA Q14831,Q8 DRBRL1,GRM7,GPRC1G, NA signalling events 418594 388396 2187338 W7 KSG80,TAS2R1 NE09,Q9H1 MGLUR7,RGS22,LPAR5, C0 GPR92,GPR93 A5PLK6,P08 RGSL1,RGSL,RGSL2,CHR Q08462,Q9 ADCY2,KIAA1060,HCAR1 172,P08908, M2,HTR1A,ADRB2RL1,A G alpha (i) R-HSA- R-HSA- R-HSA- NA 3 6 FALSE FALSE FALSE FALSE 395 TRUE 8.14683544 4 NA NA NA BXC0,Q9NY ,GPR104,GPR81,HCA1,F NA Q14831,Q8 DRBRL1,GRM7,GPRC1G, NA signalling events 418594 388396 111885 W7 KSG80,TAS2R1 NE09,Q9H1 MGLUR7,RGS22,LPAR5, C0 GPR92,GPR93 RGSL1,RGSL,RGSL2,ADR A5PLK6,P25 P11229,P21 A1D,ADRA1A,ADRA1C,P CHRM1,TACR2,NK2R,NK 100,P35348, G alpha (q) R-HSA- R-HSA- R-HSA- 452,P28336, ROKR2,GPR73L1,PKR2,L 5 NA 6 FALSE TRUE TRUE TRUE 212 TRUE 11.1084906 4 NAR,TAC2R,NMBR,CCKA NA NA NA NA Q8NFJ6,Q9 NA signalling events 416476 388396 114508 P32238,P34 PAR5,GPR92,GPR93,NP R,CCKRA,GRK5,GPRK5 H1C0,Q9Y5X 947 FFR2,GPR74,NPFF2,NP 5 GPR RGSL1,RGSL,RGSL2,ADR A5PLK6,P25 P11229,P21 A1D,ADRA1A,ADRA1C,P CHRM1,TACR2,NK2R,NK 100,P35348, G alpha (q) R-HSA- R-HSA- R-HSA- 452,P28336, ROKR2,GPR73L1,PKR2,L 5 NA 6 FALSE FALSE FALSE TRUE 212 TRUE 11.1084906 4 NAR,TAC2R,NMBR,CCKA NA NA NA NA Q8NFJ6,Q9 NA signalling events 416476 388396 881907 P32238,P34 PAR5,GPR92,GPR93,NP R,CCKRA,GRK5,GPRK5 H1C0,Q9Y5X 947 FFR2,GPR74,NPFF2,NP 5 GPR O14709,O4 ZNF197,ZKSCAN9,ZNF1 A6NP11,P17 3345,P1703 66,ZNF208,ZNF91L,ZNF 017,P52742, ZNF716,ZNF14,GIOT4,K 5,P52736,P5 28,KOX24,ZNF133,ZNF1 Q3ZCX4,Q6 OX6,ZNF135,ZNF61,ZNF 2742,Q3ZCX 50,ZNF135,ZNF61,ZNF7 ZMY9,Q6ZR 78L1,ZNF568,ZNF517,Z 4,Q5JVG2,Q 8L1,ZNF568,ZNF484,ZN Generic 52,Q86WZ6 NF493,ZNF227,ZNF615, 6P3V2,Q6P9 R-HSA- R-HSA- R-HSA- Q8TC21,Q9 F585A,ZNF530,KIAA150 Transcription 15 2 17 FALSE FALSE FALSE TRUE 1169 TRUE 11.774166 4 ,Q8N8J6,Q8 ZNF485,ZFP28,KIAA143 NA ZNF596,ZNF214,BAZ1 NA A1,Q6ZMW NA 212436 73857 8878171 UL59 8,ZNF782,ZNF493,ZNF3 Pathway NCK3,Q8NH 1,ZNF471,ERP1,KIAA139 2,Q6ZR52,Q 4,KOX32,ZNF606,KIAA18 Y6,Q9BX82, 6,ZIM2,ZNF656,ZNF492, 8IZ26,Q8W 52,ZNF328,ZNF570,ZIM Q9NZV7,Q9 KIAA1473,ZNF115,ZNF2 XB4,Q96NI8 3,ZNF657,ZNF287,ZKSC P255,Q9Y2 57,BMZF4,ZNF175 ,Q96PE6,Q9 AN13,ZNF215,BAZ2,ZKS Q1,Q9Y473 HBT7,Q9UL CAN11 58

O14709,O4 ZNF197,ZKSCAN9,ZNF1 A6NP11,P17 3345,P1703 66,ZNF208,ZNF91L,ZNF 017,P52742, ZNF716,ZNF14,GIOT4,K 5,P52736,P5 28,KOX24,ZNF133,ZNF1 Q3ZCX4,Q6 OX6,ZNF135,ZNF61,ZNF 2742,Q3ZCX 50,ZNF135,ZNF61,ZNF7 ZMY9,Q6ZR 78L1,ZNF568,ZNF517,Z 4,Q5JVG2,Q 8L1,ZNF568,ZNF484,ZN Generic 52,Q86WZ6 NF493,ZNF227,ZNF615, 6P3V2,Q6P9 R-HSA- R-HSA- R-HSA- Q8TC21,Q9 F585A,ZNF530,KIAA150 Transcription 15 2 17 FALSE FALSE FALSE TRUE 1169 TRUE 11.774166 4 ,Q8N8J6,Q8 ZNF485,ZFP28,KIAA143 NA ZNF596,ZNF214,BAZ1 NA A1,Q6ZMW NA 212436 73857 2032785 UL59 8,ZNF782,ZNF493,ZNF3 Pathway NCK3,Q8NH 1,ZNF471,ERP1,KIAA139 2,Q6ZR52,Q 4,KOX32,ZNF606,KIAA18 Y6,Q9BX82, 6,ZIM2,ZNF656,ZNF492, 8IZ26,Q8W 52,ZNF328,ZNF570,ZIM Q9NZV7,Q9 KIAA1473,ZNF115,ZNF2 XB4,Q96NI8 3,ZNF657,ZNF287,ZKSC P255,Q9Y2 57,BMZF4,ZNF175 ,Q96PE6,Q9 AN13,ZNF215,BAZ2,ZKS Q1,Q9Y473 HBT7,Q9UL CAN11 58 O14709,O4 ZNF197,ZKSCAN9,ZNF1 A6NP11,P17 3345,P1703 66,ZNF208,ZNF91L,ZNF 017,P52742, ZNF716,ZNF14,GIOT4,K 5,P52736,P5 28,KOX24,ZNF133,ZNF1 Q3ZCX4,Q6 OX6,ZNF135,ZNF61,ZNF 2742,Q3ZCX 50,ZNF135,ZNF61,ZNF7 ZMY9,Q6ZR 78L1,ZNF568,ZNF517,Z 4,Q5JVG2,Q 8L1,ZNF568,ZNF484,ZN Generic 52,Q86WZ6 NF493,ZNF227,ZNF615, 6P3V2,Q6P9 R-HSA- R-HSA- R-HSA- Q8TC21,Q9 F585A,ZNF530,KIAA150 Transcription 15 2 17 FALSE FALSE FALSE TRUE 1169 TRUE 11.774166 4 ,Q8N8J6,Q8 ZNF485,ZFP28,KIAA143 NA ZNF596,ZNF214,BAZ1 NA A1,Q6ZMW NA 212436 73857 8878159 UL59 8,ZNF782,ZNF493,ZNF3 Pathway NCK3,Q8NH 1,ZNF471,ERP1,KIAA139 2,Q6ZR52,Q 4,KOX32,ZNF606,KIAA18 Y6,Q9BX82, 6,ZIM2,ZNF656,ZNF492, 8IZ26,Q8W 52,ZNF328,ZNF570,ZIM Q9NZV7,Q9 KIAA1473,ZNF115,ZNF2 XB4,Q96NI8 3,ZNF657,ZNF287,ZKSC P255,Q9Y2 57,BMZF4,ZNF175 ,Q96PE6,Q9 AN13,ZNF215,BAZ2,ZKS Q1,Q9Y473 HBT7,Q9UL CAN11 58

O14709,O4 ZNF197,ZKSCAN9,ZNF1 A6NP11,P17 3345,P1703 66,ZNF208,ZNF91L,ZNF 017,P52742, ZNF716,ZNF14,GIOT4,K 5,P52736,P5 28,KOX24,ZNF133,ZNF1 Q3ZCX4,Q6 OX6,ZNF135,ZNF61,ZNF 2742,Q3ZCX 50,ZNF135,ZNF61,ZNF7 ZMY9,Q6ZR 78L1,ZNF568,ZNF517,Z 4,Q5JVG2,Q 8L1,ZNF568,ZNF484,ZN Generic 52,Q86WZ6 NF493,ZNF227,ZNF615, 6P3V2,Q6P9 R-HSA- R-HSA- R-HSA- Q8TC21,Q9 F585A,ZNF530,KIAA150 Transcription 15 2 17 FALSE FALSE FALSE TRUE 1169 TRUE 11.774166 4 ,Q8N8J6,Q8 ZNF485,ZFP28,KIAA143 NA ZNF596,ZNF214,BAZ1 NA A1,Q6ZMW NA 212436 73857 8878166 UL59 8,ZNF782,ZNF493,ZNF3 Pathway NCK3,Q8NH 1,ZNF471,ERP1,KIAA139 2,Q6ZR52,Q 4,KOX32,ZNF606,KIAA18 Y6,Q9BX82, 6,ZIM2,ZNF656,ZNF492, 8IZ26,Q8W 52,ZNF328,ZNF570,ZIM Q9NZV7,Q9 KIAA1473,ZNF115,ZNF2 XB4,Q96NI8 3,ZNF657,ZNF287,ZKSC P255,Q9Y2 57,BMZF4,ZNF175 ,Q96PE6,Q9 AN13,ZNF215,BAZ2,ZKS Q1,Q9Y473 HBT7,Q9UL CAN11 58 O14709,O4 ZNF197,ZKSCAN9,ZNF1 A6NP11,P17 3345,P1703 66,ZNF208,ZNF91L,ZNF 017,P52742, ZNF716,ZNF14,GIOT4,K 5,P52736,P5 28,KOX24,ZNF133,ZNF1 Q3ZCX4,Q6 OX6,ZNF135,ZNF61,ZNF 2742,Q3ZCX 50,ZNF135,ZNF61,ZNF7 ZMY9,Q6ZR 78L1,ZNF568,ZNF517,Z 4,Q5JVG2,Q 8L1,ZNF568,ZNF484,ZN Generic 52,Q86WZ6 NF493,ZNF227,ZNF615, 6P3V2,Q6P9 R-HSA- R-HSA- R-HSA- Q8TC21,Q9 F585A,ZNF530,KIAA150 Transcription 15 2 17 FALSE FALSE FALSE TRUE 1169 TRUE 11.774166 4 ,Q8N8J6,Q8 ZNF485,ZFP28,KIAA143 NA ZNF596,ZNF214,BAZ1 NA A1,Q6ZMW NA 212436 73857 3700989 UL59 8,ZNF782,ZNF493,ZNF3 Pathway NCK3,Q8NH 1,ZNF471,ERP1,KIAA139 2,Q6ZR52,Q 4,KOX32,ZNF606,KIAA18 Y6,Q9BX82, 6,ZIM2,ZNF656,ZNF492, 8IZ26,Q8W 52,ZNF328,ZNF570,ZIM Q9NZV7,Q9 KIAA1473,ZNF115,ZNF2 XB4,Q96NI8 3,ZNF657,ZNF287,ZKSC P255,Q9Y2 57,BMZF4,ZNF175 ,Q96PE6,Q9 AN13,ZNF215,BAZ2,ZKS Q1,Q9Y473 HBT7,Q9UL CAN11 58

Golgi Associated R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 56 TRUE 5.83928571 4 NA NA NA NA NA NA P11717 IGF2R,MPRI NA Vesicle Biogenesis 432722 421837

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H 4/H,H4FH;,HIST1H4I,H4/ HATs acetylate R-HSA- R-HSA- P62805,Q9H O75528,Q9 TADA3,ADA3,TADA3L,M 2 NA 2 TRUE NA FALSE TRUE TRUE 108 TRUE 12.6851852 4 M,H4FM;,HIST1H4J,H4/E NA NA NA NA NA histones 3214847 3247509 7Z6 6EZ8 CRS1,INO80Q,MSP58 ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, KAT8,MOF,MYST1,PP70 73 Highly sodium permeable R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 7 TRUE 3.28571429 4 P17787 CHRNB2 NA NA NA NA NA NA NA acetylcholine 629587 622327 nicotinic receptors Highly sodium permeable R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 7 TRUE 3.28571429 4 P17787 CHRNB2 NA NA NA NA NA NA NA acetylcholine 629587 622323 nicotinic receptors

P01891,P01 892,P04439, P05534,P10 314,P10316, P13746,P16 188,P16189, P16190,P18 HLA- Interferon gamma R-HSA- R-HSA- R-HSA- 462,P19320, 1 NA 3 FALSE FALSE FALSE FALSE 93 TRUE 7.08602151 4 Q9UDY6 TRIM10,RFB30,RNF9 NA NA NA NA A,HLAA,VCAM1,TRIM2,K NA signaling 877300 913531 877312 P30443,P30 IAA0517,RNF86 447,P30450, P30453,P30 455,P30456, P30457,P30 459,P30512, Q09160,Q9 C040

P49641,Q13 MAN2A2,MANA2X,CUX1 R-HSA- R-HSA- Intra-Golgi traffic 1 1 4 FALSE NA FALSE FALSE FALSE 44 TRUE 4.06818182 4 Q13948 CUX1,CUTL1 NA O60476 MAN1A2,MAN1B NA 948,Q14746 ,CUTL1,COG2,LDLC,RAB NA 6811438 6811442 ,Q14964 39A,RAB39 Intrinsic Pathway R-HSA- R-HSA- P00451,P07 F8,F8C,SERPINE2,PI7,PN of Fibrin Clot NA NA 2 FALSE NA FALSE FALSE FALSE 22 TRUE 5.45454545 4 NA NA NA NA NA NA NA 140837 140877 093 1 Formation R-HSA- R-HSA- Q86Y91,Q9 KIF18B,KIF16B,C20orf23 Kinesins 1 NA 2 TRUE NA FALSE TRUE TRUE 44 TRUE 4.81818182 4 Q3ZCM7 TUBB8 NA NA NA NA NA 983189 983231 6L93 ,KIAA1590,SNX23 SOAT2,ACACT2,ACAT2,A R-HSA- R-HSA- O75908,O9 LDL clearance 2 NA NA FALSE NA FALSE FALSE FALSE 19 TRUE 9.47368421 4 P2A2,ADTAB,CLAPA2,HI NA NA NA NA NA NA NA 8964038 8964043 4973 P9,HYPJ,KIAA0899 Linoleic acid (LA) R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 8 TRUE 4.5 4 NA NA NA NA NA NA O95864 FADS2 NA metabolism 2046105 2046104 MTOR,FRAP,FRAP1,FRA R-HSA- R-HSA- P42345,Q8 Macroautophagy 1 NA 2 FALSE NA FALSE FALSE FALSE 68 TRUE 5.52941176 4 P49815 TSC2,TSC4 NA NA NA NA P2,RAFT1,RAPT1,ATG4A NA 1632852 8953897 WYN0 ,APG4A,AUTL2 mRNA Splicing - R-HSA- R-HSA- O75533,Q8 SNRNP200,ASCC3L1,HEL 2 NA 1 FALSE NA FALSE FALSE FALSE 55 TRUE 16.4727273 4 SF3B1,SAP155,DDX42 NA NA NA NA O75643 NA Minor Pathway 72165 72172 6XP3 IC2,KIAA0788 Muscarinic R-HSA- R-HSA- acetylcholine 1 NA 1 TRUE NA FALSE TRUE TRUE 5 TRUE 5 4 P11229 CHRM1 NA NA NA NA P08172 CHRM2 NA 390648 375280 receptors Na+/Cl- dependent SLC6A2,NAT1,NET1,SLC R-HSA- R-HSA- P23975,P54 neurotransmitter NA NA 2 TRUE NA FALSE TRUE TRUE 19 TRUE 4.52631579 4 NA NA NA NA NA NA 6A5,SLC18A1,VAT1,VMA NA 442660 425366 219 transporters T1

Neurofascin R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 7 TRUE 4.14285714 4 NA NA NA NA NA NA P16157 ANK1,ANK NA interactions 447043 373760 Nitric oxide R-HSA- R-HSA- R-HSA- stimulates NA NA 1 TRUE TRUE TRUE TRUE 25 TRUE 5.48 4 NA NA NA NA NA NA P29475 NOS1 NA 392154 418346 418457 guanylate cyclase Nuclear Receptor R-HSA- R-HSA- transcription NA NA 1 TRUE NA FALSE TRUE TRUE 51 TRUE 5.29411765 4 NA NA NA NA NA NA Q14541 HNF4G,NR2A2 NA 383280 212436 pathway Orexin and neuropeptides FF R-HSA- R-HSA- NPFFR2,GPR74,NPFF2, and QRFP bind to NA NA 1 TRUE NA FALSE TRUE TRUE 8 TRUE 4 4 NA NA NA NA NA NA Q9Y5X5 NA 389397 375276 NPGPR their respective receptors Peptide ligand- R-HSA- R-HSA- R-HSA- P28336,P32 2 NA 1 FALSE FALSE FALSE TRUE 189 TRUE 4.55026455 4 NMBR,CCKAR,CCKRA NA NA NA NA Q8NFJ6 PROKR2,GPR73L1,PKR2 NA binding receptors 375276 373076 444473 238 Peptide ligand- R-HSA- R-HSA- R-HSA- P28336,P32 2 NA 1 FALSE TRUE TRUE TRUE 189 TRUE 4.55026455 4 NMBR,CCKAR,CCKRA NA NA NA NA Q8NFJ6 PROKR2,GPR73L1,PKR2 NA binding receptors 375276 373076 389397 238 Peptide ligand- R-HSA- R-HSA- R-HSA- P28336,P32 2 NA 1 FALSE FALSE FALSE TRUE 189 TRUE 4.55026455 4 NMBR,CCKAR,CCKRA NA NA NA NA Q8NFJ6 PROKR2,GPR73L1,PKR2 NA binding receptors 375276 373076 388479 238 Peptide ligand- R-HSA- R-HSA- R-HSA- P28336,P32 2 NA 1 FALSE FALSE FALSE TRUE 189 TRUE 4.55026455 4 NMBR,CCKAR,CCKRA NA NA NA NA Q8NFJ6 PROKR2,GPR73L1,PKR2 NA binding receptors 375276 373076 444821 238 Peptide ligand- R-HSA- R-HSA- R-HSA- P28336,P32 2 NA 1 FALSE FALSE FALSE TRUE 189 TRUE 4.55026455 4 NMBR,CCKAR,CCKRA NA NA NA NA Q8NFJ6 PROKR2,GPR73L1,PKR2 NA binding receptors 375276 373076 380108 238 Peptide ligand- R-HSA- R-HSA- R-HSA- P28336,P32 2 NA 1 FALSE TRUE TRUE TRUE 189 TRUE 4.55026455 4 NMBR,CCKAR,CCKRA NA NA NA NA Q8NFJ6 PROKR2,GPR73L1,PKR2 NA binding receptors 375276 373076 380095 238 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 8847453 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE TRUE TRUE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 6814848 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660508 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660524 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660517 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE TRUE TRUE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660516 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660502 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE TRUE TRUE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660499 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1483196 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE TRUE TRUE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1483248 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE TRUE TRUE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660514 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660510 R-HSA- R-HSA- R-HSA- PI Metabolism 1 NA NA FALSE FALSE FALSE TRUE 84 TRUE 6.69047619 4 Q5GJ75 TNFAIP8L3,TIPE3 NA NA NA NA NA NA NA 1483255 1483257 1660537 HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H 4/H,H4FH;,HIST1H4I,H4/ M,H4FM;,HIST1H4J,H4/E P62805,Q03 PKMTs methylate R-HSA- R-HSA- ,H4FE;,HIST1H4K,H4/D,H SETDB2,C13orf4,CLLD8,K 4 NA 1 TRUE NA FALSE TRUE TRUE 47 TRUE 9.04255319 4 112,Q9BYW NA NA NA NA Q96T68 NA histone lysines 3214841 3247509 4FD;,HIST1H4L,H4/K,H4F MT1F 2,Q9UPS6 K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, MECOM,EVI1,MDS1,SET D2,HIF1,HYPB,KIAA1732, KMT3A,SET2,HSPC069,S ETD1B,KIAA1076,KMT2 G,SET1B

P01009,P11 SERPINA1,AAT,PI,PRO06 Post-translational R-HSA- R-HSA- QSOX1,QSCN6,UNQ252 047,P35555, 84,PRO2209,LAMC1,LA protein 1 1 5 FALSE NA FALSE FALSE FALSE 107 TRUE 6.28971963 4 O00391 NA P02751 FN1,FN NA NA 8957275 597592 0/PRO6013 Q14766,Q9 MB2,FBN1,FBN,LTBP1,E phosphorylation NRM1 NAM POU5F1 (OCT4), SOX2, NANOG R-HSA- R-HSA- activate genes 1 NA NA TRUE NA FALSE TRUE TRUE 13 TRUE 9.23076923 4 Q9NSC2 SALL1,SAL1,ZNF794 NA NA NA NA NA NA NA 2892247 452723 related to proliferation Processing of Capped Intron- R-HSA- R-HSA- R-HSA- Q00839,Q1 HNRNPU,C1orf199,HNR 2 NA NA FALSE FALSE FALSE TRUE 243 TRUE 9.81069959 4 NA NA NA NA NA NA NA Containing Pre- 72203 8953854 72172 5366 PU,SAFA,U21.1,PCBP2 mRNA Processing of Capped Intron- R-HSA- R-HSA- R-HSA- Q00839,Q1 HNRNPU,C1orf199,HNR 2 NA NA FALSE FALSE FALSE TRUE 243 TRUE 9.81069959 4 NA NA NA NA NA NA NA Containing Pre- 72203 8953854 72202 5366 PU,SAFA,U21.1,PCBP2 mRNA Processing of Capped Intron- R-HSA- R-HSA- R-HSA- Q00839,Q1 HNRNPU,C1orf199,HNR 2 NA NA FALSE TRUE TRUE TRUE 243 TRUE 9.81069959 4 NA NA NA NA NA NA NA Containing Pre- 72203 8953854 72187 5366 PU,SAFA,U21.1,PCBP2 mRNA RA biosynthesis R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 22 TRUE 3.86363636 4 P07327 ADH1A,ADH1 NA NA NA NA P08319 ADH4 NA pathway 5365859 5362517

Recognition and association of DNA glycosylase with R-HSA- R-HSA- O95243,Q1 NA NA 2 FALSE NA FALSE FALSE FALSE 8 TRUE 4.625 4 NA NA NA NA NA NA MBD4,MED1,TDG NA site containing an 110328 73928 3569 affected pyrimidine

Regulation of Insulin-like Growth Factor (IGF) P01009,P11 SERPINA1,AAT,PI,PRO06 transport and R-HSA- R-HSA- O00391,P20 QSOX1,QSCN6,UNQ252 047,P35555, 84,PRO2209,LAMC1,LA 2 1 5 FALSE NA FALSE FALSE FALSE 124 TRUE 6.07258065 4 NA P02751 FN1,FN NA NA uptake by Insulin- 381426 392499 151 0/PRO6013,KLK2 Q14766,Q9 MB2,FBN1,FBN,LTBP1,E like Growth Factor NRM1 NAM Binding Proteins (IGFBPs)

RNA Polymerase III Abortive And R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 41 TRUE 11.8536585 4 Q9UKN8 GTF3C4 NA NA NA NA NA NA NA Retractive 749476 74158 Initiation

SEMA3A-Plexin repulsion signaling R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 14 TRUE 11.3571429 4 NA NA NA NA NA NA P07332 FES,FPS FES by inhibiting 399955 373755 Integrin adhesion

Sema4D mediated inhibition of cell R-HSA- R-HSA- PLXNB1,KIAA0407,PLXN NA NA 1 FALSE NA FALSE FALSE FALSE 8 TRUE 14.625 4 NA NA NA NA NA NA O43157 NA attachment and 416550 400685 5,SEP migration

Serotonin R-HSA- R-HSA- HTR1A,ADRB2RL1,ADRB NA NA 1 TRUE NA FALSE TRUE TRUE 12 TRUE 4 4 NA NA NA NA NA NA P08908 NA receptors 390666 375280 RL1

Signaling by R-HSA- R-HSA- FGFR1,BFGFR,CEK,FGF plasma membrane NA NA 1 FALSE NA FALSE FALSE FALSE 3 TRUE 11.6666667 4 NA NA NA NA NA NA P11362 FGFR1 8853336 1839124 BR,FLG,FLT2,HBGFR FGFR1 fusions

Sodium/Calcium R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 11 TRUE 8.72727273 4 NA NA NA NA NA NA P57103 SLC8A3,NCX3 NA exchangers 425561 425393 Surfactant R-HSA- R-HSA- SFTPA1,COLEC4,PSAP,SF ADGRF5,GPR116,KIAA0 1 1 NA FALSE NA FALSE FALSE FALSE 30 TRUE 3.73333333 4 Q8IWL2 NA Q8IZF2 NA NA NA NA metabolism 5683826 392499 TP1,SFTPA,SFTPA1B 758 Synthesis of IP3 R-HSA- R-HSA- and IP4 in the 1 NA 1 FALSE NA FALSE FALSE FALSE 26 TRUE 8.57692308 4 Q4KWH8 PLCH1,KIAA1069,PLCL3 NA NA NA NA Q13572 ITPK1 NA 1855204 1483249 cytosol R-HSA- R-HSA- AGPAT4,UNQ499/PRO1 Synthesis of PA 1 NA NA TRUE NA FALSE TRUE TRUE 39 TRUE 4.76923077 4 Q9NRZ5 NA NA NA NA NA NA NA 1483166 1483206 016 Synthesis of PIPs at the early R-HSA- R-HSA- Q96PE3,Q9 NA NA 2 TRUE NA FALSE TRUE TRUE 16 TRUE 5.1875 4 NA NA NA NA NA NA INPP4A,PI4K2A NA endosome 1660516 1483255 BTU6 membrane Synthesis of PIPs R-HSA- R-HSA- at the Golgi NA NA 1 TRUE NA FALSE TRUE TRUE 18 TRUE 5.77777778 4 NA NA NA NA NA NA Q9BTU6 PI4K2A NA 1660514 1483255 membrane Synthesis of PIPs Q96PE3,Q9 R-HSA- R-HSA- INPP4A,RUFY1,RABIP4,Z at the plasma NA NA 3 TRUE NA FALSE TRUE TRUE 53 TRUE 8.66037736 4 NA NA NA NA NA NA 6T51,Q9BT NA 1660499 1483255 FYVE12,PI4K2A membrane U6 Tachykinin R-HSA- R-HSA- TACR2,NK2R,NKNAR,TA receptors bind 1 NA NA TRUE NA FALSE TRUE TRUE 5 TRUE 4.4 4 P21452 NA NA NA NA NA NA NA 380095 375276 C2R tachykinins The canonical retinoid cycle in R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE FALSE FALSE FALSE 23 TRUE 3.73913043 4 P10745 RBP3 NA NA NA NA P02766 TTR,PALB NA rods (twilight 2453902 2187338 2466712 vision) TP53 Regulates Transcription of R-HSA- R-HSA- O60238,P04 BNIP3L,BNIP3A,BNIP3H, Genes Involved in 3 1 1 FALSE NA FALSE FALSE FALSE 20 TRUE 8.95 4 NA P04637 TP53,P53 NA P04637 TP53,P53 NA 6803204 5633008 637,Q13315 NIX,TP53,P53,ATM Cytochrome C Release TP53 regulates transcription of several additional cell death genes R-HSA- R-HSA- whose specific 1 1 1 FALSE NA FALSE FALSE FALSE 14 TRUE 7.28571429 4 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA 6803205 5633008 roles in p53- dependent apoptosis remain uncertain Transcriptional activation of R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 56 TRUE 9.625 4 NA NA NA NA NA NA P49448 GLUD2,GLUDP1 NA mitochondrial 2151201 1592230 biogenesis Transcriptional regulation of R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 45 TRUE 18.0222222 4 NA NA NA NA NA NA Q96SZ4 ZSCAN10,ZNF206 NA pluripotent stem 452723 1266738 2892245 cells Transcriptional regulation of R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 45 TRUE 18.0222222 4 NA NA NA NA NA NA Q96SZ4 ZSCAN10,ZNF206 NA pluripotent stem 452723 1266738 2892247 cells Transcriptional regulation of R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 84 TRUE 8.44047619 4 P35558 PCK1,PEPCK1 NA NA NA NA P14672 SLC2A4,GLUT4 NA white adipocyte 381340 1266738 differentiation Transport of R-HSA- R-HSA- SLC35B4,YEA4,PSEC005 NA NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 3.55555556 4 NA NA NA NA NA NA Q969S0 NA nucleotide sugars 727802 425397 5 Zinc efflux and compartmentaliza R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 7 TRUE 3.57142857 4 NA NA NA NA NA NA Q99726 SLC30A3,ZNT3 NA tion by the SLC30 435368 435354 family ChREBP activates R-HSA- R-HSA- O00763,P49 ACACB,ACC2,ACCB,FASN metabolic gene NA NA 2 FALSE NA FALSE FALSE FALSE 8 TRUE 4.625 4.5 NA NA NA NA NA NA NA 163765 163685 327 ,FAS expression Common Pathway R-HSA- R-HSA- P00451,P07 F8,F8C,SERPINE2,PI7,PN of Fibrin Clot 1 NA 3 FALSE NA FALSE FALSE FALSE 22 TRUE 7.18181818 4.5 P00488 F13A1,F13A NA NA NA NA NA 140875 140877 093,P07225 1,PROS1,PROS Formation Formation of tubulin folding R-HSA- R-HSA- P50991,Q92 CCT4,CCTD,SRB,CCT6B,C NA NA 3 FALSE NA FALSE FALSE FALSE 26 TRUE 6.11538462 4.5 NA NA NA NA NA NA NA intermediates by 389960 389958 526,Q99832 CT7,CCTH,NIP7-1 CCT/TriC

Import of O00763,O4 ACACB,ACC2,ACCB,SLC2 palmitoyl-CoA into R-HSA- R-HSA- NA NA 3 FALSE NA FALSE FALSE FALSE 12 TRUE 6.66666667 4.5 NA NA NA NA NA NA 3772,P2378 5A20,CAC,CACT,CPT2,CP NA the mitochondrial 200425 8978868 6 T1 matrix

O14983,O6 ATP2A1,ABCC9,SUR2,AT R-HSA- R-HSA- P29475,P57 NOS1,SLC8A3,NCX3,TRD Ion homeostasis 4 NA 3 FALSE NA FALSE FALSE FALSE 52 TRUE 8.15384615 4.5 0706,P1661 P2A2,ATP2B,ITPR1,INSP NA NA NA NA NA 5578775 5576891 103,Q13061 N 5,Q14643 3R1 Josephin domain R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 69.25 4.5 NA NA NA NA NA NA P55072 VCP NA DUBs 5689877 5688426 Prefoldin mediated transfer R-HSA- R-HSA- P50991,Q92 CCT4,CCTD,SRB,CCT6B,C NA NA 3 FALSE NA FALSE FALSE FALSE 28 TRUE 5.92857143 4.5 NA NA NA NA NA NA NA of substrate to 389957 389958 526,Q99832 CT7,CCTH,NIP7-1 CCT/TriC Activation of MMP15,MMP16,C8orf57 Matrix R-HSA- R-HSA- P51511,P51 1 NA 3 TRUE NA FALSE TRUE TRUE 33 TRUE 6.24242424 5 P20151 KLK2 NA NA NA NA ,MMPX2,MMP24,MT5M NA Metalloproteinase 1592389 1474228 512,Q9Y5R2 MP s R-HSA- R-HSA- P25100,P35 ADRA1D,ADRA1A,ADRA Adrenoceptors NA NA 2 TRUE NA FALSE TRUE TRUE 9 TRUE 6.55555556 5 NA NA NA NA NA NA NA 390696 375280 348 1C Basigin R-HSA- R-HSA- 1 NA NA TRUE NA FALSE TRUE TRUE 25 TRUE 6.32 5 P32004 L1CAM,CAML1,MIC5 NA NA NA NA NA NA NA interactions 210991 202733 A6NMZ7,A8 TX70,P0245 COL6A6,COL6A5,COL29A A8TX70,O00 COL6A5,COL29A1,VWA4 8,P02462,P1 1,VWA4,COL2A1,COL4A 469,P02462, Collagen ,PLOD2,COL4A1,COL11A 2107,P2084 1,COL11A1,COLL6,COL9 P12107,P20 biosynthesis and R-HSA- R-HSA- R-HSA- 1,COLL6,COL9A1,COL4A P13674,Q14 9,P20908,P2 A1,COL5A1,COL8A1,C3or 9 2 14 FALSE TRUE TRUE TRUE 67 TRUE 5.2238806 5 849,P53420, NA P4HA1,P4HA,COL19A1 NA NA modifying 1650814 1474290 8948216 4,COL14A1,UND,P3H3,L 993 7658,Q1499 f7,COL19A1,COL24A1,C Q05707,Q8I enzymes EPREL2,COL17A1,BP180, 3,Q17RW2, OL28A1,COL28,COL13A1 VL6,Q9UMD BPAG2 Q2UY09,Q5 ,COL22A1,PCOLCE2,PCPE 9 TAT6,Q8NF 2,UNQ250/PRO287 W1,Q9UKZ9

Competing endogenous RNAs R-HSA- R-HSA- 1 NA 1 TRUE NA FALSE TRUE TRUE 19 TRUE 9.84210526 5 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA (ceRNAs) regulate 8948700 8943723 PTEN translation O14815,P11 047,P14543, CAPN9,NCL4,LAMC1,LA Degradation of the Q13751,Q8 LAMB3,LAMNB1,ADAM P15502,P35 MB2,NID1,NID,ELN,FBN R-HSA- R-HSA- R-HSA- P02751,Q9P FN1,FN,ADAMTS9,KIAA extracellular 3 2 9 TRUE TRUE TRUE TRUE 111 TRUE 6.18018018 5 TE60,Q9274 TS18,ADAMTS21,HTRA1 NA NA 555,P49862, 1,FBN,KLK7,PRSS6,SCCE, NA 1474228 1474244 1442490 2N4 1312 matrix 3 ,HTRA,PRSS11 P51511,Q9P MMP15,ADAMTS9,KIAA 2N4,Q9UM 1312,CAPN11 Q6 O14815,P11 047,P14543, CAPN9,NCL4,LAMC1,LA Degradation of the Q13751,Q8 LAMB3,LAMNB1,ADAM P15502,P35 MB2,NID1,NID,ELN,FBN R-HSA- R-HSA- R-HSA- P02751,Q9P FN1,FN,ADAMTS9,KIAA extracellular 3 2 9 TRUE TRUE TRUE TRUE 111 TRUE 6.18018018 5 TE60,Q9274 TS18,ADAMTS21,HTRA1 NA NA 555,P49862, 1,FBN,KLK7,PRSS6,SCCE, NA 1474228 1474244 1592389 2N4 1312 matrix 3 ,HTRA,PRSS11 P51511,Q9P MMP15,ADAMTS9,KIAA 2N4,Q9UM 1312,CAPN11 Q6 Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE TRUE TRUE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 3000178 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE TRUE TRUE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 1566977 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE TRUE TRUE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 3000157 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE TRUE TRUE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 1566948 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE FALSE FALSE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 1474290 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE TRUE TRUE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 1474228 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE TRUE TRUE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 216083 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE FALSE FALSE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 8941237 420 462,P20908 organization Extracellular R-HSA- R-HSA- P02462,P53 P02458,P02 matrix 2 1 3 NA FALSE TRUE TRUE TRUE 296 TRUE 6.24662162 5 COL4A1,COL4A4 NA P02751 FN1,FN NA COL2A1,COL4A1,COL5A1 NA 1474244 3000171 420 462,P20908 organization RASGRF2,GRF2,MCF2L, O14827,O1 KIAA0362,OST,PLXNB1,K 5068,O4315 G alpha (12/13) R-HSA- R-HSA- IAA0407,PLXN5,SEP,ADR 1 NA 7 FALSE NA FALSE FALSE FALSE 79 TRUE 11.556962 5 Q92888 ARHGEF1 NA NA NA NA 7,P25100,P3 NA signalling events 416482 388396 A1D,ADRA1A,ADRA1C,P 5348,Q8TC REX1,KIAA1415,ARHGEF U6,Q92974 2,KIAA0651,LFP40 Gene and protein expression by JAK- R-HSA- R-HSA- HSPA9,GRP75,HSPA9B, STAT signaling 1 1 NA FALSE NA FALSE FALSE FALSE 39 TRUE 9.1025641 5 O00170 AIP,XAP2 NA P38646 NA NA NA NA 8950505 9020591 mt-HSP70 after Interleukin- 12 stimulation GLI proteins bind promoters of Hh R-HSA- R-HSA- responsive genes 1 NA NA TRUE NA FALSE TRUE TRUE 7 TRUE 5.28571429 5 P10070 GLI2,THP NA NA NA NA NA NA NA 5635851 5632684 to promote transcription P01891,P01 892,P02458, P04234,P04 439,P05534, P10314,P10 316,P13746, ICAM3,KIR2DL1,CD158A, P16188,P16 Immunoregulatory P32942,P43 NKAT1,TREML4,TLT4,U HLA- 189,P16190, interactions 626,Q6UXN NQ9425/PRO34675,SIG A,HLAA,COL2A1,CD3D,T R-HSA- R-HSA- P18462,P19 between a 6 NA 6 FALSE NA FALSE FALSE FALSE 217 TRUE 7.55760369 5 2,Q96LC7,Q LEC10,SLG2,UNQ477/PR NA NA NA NA 3D,VCAM1,LILRA2,ILT1,L NA 198933 1280218 320,P30443, Lymphoid and a 9UMD9,Q9Y O940,COL17A1,BP180,B IR7,LILRB1,ILT2,LIR1,MI P30447,P30 non-Lymphoid cell 336 PAG2,SIGLEC9,UNQ668/ R7 450,P30453, PRO1302 P30455,P30 456,P30457, P30459,P30 512,Q09160 ,Q8N149,Q8 NHL6

Interleukin-10 R-HSA- R-HSA- CD80,CD28LG,CD28LG1, NA 1 NA FALSE NA FALSE FALSE FALSE 47 TRUE 6.23404255 5 NA NA NA P33681 NA NA NA NA signaling 6783783 449147 LAB7 Keratan sulfate R-HSA- R-HSA- B3GNT3,B3GALT8,TME 1 NA 1 FALSE NA FALSE FALSE FALSE 28 TRUE 4.78571429 5 Q9Y2A9 NA NA NA NA O60512 B4GALT3 NA biosynthesis 2022854 1638074 M3,UNQ637/PRO1266 Lysosome Vesicle R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 35 TRUE 8.34285714 5 NA NA NA NA NA NA P09497 CLTB NA Biogenesis 432720 421837 mitochondrial fatty acid beta- R-HSA- R-HSA- oxidation of NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 5.66666667 5 NA NA NA NA NA NA P42126 ECI1,DCI NA 77288 77289 unsaturated fatty acids Q05519,Q1 SRSF11,SFRS11,CPSF1,C mRNA 3'-end R-HSA- R-HSA- 0570,Q8N6 1 NA 5 TRUE NA FALSE TRUE TRUE 57 TRUE 6.54385965 5 P38919 EIF4A3,DDX48,KIAA0111 NA NA NA NA PSF160,CPSF7,THOC2,CX NA processing 72187 72203 84,Q8NI27, orf3,CPSF3,CPSF73 Q9UKF6 N-Glycan R-HSA- R-HSA- antennae NA NA 1 FALSE NA FALSE FALSE FALSE 15 TRUE 5.4 5 NA NA NA NA NA NA O60512 B4GALT3 NA 975577 975576 elongation

N-glycan trimming in the ER and R-HSA- R-HSA- R-HSA- 1 NA 1 TRUE FALSE TRUE TRUE 35 TRUE 29.6571429 5 Q13724 MOGS,GCS1 NA NA NA NA P55072 VCP NA Calnexin/Calreticul 532668 446203 901042 in cycle

Nef mediated downregulation of R-HSA- R-HSA- MHC class I NA NA 1 FALSE NA FALSE FALSE FALSE 11 TRUE 6.09090909 5 NA NA NA NA NA NA P01892 HLA-A,HLAA NA 164940 164938 complex cell surface expression

UNC5C,UNC5H3,UNC5D, Netrin mediated R-HSA- R-HSA- P12931,P43 O95185,Q6 2 NA 2 TRUE NA FALSE TRUE TRUE 8 TRUE 20.125 5 SRC,SRC1,DCC,IGDCC1 SRC NA NA NA KIAA1777,UNC5H4,UNQ NA repulsion signals 418886 373752 146 UXZ4 6012/PRO34692 Phase I - R-HSA- R-HSA- R-HSA- Functionalization 1 NA NA FALSE TRUE TRUE TRUE 106 TRUE 5.5754717 5 P27540 ARNT,BHLHE2 NA NA NA NA NA NA NA 211945 211859 71384 of compounds Phase I - R-HSA- R-HSA- R-HSA- Functionalization 1 NA NA FALSE FALSE FALSE TRUE 106 TRUE 5.5754717 5 P27540 ARNT,BHLHE2 NA NA NA NA NA NA NA 211945 211859 211897 of compounds Phase I - R-HSA- R-HSA- R-HSA- Functionalization 1 NA NA FALSE FALSE FALSE TRUE 106 TRUE 5.5754717 5 P27540 ARNT,BHLHE2 NA NA NA NA NA NA NA 211945 211859 140179 of compounds Phase I - R-HSA- R-HSA- R-HSA- Functionalization 1 NA NA FALSE TRUE TRUE TRUE 106 TRUE 5.5754717 5 P27540 ARNT,BHLHE2 NA NA NA NA NA NA NA 211945 211859 8937144 of compounds Phase I - R-HSA- R-HSA- R-HSA- Functionalization 1 NA NA FALSE FALSE FALSE TRUE 106 TRUE 5.5754717 5 P27540 ARNT,BHLHE2 NA NA NA NA NA NA NA 211945 211859 217271 of compounds Phase I - R-HSA- R-HSA- R-HSA- Functionalization 1 NA NA FALSE FALSE FALSE TRUE 106 TRUE 5.5754717 5 P27540 ARNT,BHLHE2 NA NA NA NA NA NA NA 211945 211859 140180 of compounds AHRR,BHLHE77,KIAA123 PPARA activates R-HSA- R-HSA- A9YTQ3,P27 P21439,P23 ABCB4,MDR3,PGY3,CPT 3 NA 2 FALSE NA FALSE FALSE FALSE 117 TRUE 7.45299145 5 4,ARNT,BHLHE2,NR1H3, NA NA NA NA NA gene expression 1989781 400206 540,Q13133 786 2,CPT1 LXRA Presynaptic depolarization and R-HSA- R-HSA- CACNA1E,CACH6,CACNL 1 NA NA FALSE NA FALSE FALSE FALSE 13 TRUE 4.46153846 5 Q15878 NA NA NA NA NA NA NA calcium channel 112308 112315 1A6 opening Progressive trimming of alpha- 1,2-linked mannose residues R-HSA- R-HSA- NA 1 NA FALSE NA FALSE FALSE FALSE 3 TRUE 5 5 NA NA NA O60476 MAN1A2,MAN1B NA NA NA NA from 964827 964739 Man9/8/7GlcNAc2 to produce Man5GlcNAc2 Regulation of R-HSA- R-HSA- R-HSA- PTEN mRNA 1 NA 1 FALSE TRUE TRUE TRUE 28 TRUE 8.07142857 5 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA 8943723 6807070 8948700 translation Retinoid cycle R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE FALSE 9 TRUE 4.77777778 5 NA NA NA NA NA NA P02766 TTR,PALB NA disease events 2453864 2474795 2466712 RHO GTPases R-HSA- R-HSA- Activate WASPs 1 1 NA FALSE NA FALSE FALSE FALSE 36 TRUE 13.5 5 Q96F07 CYFIP2,KIAA1168,PIR121 NA Q7L576 CYFIP1,KIAA0068 NA NA NA NA 5663213 195258 and WAVEs Scavenging by R-HSA- R-HSA- P02462,Q9B COL4A1,COLEC11,UNQ5 1 NA 2 FALSE NA FALSE FALSE FALSE 19 TRUE 6.84210526 5 P02462 COL4A1 NA NA NA NA NA Class A Receptors 3000480 2173782 WP8 96/PRO1182 Serotonin R-HSA- R-HSA- R-HSA- clearance from the 1 NA 1 FALSE FALSE FALSE FALSE 3 TRUE 6 5 P31645 SLC6A4,HTT,SERT NA NA NA NA P31645 SLC6A4,HTT,SERT NA 380615 112311 380612 synaptic cleft Sialic acid R-HSA- R-HSA- ST3GAL5,SIAT9,UNQ251 NA NA 1 FALSE NA FALSE FALSE FALSE 33 TRUE 4.87878788 5 NA NA NA NA NA NA Q9UNP4 NA metabolism 4085001 446219 0/PRO5998 Signal regulatory R-HSA- R-HSA- SFTPA1,COLEC4,PSAP,SF protein family 1 NA NA FALSE NA FALSE FALSE FALSE 13 TRUE 23.1538462 5 Q8IWL2 NA NA NA NA NA NA NA 391160 1500931 TP1,SFTPA,SFTPA1B interactions The retinoid cycle R-HSA- R-HSA- in cones (daylight 1 NA NA FALSE NA FALSE FALSE FALSE 7 TRUE 4.42857143 5 P10745 RBP3 NA NA NA NA NA NA NA 2187335 2187338 vision) Activation of the TFAP2 (AP-2) R-HSA- R-HSA- WWOX,FOR,SDR41C1, family of NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 12 5.5 NA NA NA NA NA NA Q9NZC7 NA 8866907 8864260 WOX1 transcription factors Activation, myristolyation of R-HSA- R-HSA- BID and NA NA 1 FALSE NA FALSE FALSE FALSE 4 TRUE 9.5 5.5 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA 75108 109606 translocation to mitochondria Apoptotic R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 52 TRUE 7.98076923 5.5 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA execution phase 75153 109581 140342 Apoptotic R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 52 TRUE 7.98076923 5.5 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA execution phase 75153 109581 111465 Apoptotic R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 52 TRUE 7.98076923 5.5 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA execution phase 75153 109581 211736 COPII-mediated R-HSA- R-HSA- TRAPPC10,EHOC1,TME P00451,P01 F8,F8C,SERPINA1,AAT,PI 1 NA 2 FALSE NA FALSE FALSE FALSE 68 TRUE 5.77941176 5.5 P48553 NA NA NA NA NA vesicle transport 204005 199977 M1 009 ,PRO0684,PRO2209 Ligand-receptor R-HSA- R-HSA- Q13635,Q4 2 NA NA TRUE NA FALSE TRUE TRUE 8 TRUE 5.875 5.5 PTCH1,PTCH,CDON,CDO NA NA NA NA NA NA NA interactions 5632681 5632684 KMG0 Reduction of R-HSA- R-HSA- O14983,P16 cytosolic Ca++ 2 NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 9.91666667 5.5 ATP2A1,ATP2A2,ATP2B NA NA NA NA P57103 SLC8A3,NCX3 NA 418359 418360 615 levels Activation of gene O00763,O7 R-HSA- R-HSA- ACACB,ACC2,ACCB,SC5D expression by NA NA 3 TRUE NA FALSE TRUE TRUE 43 TRUE 8.90697674 6 NA NA NA NA NA NA 5845,P4932 NA 2426168 1655829 ,SC5DL,FASN,FAS SREBF (SREBP) 7 R-HSA- R-HSA- Q13635,Q4 Activation of SMO 2 NA 1 TRUE NA FALSE TRUE TRUE 18 TRUE 7.44444444 6 PTCH1,PTCH,CDON,CDO NA NA NA NA O95995 GAS8,DRC4,GAS11 NA 5635838 5632684 KMG0 alpha-linolenic R-HSA- R-HSA- acid (ALA) NA NA 1 FALSE NA FALSE FALSE FALSE 13 TRUE 5.46153846 6 NA NA NA NA NA NA O95864 FADS2 NA 2046106 2046104 metabolism Q01826,Q0 Apoptotic cleavage R-HSA- R-HSA- R-HSA- SATB1,PRKCQ,PRKCT,CA NA NA 3 TRUE FALSE TRUE TRUE 38 TRUE 8.39473684 6 NA NA NA NA NA NA 4759,Q1479 PRKCQ of cellular proteins 111465 75153 351906 SP8,MCH5 0 Q01826,Q0 Apoptotic cleavage R-HSA- R-HSA- R-HSA- SATB1,PRKCQ,PRKCT,CA NA NA 3 TRUE FALSE TRUE TRUE 38 TRUE 8.39473684 6 NA NA NA NA NA NA 4759,Q1479 PRKCQ of cellular proteins 111465 75153 352238 SP8,MCH5 0 Q01826,Q0 Apoptotic cleavage R-HSA- R-HSA- R-HSA- SATB1,PRKCQ,PRKCT,CA NA NA 3 TRUE TRUE TRUE TRUE 38 TRUE 8.39473684 6 NA NA NA NA NA NA 4759,Q1479 PRKCQ of cellular proteins 111465 75153 264870 SP8,MCH5 0 Budding and R-HSA- R-HSA- Q96PU5,Q9 NEDD4L,KIAA0439,NEDL maturation of HIV 1 NA 2 FALSE NA FALSE FALSE FALSE 36 TRUE 29.0277778 6 Q9NZ09 UBAP1,NAG20 NA NA NA NA NA 162588 162599 UK41 3,VPS28 virion CTAGE5,MEA11,MEA6, Cargo R-HSA- R-HSA- CTAGE5,MEA11,MEA6, O15320,P00 MGEA11,MGEA6,F8,F8C concentration in 1 NA 3 FALSE NA FALSE FALSE FALSE 33 TRUE 6.27272727 6 O15320 NA NA NA NA NA 5694530 199977 MGEA11,MGEA6 451,P01009 ,SERPINA1,AAT,PI,PRO0 the ER 684,PRO2209 O14641,O6 DVL2,SNAP91,KIAA0656, 0641,P0113 EGF,CD3D,T3D,CHRM2,C Cargo recognition 3,P04234,P0 LTB,IGF2R,MPRI,GRK3,A for clathrin- R-HSA- R-HSA- AP2A2,ADTAB,CLAPA2,H 8172,P0949 1 NA 11 TRUE NA FALSE TRUE TRUE 99 TRUE 16.5757576 6 O94973 NA NA NA NA DRBK2,BARK2,CLTCL1,CL NA mediated 8856825 8856828 IP9,HYPJ,KIAA0899 7,P11717,P3 H22,CLTCL,CLTD,COPS5, endocytosis 5626,P5367 CSN5,JAB1,SLC2A8,GLU 5,Q92905,Q T8,GLUTX1 9NY64

Caspase-mediated cleavage of R-HSA- R-HSA- P06396,Q14 1 NA 2 TRUE NA FALSE TRUE TRUE 12 TRUE 8.08333333 6 O43903 GAS2 NA NA NA NA GSN,CASP8,MCH5 NA cytoskeletal 264870 111465 790 proteins

O14641,O6 0641,P0113 DVL2,SNAP91,KIAA0656, 3,P04234,P0 EGF,CD3D,T3D,CHRM2,C Clathrin-mediated R-HSA- R-HSA- R-HSA- AP2A2,ADTAB,CLAPA2,H 1 NA 9 FALSE TRUE TRUE TRUE 137 TRUE 13.2992701 6 O94973 NA NA NA NA 8172,P0949 LTB,IGF2R,MPRI,CLTCL1, NA endocytosis 8856828 199991 8856825 IP9,HYPJ,KIAA0899 7,P11717,P5 CLH22,CLTCL,CLTD,SLC2 3675,Q9NY A8,GLUT8,GLUTX1 64 A6NMZ7,A8 TX70,P0245 COL6A6,COL6A5,COL29A 8,P02462,P1 A8TX70,P02 COL6A5,COL29A1,VWA4 1,VWA4,COL2A1,COL4A 2107,P2084 462,P12107, ,COL4A1,COL11A1,COLL 1,COL11A1,COLL6,COL9 Collagen chain R-HSA- R-HSA- 9,P20908,P2 7 1 13 TRUE NA FALSE TRUE TRUE 44 TRUE 6.09090909 6 P20849,P53 6,COL9A1,COL4A4,COL1 NA Q14993 COL19A1 NA A1,COL5A1,COL8A1,C3or NA trimerization 8948216 1650814 7658,Q1499 420,Q05707 4A1,UND,COL17A1,BP18 f7,COL19A1,COL24A1,C 3,Q17RW2, ,Q9UMD9 0,BPAG2 OL28A1,COL28,COL13A1 Q2UY09,Q5 ,COL22A1 TAT6,Q8NF W1 A6NMZ7,A8 TX70,P0245 COL6A6,COL6A5,COL29A A8TX70,P02 COL6A5,COL29A1,VWA4 8,P02462,P1 1,VWA4,COL2A1,COL4A 462,P12107, ,COL4A1,COL11A1,COLL Collagen R-HSA- R-HSA- 2107,P2084 1,COL11A1,COLL6,COL9 7 1 11 TRUE NA FALSE TRUE TRUE 40 TRUE 7.225 6 P20849,P53 6,COL9A1,COL4A4,COL1 NA Q14993 COL19A1 NA NA degradation 1442490 1474228 9,P20908,P2 A1,COL5A1,COL8A1,C3or 420,Q05707 4A1,UND,COL17A1,BP18 7658,P5151 f7,MMP15,COL19A1,COL ,Q9UMD9 0,BPAG2 1,Q14993,Q 13A1 5TAT6 O15020,P16 SPTBN2,KIAA0302,SCA5, COPI-mediated R-HSA- R-HSA- 157,Q14746 ANK1,ANK,COG2,LDLC,A anterograde 1 NA 5 FALSE NA FALSE FALSE FALSE 83 TRUE 7.42168675 6 Q3ZCM7 TUBB8 NA NA NA NA NA 6807878 199977 ,Q8N6H7,Q RFGAP2,ZNF289,Nbla10 transport 9Y678 535,COPG1,COPG R-HSA- R-HSA- CYP2E1 reactions NA NA 1 TRUE NA FALSE TRUE TRUE 11 TRUE 6.63636364 6 NA NA NA NA NA NA P24903 CYP2F1 NA 211999 211981 DNA Damage R-HSA- R-HSA- Q01831,Q1 Q92905,Q9 COPS5,CSN5,JAB1,MCRS Recognition in GG- 2 NA 2 FALSE NA FALSE FALSE FALSE 38 TRUE 27 6 XPC,XPCC,CUL4A NA NA NA NA NA 5696394 5696399 3619 6EZ8 1,INO80Q,MSP58 NER E3 ubiquitin P01892,P04 HLA- ligases R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 NA 3 FALSE NA FALSE FALSE FALSE 57 TRUE 26.8421053 6 P51668 NA NA NA NA 439,P55072, A,HLAA,VCP,PRKDC,HYR NA ubiquitinate target 8866654 8852135 CH5,UBCH5A P78527 C,HYRC1 proteins Endosomal Sorting Complex Required R-HSA- R-HSA- VPS36,C13orf9,EAP45,C 1 1 1 FALSE NA FALSE FALSE FALSE 31 TRUE 30.0322581 6 Q9NZ09 UBAP1,NAG20 NA Q86VN1 NA Q9UK41 VPS28 NA For Transport 917729 199991 GI-145 (ESCRT) ER Quality Control R-HSA- R-HSA- Compartment NA NA 1 FALSE NA FALSE FALSE FALSE 21 TRUE 42.5238095 6 NA NA NA NA NA NA Q13438 OS9 NA 901032 901042 (ERQC) R-HSA- R-HSA- HSF1 activation NA NA 1 FALSE NA FALSE FALSE FALSE 30 TRUE 17.2333333 6 NA NA NA NA NA NA P55072 VCP NA 3371511 3371556 HSF1-dependent R-HSA- R-HSA- R-HSA- MTOR,FRAP,FRAP1,FRA NA NA 1 FALSE FALSE FALSE FALSE 37 TRUE 15.8108108 6 NA NA NA NA NA NA P42345 NA transactivation 3371571 3371556 3371568 P2,RAFT1,RAPT1 SRGAP3,ARHGAP14,KIA O43295,Q7 A0411,KIAA1156,MEGA Inactivation of R-HSA- R-HSA- SRGAP1,ARHGAP13,KIA NA 1 3 TRUE NA FALSE TRUE TRUE 8 TRUE 13.375 6 NA NA NA Q7Z6B7 NA Z6B7,Q9Y6 P,SRGAP2,SRGAP1,ARH NA CDC42 and RAC1 428543 376176 A1304 N7 GAP13,KIAA1304,ROBO 1,DUTT1 Interleukin-4 and R-HSA- R-HSA- P00488,P04 P02751,P04 P04637,P18 Interleukin-13 2 2 3 FALSE NA FALSE FALSE FALSE 112 TRUE 10.0178571 6 F13A1,F13A,TP53,P53 NA FN1,FN,TP53,P53 NA TP53,P53,LBP,VCAM1 NA 6785807 449147 637 637 428,P19320 signaling IRAK4 deficiency R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 11.8 6 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA (TLR5) 5603037 5602358 IRF3-mediated R-HSA- R-HSA- induction of type I 1 NA 1 FALSE NA FALSE FALSE FALSE 13 TRUE 8.53846154 6 Q7RTR2 NLRC3,NOD3 NA NA NA NA P78527 PRKDC,HYRC,HYRC1 NA 3270619 1834941 IFN Iron uptake and R-HSA- R-HSA- R-HSA- HEPH,KIAA0698,UNQ25 NA NA 1 FALSE FALSE FALSE FALSE 59 TRUE 19.4745763 6 NA NA NA NA NA NA Q9BQS7 NA transport 917937 382551 917977 62/PRO6242 Membrane binding R-HSA- R-HSA- and targetting of 1 NA 1 FALSE NA FALSE FALSE FALSE 15 TRUE 58.6 6 Q9NZ09 UBAP1,NAG20 NA NA NA NA Q9UK41 VPS28 NA 174490 174495 GAG proteins

Negative regulation of activity of TFAP2 R-HSA- R-HSA- WWOX,FOR,SDR41C1, NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 8.8 6 NA NA NA NA NA NA Q9NZC7 NA (AP-2) family 8866904 8864260 WOX1 transcription factors R-HSA- R-HSA- R-HSA- O75093,P43 SLIT1,KIAA0813,MEGF4, Q04759,Q9 PRKCQ,PRKCT,ROBO1,D Netrin-1 signaling 2 NA 2 FALSE TRUE TRUE TRUE 50 TRUE 12.4 6 NA NA NA NA PRKCQ 373752 422475 418886 146 SLIL1,DCC,IGDCC1 Y6N7 UTT1 R-HSA- R-HSA- R-HSA- O75093,P43 SLIT1,KIAA0813,MEGF4, Q04759,Q9 PRKCQ,PRKCT,ROBO1,D Netrin-1 signaling 2 NA 2 FALSE TRUE TRUE TRUE 50 TRUE 12.4 6 NA NA NA NA PRKCQ 373752 422475 418890 146 SLIL1,DCC,IGDCC1 Y6N7 UTT1 R-HSA- R-HSA- R-HSA- O75093,P43 SLIT1,KIAA0813,MEGF4, Q04759,Q9 PRKCQ,PRKCT,ROBO1,D Netrin-1 signaling 2 NA 2 FALSE TRUE TRUE TRUE 50 TRUE 12.4 6 NA NA NA NA PRKCQ 373752 422475 418885 146 SLIL1,DCC,IGDCC1 Y6N7 UTT1 R-HSA- R-HSA- R-HSA- O75093,P43 SLIT1,KIAA0813,MEGF4, Q04759,Q9 PRKCQ,PRKCT,ROBO1,D Netrin-1 signaling 2 NA 2 FALSE TRUE TRUE TRUE 50 TRUE 12.4 6 NA NA NA NA PRKCQ 373752 422475 376172 146 SLIL1,DCC,IGDCC1 Y6N7 UTT1 Processing of Q10570,Q8 R-HSA- R-HSA- CPSF1,CPSF160,CPSF7,C Intronless Pre- NA NA 3 FALSE NA FALSE FALSE FALSE 19 TRUE 8.78947368 6 NA NA NA NA NA NA N684,Q9UK NA 77595 75067 PSF3,CPSF73 mRNAs F6 Regulation of O75093,P12 SLIT1,KIAA0813,MEGF4, commissural axon R-HSA- R-HSA- 4 NA 1 TRUE NA FALSE TRUE TRUE 10 TRUE 12.5 6 931,P43146, SLIL1,SRC,SRC1,DCC,IGD SRC NA NA NA Q9Y6N7 ROBO1,DUTT1 NA pathfinding by SLIT 428542 376176 Q99435 CC1,NELL2,NRP2 and ROBO Regulation of FZD R-HSA- R-HSA- RSPO2,UNQ9384/PRO3 NA NA 1 TRUE NA FALSE TRUE TRUE 21 TRUE 41.8571429 6 NA NA NA NA NA NA Q6UXX9 NA by ubiquitination 4641263 201681 4209 Regulation of gene expression by R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 11 TRUE 12.9090909 6 P27540 ARNT,BHLHE2 NA NA NA NA NA NA NA Hypoxia-inducible 1234158 1234174 Factor Retinoid R-HSA- R-HSA- metabolism and NA NA 1 FALSE NA FALSE FALSE FALSE 44 TRUE 7.70454545 6 NA NA NA NA NA NA P02766 TTR,PALB NA 975634 6806667 transport Retinoid R-HSA- R-HSA- metabolism and NA NA 1 FALSE NA FALSE FALSE FALSE 44 TRUE 7.70454545 6 NA NA NA NA NA NA P02766 TTR,PALB NA 975634 2187338 transport ROS, RNS R-HSA- R-HSA- production in NA NA 1 FALSE NA FALSE FALSE FALSE 32 TRUE 6.15625 6 NA NA NA NA NA NA P29475 NOS1 NA 1222556 168249 phagocytes RUNX1 regulates transcription of R-HSA- R-HSA- genes involved in 1 NA NA FALSE NA FALSE FALSE FALSE 5 TRUE 12 6 P42702 LIFR NA NA NA NA NA NA NA 8939247 8878171 interleukin signaling

TP53 Regulates Transcription of R-HSA- R-HSA- P04637,Q13 2 1 1 FALSE NA FALSE FALSE FALSE 12 TRUE 10 6 TP53,P53,ATM NA P04637 TP53,P53 NA P04637 TP53,P53 NA Caspase Activators 6803207 5633008 315 and Caspases

Translocation of SLC2A4 (GLUT4) to R-HSA- R-HSA- P14672,P31 SLC2A4,GLUT4,AKT2,SF 1 NA 3 FALSE NA FALSE FALSE FALSE 51 TRUE 10.1372549 6 Q3ZCM7 TUBB8 NA NA NA NA AKT2 the plasma 1445148 199991 751,P31947 N,HME1 membrane Type I R-HSA- R-HSA- Q13751,Q9 LAMB3,LAMNB1,COL17 hemidesmosome 2 NA NA FALSE NA FALSE FALSE FALSE 9 TRUE 6.44444444 6 NA NA NA NA NA NA NA 446107 446728 UMD9 A1,BP180,BPAG2 assembly XAV939 inhibits R-HSA- R-HSA- TNKS,PARP5A,PARPL,TI tankyrase, NA NA 1 FALSE NA FALSE FALSE FALSE 2 TRUE 6 6 NA NA NA NA NA NA O95271 NA 5545619 4791275 N1,TINF1,TNKS1 stabilizing AXIN R-HSA- R-HSA- R-HSA- Xenobiotics 1 NA 1 FALSE FALSE FALSE TRUE 23 TRUE 6.47826087 6 P27540 ARNT,BHLHE2 NA NA NA NA P24903 CYP2F1 NA 211981 211897 211957 R-HSA- R-HSA- R-HSA- Xenobiotics 1 NA 1 FALSE TRUE TRUE TRUE 23 TRUE 6.47826087 6 P27540 ARNT,BHLHE2 NA NA NA NA P24903 CYP2F1 NA 211981 211897 211999 A6NMZ7,A8 A8TX70,P02 COL6A5,COL29A1,VWA4 TX70,P0245 COL6A6,COL6A5,COL29A Assembly of 462,P12107, ,COL4A1,COL11A1,COLL 8,P02462,P1 1,VWA4,COL2A1,COL4A collagen fibrils and R-HSA- R-HSA- R-HSA- P20849,P53 6,COL9A1,COL4A4,COL1 8 NA 9 FALSE TRUE TRUE TRUE 58 TRUE 6.43103448 6.5 NA NA NA NA 2107,P2084 1,COL11A1,COLL6,COL9 NA other multimeric 2022090 1474290 2243919 420,Q05707 4A1,UND,LAMB3,LAMN 9,P20908,P2 A1,COL5A1,COL8A1,C3or structures ,Q13751,Q9 B1,COL17A1,BP180,BPA 7658,Q17R f7,COL24A1 UMD9 G2 W2 A6NMZ7,A8 A8TX70,P02 COL6A5,COL29A1,VWA4 TX70,P0245 COL6A6,COL6A5,COL29A Assembly of 462,P12107, ,COL4A1,COL11A1,COLL 8,P02462,P1 1,VWA4,COL2A1,COL4A collagen fibrils and R-HSA- R-HSA- R-HSA- P20849,P53 6,COL9A1,COL4A4,COL1 8 NA 9 FALSE TRUE TRUE TRUE 58 TRUE 6.43103448 6.5 NA NA NA NA 2107,P2084 1,COL11A1,COLL6,COL9 NA other multimeric 2022090 1474290 2214320 420,Q05707 4A1,UND,LAMB3,LAMN 9,P20908,P2 A1,COL5A1,COL8A1,C3or structures ,Q13751,Q9 B1,COL17A1,BP180,BPA 7658,Q17R f7,COL24A1 UMD9 G2 W2

Regulation of TP53 P04637,Q8 Activity through R-HSA- R-HSA- TP53,P53,BANP,BEND1, P04637,P31 3 1 2 FALSE NA FALSE FALSE FALSE 14 TRUE 14.5714286 6.5 N9N5,Q9Y2 NA P04637 TP53,P53 NA TP53,P53,AKT2 AKT2 Association with 6804759 5633007 SMAR1,AKT3,PKBG 751 43 Co-factors

RUNX1 and FOXP3 control the development of R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 9 6.5 NA NA NA NA NA NA P17927 CR1,C3BR NA regulatory T 8877330 8878171 lymphocytes (Tregs) Acetylcholine R-HSA- R-HSA- O14795,P20 UNC13B,UNC13,RAB3A, Neurotransmitter NA NA 3 FALSE NA FALSE FALSE FALSE 17 TRUE 8.70588235 7 NA NA NA NA NA NA NA 264642 112310 336,P28329 CHAT Release Cycle Acyl chain R-HSA- R-HSA- OSBPL8,KIAA1451,ORP8 NA NA 1 TRUE NA FALSE TRUE TRUE 22 TRUE 6.27272727 7 NA NA NA NA NA NA Q9BZF1 NA remodelling of PS 1482801 1483206 ,OSBP10

P01891,P01 892,P04439, P05534,P10 314,P10316, Antigen P13746,P16 Presentation: 188,P16189, ERAP1,APPILS,ARTS1,KI Folding, assembly R-HSA- R-HSA- P16190,P18 1 NA 1 FALSE NA FALSE FALSE FALSE 25 TRUE 6.56 7 Q9NZ08 AA0525,UNQ584/PRO1 NA NA NA NA HLA-A,HLAA NA and peptide 983170 983169 462,P30443, 154 loading of class I P30447,P30 MHC 450,P30453, P30455,P30 456,P30457, P30459,P30 512,Q09160

A9YTQ3,O0 AHRR,BHLHE77,KIAA123 Aryl hydrocarbon R-HSA- R-HSA- 3 NA NA TRUE NA FALSE TRUE TRUE 7 TRUE 7.71428571 7 0170,P2754 4,AIP,XAP2,ARNT,BHLHE NA NA NA NA NA NA NA receptor signalling 8937144 211945 0 2 COPI-independent R-HSA- R-HSA- Q3ZCM7,Q9 TUBB8,RAB3GAP2,KIAA Golgi-to-ER 2 NA NA FALSE NA FALSE FALSE FALSE 34 TRUE 8.85294118 7 NA NA NA NA NA NA NA 6811436 8856688 H2M9 0839 retrograde traffic Defective GALNT12 causes R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 18 TRUE 7.11111111 7 NA NA NA NA NA NA Q8IXK2 GALNT12 NA colorectal cancer 1 5083636 3906995 (CRCS1) Dopamine R-HSA- R-HSA- O14795,P20 Neurotransmitter NA NA 2 FALSE NA FALSE FALSE FALSE 23 TRUE 7.47826087 7 NA NA NA NA NA NA UNC13B,UNC13,RAB3A NA 212676 112310 336 Release Cycle

A6NMZ7,A8 COL6A6,COL6A5,COL29A TX70,O7509 A8TX70,P02 1,VWA4,LRP4,KIAA0816, COL6A5,COL29A1,VWA4 6,P02458,P0 R-HSA- R-HSA- 462,P20849, LRP10,MEGF7,COL2A1,C ECM proteoglycans 5 1 10 TRUE NA FALSE TRUE TRUE 56 TRUE 8.26785714 7 ,COL4A1,COL9A1,COL4A NA P02751 FN1,FN NA 2462,P1104 NA 3000178 1474244 P53420,P53 OL4A1,LAMC1,LAMB2,C 4,ITGA8 7,P20849,P2 708 OL9A1,COL5A1,ITGA9,D 0908,Q1379 AG1 7,Q14118

R-HSA- R-HSA- CYP4F12,UNQ568/PRO1 Eicosanoids NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 7.83333333 7 NA NA NA NA NA NA Q9HCS2 NA 211979 211897 129 Endogenous R-HSA- R-HSA- R-HSA- P11511,P27 CYP19A1,ARO1,CYAR,CY 2 NA NA FALSE FALSE FALSE FALSE 27 TRUE 8.85185185 7 NA NA NA NA NA NA NA sterols 211976 211897 211994 540 P19,ARNT,BHLHE2 R-HSA- R-HSA- P24903,Q9H CYP2F1,CYP4F12,UNQ56 Fatty acids NA NA 2 FALSE NA FALSE FALSE FALSE 15 TRUE 6.6 7 NA NA NA NA NA NA NA 211935 211897 CS2 8/PRO1129 Fibronectin matrix R-HSA- R-HSA- NA 1 NA TRUE NA FALSE TRUE TRUE 6 TRUE 10.8333333 7 NA NA NA P02751 FN1,FN NA NA NA NA formation 1566977 1474244 Folding of actin by R-HSA- R-HSA- P50991,Q92 CCT4,CCTD,SRB,CCT6B,C NA NA 3 FALSE NA FALSE FALSE FALSE 10 TRUE 7.4 7 NA NA NA NA NA NA NA CCT/TriC 390450 389958 526,Q99832 CT7,CCTH,NIP7-1

GABA receptor R-HSA- R-HSA- R-HSA- P14867,P47 1 NA 2 TRUE FALSE TRUE TRUE 56 TRUE 14.125 7 P47870 GABRB2 NA NA NA NA GABRA1,GABRA2 NA activation 977443 112314 977442 869 GABA receptor R-HSA- R-HSA- R-HSA- P14867,P47 1 NA 2 TRUE TRUE TRUE TRUE 56 TRUE 14.125 7 P47870 GABRB2 NA NA NA NA GABRA1,GABRA2 NA activation 977443 112314 977441 869 GABA receptor R-HSA- R-HSA- R-HSA- P14867,P47 1 NA 2 TRUE FALSE TRUE TRUE 56 TRUE 14.125 7 P47870 GABRB2 NA NA NA NA GABRA1,GABRA2 NA activation 977443 112314 977444 869 GABA synthesis, R-HSA- R-HSA- R-HSA- release, reuptake NA NA 1 FALSE FALSE FALSE FALSE 19 TRUE 8.63157895 7 NA NA NA NA NA NA P20336 RAB3A NA 888590 112310 888568 and degradation GABA synthesis, R-HSA- R-HSA- R-HSA- release, reuptake NA NA 1 FALSE FALSE FALSE FALSE 19 TRUE 8.63157895 7 NA NA NA NA NA NA P20336 RAB3A NA 888590 112310 916853 and degradation GABA synthesis, R-HSA- R-HSA- R-HSA- release, reuptake NA NA 1 FALSE FALSE FALSE FALSE 19 TRUE 8.63157895 7 NA NA NA NA NA NA P20336 RAB3A NA 888590 112310 888593 and degradation Glutamate O00341,O1 R-HSA- R-HSA- SLC1A7,EAAT5,UNC13B, Neurotransmitter NA NA 3 FALSE NA FALSE FALSE FALSE 24 TRUE 7.25 7 NA NA NA NA NA NA 4795,P2033 NA 210500 112310 UNC13,RAB3A Release Cycle 6 A6NMZ7,A8 TX70,P0245 COL6A6,COL6A5,COL29A A8TX70,P02 8,P02462,P1 Integrin cell COL6A5,COL29A1,VWA4 1,VWA4,COL2A1,COL4A R-HSA- R-HSA- 462,P20849, 9320,P2084 surface 6 1 11 TRUE NA FALSE TRUE TRUE 66 TRUE 8.28787879 7 ,COL4A1,COL9A1,ICAM3, NA P02751 FN1,FN NA 1,VCAM1,COL9A1,COL5 NA 216083 1474244 P32942,P53 9,P20908,P2 interactions COL4A4,ITGA8 A1,COL8A1,C3orf7,FBN1 420,P53708 7658,P3555 ,FBN,ITGA9,COL13A1 5,Q13797,Q 5TAT6 EPHB2,DRT,EPHT3,EPTH L1CAM R-HSA- R-HSA- R-HSA- P29323,P32 2 NA 1 FALSE TRUE TRUE TRUE 100 TRUE 11.73 7 3,ERK,HEK5,TYRO5,L1CA EPHB2 NA NA NA P11047 LAMC1,LAMB2 NA interactions 373760 422475 447038 004 M,CAML1,MIC5 EPHB2,DRT,EPHT3,EPTH L1CAM R-HSA- R-HSA- R-HSA- P29323,P32 2 NA 1 FALSE TRUE TRUE TRUE 100 TRUE 11.73 7 3,ERK,HEK5,TYRO5,L1CA EPHB2 NA NA NA P11047 LAMC1,LAMB2 NA interactions 373760 422475 447043 004 M,CAML1,MIC5 EPHB2,DRT,EPHT3,EPTH L1CAM R-HSA- R-HSA- R-HSA- P29323,P32 2 NA 1 FALSE TRUE TRUE TRUE 100 TRUE 11.73 7 3,ERK,HEK5,TYRO5,L1CA EPHB2 NA NA NA P11047 LAMC1,LAMB2 NA interactions 373760 422475 445144 004 M,CAML1,MIC5 EPHB2,DRT,EPHT3,EPTH L1CAM R-HSA- R-HSA- R-HSA- P29323,P32 2 NA 1 FALSE TRUE TRUE TRUE 100 TRUE 11.73 7 3,ERK,HEK5,TYRO5,L1CA EPHB2 NA NA NA P11047 LAMC1,LAMB2 NA interactions 373760 422475 447041 004 M,CAML1,MIC5 EPHB2,DRT,EPHT3,EPTH L1CAM R-HSA- R-HSA- R-HSA- P29323,P32 2 NA 1 FALSE TRUE TRUE TRUE 100 TRUE 11.73 7 3,ERK,HEK5,TYRO5,L1CA EPHB2 NA NA NA P11047 LAMC1,LAMB2 NA interactions 373760 422475 437239 004 M,CAML1,MIC5 EPHB2,DRT,EPHT3,EPTH L1CAM R-HSA- R-HSA- R-HSA- P29323,P32 2 NA 1 FALSE TRUE TRUE TRUE 100 TRUE 11.73 7 3,ERK,HEK5,TYRO5,L1CA EPHB2 NA NA NA P11047 LAMC1,LAMB2 NA interactions 373760 422475 445095 004 M,CAML1,MIC5 O75691,O9 UTP20,DRIM,RPP14,RPS Major pathway of 5059,P4678 9,RPS13,TBL3,SAZD,RPL rRNA processing in R-HSA- R-HSA- 1,P62277,Q 1 1 8 FALSE NA FALSE FALSE FALSE 185 TRUE 11.372973 7 P23396 RPS3,OK/SW-cl.26 NA O00541 PES1 NA 10L,MPHOSPH6,MPP6,N NA the nucleolus and 6791226 8868773 12788,Q96L OP58,NOL5,NOP5,HSPC cytosol 21,Q99547, 120 Q9Y2X3 MHC class II AP2A2,ADTAB,CLAPA2,H R-HSA- R-HSA- O94973,Q3 antigen 2 NA 1 FALSE NA FALSE FALSE FALSE 108 TRUE 7.99074074 7 IP9,HYPJ,KIAA0899,TUB NA NA NA NA O15020 SPTBN2,KIAA0302,SCA5 NA 2132295 1280218 ZCM7 presentation B8

A6NMZ7,A8 COL6A6,COL6A5,COL29A A8TX70,P02 COL6A5,COL29A1,VWA4 TX70,O0045 1,VWA4,GFRA2,GDNFR NCAM1 R-HSA- R-HSA- 462,P20849, ,COL4A1,COL9A1,COL4A 1,P02458,P0 B,RETL2,TRNR2,COL2A1 5 NA 8 TRUE NA FALSE TRUE TRUE 37 TRUE 6.64864865 7 NA NA NA NA NA interactions 419037 375165 P53420,Q13 4,CACNA1C,CACH2,CACN 2462,P2084 ,COL4A1,COL9A1,COL5A 936 2,CACNL1A1,CCHL1A1 9,P20908,Q 1,CACNA1D,CACH3,CAC 01668 N4,CACNL1A2,CCHL1A2

Negative regulation of TCF- dependent R-HSA- R-HSA- CCDC88C,DAPLE,KIAA15 1 NA 1 TRUE NA FALSE TRUE TRUE 5 TRUE 6 7 Q9P219 NA NA NA NA O14641 DVL2 NA signaling by DVL- 5368598 201681 09 interacting proteins Norepinephrine R-HSA- R-HSA- O14795,P20 Neurotransmitter NA NA 2 FALSE NA FALSE FALSE FALSE 18 TRUE 9.33333333 7 NA NA NA NA NA NA UNC13B,UNC13,RAB3A NA 181430 112310 336 Release Cycle Regulation of cholesterol R-HSA- R-HSA- R-HSA- RAN,ARA24,OK/SW- 1 NA NA FALSE TRUE TRUE TRUE 56 TRUE 8.16071429 7 P62826 NA NA NA NA NA NA NA biosynthesis by 1655829 8957322 2426168 cl.81 SREBP (SREBF) Regulation of R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, cortical dendrite 1 NA 1 TRUE NA FALSE TRUE TRUE 4 TRUE 7 7 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA 8985801 376176 SLIL1 branching RHO GTPases R-HSA- R-HSA- Q3ZCM7,Q7 TUBB8,CLASP1,KIAA062 O14641,P50 2 NA 2 FALSE NA FALSE FALSE FALSE 121 TRUE 13.7768595 7 MAST1 NA NA NA DVL2,KNTC1,KIAA0166 NA Activate Formins 5663220 195258 Z460 2,MAST1 748 HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H SMARCA4,BAF190A,BR RMTs methylate R-HSA- R-HSA- P62805,Q86 4/H,H4FH;,HIST1H4I,H4/ P51532,Q99 G1,SNF2B,SNF2L4,PRM 2 NA 2 TRUE NA FALSE TRUE TRUE 49 TRUE 15.6326531 7 NA NA NA NA NA histone arginines 3214858 3247509 U86 M,H4FM;,HIST1H4J,H4/E 873 T1,HMT2,HRMT1L2,IR1B ,H4FE;,HIST1H4K,H4/D,H 4 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, PBRM1,BAF180,PB1

RNA Polymerase III Transcription R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 28 TRUE 16.0714286 7 Q9UKN8 GTF3C4 NA NA NA NA NA NA NA Initiation From 76061 76046 Type 1 Promoter RNA Polymerase III Transcription R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 27 TRUE 16.5925926 7 Q9UKN8 GTF3C4 NA NA NA NA NA NA NA Initiation From 76066 76046 Type 2 Promoter RUNX1 interacts with co-factors whose precise R-HSA- R-HSA- SMARCA4,BAF190A,BR 1 NA 1 FALSE NA FALSE FALSE FALSE 37 TRUE 9.35135135 7 Q86U86 PBRM1,BAF180,PB1 NA NA NA NA P51532 NA effect on RUNX1 8939243 8878171 G1,SNF2B,SNF2L4 targets is not known Serotonin R-HSA- R-HSA- O14795,P20 Neurotransmitter NA NA 2 FALSE NA FALSE FALSE FALSE 18 TRUE 8.44444444 7 NA NA NA NA NA NA UNC13B,UNC13,RAB3A NA 181429 112310 336 Release Cycle Synaptic adhesion- R-HSA- R-HSA- P23468,P48 PTPRD,GRIA4,GLUR4,G 1 NA 3 FALSE NA FALSE FALSE FALSE 21 TRUE 6.47619048 7 P23468 PTPRD NA NA NA NA NA like molecules 8849932 6794362 058,Q12879 RIN2A,NMDAR2A

Synthesis of bile acids and bile salts R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 24 TRUE 8.83333333 7 O95342 ABCB11,BSEP NA NA NA NA NA NA NA via 7alpha- 193368 192105 hydroxycholesterol

Synthesis of R-HSA- R-HSA- Leukotrienes (LT) NA 1 1 FALSE NA FALSE FALSE FALSE 21 TRUE 7.76190476 7 NA NA NA P16444 DPEP1,MDP,RDP NA P33527 ABCC1,MRP,MRP1 NA 2142691 2142753 and Eoxins (EX) TP53,P53,AKT2,SFN,HM P04637,P31 E1,MTOR,FRAP,FRAP1,F P04637,P49 TP53,P53,TSC2,TSC4,TN 751,P31947, TP53 Regulates R-HSA- R-HSA- RAP2,RAFT1,RAPT1,COX 4 1 7 FALSE NA FALSE FALSE FALSE 89 TRUE 9.16853933 7 815,Q9UPQ RC6B,KIAA1093,AKT3,PK NA P04637 TP53,P53 NA P42345,Q8 AKT2 Metabolic Genes 5628897 3700989 18,OXA1L2,TACO1,CCDC 9,Q9Y243 BG N8Q8,Q9BS 44,PRO0477,TNRC6B,KI H4,Q9UPQ9 AA1093 TP53 Regulates Transcription of R-HSA- R-HSA- 1 1 1 FALSE NA FALSE FALSE FALSE 12 TRUE 9.16666667 7 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA Death Receptors 6803211 5633008 and Ligands TRAF6 mediated R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 28 TRUE 11.7857143 7 NA NA NA NA NA NA O95786 DDX58 NA IRF7 activation 933541 168928 R-HSA- R-HSA- Unwinding of DNA NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 5.08333333 7 NA NA NA NA NA NA Q9BRX5 GINS3,PSF3 NA 176974 69190 Amplification of signal from unattached R-HSA- R-HSA- CLASP1,KIAA0622,MAST 1 NA 1 FALSE NA FALSE FALSE FALSE 94 TRUE 14.606383 7.5 Q7Z460 MAST1 NA NA NA P50748 KNTC1,KIAA0166 NA kinetochores via a 141444 141424 1 MAD2 inhibitory signal R-HSA- R-HSA- CS/DS degradation 1 NA NA FALSE NA FALSE FALSE FALSE 14 TRUE 7.78571429 7.5 P15848 ARSB NA NA NA NA NA NA NA 2024101 1793185 EPHB2,DRT,EPHT3,EPTH EPHA3,ETK,ETK1,HEK,TY EPH-Ephrin R-HSA- R-HSA- R-HSA- P29323,Q15 EPHB2,EPH P29320,P54 EPHA3,EPH 2 1 3 FALSE TRUE TRUE TRUE 92 TRUE 11.6413043 7.5 3,ERK,HEK5,TYRO5,EPH Q15375 EPHA7,EHK3,HEK11 EPHA7 RO4,EPHA5,BSK,EHK1,H signaling 2682334 422475 3928664 375 A7 756,Q15375 A5,EPHA7 A7,EHK3,HEK11 EK7,EPHA7,EHK3,HEK11 EPHB2,DRT,EPHT3,EPTH EPHA3,ETK,ETK1,HEK,TY EPH-Ephrin R-HSA- R-HSA- R-HSA- P29323,Q15 EPHB2,EPH P29320,P54 EPHA3,EPH 2 1 3 FALSE TRUE TRUE TRUE 92 TRUE 11.6413043 7.5 3,ERK,HEK5,TYRO5,EPH Q15375 EPHA7,EHK3,HEK11 EPHA7 RO4,EPHA5,BSK,EHK1,H signaling 2682334 422475 3928662 375 A7 756,Q15375 A5,EPHA7 A7,EHK3,HEK11 EK7,EPHA7,EHK3,HEK11 EPHB2,DRT,EPHT3,EPTH EPHA3,ETK,ETK1,HEK,TY EPH-Ephrin R-HSA- R-HSA- R-HSA- P29323,Q15 EPHB2,EPH P29320,P54 EPHA3,EPH 2 1 3 FALSE TRUE TRUE TRUE 92 TRUE 11.6413043 7.5 3,ERK,HEK5,TYRO5,EPH Q15375 EPHA7,EHK3,HEK11 EPHA7 RO4,EPHA5,BSK,EHK1,H signaling 2682334 422475 3928663 375 A7 756,Q15375 A5,EPHA7 A7,EHK3,HEK11 EK7,EPHA7,EHK3,HEK11 EPHB2,DRT,EPHT3,EPTH EPHA3,ETK,ETK1,HEK,TY EPH-Ephrin R-HSA- R-HSA- R-HSA- P29323,Q15 EPHB2,EPH P29320,P54 EPHA3,EPH 2 1 3 FALSE TRUE TRUE TRUE 92 TRUE 11.6413043 7.5 3,ERK,HEK5,TYRO5,EPH Q15375 EPHA7,EHK3,HEK11 EPHA7 RO4,EPHA5,BSK,EHK1,H signaling 2682334 422475 3928665 375 A7 756,Q15375 A5,EPHA7 A7,EHK3,HEK11 EK7,EPHA7,EHK3,HEK11 Gamma- R-HSA- R-HSA- P07225,P22 carboxylation of NA NA 2 FALSE NA FALSE FALSE FALSE 10 TRUE 7.5 7.5 NA NA NA NA NA NA PROS1,PROS,PROZ NA 159740 159854 891 protein precursors NCAM signaling R-HSA- R-HSA- R-HSA- O15020,P01 SPTBN2,KIAA0302,SCA5, for neurite out- NA 1 2 FALSE TRUE TRUE TRUE 58 TRUE 18.1896552 7.5 NA NA NA P01112 HRAS,HRAS1 NA NA 375165 422475 419037 112 HRAS,HRAS1 growth Negative regulators of R-HSA- R-HSA- P51668,Q15 UBE2D1,SFT,UBC5A,UB 2 NA 1 TRUE NA FALSE TRUE TRUE 34 TRUE 31.1764706 7.5 NA NA NA NA O95786 DDX58 NA DDX58/IFIH1 936440 168928 366 CH5,UBCH5A,PCBP2 signaling

Neurotransmitter receptors and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 154 TRUE 13.2337662 7.5 NA NA NA NA NA NA O75311 GLRA3 NA postsynaptic signal 112314 112315 977443 transmission

Neurotransmitter receptors and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 154 TRUE 13.2337662 7.5 NA NA NA NA NA NA O75311 GLRA3 NA postsynaptic signal 112314 112315 399721 transmission

Neurotransmitter receptors and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 154 TRUE 13.2337662 7.5 NA NA NA NA NA NA O75311 GLRA3 NA postsynaptic signal 112314 112315 181431 transmission

Neurotransmitter receptors and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 154 TRUE 13.2337662 7.5 NA NA NA NA NA NA O75311 GLRA3 NA postsynaptic signal 112314 112315 451326 transmission

Neurotransmitter receptors and R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 154 TRUE 13.2337662 7.5 NA NA NA NA NA NA O75311 GLRA3 NA postsynaptic signal 112314 112315 442755 transmission

Pre-NOTCH R-HSA- R-HSA- O14983,P16 2 NA 1 FALSE NA FALSE FALSE FALSE 18 TRUE 7.83333333 7.5 ATP2A1,ATP2A2,ATP2B NA NA NA NA Q04721 NOTCH2 NA Processing in Golgi 1912420 1912422 615

Regulation of R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 36 TRUE 32.0277778 7.5 O75604 USP2,UBP41 NA NA NA NA Q14790 CASP8,MCH5 NA TNFR1 signaling 5357905 75893 Role of ABL in R-HSA- R-HSA- CLASP1,KIAA0622,MAST ROBO-SLIT 1 NA 1 TRUE NA FALSE TRUE TRUE 8 TRUE 7.75 7.5 Q7Z460 MAST1 NA NA NA Q9Y6N7 ROBO1,DUTT1 NA 428890 376176 1 signaling Role of second Q13507,Q9 R-HSA- R-HSA- P43146,Q9 TRPC3,TRP3,TRPC4,TRP messengers in 2 NA 3 TRUE NA FALSE TRUE TRUE 10 TRUE 10.6 7.5 DCC,IGDCC1,TRPC5,TRP5 NA NA NA NA UBN4,Q9Y2 NA 418890 373752 UL62 C6,TRP6 netrin-1 signaling 10 Sema4D induced PLXNB1,KIAA0407,PLXN cell migration and R-HSA- R-HSA- O43157,Q7 NA NA 2 FALSE NA FALSE FALSE FALSE 20 TRUE 8.3 7.5 NA NA NA NA NA NA 5,SEP,MYH14,KIAA2034, NA growth-cone 416572 400685 Z406 FP17425 collapse Activation of R-HSA- R-HSA- P42262,P48 GRIA2,GLUR2,GRIA4,GL NA NA 2 FALSE NA FALSE FALSE FALSE 4 TRUE 8.5 8 NA NA NA NA NA NA NA AMPA receptors 399710 399721 058 UR4 Activation of PUMA and R-HSA- R-HSA- 1 1 1 FALSE NA FALSE FALSE FALSE 9 TRUE 14 8 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA translocation to 139915 114452 mitochondria

Anchoring fibril R-HSA- R-HSA- P02462,P53 COL4A1,COL4A4,LAMB3, 3 NA 1 TRUE NA FALSE TRUE TRUE 7 TRUE 7.57142857 8 NA NA NA NA P02462 COL4A1 NA formation 2214320 2022090 420,Q13751 LAMNB1

R-HSA- R-HSA- CHL1 interactions NA NA 1 TRUE NA FALSE TRUE TRUE 9 TRUE 9.33333333 8 NA NA NA NA NA NA P16157 ANK1,ANK NA 447041 373760 Deactivation of the beta-catenin R-HSA- R-HSA- BTRC,BTRCP,FBW1A,FB P31751,Q9H AKT2,CHD8,HELSNF1,KIA 1 NA 3 TRUE NA FALSE TRUE TRUE 42 TRUE 28.452381 8 Q9Y297 NA NA NA NA AKT2 transactivating 3769402 201681 XW1A CK8,Q9HCS4 A1564,TCF7L1,TCF3 complex DSCAM R-HSA- R-HSA- 1 NA NA TRUE NA FALSE TRUE TRUE 11 TRUE 18.0909091 8 P43146 DCC,IGDCC1 NA NA NA NA NA NA NA interactions 376172 373752 EGFR R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 25 TRUE 44.4 8 NA NA NA NA NA NA P01133 EGF NA downregulation 182971 177929 P01891,P01 892,P04439, P05534,P10 314,P10316, P13746,P16 188,P16189, Endosomal/Vacuol R-HSA- R-HSA- P16190,P18 NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 7.58333333 8 NA NA NA NA NA NA HLA-A,HLAA NA ar pathway 1236977 1236975 462,P30443, P30447,P30 450,P30453, P30455,P30 456,P30457, P30459,P30 512,Q09160

Energy dependent regulation of R-HSA- R-HSA- MTOR,FRAP,FRAP1,FRA 1 NA 1 TRUE NA FALSE TRUE TRUE 29 TRUE 8.13793103 8 P49815 TSC2,TSC4 NA NA NA NA P42345 NA mTOR by LKB1- 380972 165159 P2,RAFT1,RAPT1 AMPK

Generation of R-HSA- R-HSA- P04234,P06 second messenger NA NA 3 FALSE NA FALSE FALSE FALSE 40 TRUE 9.4 8 NA NA NA NA NA NA CD3D,T3D,LCK,LCP2 LCK 202433 202403 239,Q13094 molecules

HSP90 chaperone cycle for steroid R-HSA- R-HSA- 1 1 NA FALSE NA FALSE FALSE FALSE 38 TRUE 10.0263158 8 Q3ZCM7 TUBB8 NA Q13451 FKBP5,AIG6,FKBP51 NA NA NA NA hormone receptors 3371497 2262752 (SHR)

Laminin R-HSA- R-HSA- P02462,P53 COL4A1,COL4A4,LAMB3, P02462,P11 COL4A1,LAMC1,LAMB2, 3 NA 3 TRUE NA FALSE TRUE TRUE 23 TRUE 8.2173913 8 NA NA NA NA NA interactions 3000157 1474244 420,Q13751 LAMNB1 047,P14543 NID1,NID

Metalloprotease R-HSA- R-HSA- P38398,Q96 BRCA1,RNF53,UIMC1,R NA NA 2 FALSE NA FALSE FALSE FALSE 31 TRUE 41.3870968 8 NA NA NA NA NA NA NA DUBs 5689901 5688426 RL1 AP80,RXRIP110

Microtubule- dependent trafficking of R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 1 TRUE 8 8 Q3ZCM7 TUBB8 NA NA NA NA NA NA NA connexons from 190840 190872 Golgi to the plasma membrane

R-HSA- R-HSA- R-HSA- MTOR,FRAP,FRAP1,FRA mTOR signalling NA NA 1 FALSE TRUE TRUE TRUE 40 TRUE 10.4 8 NA NA NA NA NA NA P42345 NA 165159 162582 380972 P2,RAFT1,RAPT1 R-HSA- R-HSA- R-HSA- MTOR,FRAP,FRAP1,FRA mTOR signalling NA NA 1 FALSE TRUE TRUE TRUE 40 TRUE 10.4 8 NA NA NA NA NA NA P42345 NA 165159 162582 166208 P2,RAFT1,RAPT1 R-HSA- R-HSA- R-HSA- MTOR,FRAP,FRAP1,FRA mTOR signalling NA NA 1 FALSE TRUE TRUE TRUE 40 TRUE 10.4 8 NA NA NA NA NA NA P42345 NA 165159 162582 165181 P2,RAFT1,RAPT1 mTORC1- R-HSA- R-HSA- MTOR,FRAP,FRAP1,FRA mediated NA NA 1 TRUE NA FALSE TRUE TRUE 23 TRUE 10.0869565 8 NA NA NA NA NA NA P42345 NA 166208 165159 P2,RAFT1,RAPT1 signalling NrCAM R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 7 TRUE 8.28571429 8 NA NA NA NA NA NA P16157 ANK1,ANK NA interactions 447038 373760 R-HSA- R-HSA- P04234,P06 PD-1 signaling NA NA 2 FALSE NA FALSE FALSE FALSE 30 TRUE 10.7 8 NA NA NA NA NA NA CD3D,T3D,LCK LCK 389948 388841 239 Phosphorylation of R-HSA- R-HSA- P04234,P06 CD3D,T3D,LCK,PTPRJ,DE CD3 and TCR zeta NA NA 3 FALSE NA FALSE FALSE FALSE 29 TRUE 8.34482759 8 NA NA NA NA NA NA LCK 202427 202403 239,Q12913 P1 chains Platelet R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE FALSE FALSE TRUE 89 TRUE 16.6179775 8 P51575 P2RX1,P2X1 NA NA NA NA Q99571 P2RX4 NA homeostasis 418346 109582 392851 Platelet R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 89 TRUE 16.6179775 8 P51575 P2RX1,P2X1 NA NA NA NA Q99571 P2RX4 NA homeostasis 418346 109582 432142 Platelet R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE FALSE FALSE TRUE 89 TRUE 16.6179775 8 P51575 P2RX1,P2X1 NA NA NA NA Q99571 P2RX4 NA homeostasis 418346 109582 418360 Platelet R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 89 TRUE 16.6179775 8 P51575 P2RX1,P2X1 NA NA NA NA Q99571 P2RX4 NA homeostasis 418346 109582 392154 Regulation of R-HSA- R-HSA- P12931,Q9 SRC,SRC1,TNRC6B,KIAA RUNX1 Expression 2 NA 1 FALSE NA FALSE FALSE FALSE 27 TRUE 14.7037037 8 SRC NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA 8934593 8878171 UPQ9 1093 and Activity

Regulation of TP53 R-HSA- R-HSA- R-HSA- P04637,Q9Y P04637,P31 Activity through 2 1 2 FALSE TRUE TRUE TRUE 30 TRUE 14.8333333 8 TP53,P53,AKT3,PKBG NA P04637 TP53,P53 NA TP53,P53,AKT2 AKT2 6804758 5633007 6811555 243 751 Acetylation

Repression of R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 14 TRUE 10.0714286 8 NA NA NA NA NA NA Q9HCS4 TCF7L1,TCF3 NA WNT target genes 4641265 195253 O14974,Q1 PPP1R12A,MBS,MYPT1, RHO GTPases R-HSA- R-HSA- CIT,CRIK,KIAA0949,STK2 NA 1 3 FALSE NA FALSE FALSE FALSE 19 TRUE 10.7894737 8 NA NA NA O14578 CIT 5058,Q7Z40 KIF14,KIAA0042,MYH14, NA activate CIT 5625900 195258 1 6 KIAA2034,FP17425 PPP1R12A,MBS,MYPT1, RHO GTPases R-HSA- R-HSA- MYLK,MLCK,MLCK1,MYL O14974,Q7 1 NA 2 FALSE NA FALSE FALSE FALSE 21 TRUE 13.952381 8 Q15746 MYLK NA NA NA MYH14,KIAA2034,FP174 NA activate PAKs 5627123 195258 K1 Z406 25 PPP1R12A,MBS,MYPT1, RHO GTPases R-HSA- R-HSA- O14974,Q7 NA NA 2 FALSE NA FALSE FALSE FALSE 19 TRUE 9.63157895 8 NA NA NA NA NA NA MYH14,KIAA2034,FP174 NA Activate ROCKs 5627117 195258 Z406 25 TNFR1-induced R-HSA- R-HSA- proapoptotic 1 NA 1 FALSE NA FALSE FALSE FALSE 14 TRUE 10.7142857 8 O75604 USP2,UBP41 NA NA NA NA Q14790 CASP8,MCH5 NA 5357786 75893 signaling Translocation of ZAP-70 to R-HSA- R-HSA- P04234,P06 NA NA 2 FALSE NA FALSE FALSE FALSE 26 TRUE 8.5 8 NA NA NA NA NA NA CD3D,T3D,LCK LCK Immunological 202430 202403 239 synapse Transport of gamma- carboxylated protein precursors R-HSA- R-HSA- P07225,P22 NA NA 2 FALSE NA FALSE FALSE FALSE 9 TRUE 8.11111111 8 NA NA NA NA NA NA PROS1,PROS,PROZ NA from the 159763 159854 891 endoplasmic reticulum to the Golgi apparatus Transport of Mature mRNA NUP214,CAIN,CAN,KIAA R-HSA- R-HSA- P38919,Q99 EIF4A3,DDX48,KIAA0111 P35658,Q05 derived from an 2 NA 3 FALSE NA FALSE FALSE FALSE 73 TRUE 16.0273973 8 NA NA NA NA 0023,SRSF11,SFRS11,TH NA 159236 72202 567 ,NUP88 519,Q8NI27 Intron-Containing OC2,CXorf3 Transcript R-HSA- R-HSA- BTRC,BTRCP,FBW1A,FB Circadian Clock 1 NA NA NA FALSE FALSE FALSE FALSE 70 TRUE 22.3857143 8.5 Q9Y297 NA NA NA NA NA NA NA 400253 1368108 XW1A R-HSA- R-HSA- BTRC,BTRCP,FBW1A,FB Circadian Clock 1 NA NA NA FALSE FALSE FALSE FALSE 70 TRUE 22.3857143 8.5 Q9Y297 NA NA NA NA NA NA NA 400253 1368071 XW1A R-HSA- R-HSA- BTRC,BTRCP,FBW1A,FB Circadian Clock 1 NA NA NA FALSE FALSE FALSE FALSE 70 TRUE 22.3857143 8.5 Q9Y297 NA NA NA NA NA NA NA 400253 1368082 XW1A DCC mediated R-HSA- R-HSA- P12931,P43 attractive 2 NA NA TRUE NA FALSE TRUE TRUE 14 TRUE 19 8.5 SRC,SRC1,DCC,IGDCC1 SRC NA NA NA NA NA NA 418885 373752 146 signaling P02458,P11 COL2A1,LAMC1,LAMB2, MET activates R-HSA- R-HSA- P12107,P12 COL11A1,COLL6,SRC,SR 047,P12107, 3 1 5 FALSE NA FALSE FALSE FALSE 18 TRUE 13.6666667 8.5 SRC P02751 FN1,FN NA COL11A1,COLL6,COL5A1 NA PTK2 signaling 8874081 8875878 931,Q13751 C1,LAMB3,LAMNB1 P20908,Q17 ,COL24A1 RW2 Nephrin family R-HSA- R-HSA- MAGI2,ACVRINP1,AIP1, P35609,Q86 ACTN2,MAGI2,ACVRINP 1 NA 2 FALSE NA FALSE FALSE FALSE 22 TRUE 15.5 8.5 Q86UL8 NA NA NA NA NA interactions 373753 1500931 KIAA0705 UL8 1,AIP1,KIAA0705 Removal of aminoterminal propeptides from R-HSA- R-HSA- P07225,P22 NA NA 2 FALSE NA FALSE FALSE FALSE 10 TRUE 9.3 8.5 NA NA NA NA NA NA PROS1,PROS,PROZ NA gamma- 159782 159854 891 carboxylated proteins Sema3A PAK R-HSA- R-HSA- dependent Axon NA NA 1 FALSE NA FALSE FALSE FALSE 16 TRUE 15.8125 8.5 NA NA NA NA NA NA P07332 FES,FPS FES 399954 373755 repulsion SLIT2:ROBO1 R-HSA- R-HSA- increases RHOA NA NA 1 TRUE NA FALSE TRUE TRUE 4 TRUE 12.25 8.5 NA NA NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA 8985586 376176 activity SUMOylation of R-HSA- R-HSA- P04637,Q12 transcription 2 1 1 FALSE NA FALSE FALSE FALSE 20 TRUE 10.8 8.5 TP53,P53,TP53BP1 NA P04637 TP53,P53 NA P04637 TP53,P53 NA 3232118 3108232 888 factors R-HSA- R-HSA- TRAIL signaling NA NA 1 FALSE NA FALSE FALSE FALSE 8 TRUE 10.75 8.5 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA 75158 73887 Transcriptional R-HSA- R-HSA- Regulation by NA NA 1 TRUE NA FALSE TRUE TRUE 34 TRUE 8.91176471 8.5 NA NA NA NA NA NA P38398 BRCA1,RNF53 NA 8953750 212436 E2F6

ABCC9,SUR2,PSMA1,HC P21439,P33 ABC-family O60706,P25 ABCB4,MDR3,PGY3,ABC R-HSA- R-HSA- R-HSA- 2,NU,PROS30,PSC2,ABC 527,P55072, proteins mediated 4 NA 6 FALSE TRUE TRUE TRUE 103 TRUE 42.5436893 9 786,Q96J66, PSMA1 NA NA NA C1,MRP,MRP1,VCP,PSM PSMD2 382556 382551 1369062 C11,MRP8,ABCB9,KIAA1 P61289,Q13 transport Q9NP78 E3,PSMD2,TRAP2,OS9 520 200,Q13438

ABCC9,SUR2,PSMA1,HC P21439,P33 ABC-family O60706,P25 ABCB4,MDR3,PGY3,ABC R-HSA- R-HSA- R-HSA- 2,NU,PROS30,PSC2,ABC 527,P55072, proteins mediated 4 NA 6 FALSE FALSE FALSE TRUE 103 TRUE 42.5436893 9 786,Q96J66, PSMA1 NA NA NA C1,MRP,MRP1,VCP,PSM PSMD2 382556 382551 1369007 C11,MRP8,ABCB9,KIAA1 P61289,Q13 transport Q9NP78 E3,PSMD2,TRAP2,OS9 520 200,Q13438

R-HSA- R-HSA- Activation of RAC1 NA NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 18.3076923 9 NA NA NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA 428540 376176 AKT phosphorylates R-HSA- R-HSA- 1 NA 1 TRUE NA FALSE TRUE TRUE 10 TRUE 19.1 9 Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 targets in the 198693 1257604 nucleus Anchoring of the R-HSA- R-HSA- O95684,Q7 FGFR1OP,FOP,CLASP1,K CDK5RAP2,CEP215,KIAA basal body to the 2 NA 1 TRUE NA FALSE TRUE TRUE 97 TRUE 10.7731959 9 MAST1 NA NA NA Q96SN8 NA 5620912 5617833 Z460 IAA0622,MAST1 1633 plasma membrane

Calcineurin R-HSA- R-HSA- PPP3CB,CALNA2,CALNB, NA NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 14.3333333 9 NA NA NA NA NA NA P16298 NA activates NFAT 2025928 1168372 CNA2 Cell surface R-HSA- R-HSA- R-HSA- interactions at the NA 1 1 FALSE TRUE TRUE TRUE 231 TRUE 12.1558442 9 NA NA NA P02751 FN1,FN NA P07225 PROS1,PROS NA 202733 109582 210991 vascular wall Cell surface R-HSA- R-HSA- R-HSA- interactions at the NA 1 1 FALSE TRUE TRUE TRUE 231 TRUE 12.1558442 9 NA NA NA P02751 FN1,FN NA P07225 PROS1,PROS NA 202733 109582 210993 vascular wall Cell surface R-HSA- R-HSA- R-HSA- interactions at the NA 1 1 FALSE TRUE TRUE TRUE 231 TRUE 12.1558442 9 NA NA NA P02751 FN1,FN NA P07225 PROS1,PROS NA 202733 109582 210990 vascular wall Defective LFNG R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 4 TRUE 11.5 9 NA NA NA NA NA NA Q04721 NOTCH2 NA causes SCDO3 5083630 3906995 Defective POMGNT1 causes R-HSA- R-HSA- Q14118,Q8 DAG1,POMGNT1,MGAT MDDGA3, NA NA 2 FALSE NA FALSE FALSE FALSE 1 TRUE 9 9 NA NA NA NA NA NA NA 5083628 3906995 WZA1 1.2,UNQ746/PRO1475 MDDGB3 and MDDGC3 Defective POMT1 causes MDDGA1, R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 1 TRUE 9 9 Q9Y6A1 POMT1 NA NA NA NA Q14118 DAG1 NA MDDGB1 and 5083633 3906995 MDDGC1 Defective POMT2 causes MDDGA2, R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 1 TRUE 9 9 NA NA NA NA NA NA Q14118 DAG1 NA MDDGB2 and 5083629 3906995 MDDGC2 AP2A2,ADTAB,CLAPA2,H CLTB,EPHA3,ETK,ETK1,H P09497,P29 EPH-ephrin IP9,HYPJ,KIAA0899,EPHB EK,TYRO4,CLTCL1,CLH22 R-HSA- R-HSA- O94973,P29 EPHB2,EPH 320,P53675, EPHA3,EPH mediated 3 1 5 TRUE NA FALSE TRUE TRUE 49 TRUE 12.2244898 9 2,DRT,EPHT3,EPTH3,ERK Q15375 EPHA7,EHK3,HEK11 EPHA7 ,CLTCL,CLTD,EPHA5,BSK, 3928665 2682334 323,Q15375 A7 P54756,Q15 A5,EPHA7 repulsion of cells ,HEK5,TYRO5,EPHA7,EH EHK1,HEK7,EPHA7,EHK3, 375 K3,HEK11 HEK11 EPHA3,ETK,ETK1,HEK,TY EPHA-mediated P29320,P54 RO4,EPHA5,BSK,EHK1,H R-HSA- R-HSA- EPHA3,EPH growth cone 1 1 4 TRUE NA FALSE TRUE TRUE 15 TRUE 18.4 9 Q15375 EPHA7,EHK3,HEK11 EPHA7 Q15375 EPHA7,EHK3,HEK11 EPHA7 756,Q15375 EK7,EPHA7,EHK3,HEK11, 3928663 2682334 A5,EPHA7 collapse ,Q7Z406 MYH14,KIAA2034,FP174 25 EPHB-mediated R-HSA- R-HSA- EPHB2,DRT,EPHT3,EPTH 1 1 1 TRUE NA FALSE TRUE TRUE 34 TRUE 16.8529412 9 P29323 EPHB2 P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA forward signaling 3928662 2682334 3,ERK,HEK5,TYRO5 FasL/ CD95L R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 13.2 9 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA signaling 75157 73887 Golgi Cisternae Pericentriolar R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 14 TRUE 20.7857143 9 NA NA NA NA NA NA Q9H2G9 BLZF1,JEM1 NA Stack 162658 68875 Reorganization Mitotic R-HSA- R-HSA- R-HSA- Q3ZCM7,Q7 TUBB8,CLASP1,KIAA062 2 NA 1 FALSE TRUE TRUE TRUE 184 TRUE 12.6358696 9 MAST1 NA NA NA P50748 KNTC1,KIAA0166 NA Prometaphase 68877 68886 380320 Z460 2,MAST1 Mitotic R-HSA- R-HSA- R-HSA- Q3ZCM7,Q7 TUBB8,CLASP1,KIAA062 2 NA 1 FALSE TRUE TRUE TRUE 184 TRUE 12.6358696 9 MAST1 NA NA NA P50748 KNTC1,KIAA0166 NA Prometaphase 68877 68886 2514853 Z460 2,MAST1 Mitotic R-HSA- R-HSA- R-HSA- Q3ZCM7,Q7 TUBB8,CLASP1,KIAA062 2 NA 1 FALSE TRUE TRUE TRUE 184 TRUE 12.6358696 9 MAST1 NA NA NA P50748 KNTC1,KIAA0166 NA Prometaphase 68877 68886 2500257 Z460 2,MAST1 P02458,P02 COL2A1,COL4A1,TTR,PA Non-integrin P02462,P12 COL4A1,COL11A1,COLL6 462,P02766, R-HSA- R-HSA- R-HSA- LB,LAMC1,LAMB2,COL1 membrane-ECM 4 1 7 TRUE TRUE TRUE TRUE 42 TRUE 11.547619 9 107,P53420, ,COL4A4,LAMB3,LAMNB NA P02751 FN1,FN NA P11047,P12 NA 3000171 1474244 3000170 1A1,COLL6,COL5A1,DAG interactions Q13751 1 107,P20908, 1 Q14118 PI5P Regulates R-HSA- R-HSA- 1 1 1 TRUE NA FALSE TRUE TRUE 9 TRUE 17.3333333 9 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA TP53 Acetylation 6811555 6804758 Pre-NOTCH Processing in the R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 8 9 NA NA NA NA NA NA Q04721 NOTCH2 NA Endoplasmic 1912399 1912422 Reticulum Recruitment of mitotic R-HSA- R-HSA- O95684,Q7 FGFR1OP,FOP,CLASP1,K CDK5RAP2,CEP215,KIAA centrosome 2 NA 1 FALSE NA FALSE FALSE FALSE 81 TRUE 12.3333333 9 MAST1 NA NA NA Q96SN8 NA 380270 380287 Z460 IAA0622,MAST1 1633 proteins and complexes Recruitment of O95684,Q3 R-HSA- R-HSA- FGFR1OP,FOP,TUBB8,C CDK5RAP2,CEP215,KIAA NuMA to mitotic 3 NA 1 TRUE NA FALSE TRUE TRUE 80 TRUE 12.5 9 ZCM7,Q7Z4 MAST1 NA NA NA Q96SN8 NA 380320 68877 LASP1,KIAA0622,MAST1 1633 centrosomes 60 Regulation of TP53,P53,MTOR,FRAP,F R-HSA- R-HSA- P04637,Q03 TP53,P53,MECOM,EVI1, P04637,P42 PTEN gene 2 1 2 FALSE NA FALSE FALSE FALSE 61 TRUE 12.4754098 9 NA P04637 TP53,P53 NA RAP1,FRAP2,RAFT1,RAP NA 8943724 6807070 112 MDS1 345 transcription T1 Regulation of TP53 R-HSA- R-HSA- P04637,Q13 Activity through 2 1 1 FALSE NA FALSE FALSE FALSE 19 TRUE 52.2105263 9 TP53,P53,ATM NA P04637 TP53,P53 NA P04637 TP53,P53 NA 6804760 5633007 315 Methylation

Resolution of R-HSA- R-HSA- Q3ZCM7,Q7 TUBB8,CLASP1,KIAA062 Sister Chromatid 2 NA 1 TRUE NA FALSE TRUE TRUE 107 TRUE 14.3551402 9 MAST1 NA NA NA P50748 KNTC1,KIAA0166 NA 2500257 68877 Z460 2,MAST1 Cohesion A6NMZ7,A8 A8TX70,P02 COL6A5,COL29A1,VWA4 TX70,P0245 COL6A6,COL6A5,COL29A R-HSA- R-HSA- R-HSA- Signaling by PDGF 4 NA 6 FALSE TRUE TRUE TRUE 53 TRUE 21.5660377 9 462,P20849, ,COL4A1,COL9A1,COL4A NA NA NA NA 8,P02462,P2 1,VWA4,COL2A1,COL4A NA 186797 9006934 186763 P53420 4 0849,P2090 1,COL9A1,COL5A1 8 TFAP2 (AP-2) family regulates R-HSA- R-HSA- KDM5B,JARID1B,PLU1,R 1 NA NA FALSE NA FALSE FALSE FALSE 5 TRUE 13.2 9 Q9UGL1 NA NA NA NA NA NA NA transcription of 8866911 8864260 BBP2H1 cell cycle factors AURKA Activation R-HSA- R-HSA- O95684,Q7 FGFR1OP,FOP,CLASP1,K CDK5RAP2,CEP215,KIAA 2 NA 1 FALSE NA FALSE FALSE FALSE 72 TRUE 13.625 9.5 MAST1 NA NA NA Q96SN8 NA by TPX2 8854518 69275 Z460 IAA0622,MAST1 1633 Downregulation of R-HSA- R-HSA- NEDD4L,KIAA0439,NEDL TGF-beta receptor NA NA 1 FALSE NA FALSE FALSE FALSE 26 TRUE 38.2307692 9.5 NA NA NA NA NA NA Q96PU5 NA 2173788 2173789 3 signaling RUNX2 regulates R-HSA- R-HSA- osteoblast 1 NA NA FALSE NA FALSE FALSE FALSE 24 TRUE 18 9.5 P12931 SRC,SRC1 SRC NA NA NA NA NA NA 8940973 8941326 differentiation SUMOylation of R-HSA- R-HSA- transcription NA NA 1 FALSE NA FALSE FALSE FALSE 44 TRUE 10 9.5 NA NA NA NA NA NA Q9UER7 DAXX,BING2,DAP6 NA 3899300 3108232 cofactors TNFR1-induced R-HSA- R-HSA- NFkappaB 1 NA NA FALSE NA FALSE FALSE FALSE 26 TRUE 16.0384615 9.5 O75604 USP2,UBP41 NA NA NA NA NA NA NA 5357956 75893 signaling pathway Activation of ATR R-HSA- R-HSA- in response to NA 1 1 TRUE NA FALSE TRUE TRUE 37 TRUE 13.6216216 10 NA NA NA Q13535 ATR,FRP1 NA Q8WXE1 ATRIP,AGS1 NA 176187 69481 replication stress Binding of TCF/LEF:CTNNB1 R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 8 TRUE 13.75 10 NA NA NA NA NA NA Q9HCS4 TCF7L1,TCF3 NA to target gene 4411364 201722 promoters CASP8 activity is R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 11.8461538 10 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA inhibited 5218900 5675482 DDX58/IFIH1- mediated R-HSA- R-HSA- R-HSA- induction of NA NA 1 FALSE TRUE TRUE TRUE 77 TRUE 24.1688312 10 NA NA NA NA NA NA O95786 DDX58 NA 168928 168249 936440 interferon- alpha/beta DDX58/IFIH1- mediated R-HSA- R-HSA- R-HSA- induction of NA NA 1 FALSE TRUE TRUE TRUE 77 TRUE 24.1688312 10 NA NA NA NA NA NA O95786 DDX58 NA 168928 168249 918233 interferon- alpha/beta DDX58/IFIH1- mediated R-HSA- R-HSA- R-HSA- induction of NA NA 1 FALSE TRUE TRUE TRUE 77 TRUE 24.1688312 10 NA NA NA NA NA NA O95786 DDX58 NA 168928 168249 933543 interferon- alpha/beta DDX58/IFIH1- mediated R-HSA- R-HSA- R-HSA- induction of NA NA 1 FALSE TRUE TRUE TRUE 77 TRUE 24.1688312 10 NA NA NA NA NA NA O95786 DDX58 NA 168928 168249 933541 interferon- alpha/beta DDX58/IFIH1- mediated R-HSA- R-HSA- R-HSA- induction of NA NA 1 FALSE TRUE TRUE TRUE 77 TRUE 24.1688312 10 NA NA NA NA NA NA O95786 DDX58 NA 168928 168249 933542 interferon- alpha/beta Dimerization of R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 11 TRUE 13.0909091 10 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA procaspase-8 69416 140534 Inhibition of TSC R-HSA- R-HSA- complex formation 1 NA 1 TRUE NA FALSE TRUE TRUE 3 TRUE 19.6666667 10 P49815 TSC2,TSC4 NA NA NA NA P31751 AKT2 AKT2 165181 165159 by PKB Loss of Nlp from R-HSA- R-HSA- O95684,Q7 FGFR1OP,FOP,CLASP1,K CDK5RAP2,CEP215,KIAA mitotic 2 NA 1 TRUE NA FALSE TRUE TRUE 69 TRUE 14.0144928 10 MAST1 NA NA NA Q96SN8 NA 380259 380284 Z460 IAA0622,MAST1 1633 centrosomes Loss of proteins required for interphase R-HSA- R-HSA- R-HSA- O95684,Q7 FGFR1OP,FOP,CLASP1,K CDK5RAP2,CEP215,KIAA 2 NA 1 FALSE TRUE TRUE TRUE 69 TRUE 14.0144928 10 MAST1 NA NA NA Q96SN8 NA microtubule 380284 380287 380259 Z460 IAA0622,MAST1 1633 organization from the centrosome MECP2 regulates R-HSA- R-HSA- RBFOX1,A2BP,A2BP1,F transcription NA NA 1 TRUE NA FALSE TRUE TRUE 5 TRUE 17.6 10 NA NA NA NA NA NA Q9NWB1 NA 9022707 8986944 OX1,HRNBP1 factors Negative R-HSA- R-HSA- regulation of MET NA NA 1 FALSE NA FALSE FALSE FALSE 21 TRUE 50.1904762 10 NA NA NA NA NA NA Q12913 PTPRJ,DEP1 NA 6807004 6806834 activity PTK6 promotes R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 7 TRUE 11.8571429 10 Q5S007 LRRK2,PARK8 LRRK2 NA NA NA NA NA NA HIF1A stabilization 8857538 8848021

Regulation by c- R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 11 TRUE 13.0909091 10 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA FLIP 3371378 140534 Regulation of R-HSA- R-HSA- R-HSA- necroptotic cell NA NA 1 TRUE TRUE TRUE TRUE 16 TRUE 12.25 10 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA 5675482 5213460 5218900 death

Regulation of PLK1 O95684,Q7 FGFR1OP,FOP,CLASP1,K PPP1R12A,MBS,MYPT1, R-HSA- R-HSA- O14974,Q9 Activity at G2/M 3 NA 2 FALSE NA FALSE FALSE FALSE 87 TRUE 23.2413793 10 Z460,Q9Y29 IAA0622,MAST1,BTRC,B MAST1 NA NA NA CDK5RAP2,CEP215,KIAA NA 2565942 69275 6SN8 Transition 7 TRCP,FBW1A,FBXW1A 1633

Resolution of D- loop Structures R-HSA- R-HSA- through Holliday 1 NA 1 FALSE NA FALSE FALSE FALSE 32 TRUE 10 10 Q13315 ATM NA NA NA NA P38398 BRCA1,RNF53 NA 5693568 5693537 Junction Intermediates RHO GTPases R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 11 TRUE 18.7272727 10 Q3ZCM7 TUBB8 NA NA NA NA NA NA NA activate IQGAPs 5626467 195258 RIPK1-mediated R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 18 TRUE 11.5555556 10 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA regulated necrosis 5213460 5218859 5675482 RUNX2 regulates R-HSA- R-HSA- chondrocyte 1 NA NA FALSE NA FALSE FALSE FALSE 5 TRUE 13 10 P10070 GLI2,THP NA NA NA NA NA NA NA 8941284 8941326 maturation Signalling to p38 R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 10.4 10 NA NA NA NA NA NA Q99578 RIT2,RIN,ROC2 NA via RIT and RIN 187706 187687 SUMOylation of R-HSA- R-HSA- DNMT1,AIM,CXXC9,DN DNA methylation 1 NA NA FALSE NA FALSE FALSE FALSE 16 TRUE 10.6875 10 P26358 NA NA NA NA NA NA NA 4655427 3108232 MT proteins TRAF3-dependent R-HSA- R-HSA- IRF activation NA NA 1 TRUE NA FALSE TRUE TRUE 14 TRUE 15.3571429 10 NA NA NA NA NA NA O95786 DDX58 NA 918233 168928 pathway TADA3,ADA3,TADA3L,T O75528,O9 NKS,PARP5A,PARPL,TIN 5271,O9578 O75604,P04 USP2,UBP41,TP53,P53,P 1,TINF1,TNKS1,DDX58,T Ub-specific 6,P04637,P6 R-HSA- R-HSA- 637,P25786, SMA1,HC2,NU,PROS30, P53,P53,PSME3,PSMD2, processing 5 1 10 FALSE NA FALSE FALSE FALSE 205 TRUE 28.8 10 PSMA1 P04637 TP53,P53 NA 1289,Q1320 PSMD2 5689880 5688426 Q92995,Q9 PSC2,USP13,ISOT3,USP9 TRAP2,USP49,RHOT1,A proteases 0,Q70CQ1,Q 3008 X,DFFRX,FAM,USP9 RHT1,USP9X,DFFRX,FA 8IXI2,Q9300 M,USP9,USP16,MSTP03 8,Q9Y5T5 9 Constitutive R-HSA- R-HSA- P49815,Q9Y P31751,P42 AKT2,MTOR,FRAP,FRAP Signaling by AKT1 2 NA 2 FALSE NA FALSE FALSE FALSE 26 TRUE 16.8846154 10.5 TSC2,TSC4,AKT3,PKBG NA NA NA NA AKT2 5674400 2219528 243 345 1,FRAP2,RAFT1,RAPT1 E17K in Cancer Gap junction R-HSA- R-HSA- R-HSA- P09497,P53 CLTB,CLTCL1,CLH22,CLTC NA NA 2 FALSE TRUE TRUE TRUE 10 TRUE 11.5 10.5 NA NA NA NA NA NA NA degradation 190873 190828 196025 675 L,CLTD TP53 Regulates Transcription of TP53,P53,SFN,HME1,PR R-HSA- R-HSA- P04637,P31 Genes Involved in 1 1 3 FALSE NA FALSE FALSE FALSE 18 TRUE 17.7222222 10.5 P04637 TP53,P53 NA P04637 TP53,P53 NA MT1,HMT2,HRMT1L2,IR NA 6804114 6791312 947,Q99873 G2 Cell Cycle 1B4 Arrest Cam-PDE 1 R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 4 TRUE 21.5 11 NA NA NA NA NA NA Q14123 PDE1C NA activation 111957 111933 CLEC7A (Dectin-1) R-HSA- R-HSA- PPP3CB,CALNA2,CALNB, induces NFAT 1 NA 1 TRUE NA FALSE TRUE TRUE 11 TRUE 16.8181818 11 Q14643 ITPR1,INSP3R1 NA NA NA NA P16298 NA 5607763 5607764 CNA2 activation Defective SLCO1B1 causes R-HSA- R-HSA- SLCO1B1,LST1,OATP1B1 hyperbilirubinemia NA NA 1 FALSE NA FALSE FALSE FALSE 1 TRUE 11 11 NA NA NA NA NA NA Q9Y6L6 NA 5619110 5619102 ,OATP2,OATPC,SLC21A6 , Rotor type (HBLRR) Defective SLCO1B1 causes R-HSA- R-HSA- SLCO1B1,LST1,OATP1B1 hyperbilirubinemia NA NA 1 FALSE NA FALSE FALSE FALSE 1 TRUE 11 11 NA NA NA NA NA NA Q9Y6L6 NA 5661182 5619102 ,OATP2,OATPC,SLC21A6 , Rotor type (HBLRR) Formation of R-HSA- R-HSA- P09497,P53 CLTB,CLTCL1,CLH22,CLTC annular gap NA NA 2 TRUE NA FALSE TRUE TRUE 9 TRUE 12.4444444 11 NA NA NA NA NA NA NA 196025 190873 675 L,CLTD junctions Nef and signal R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 19.8888889 11 Q92608 DOCK2,KIAA0209 NA NA NA NA P06239 LCK LCK transduction 164944 164952 NFG and proNGF R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 3 TRUE 10.3333333 11 Q17R88 SORCS3 NA NA NA NA NA NA NA binds to p75NTR 205017 193704 Notch-HLH R-HSA- R-HSA- transcription NA NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 14.5384615 11 NA NA NA NA NA NA Q04721 NOTCH2 NA 350054 212436 pathway NOTCH2 intracellular R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 15 11 NA NA NA NA NA NA Q04721 NOTCH2 NA domain regulates 2197563 1980145 transcription NOTCH4 Intracellular R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 20 TRUE 14.3 11 NA NA NA NA NA NA Q04721 NOTCH2 NA Domain Regulates 9013695 9013694 Transcription RNA Polymerase I R-HSA- R-HSA- P18074,Q03 ERCC2,XPD,XPDC,ERCC6, Transcription NA NA 3 FALSE NA FALSE FALSE FALSE 48 TRUE 20.0833333 11 NA NA NA NA NA NA NA 73762 73854 468,Q9H9Y6 CSB,POLR1B Initiation

SRC,SRC1,KDM7A,JHDM P12931,Q6Z P01112,Q6V Signaling by BRAF R-HSA- R-HSA- 1D,KDM7,KIAA1718,APB P01112,P02 HRAS,HRAS1,KSR2,CNKS 4 2 3 FALSE NA FALSE FALSE FALSE 58 TRUE 16.6896552 11 MT4,Q7Z5R SRC HRAS,HRAS1,FN1,FN NA AB6,Q8WXI NA and RAF fusions 6802952 6802957 B1IP,PREL1,RARP1,RIA 751 R2,CNK2,KIAA0902 6,Q86XD5 2 M,FAM131B,KIAA0773

Signaling by R-HSA- R-HSA- O95684,P39 FGFR1OP,FOP,CUX1,CU P39880,Q9 CUX1,CUTL1,ZMYM2,FI cytosolic FGFR1 3 NA 2 FALSE NA FALSE FALSE FALSE 18 TRUE 20.7777778 11 NA NA NA NA NA 1839117 1839124 880,P42229 TL1,STAT5A,STAT5 UBW7 M,RAMP,ZNF198 fusion mutants Trafficking of R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 31 TRUE 11.8064516 11 NA NA NA NA NA NA P48058 GRIA4,GLUR4 NA AMPA receptors 399719 399721 416993 Trafficking of R-HSA- R-HSA- P42262,P48 GRIA2,GLUR2,GRIA4,GL GluR2-containing NA NA 2 TRUE NA FALSE TRUE TRUE 17 TRUE 12.8235294 11 NA NA NA NA NA NA NA 416993 399719 058 UR4 AMPA receptors Unblocking of P35609,P42 ACTN2,GRIA2,GLUR2,G NMDA receptors, R-HSA- R-HSA- 1 NA 4 FALSE NA FALSE FALSE FALSE 20 TRUE 11.6 11 Q15700 DLG2 NA NA NA NA 262,P48058, RIA4,GLUR4,GRIN2A,N NA glutamate binding 438066 442755 Q12879 MDAR2A and activation

MECP2 regulates R-HSA- R-HSA- P42262,Q12 GRIA2,GLUR2,GRIN2A, neuronal receptors NA 1 3 TRUE NA FALSE TRUE TRUE 18 TRUE 13.8888889 11.5 NA NA NA Q13451 FKBP5,AIG6,FKBP51 NA NA 9022699 8986944 879,Q13507 NMDAR2A,TRPC3,TRP3 and channels

NOTCH2 Activation and Transmission R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 22 TRUE 44.6363636 11.5 NA NA NA NA NA NA Q04721 NOTCH2 NA of Signal to the 2979096 1980145 Nucleus

PTK6 Regulates RHO GTPases, RAS R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 14 TRUE 26 11.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA GTPase and MAP 8849471 8848021 kinases Regulation of Q0VDF9,Q1 HSF1-mediated R-HSA- R-HSA- HSPA14,HSP60,HSP70L1, P38646,Q13 HSPA9,GRP75,HSPA9B, NUP214,CAIN,CAN,KIAA 3 2 1 FALSE NA FALSE FALSE FALSE 82 TRUE 19.6097561 11.5 3315,Q9956 NA NA P35658 NA heat shock 3371453 3371556 ATM,NUP88 535 mt-HSP70,ATR,FRP1 0023 7 response A tetrasaccharide linker sequence is R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 26 TRUE 9.76923077 12 NA NA NA NA NA NA Q86Y38 XYLT1,XT1 NA required for GAG 1971475 1793185 synthesis A tetrasaccharide linker sequence is R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 26 TRUE 9.76923077 12 NA NA NA NA NA NA Q86Y38 XYLT1,XT1 NA required for GAG 1971475 1638091 synthesis CREB phosphorylation R-HSA- R-HSA- P35609,Q12 ACTN2,GRIN2A,NMDAR through the 1 NA 2 FALSE NA FALSE FALSE FALSE 18 TRUE 16.6111111 12 Q15700 DLG2 NA NA NA NA NA 442729 438064 879 2A activation of CaMKII Disassembly of the destruction complex and R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 31 TRUE 20.2580645 12 NA NA NA NA NA NA O14641 DVL2 NA recruitment of 4641262 201681 AXIN to the membrane Homologous DNA R-HSA- R-HSA- R-HSA- Pairing and Strand 1 NA 1 TRUE TRUE TRUE TRUE 42 TRUE 14.952381 12 Q13315 ATM NA NA NA NA P38398 BRCA1,RNF53 NA 5693579 5685942 5693616 Exchange NTRK2 activates R-HSA- R-HSA- 1 NA NA TRUE NA FALSE TRUE TRUE 5 TRUE 24.4 12 Q8IZD9 DOCK3,KIAA0299,MOCA NA NA NA NA NA NA NA RAC1 9032759 9032500 Ras activation O14827,P01 RASGRF2,GRF2,HRAS,H upon Ca2+ influx R-HSA- R-HSA- 112,P35609, RAS1,ACTN2,GRIN2A,N 1 1 5 TRUE NA FALSE TRUE TRUE 20 TRUE 17.15 12 Q15700 DLG2 NA P01112 HRAS,HRAS1 NA NA through NMDA 442982 442742 Q12879,Q1 MDAR2A,RASGRF1,CDC receptor 3972 25,GNRP,GRF1 P04637,P38 Regulation of TP53 TP53,P53,BRCA1,RNF53, R-HSA- R-HSA- P04637,Q13 P04637,Q13 398,Q6P1X5 Activity through 3 2 5 FALSE NA FALSE FALSE FALSE 92 TRUE 22.1086957 12 TP53,P53,ATM,TAF1L NA TP53,P53,ATR,FRP1 NA TAF2,CIF150,TAF2B,TAF NA 6804756 5633007 315,Q8IZX4 535 ,Q8IZX4,Q8 Phosphorylation 1L,ATRIP,AGS1 WXE1 Resolution of D- loop Structures R-HSA- R-HSA- through Synthesis- 1 NA 1 FALSE NA FALSE FALSE FALSE 26 TRUE 11.6923077 12 Q13315 ATM NA NA NA NA P38398 BRCA1,RNF53 NA 5693554 5693537 Dependent Strand Annealing (SDSA) RUNX3 regulates R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 8 TRUE 14.875 12 NA NA NA NA NA NA Q9HCS4 TCF7L1,TCF3 NA WNT signaling 8951430 8878159 SUMOylation of DNA damage R-HSA- R-HSA- Q01831,Q9 P35658,P38 NUP214,CAIN,CAN,KIAA 2 NA 3 FALSE NA FALSE FALSE FALSE 76 TRUE 17.4473684 12 XPC,XPCC,NUP88 NA NA NA NA NA response and 3108214 3108232 9567 398,Q13569 0023,BRCA1,RNF53,TDG repair proteins Transcriptional R-HSA- R-HSA- R-HSA- Regulation by 1 NA 1 TRUE FALSE TRUE TRUE 63 TRUE 13.7301587 12 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA 8986944 212436 9022927 MECP2 Transcriptional R-HSA- R-HSA- R-HSA- Regulation by 1 NA 1 TRUE FALSE TRUE TRUE 63 TRUE 13.7301587 12 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA 8986944 212436 9022702 MECP2 Transcriptional R-HSA- R-HSA- R-HSA- Regulation by 1 NA 1 TRUE TRUE TRUE TRUE 63 TRUE 13.7301587 12 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA 8986944 212436 9022699 MECP2 Transcriptional R-HSA- R-HSA- R-HSA- Regulation by 1 NA 1 TRUE TRUE TRUE TRUE 63 TRUE 13.7301587 12 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA 8986944 212436 9022707 MECP2 Transcriptional R-HSA- R-HSA- R-HSA- Regulation by 1 NA 1 TRUE TRUE TRUE TRUE 63 TRUE 13.7301587 12 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA 8986944 212436 9022692 MECP2

Caspase activation via Death R-HSA- R-HSA- R-HSA- O00206,Q1 NA NA 2 FALSE TRUE TRUE TRUE 18 TRUE 13.7777778 12.5 NA NA NA NA NA NA TLR4,CASP8,MCH5 NA Receptors in the 140534 5357769 3371378 4790 presence of ligand

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H R-HSA- R-HSA- Meiotic synapsis 1 1 1 FALSE NA FALSE FALSE FALSE 60 TRUE 19.3166667 12.5 P62805 4/H,H4FH;,HIST1H4I,H4/ NA Q13535 ATR,FRP1 NA P38398 BRCA1,RNF53 NA 1221632 1500620 M,H4FM;,HIST1H4J,H4/E ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

TP53,P53,UBE2D1,SFT,U O95786,P04 Ovarian tumor R-HSA- R-HSA- P04637,P51 DDX58,TP53,P53,VCP,N 3 1 4 FALSE NA FALSE FALSE FALSE 38 TRUE 33.9473684 12.5 BC5A,UBCH5,UBCH5A,N NA P04637 TP53,P53 NA 637,P55072, NA domain proteases 5689896 5688426 668,Q9HC29 OD1,CARD4 OD2,CARD15,IBD1 Q9Y239 R-HSA- R-HSA- Rap1 signalling 1 NA NA FALSE NA FALSE FALSE FALSE 16 TRUE 15.5 12.5 P22612 PRKACG NA NA NA NA NA NA NA 392517 1280218

O94973,P32 AP2A2,ADTAB,CLAPA2,H Recycling pathway R-HSA- R-HSA- 3 NA 1 TRUE NA FALSE TRUE TRUE 28 TRUE 16.5357143 12.5 004,Q3ZCM IP9,HYPJ,KIAA0899,L1CA NA NA NA NA Q9UK32 RPS6KA6,RSK4 RPS6KA6 of L1 437239 373760 7 M,CAML1,MIC5,TUBB8

WNT mediated R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 8 TRUE 11.5 12.5 NA NA NA NA NA NA O14641 DVL2 NA activation of DVL 201688 201681 Activation of NIMA R-HSA- R-HSA- NEK9,KIAA1995,NEK8,N Kinases NEK9, NA 1 NA FALSE NA FALSE FALSE FALSE 7 TRUE 16.8571429 13 NA NA NA Q8TD19 NA NA NA NA 2980767 2980766 ERCC NEK6, NEK7 Condensation of R-HSA- R-HSA- SMC2,CAPE,SMC2L1,PR Prometaphase NA 1 NA TRUE NA FALSE TRUE TRUE 11 TRUE 13 13 NA NA NA O95347 NA NA NA NA 2514853 68877 O0324 Chromosomes Downregulation of UBE2D1,SFT,UBC5A,UB USP9X,DFFRX,FAM,USP SMAD2/3:SMAD4 R-HSA- R-HSA- P51668,Q93 Q93008,Q9 2 NA 2 FALSE NA FALSE FALSE FALSE 23 TRUE 44.5652174 13 CH5,UBCH5A,USP9X,DFF NA NA NA NA 9,NEDD4L,KIAA0439,NE NA transcriptional 2173795 2173793 008 6PU5 RX,FAM,USP9 DL3 activity

R-HSA- R-HSA- HDL assembly 1 NA NA FALSE NA FALSE FALSE FALSE 8 TRUE 19.25 13 P22612 PRKACG NA NA NA NA NA NA NA 8963896 8963898 HDR through Homologous R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE FALSE FALSE TRUE 66 TRUE 25.0454545 13 Q13315 ATM NA NA NA NA P38398 BRCA1,RNF53 NA Recombination 5685942 5693567 5693537 (HRR) HDR through Homologous R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 66 TRUE 25.0454545 13 Q13315 ATM NA NA NA NA P38398 BRCA1,RNF53 NA Recombination 5685942 5693567 5693579 (HRR) HDR through R-HSA- R-HSA- P38398,Q8 BRCA1,RNF53,ATRIP,AG Single Strand 1 1 2 FALSE NA FALSE FALSE FALSE 37 TRUE 16.1891892 13 Q13315 ATM NA Q13535 ATR,FRP1 NA NA 5685938 5693567 WXE1 S1 Annealing (SSA) NADE modulates R-HSA- R-HSA- BEX3,DXS6984E,NADE,N NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 12.1666667 13 NA NA NA NA NA NA Q00994 NA death signalling 205025 204998 GFRAP1

NOTCH3 Activation and Transmission R-HSA- R-HSA- R-HSA- O00308,P01 NA NA 2 FALSE FALSE FALSE FALSE 25 TRUE 42 13 NA NA NA NA NA NA WWP2,EGF NA of Signal to the 9013507 9012852 9017802 133 Nucleus

Presynaptic phase of homologous R-HSA- R-HSA- P38398,Q8 BRCA1,RNF53,ATRIP,AG 1 1 2 TRUE NA FALSE TRUE TRUE 39 TRUE 15.7948718 13 Q13315 ATM NA Q13535 ATR,FRP1 NA NA DNA pairing and 5693616 5693579 WXE1 S1 strand exchange RNA Polymerase I R-HSA- R-HSA- P18074,Q9H ERCC2,XPD,XPDC,POLR1 Transcription NA NA 2 FALSE NA FALSE FALSE FALSE 33 TRUE 23.1515152 13 NA NA NA NA NA NA NA 73863 73864 9Y6 B Termination P01112,Q6V Signaling by RAS R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL P01112,P02 HRAS,HRAS1,KSR2,CNKS 2 2 3 FALSE NA FALSE FALSE FALSE 51 TRUE 19 13 SRC HRAS,HRAS1,FN1,FN NA AB6,Q8WXI NA mutants 6802949 6802957 5R6 1,RARP1,RIAM 751 R2,CNK2,KIAA0902 2 Syndecan R-HSA- R-HSA- NA 1 1 TRUE NA FALSE TRUE TRUE 20 TRUE 16.15 13 NA NA NA P02751 FN1,FN NA P20908 COL5A1 NA interactions 3000170 3000171 VEGFA-VEGFR2 R-HSA- R-HSA- R-HSA- P22612,Q96 PRKACG,CYFIP2,KIAA116 2 1 NA FALSE TRUE TRUE TRUE 95 TRUE 19.1263158 13 NA Q7L576 CYFIP1,KIAA0068 NA NA NA NA Pathway 4420097 194138 5218921 F07 8,PIR121 VEGFA-VEGFR2 R-HSA- R-HSA- R-HSA- P22612,Q96 PRKACG,CYFIP2,KIAA116 2 1 NA FALSE TRUE TRUE TRUE 95 TRUE 19.1263158 13 NA Q7L576 CYFIP1,KIAA0068 NA NA NA NA Pathway 4420097 194138 5218920 F07 8,PIR121 NF-kB activation through FADD/RIP- R-HSA- R-HSA- O95786,Q1 1 pathway NA NA 2 TRUE NA FALSE TRUE TRUE 12 TRUE 20.5 13.5 NA NA NA NA NA NA DDX58,CASP8,MCH5 NA 933543 168928 4790 mediated by caspase-8 and -10 HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H BRCA1,RNF53,PRKDC,HY Nonhomologous R-HSA- R-HSA- P62805,Q12 4/H,H4FH;,HIST1H4I,H4/ P38398,P78 3 NA 3 FALSE NA FALSE FALSE FALSE 52 TRUE 18.6923077 13.5 NA NA NA NA RC,HYRC1,UIMC1,RAP80 NA End-Joining (NHEJ) 5693571 5693532 888,Q13315 M,H4FM;,HIST1H4J,H4/E 527,Q96RL1 ,RXRIP110 ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, TP53BP1,ATM PRKACG,CACNA1C,CACH P22612,Q13 2,CACN2,CACNL1A1,CCH SLC2A2,GLUT2,CACNA1 Regulation of R-HSA- R-HSA- R-HSA- P11168,Q01 4 NA 2 FALSE TRUE TRUE TRUE 80 TRUE 16.2 13.5 936,Q14643 L1A1,ITPR1,INSP3R1,CA NA NA NA NA D,CACH3,CACN4,CACNL1 NA insulin secretion 422356 163685 381676 668 ,Q15878 CNA1E,CACH6,CACNL1A A2,CCHL1A2 6 PRKACG,CACNA1C,CACH P22612,Q13 2,CACN2,CACNL1A1,CCH SLC2A2,GLUT2,CACNA1 Regulation of R-HSA- R-HSA- R-HSA- P11168,Q01 4 NA 2 FALSE FALSE FALSE TRUE 80 TRUE 16.2 13.5 936,Q14643 L1A1,ITPR1,INSP3R1,CA NA NA NA NA D,CACH3,CACN4,CACNL1 NA insulin secretion 422356 163685 400451 668 ,Q15878 CNA1E,CACH6,CACNL1A A2,CCHL1A2 6 PRKACG,CACNA1C,CACH P22612,Q13 2,CACN2,CACNL1A1,CCH SLC2A2,GLUT2,CACNA1 Regulation of R-HSA- R-HSA- R-HSA- P11168,Q01 4 NA 2 FALSE FALSE FALSE TRUE 80 TRUE 16.2 13.5 936,Q14643 L1A1,ITPR1,INSP3R1,CA NA NA NA NA D,CACH3,CACN4,CACNL1 NA insulin secretion 422356 163685 399997 668 ,Q15878 CNA1E,CACH6,CACNL1A A2,CCHL1A2 6 PRKACG,CACNA1C,CACH P22612,Q13 2,CACN2,CACNL1A1,CCH SLC2A2,GLUT2,CACNA1 Regulation of R-HSA- R-HSA- R-HSA- P11168,Q01 4 NA 2 FALSE TRUE TRUE TRUE 80 TRUE 16.2 13.5 936,Q14643 L1A1,ITPR1,INSP3R1,CA NA NA NA NA D,CACH3,CACN4,CACNL1 NA insulin secretion 422356 163685 400042 668 ,Q15878 CNA1E,CACH6,CACNL1A A2,CCHL1A2 6 Transfer of LPS R-HSA- R-HSA- from LBP carrier to NA NA 1 TRUE NA FALSE TRUE TRUE 2 TRUE 13.5 13.5 NA NA NA NA NA NA P18428 LBP NA 166020 166016 CD14 Chk1/Chk2(Cds1) mediated R-HSA- R-HSA- inactivation of NA NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 17 14 NA NA NA NA NA NA P31947 SFN,HME1 NA 75035 69473 Cyclin B:Cdk1 complex Formation of R-HSA- R-HSA- Q01831,Q1 Incision Complex 2 NA 1 FALSE NA FALSE FALSE FALSE 43 TRUE 35.3023256 14 XPC,XPCC,CUL4A NA NA NA NA P18074 ERCC2,XPD,XPDC NA 5696395 5696399 3619 in GG-NER SMARCA4,BAF190A,BR Interleukin-7 R-HSA- R-HSA- P51532,P55 1 NA 3 FALSE NA FALSE FALSE FALSE 25 TRUE 16.16 14 P42229 STAT5A,STAT5 NA NA NA NA G1,SNF2B,SNF2L4,RAG NA signaling 1266695 449147 895,Q9Y4H2 2,IRS2 MyD88 deficiency R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 11 TRUE 15.2727273 14 NA NA NA NA NA NA O00206 TLR4 NA (TLR2/4) 5602498 5602358 CFH,HF,HF1,HF2,CR2,C3 Regulation of R-HSA- R-HSA- P08603,P20 DR,CFHR1,CFHL,CFHL1,C P07225,P10 PROS1,PROS,C7,CR1,C3 Complement 3 NA 3 FALSE NA FALSE FALSE FALSE 127 TRUE 11.0551181 14 NA NA NA NA NA 977606 166658 023,Q03591 FHL1P,CFHR1P,FHR1,HF 643,P17927 BR cascade L1,HFL2 R-HSA- R-HSA- O00451,Q9 GFRA2,GDNFRB,RETL2, RET signaling 1 NA 2 FALSE NA FALSE FALSE FALSE 41 TRUE 23.4878049 14 P22612 PRKACG NA NA NA NA NA 8853659 422475 Y4H2 TRNR2,IRS2 TP53 Regulates Transcription of R-HSA- R-HSA- Genes Involved in 1 1 1 FALSE NA FALSE FALSE FALSE 14 TRUE 14.7857143 14 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA 6804116 6791312 G1 Cell Cycle Arrest Interleukin-2 R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 16.4166667 14.5 P42229 STAT5A,STAT5 NA NA NA NA P06239 LCK LCK signaling 9020558 451927 Interleukin-21 R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 10 TRUE 14.8 14.5 P42229 STAT5A,STAT5 NA NA NA NA NA NA NA signaling 9020958 451927

RNA Polymerase II P18074,P18 ERCC2,XPD,XPDC,NELFE, R-HSA- R-HSA- Pre-transcription 1 NA 4 FALSE NA FALSE FALSE FALSE 84 TRUE 21.2261905 14.5 Q8IZX4 TAF1L NA NA NA NA 615,Q6P1X5 RD,RDBP,TAF2,CIF150,T NA 674695 73857 Events ,Q8IZX4 AF2B,TAF1L

Activated NTRK2 R-HSA- R-HSA- R-HSA- signals through 1 NA NA FALSE TRUE TRUE TRUE 7 TRUE 30.1428571 15 P12931 SRC,SRC1 SRC NA NA NA NA NA NA 9032500 9006115 9032759 FYN Cooperation of PDCL (PhLP1) and R-HSA- R-HSA- P50991,Q92 CCT4,CCTD,SRB,CCT6B,C TRiC/CCT in G- NA NA 3 FALSE NA FALSE FALSE FALSE 42 TRUE 17.0238095 15 NA NA NA NA NA NA NA 6814122 390466 526,Q99832 CT7,CCTH,NIP7-1 protein beta folding CREB phosphorylation R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 30 TRUE 20.5333333 15 NA NA NA NA NA NA Q9UK32 RPS6KA6,RSK4 RPS6KA6 through the 442742 438064 442982 activation of Ras CREB phosphorylation R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 30 TRUE 20.5333333 15 NA NA NA NA NA NA Q9UK32 RPS6KA6,RSK4 RPS6KA6 through the 442742 438064 444257 activation of Ras Eukaryotic R-HSA- R-HSA- P46781,P62 Translation 1 NA 3 FALSE NA FALSE FALSE FALSE 94 TRUE 20 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA 72764 72766 277,Q96L21 Termination Formation of a R-HSA- R-HSA- P46781,P62 pool of free 40S 1 NA 3 FALSE NA FALSE FALSE FALSE 102 TRUE 19.1666667 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA 72689 72737 277,Q96L21 subunits Growth hormone R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 24 TRUE 18.3333333 15 P42229 STAT5A,STAT5 NA NA NA NA Q9Y4H2 IRS2 NA receptor signaling 982772 1280215

GTP hydrolysis and R-HSA- R-HSA- P46781,P62 joining of the 60S 1 NA 3 FALSE NA FALSE FALSE FALSE 113 TRUE 18.0265487 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA 72706 72737 277,Q96L21 ribosomal subunit

L13a-mediated translational R-HSA- R-HSA- P46781,P62 silencing of 1 NA 3 FALSE NA FALSE FALSE FALSE 112 TRUE 18.2410714 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA 156827 72613 277,Q96L21 Ceruloplasmin expression Nonsense Mediated Decay RPS3,OK/SW- (NMD) enhanced R-HSA- R-HSA- P23396,P38 P46781,P62 2 NA 3 FALSE NA FALSE FALSE FALSE 116 TRUE 18.7586207 15 cl.26,EIF4A3,DDX48,KIA NA NA NA NA RPS9,RPS13,RPL10L NA by the Exon 975957 927802 919 277,Q96L21 A0111 Junction Complex (EJC) Nonsense Mediated Decay (NMD) R-HSA- R-HSA- P46781,P62 1 NA 3 FALSE NA FALSE FALSE FALSE 96 TRUE 20.4479167 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA independent of the 975956 927802 277,Q96L21 Exon Junction Complex (EJC) Peptide chain R-HSA- R-HSA- P46781,P62 1 NA 3 FALSE NA FALSE FALSE FALSE 90 TRUE 20.7666667 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA elongation 156902 156842 277,Q96L21 HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H Processing of DNA P38398,Q8 BRCA1,RNF53,ATRIP,AG R-HSA- R-HSA- P62805,Q12 4/H,H4FH;,HIST1H4I,H4/ double-strand 3 1 3 FALSE NA FALSE FALSE FALSE 81 TRUE 28.3333333 15 NA Q13535 ATR,FRP1 NA WXE1,Q96R S1,UIMC1,RAP80,RXRIP NA 5693607 5693567 888,Q13315 M,H4FM;,HIST1H4J,H4/E break ends L1 110 ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, TP53BP1,ATM Selenocysteine R-HSA- R-HSA- P46781,P62 1 NA 3 FALSE NA FALSE FALSE FALSE 94 TRUE 19.8297872 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA synthesis 2408557 2408522 277,Q96L21 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 9010553 SLIL1 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 428543 SLIL1 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 8985801 SLIL1 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 8985586 SLIL1 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 428542 SLIL1 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 428890 SLIL1 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 428540 SLIL1 Signaling by ROBO R-HSA- R-HSA- R-HSA- SLIT1,KIAA0813,MEGF4, 1 NA 1 FALSE TRUE TRUE TRUE 219 TRUE 30.2420091 15 O75093 NA NA NA NA Q9Y6N7 ROBO1,DUTT1 NA receptors 376176 422475 9010642 SLIL1 SRP-dependent P46781,P62 cotranslational R-HSA- R-HSA- RPS9,RPS13,RPL10L,SEC 1 NA 4 FALSE NA FALSE FALSE FALSE 115 TRUE 16.7217391 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA 277,Q96L21 NA protein targeting 1799339 72766 61A2 ,Q9H9S3 to membrane Viral mRNA R-HSA- R-HSA- P46781,P62 1 NA 3 FALSE NA FALSE FALSE FALSE 98 TRUE 20.2244898 15 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13,RPL10L NA Translation 192823 168273 277,Q96L21 AKT phosphorylates R-HSA- R-HSA- P49815,Q9Y 2 NA 1 TRUE NA FALSE TRUE TRUE 14 TRUE 19.7142857 15.5 TSC2,TSC4,AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 targets in the 198323 1257604 243 cytosol CLEC7A/inflamma R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 6 TRUE 20.1666667 15.5 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA some pathway 5660668 5607764 TP53,P53,HIST1H4A,H4/ A,H4FA;,HIST1H4B,H4/I, H4FI;,HIST1H4C,H4/G,H4 FG;,HIST1H4D,H4/B,H4F B;,HIST1H4E,H4/J,H4FJ;, HIST1H4F,H4/C,H4FC;,HI G2/M DNA P04637,P62 ST1H4H,H4/H,H4FH;,HIS P04637,P38 TP53,P53,BRCA1,RNF53, R-HSA- R-HSA- R-HSA- P04637,Q13 damage 4 2 4 TRUE TRUE TRUE TRUE 78 TRUE 20.7948718 15.5 805,Q12888 T1H4I,H4/M,H4FM;,HIST NA TP53,P53,ATR,FRP1 NA 398,Q8WXE ATRIP,AGS1,UIMC1,RAP NA 69473 69481 75035 535 checkpoint ,Q13315 1H4J,H4/E,H4FE;,HIST1H 1,Q96RL1 80,RXRIP110 4K,H4/D,H4FD;,HIST1H4 L,H4/K,H4FK;,HIST2H4A, H4/N,H4F2,H4FN,HIST2 H4;,HIST2H4B,H4/O,H4F O;,HIST4H4,TP53BP1,AT M HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H HDACs deacetylate R-HSA- R-HSA- 1 NA NA TRUE NA FALSE TRUE TRUE 60 TRUE 19.9833333 15.5 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA NA NA NA histones 3214815 3247509 M,H4FM;,HIST1H4J,H4/E ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

IRAK4 deficiency R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 12 TRUE 15.5 15.5 NA NA NA NA NA NA O00206 TLR4 NA (TLR2/4) 5603041 5602358 Antigen activates B Cell Receptor (BCR) leading to R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 95 TRUE 17.1894737 16 Q14643 ITPR1,INSP3R1 NA NA NA NA NA NA NA generation of 983695 983705 second messengers FCERI mediated R-HSA- R-HSA- P16298,Q13 PPP3CB,CALNA2,CALNB, 1 NA 2 FALSE NA FALSE FALSE FALSE 107 TRUE 17.0934579 16 Q14643 ITPR1,INSP3R1 NA NA NA NA NA Ca+2 mobilization 2871809 2454202 094 CNA2,LCP2 FCERI mediated R-HSA- R-HSA- P01112,Q13 NA 1 2 FALSE NA FALSE FALSE FALSE 108 TRUE 20.8333333 16 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,LCP2 NA MAPK activation 2871796 2454202 094 PSMA1,HC2,NU,PROS30 ,PSC2,UBE2D1,SFT,UBC FCERI mediated R-HSA- R-HSA- P25786,P51 P61289,Q04 PSME3,PRKCQ,PRKCT,PS PRKCQ,PSM 3 NA 3 FALSE NA FALSE FALSE FALSE 157 TRUE 39.5987261 16 5A,UBCH5,UBCH5A,BTR PSMA1 NA NA NA NF-kB activation 2871837 2454202 668,Q9Y297 759,Q13200 MD2,TRAP2 D2 C,BTRCP,FBW1A,FBXW1 A R-HSA- R-HSA- FCGR activation 1 NA NA FALSE NA FALSE FALSE FALSE 94 TRUE 15.712766 16 P09769 FGR,SRC2 FGR NA NA NA NA NA NA 2029481 2029480 GPVI-mediated R-HSA- R-HSA- O95866,P06 MPIG6B,C6orf25,G6B,G NA NA 3 FALSE NA FALSE FALSE FALSE 33 TRUE 21.030303 16 NA NA NA NA NA NA LCK activation cascade 114604 76002 239,Q13094 6B-B,LCK,LCP2

Initial triggering of R-HSA- R-HSA- R-HSA- COLEC11,UNQ596/PRO1 NA NA 1 FALSE FALSE FALSE FALSE 103 TRUE 12.7961165 16 NA NA NA NA NA NA Q9BWP8 NA complement 166663 166658 173736 182 Initial triggering of R-HSA- R-HSA- R-HSA- COLEC11,UNQ596/PRO1 NA NA 1 FALSE FALSE FALSE FALSE 103 TRUE 12.7961165 16 NA NA NA NA NA NA Q9BWP8 NA complement 166663 166658 166786 182 Interleukin-3, R-HSA- R-HSA- R-HSA- Interleukin-5 and 1 NA NA FALSE FALSE FALSE FALSE 44 TRUE 22.75 16 P42229 STAT5A,STAT5 NA NA NA NA NA NA NA 512988 449147 912526 GM-CSF signaling Interleukin-3, R-HSA- R-HSA- R-HSA- Interleukin-5 and 1 NA NA FALSE FALSE FALSE FALSE 44 TRUE 22.75 16 P42229 STAT5A,STAT5 NA NA NA NA NA NA NA 512988 449147 912631 GM-CSF signaling Nuclear signaling R-HSA- R-HSA- P12931,P42 SRC,SRC1,STAT5A,STAT WWOX,FOR,SDR41C1, 2 NA 1 TRUE NA FALSE TRUE TRUE 27 TRUE 17.1481481 16 SRC NA NA NA Q9NZC7 NA by ERBB4 1251985 1236394 229 5 WOX1 Oncogene Induced R-HSA- R-HSA- P04637,Q9 TP53,P53,TNRC6B,KIAA1 P04637,Q9 TP53,P53,TNRC6B,KIAA1 2 1 2 FALSE NA FALSE FALSE FALSE 35 TRUE 36.4857143 16 NA P04637 TP53,P53 NA NA Senescence 2559585 2559583 UPQ9 093 UPQ9 093 P01133,P06 EGF,LCK,AKT2,MTOR,FR PIP3 activates AKT R-HSA- R-HSA- R-HSA- P12931,Q9Y CD80,CD28LG,CD28LG1, 239,P31751, 2 1 5 FALSE TRUE TRUE TRUE 279 TRUE 29.5412186 16 SRC,SRC1,AKT3,PKBG SRC P33681 NA AP,FRAP1,FRAP2,RAFT1 LCK,AKT2 signaling 1257604 9006925 198323 243 LAB7 P42345,Q9Y ,RAPT1,IRS2 4H2 P01133,P06 EGF,LCK,AKT2,MTOR,FR PIP3 activates AKT R-HSA- R-HSA- R-HSA- P12931,Q9Y CD80,CD28LG,CD28LG1, 239,P31751, 2 1 5 FALSE FALSE FALSE TRUE 279 TRUE 29.5412186 16 SRC,SRC1,AKT3,PKBG SRC P33681 NA AP,FRAP1,FRAP2,RAFT1 LCK,AKT2 signaling 1257604 9006925 6807070 243 LAB7 P42345,Q9Y ,RAPT1,IRS2 4H2 P01133,P06 EGF,LCK,AKT2,MTOR,FR PIP3 activates AKT R-HSA- R-HSA- R-HSA- P12931,Q9Y CD80,CD28LG,CD28LG1, 239,P31751, 2 1 5 FALSE TRUE TRUE TRUE 279 TRUE 29.5412186 16 SRC,SRC1,AKT3,PKBG SRC P33681 NA AP,FRAP1,FRAP2,RAFT1 LCK,AKT2 signaling 1257604 9006925 199418 243 LAB7 P42345,Q9Y ,RAPT1,IRS2 4H2 P01133,P06 EGF,LCK,AKT2,MTOR,FR PIP3 activates AKT R-HSA- R-HSA- R-HSA- P12931,Q9Y CD80,CD28LG,CD28LG1, 239,P31751, 2 1 5 FALSE TRUE TRUE TRUE 279 TRUE 29.5412186 16 SRC,SRC1,AKT3,PKBG SRC P33681 NA AP,FRAP1,FRAP2,RAFT1 LCK,AKT2 signaling 1257604 9006925 198693 243 LAB7 P42345,Q9Y ,RAPT1,IRS2 4H2 Regulation of actin dynamics for R-HSA- R-HSA- 1 1 NA FALSE NA FALSE FALSE FALSE 143 TRUE 13.8251748 16 Q96F07 CYFIP2,KIAA1168,PIR121 NA Q7L576 CYFIP1,KIAA0068 NA NA NA NA phagocytic cup 2029482 2029480 formation Role of R-HSA- R-HSA- phospholipids in 1 NA NA FALSE NA FALSE FALSE FALSE 107 TRUE 15.7196262 16 Q14643 ITPR1,INSP3R1 NA NA NA NA NA NA NA 2029485 2029480 phagocytosis RUNX3 regulates R-HSA- R-HSA- CDKN1A 1 1 1 FALSE NA FALSE FALSE FALSE 7 TRUE 19 16 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA 8941855 8878159 transcription Scavenging of R-HSA- R-HSA- heme from NA NA 1 FALSE NA FALSE FALSE FALSE 92 TRUE 13.8478261 16 NA NA NA NA NA NA Q86VB7 CD163,M130 NA 2168880 2173782 plasma Signal R-HSA- R-HSA- 1 NA 1 TRUE NA FALSE TRUE TRUE 21 TRUE 24.047619 16 P32004 L1CAM,CAML1,MIC5 NA NA NA NA Q13797 ITGA9 NA transduction by L1 445144 373760 R-HSA- R-HSA- R-HSA- Signaling by EGFR NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 42.8139535 16 NA NA NA NA NA NA P01133 EGF NA 177929 9006934 182971 R-HSA- R-HSA- R-HSA- Signaling by EGFR NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 42.8139535 16 NA NA NA NA NA NA P01133 EGF NA 177929 9006934 212718 R-HSA- R-HSA- R-HSA- Signaling by EGFR NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 42.8139535 16 NA NA NA NA NA NA P01133 EGF NA 177929 9006934 179812 R-HSA- R-HSA- R-HSA- Signaling by EGFR NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 42.8139535 16 NA NA NA NA NA NA P01133 EGF NA 177929 9006934 180292 R-HSA- R-HSA- R-HSA- Signaling by EGFR NA NA 1 FALSE TRUE TRUE TRUE 43 TRUE 42.8139535 16 NA NA NA NA NA NA P01133 EGF NA 177929 9006934 180336 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 3772470 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 4641257 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 4641258 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 4641263 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 201722 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 4641262 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 201688 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 5368598 response to WNT W0 EMEN2,KRM2 TCF dependent O14641,O9 DVL2,TNKS,PARP5A,PAR R-HSA- R-HSA- R-HSA- signaling in NA NA 3 FALSE TRUE TRUE TRUE 203 TRUE 32.9655172 16 NA NA NA NA NA NA 5271,Q8NC PL,TIN1,TINF1,TNKS1,KR NA 201681 195721 3769402 response to WNT W0 EMEN2,KRM2 VEGFR2 mediated R-HSA- R-HSA- P31751,P42 AKT2,MTOR,FRAP,FRAP vascular 1 NA 2 TRUE NA FALSE TRUE TRUE 27 TRUE 20.6296296 16 Q9Y243 AKT3,PKBG NA NA NA NA AKT2 5218920 4420097 345 1,FRAP2,RAFT1,RAPT1 permeability Activation of NOXA and R-HSA- R-HSA- 1 1 1 FALSE NA FALSE FALSE FALSE 5 TRUE 19.6 17 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA translocation to 111448 114452 mitochondria

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H 4/H,H4FH;,HIST1H4I,H4/ P02766,P04 TTR,PALB,SEMG1,SEMG Amyloid fiber R-HSA- R-HSA- P62805,Q93 2 NA 4 FALSE NA FALSE FALSE FALSE 79 TRUE 27.2278481 17 M,H4FM;,HIST1H4J,H4/E NA NA NA NA 279,P06396, ,GSN,USP9X,DFFRX,FA NA formation 977225 392499 008 ,H4FE;,HIST1H4K,H4/D,H Q93008 M,USP9 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, USP9X,DFFRX,FAM,USP 9 APC-Cdc20 mediated R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE NA FALSE FALSE FALSE 25 TRUE 46.36 17 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA degradation of 179409 179419 CH5,UBCH5A Nek2A APC/C:Cdc20 mediated R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA TRUE NA FALSE TRUE TRUE 23 TRUE 51.5217391 17 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA degradation of 174048 176409 CH5,UBCH5A Cyclin B P16298,Q9H PPP3CB,CALNA2,CALNB, R-HSA- R-HSA- Q14643,Q9 ITPR1,INSP3R1,TNRC6B, Ca2+ pathway 2 NA 3 FALSE NA FALSE FALSE FALSE 62 TRUE 18.1935484 17 NA NA NA NA CS4,Q9UPQ CNA2,TCF7L1,TCF3,TNR NA 4086398 3858494 UPQ9 KIAA1093 9 C6B,KIAA1093 LCK,AKT2,MTOR,FRAP,F CD28 dependent R-HSA- R-HSA- CD80,CD28LG,CD28LG1, P06239,P31 1 1 3 TRUE NA FALSE TRUE TRUE 22 TRUE 24.6363636 17 Q9Y243 AKT3,PKBG NA P33681 NA RAP1,FRAP2,RAFT1,RAP LCK,AKT2 PI3K/Akt signaling 389357 389356 LAB7 751,P42345 T1 Conversion from APC/C:Cdc20 to R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE NA FALSE FALSE FALSE 19 TRUE 17.1578947 17 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA APC/C:Cdh1 in late 176407 174143 CH5,UBCH5A anaphase PPP3CB,CALNA2,CALNB, R-HSA- R-HSA- P16298,P27 DARPP-32 events 1 NA 3 FALSE NA FALSE FALSE FALSE 24 TRUE 25.9166667 17 P22612 PRKACG NA NA NA NA CNA2,PDE4A,DPDE2,PDE NA 180024 111885 815,Q08493 4C,DPDE1 Inactivation of APC/C via direct R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE NA FALSE FALSE FALSE 20 TRUE 17.3 17 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA inhibition of the 141430 141405 CH5,UBCH5A APC/C complex Integrin alphaIIb R-HSA- R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL 2 1 NA FALSE TRUE TRUE TRUE 27 TRUE 24.9259259 17 SRC P02751 FN1,FN NA NA NA NA beta3 signaling 354192 9006921 372708 5R6 1,RARP1,RIAM Integrin alphaIIb R-HSA- R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL 2 1 NA FALSE TRUE TRUE TRUE 27 TRUE 24.9259259 17 SRC P02751 FN1,FN NA NA NA NA beta3 signaling 354192 76009 372708 5R6 1,RARP1,RIAM Integrin alphaIIb R-HSA- R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL 2 1 NA FALSE TRUE TRUE TRUE 27 TRUE 24.9259259 17 SRC P02751 FN1,FN NA NA NA NA beta3 signaling 354192 9006921 354194 5R6 1,RARP1,RIAM Integrin alphaIIb R-HSA- R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL 2 1 NA FALSE TRUE TRUE TRUE 27 TRUE 24.9259259 17 SRC P02751 FN1,FN NA NA NA NA beta3 signaling 354192 76009 354194 5R6 1,RARP1,RIAM Interleukin-15 R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 14 TRUE 25.7857143 17 P42229 STAT5A,STAT5 NA NA NA NA NA NA NA signaling 8983432 451927 R-HSA- R-HSA- IRS activation NA NA 1 TRUE NA FALSE TRUE TRUE 5 TRUE 15 17 NA NA NA NA NA NA Q9Y4H2 IRS2 NA 74713 74751 P01112,Q6V MAP2K and MAPK R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL P01112,P02 HRAS,HRAS1,KSR2,CNKS 2 2 3 TRUE NA FALSE TRUE TRUE 38 TRUE 23.5 17 SRC HRAS,HRAS1,FN1,FN NA AB6,Q8WXI NA activation 5674135 5673001 5R6 1,RARP1,RIAM 751 R2,CNK2,KIAA0902 2 p130Cas linkage to R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL MAPK signaling for 2 1 NA TRUE NA FALSE TRUE TRUE 15 TRUE 20.7333333 17 SRC P02751 FN1,FN NA NA NA NA 372708 354192 5R6 1,RARP1,RIAM integrins

Paradoxical P01112,Q6V activation of RAF R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL P01112,P02 HRAS,HRAS1,KSR2,CNKS 2 2 3 FALSE NA FALSE FALSE FALSE 38 TRUE 24.2105263 17 SRC HRAS,HRAS1,FN1,FN NA AB6,Q8WXI NA signaling by kinase 6802955 6802957 5R6 1,RARP1,RIAM 751 R2,CNK2,KIAA0902 2 inactive BRAF

Phosphorylation of R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE NA FALSE FALSE FALSE 19 TRUE 20.5263158 17 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA the APC/C 176412 176814 CH5,UBCH5A KDM4B,JHDM3B,JMJD2 B,KIAA0876,TP53,P53,HI ST1H4A,H4/A,H4FA;,HIS T1H4B,H4/I,H4FI;,HIST1 H4C,H4/G,H4FG;,HIST1H Recruitment and 4D,H4/B,H4FB;,HIST1H4 ATM-mediated O94953,P04 E,H4/J,H4FJ;,HIST1H4F,H phosphorylation of R-HSA- R-HSA- 637,P62805, 4/C,H4FC;,HIST1H4H,H4/ P04637,P38 TP53,P53,BRCA1,RNF53, repair and 5 1 3 FALSE NA FALSE FALSE FALSE 59 TRUE 31.7457627 17 NA P04637 TP53,P53 NA NA 5693565 5693606 Q12888,Q1 H,H4FH;,HIST1H4I,H4/M, 398,Q96RL1 UIMC1,RAP80,RXRIP110 signaling proteins 3315 H4FM;,HIST1H4J,H4/E,H at DNA double 4FE;,HIST1H4K,H4/D,H4 strand breaks FD;,HIST1H4L,H4/K,H4FK ;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, TP53BP1,ATM

Regulation of R-HSA- R-HSA- P42858,Q9 HTT,HD,IT15,TNRC6B,KI P42858,Q9 HTT,HD,IT15,TNRC6B,KI MECP2 expression 2 NA 2 TRUE NA FALSE TRUE TRUE 32 TRUE 18.21875 17 NA NA NA NA NA 9022692 8986944 UPQ9 AA1093 UPQ9 AA1093 and activity Regulation of TLR R-HSA- R-HSA- SFTPA1,COLEC4,PSAP,SF O00206,P18 by endogenous 1 NA 2 FALSE NA FALSE FALSE FALSE 16 TRUE 14.0625 17 Q8IWL2 NA NA NA NA TLR4,LBP NA 5686938 168898 TP1,SFTPA,SFTPA1B 428 ligand PSMA1,HC2,NU,PROS30 P25786,P51 ,PSC2,UBE2D1,SFT,UBC Separation of R-HSA- R-HSA- PSMA1,MA P50748,P61 KNTC1,KIAA0166,PSME3 4 1 3 FALSE NA FALSE FALSE FALSE 171 TRUE 34.6900585 17 668,Q3ZCM 5A,UBCH5,UBCH5A,TUB Q9UJX4 ANAPC5,APC5 NA PSMD2 Sister Chromatids 2467813 68882 ST1 289,Q13200 ,PSMD2,TRAP2 7,Q7Z460 B8,CLASP1,KIAA0622,M AST1 Signaling by P01112,Q6V moderate kinase R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL P01112,P02 HRAS,HRAS1,KSR2,CNKS 2 2 3 FALSE NA FALSE FALSE FALSE 38 TRUE 24.2105263 17 SRC HRAS,HRAS1,FN1,FN NA AB6,Q8WXI NA activity BRAF 6802946 6802957 5R6 1,RARP1,RIAM 751 R2,CNK2,KIAA0902 2 mutants

Transcription of R-HSA- R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C 1 NA 3 FALSE TRUE TRUE TRUE 74 TRUE 23.6351351 17 Q8IZX4 TAF1L NA NA NA NA NA the HIV genome 167172 162599 167160 1X5,Q8IZX4 IF150,TAF2B,TAF1L Transcription of R-HSA- R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C 1 NA 3 FALSE TRUE TRUE TRUE 74 TRUE 23.6351351 17 Q8IZX4 TAF1L NA NA NA NA NA the HIV genome 167172 162599 167287 1X5,Q8IZX4 IF150,TAF2B,TAF1L

Transcription of R-HSA- R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C 1 NA 3 FALSE FALSE FALSE TRUE 74 TRUE 23.6351351 17 Q8IZX4 TAF1L NA NA NA NA NA the HIV genome 167172 162599 167169 1X5,Q8IZX4 IF150,TAF2B,TAF1L

O00451,O1 GFRA2,GDNFRB,RETL2, 4827,O1502 TRNR2,RASGRF2,GRF2, 0,P01112,P0 SPTBN2,KIAA0302,SCA5, RAF/MAP kinase R-HSA- R-HSA- R-HSA- 1 1 9 FALSE TRUE TRUE TRUE 244 TRUE 31.5327869 17.5 Q15700 DLG2 NA P01112 HRAS,HRAS1 NA 1133,P3560 HRAS,HRAS1,EGF,ACTN NA cascade 5673001 5684996 5673000 9,Q12879,Q 2,GRIN2A,NMDAR2A,RA 13972,Q9Y4 SGRF1,CDC25,GNRP,GR H2 F1,IRS2 O00451,O1 GFRA2,GDNFRB,RETL2, 4827,O1502 TRNR2,RASGRF2,GRF2, 0,P01112,P0 SPTBN2,KIAA0302,SCA5, RAF/MAP kinase R-HSA- R-HSA- R-HSA- 1 1 9 FALSE TRUE TRUE TRUE 244 TRUE 31.5327869 17.5 Q15700 DLG2 NA P01112 HRAS,HRAS1 NA 1133,P3560 HRAS,HRAS1,EGF,ACTN NA cascade 5673001 5684996 5658442 9,Q12879,Q 2,GRIN2A,NMDAR2A,RA 13972,Q9Y4 SGRF1,CDC25,GNRP,GR H2 F1,IRS2 O00451,O1 GFRA2,GDNFRB,RETL2, 4827,O1502 TRNR2,RASGRF2,GRF2, 0,P01112,P0 SPTBN2,KIAA0302,SCA5, RAF/MAP kinase R-HSA- R-HSA- R-HSA- 1 1 9 FALSE TRUE TRUE TRUE 244 TRUE 31.5327869 17.5 Q15700 DLG2 NA P01112 HRAS,HRAS1 NA 1133,P3560 HRAS,HRAS1,EGF,ACTN NA cascade 5673001 5684996 5674135 9,Q12879,Q 2,GRIN2A,NMDAR2A,RA 13972,Q9Y4 SGRF1,CDC25,GNRP,GR H2 F1,IRS2 O00451,O1 GFRA2,GDNFRB,RETL2, 4827,O1502 TRNR2,RASGRF2,GRF2, 0,P01112,P0 SPTBN2,KIAA0302,SCA5, RAF/MAP kinase R-HSA- R-HSA- R-HSA- 1 1 9 FALSE TRUE TRUE TRUE 244 TRUE 31.5327869 17.5 Q15700 DLG2 NA P01112 HRAS,HRAS1 NA 1133,P3560 HRAS,HRAS1,EGF,ACTN NA cascade 5673001 5684996 5675221 9,Q12879,Q 2,GRIN2A,NMDAR2A,RA 13972,Q9Y4 SGRF1,CDC25,GNRP,GR H2 F1,IRS2 Signaling by high- P01112,Q6V R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL P01112,P02 HRAS,HRAS1,KSR2,CNKS kinase activity 2 2 3 FALSE NA FALSE FALSE FALSE 34 TRUE 25.5 17.5 SRC HRAS,HRAS1,FN1,FN NA AB6,Q8WXI NA 6802948 6802957 5R6 1,RARP1,RIAM 751 R2,CNK2,KIAA0902 BRAF mutants 2

Downregulation of R-HSA- R-HSA- R-HSA- NA NA 1 TRUE TRUE TRUE TRUE 29 TRUE 42.3793103 18 NA NA NA NA NA NA P01133 EGF NA ERBB2 signaling 8863795 1227986 1358803

ERBB2 Activates R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 19.2307692 18 NA NA NA NA NA NA P01133 EGF NA PTK6 Signaling 8847993 1227986 ERBB2 Activates R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE TRUE 13 TRUE 19.2307692 18 NA NA NA NA NA NA P01133 EGF NA PTK6 Signaling 8847993 8848021 ERBB2 Regulates R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 15 TRUE 18 18 NA NA NA NA NA NA P01133 EGF NA Cell Motility 6785631 1227986 Interleukin-9 R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 9 TRUE 15.5555556 18 P42229 STAT5A,STAT5 NA NA NA NA NA NA NA signaling 8985947 451927 Nef Mediated CD4 R-HSA- R-HSA- AP2A2,ADTAB,CLAPA2,H 1 NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 16.9 18 O94973 NA NA NA NA P06239 LCK LCK Down-regulation 167590 164938 IP9,HYPJ,KIAA0899 Nef Mediated CD8 R-HSA- R-HSA- AP2A2,ADTAB,CLAPA2,H 1 NA NA FALSE NA FALSE FALSE FALSE 8 TRUE 14.375 18 O94973 NA NA NA NA NA NA NA Down-regulation 182218 164938 IP9,HYPJ,KIAA0899 PLC beta mediated R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE FALSE 45 TRUE 20.5555556 18 Q14643 ITPR1,INSP3R1 NA NA NA NA NA NA NA events 112043 112040 111996 Post- transcriptional R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 7 TRUE 18.1428571 18 Q9UPQ9 TNRC6B,KIAA1093 NA NA NA NA Q9UPQ9 TNRC6B,KIAA1093 NA silencing by small 426496 211000 RNAs Prolactin receptor R-HSA- R-HSA- P42229,Q9Y STAT5A,STAT5,BTRC,BT 2 NA NA FALSE NA FALSE FALSE FALSE 15 TRUE 22.2666667 18 NA NA NA NA NA NA NA signaling 1170546 1280215 297 RCP,FBW1A,FBXW1A Retrograde R-HSA- R-HSA- AP2A2,ADTAB,CLAPA2,H neurotrophin 1 NA NA FALSE NA FALSE FALSE FALSE 14 TRUE 14.6428571 18 O94973 NA NA NA NA NA NA NA 177504 187037 IP9,HYPJ,KIAA0899 signalling RUNX2 regulates R-HSA- R-HSA- genes involved in 1 NA 1 FALSE NA FALSE FALSE FALSE 8 TRUE 21.375 18 Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 8941332 8878166 cell migration Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 45 TRUE 42.8 18 NA NA NA NA NA NA P01133 EGF NA ERBB4 1236394 9006934 1250347 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 45 TRUE 42.8 18 NA NA NA NA NA NA P01133 EGF NA ERBB4 1236394 9006934 1251985 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 45 TRUE 42.8 18 NA NA NA NA NA NA P01133 EGF NA ERBB4 1236394 9006934 1250342 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 45 TRUE 42.8 18 NA NA NA NA NA NA P01133 EGF NA ERBB4 1236394 9006934 1253288 VLDLR AP2A2,ADTAB,CLAPA2,H R-HSA- R-HSA- O94973,Q1 internalisation and 2 NA NA FALSE NA FALSE FALSE FALSE 12 TRUE 12.9166667 18 IP9,HYPJ,KIAA0899,NR1 NA NA NA NA NA NA NA 8866427 8964043 3133 degradation H3,LXRA WNT5A- dependent R-HSA- R-HSA- AP2A2,ADTAB,CLAPA2,H internalization of 1 NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 13.5384615 18 O94973 NA NA NA NA P09497 CLTB NA 5140745 4086400 IP9,HYPJ,KIAA0899 FZD2, FZD5 and ROR2 WNT5A- dependent R-HSA- R-HSA- AP2A2,ADTAB,CLAPA2,H O14641,P09 1 NA 2 TRUE NA FALSE TRUE TRUE 15 TRUE 17.4 18 O94973 NA NA NA NA DVL2,CLTB NA internalization of 5099900 4086400 IP9,HYPJ,KIAA0899 497 FZD4 p75NTR negatively R-HSA- R-HSA- regulates cell cycle NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 17.6666667 18.5 NA NA NA NA NA NA Q9UKN5 PRDM4,PFM1 NA 193670 193704 via SC1

Sensing of DNA R-HSA- R-HSA- Double Strand 1 NA NA FALSE NA FALSE FALSE FALSE 6 TRUE 17.6666667 18.5 Q13315 ATM NA NA NA NA NA NA NA 5693548 5693606 Breaks ARMS-mediated R-HSA- R-HSA- KIDINS220,ARMS,KIAA1 1 NA NA FALSE NA FALSE FALSE FALSE 7 TRUE 15.4285714 19 Q9ULH0 NA NA NA NA NA NA NA activation 170984 169893 250 R-HSA- R-HSA- P01112,P06 DAP12 signaling NA 1 3 FALSE NA FALSE FALSE FALSE 29 TRUE 31.9310345 19 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,LCK,LCP2 LCK 2424491 2172127 239,Q13094

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, Deposition of new H4/C,H4FC;,HIST1H4H,H CENPA-containing R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 54 TRUE 21.1851852 19 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA NA NA NA nucleosomes at 606279 774815 M,H4FM;,HIST1H4J,H4/E the centromere ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

ESR-mediated R-HSA- R-HSA- R-HSA- NA 1 NA FALSE TRUE TRUE TRUE 128 TRUE 22.7890625 19 NA NA NA Q13451 FKBP5,AIG6,FKBP51 NA NA NA NA signaling 8939211 9006931 9018519

NR5A2,B1F,CPF,FTF,KD M4B,JHDM3B,JMJD2B,KI AA0876,HIST1H4A,H4/A, H4FA;,HIST1H4B,H4/I,H4 FI;,HIST1H4C,H4/G,H4F G;,HIST1H4D,H4/B,H4FB ;,HIST1H4E,H4/J,H4FJ;,HI O00482,O9 Estrogen- ST1H4F,H4/C,H4FC;,HIST PRMT1,HMT2,HRMT1L2, R-HSA- R-HSA- 4953,P6280 Q99873,Q9 dependent gene 5 NA 2 TRUE NA FALSE TRUE TRUE 122 TRUE 22.6393443 19 1H4H,H4/H,H4FH;,HIST1 NA NA NA NA IR1B4,TNRC6B,KIAA109 NA 9018519 8939211 5,Q4ZG55,Q UPQ9 expression H4I,H4/M,H4FM;,HIST1H 3 9UPQ9 4J,H4/E,H4FE;,HIST1H4K ,H4/D,H4FD;,HIST1H4L,H 4/K,H4FK;,HIST2H4A,H4/ N,H4F2,H4FN,HIST2H4;, HIST2H4B,H4/O,H4FO;,H IST4H4,GREB1,KIAA057 5,TNRC6B,KIAA1093

Formation of the ternary complex, R-HSA- R-HSA- P46781,P62 1 NA 2 FALSE NA FALSE FALSE FALSE 52 TRUE 19.0961538 19 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13 NA and subsequently, 72695 72737 277 the 43S complex HIV elongation R-HSA- R-HSA- arrest and NA NA 1 TRUE NA FALSE TRUE TRUE 36 TRUE 29.25 19 NA NA NA NA NA NA P18615 NELFE,RD,RDBP NA 167287 167172 recovery MET interacts with R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 5 TRUE 12.8 19 NA NA NA NA NA NA Q68CZ2 TNS3,TEM6,TENS1,TPP NA TNS proteins 8875513 8875878 TP53,P53,HIST1H4A,H4/ A,H4FA;,HIST1H4B,H4/I, H4FI;,HIST1H4C,H4/G,H4 FG;,HIST1H4D,H4/B,H4F B;,HIST1H4E,H4/J,H4FJ;, HIST1H4F,H4/C,H4FC;,HI Oxidative Stress P04637,P62 ST1H4H,H4/H,H4FH;,HIS R-HSA- R-HSA- P04637,Q9 TP53,P53,TNRC6B,KIAA1 Induced 3 1 2 FALSE NA FALSE FALSE FALSE 95 TRUE 29.7789474 19 805,Q9UPQ T1H4I,H4/M,H4FM;,HIST NA P04637 TP53,P53 NA NA 2559580 2559583 UPQ9 093 Senescence 9 1H4J,H4/E,H4FE;,HIST1H 4K,H4/D,H4FD;,HIST1H4 L,H4/K,H4FK;,HIST2H4A, H4/N,H4F2,H4FN,HIST2 H4;,HIST2H4B,H4/O,H4F O;,HIST4H4,TNRC6B,KIA A1093 Pausing and R-HSA- R-HSA- recovery of HIV NA NA 1 TRUE NA FALSE TRUE TRUE 36 TRUE 29.25 19 NA NA NA NA NA NA P18615 NELFE,RD,RDBP NA 167290 167172 elongation Pausing and recovery of Tat- R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 35 TRUE 29.6 19 NA NA NA NA NA NA P18615 NELFE,RD,RDBP NA mediated HIV 167238 167172 elongation PI3K events in R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 16 TRUE 31 19 NA NA NA NA NA NA P01133 EGF NA ERBB2 signaling 1963642 1227986 TP53,P53,HIST1H4A,H4/ A,H4FA;,HIST1H4B,H4/I, H4FI;,HIST1H4C,H4/G,H4 FG;,HIST1H4D,H4/B,H4F B;,HIST1H4E,H4/J,H4FJ;, HIST1H4F,H4/C,H4FC;,HI Pre-NOTCH P04637,P62 ST1H4H,H4/H,H4FH;,HIS P04637,Q04 R-HSA- R-HSA- TP53,P53,NOTCH2,TNRC Transcription and 3 1 3 FALSE NA FALSE FALSE FALSE 74 TRUE 22.2297297 19 805,Q9UPQ T1H4I,H4/M,H4FM;,HIST NA P04637 TP53,P53 NA 721,Q9UPQ NA 1912408 1912422 6B,KIAA1093 Translation 9 1H4J,H4/E,H4FE;,HIST1H 9 4K,H4/D,H4FD;,HIST1H4 L,H4/K,H4FK;,HIST2H4A, H4/N,H4F2,H4FN,HIST2 H4;,HIST2H4B,H4/O,H4F O;,HIST4H4,TNRC6B,KIA A1093 SLIT1,KIAA0813,MEGF4, P46781,P61 Regulation of O75093,P23 SLIL1,RPS3,OK/SW- 289,P62277, RPS9,PSME3,RPS13,PS R-HSA- R-HSA- expression of SLITs 4 NA 7 TRUE NA FALSE TRUE TRUE 173 TRUE 34.3872832 19 396,P25786, cl.26,PSMA1,HC2,NU,PR PSMA1 NA NA NA Q13200,Q1 MD2,TRAP2,DAG1,RPL1 PSMD2 9010553 376176 and ROBOs P38919 OS30,PSC2,EIF4A3,DDX4 4118,Q96L2 0L,ROBO1,DUTT1 8,KIAA0111 1,Q9Y6N7 Ribosomal R-HSA- R-HSA- P46781,P62 scanning and start 1 NA 2 FALSE NA FALSE FALSE FALSE 59 TRUE 17.779661 19 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13 NA 72702 72737 277 codon recognition RNA Polymerase II R-HSA- R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, Transcription NA NA 2 FALSE TRUE TRUE TRUE 61 TRUE 24.6557377 19 NA NA NA NA NA NA NA 75955 73857 113418 615 RD,RDBP Elongation RNA Polymerase II R-HSA- R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, Transcription NA NA 2 FALSE TRUE TRUE TRUE 61 TRUE 24.6557377 19 NA NA NA NA NA NA NA 75955 73857 112382 615 RD,RDBP Elongation ROBO receptors R-HSA- R-HSA- PPP3CB,CALNA2,CALNB, 1 NA 1 TRUE NA FALSE TRUE TRUE 9 TRUE 22.2222222 19 P22612 PRKACG NA NA NA NA P16298 NA bind AKAP5 9010642 376176 CNA2 Tat-mediated HIV R-HSA- R-HSA- elongation arrest NA NA 1 TRUE NA FALSE TRUE TRUE 35 TRUE 29.6 19 NA NA NA NA NA NA P18615 NELFE,RD,RDBP NA 167243 167172 and recovery

TP53 Regulates P04637,P18 TP53,P53,ERCC2,XPD,XP R-HSA- R-HSA- P04637,Q13 P04637,Q13 Transcription of 2 2 4 FALSE NA FALSE FALSE FALSE 65 TRUE 25.1538462 19 TP53,P53,ATM NA TP53,P53,ATR,FRP1 NA 074,P18615, DC,NELFE,RD,RDBP,BRC NA 6796648 3700989 315 535 DNA Repair Genes P38398 A1,RNF53

Translation R-HSA- R-HSA- P46781,P62 initiation complex 1 NA 2 FALSE NA FALSE FALSE FALSE 59 TRUE 17.8983051 19 P23396 RPS3,OK/SW-cl.26 NA NA NA NA RPS9,RPS13 NA 72649 72662 277 formation O95059,P35 RPP14,NUP214,CAIN,CA tRNA processing in R-HSA- R-HSA- P62826,Q52 RAN,ARA24,OK/SW- 3 NA 4 FALSE NA FALSE FALSE FALSE 58 TRUE 16.5 19 NA NA NA NA 658,Q10570 N,KIAA0023,CPSF1,CPSF NA the nucleus 6784531 72306 LJ0,Q99567 cl.81,FAM98B,NUP88 ,Q52LJ0 160,FAM98B MicroRNA RAN,ARA24,OK/SW- R-HSA- R-HSA- P62826,Q9 DICER1,DICER,HERNA,KI (miRNA) 2 NA 1 FALSE NA FALSE FALSE FALSE 26 TRUE 27.5 19.5 cl.81,DROSHA,RN3,RNA NA NA NA NA Q9UPY3 NA 203927 211000 NRR4 AA0928 biogenesis SE3L,RNASEN RUNX3 regulates R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 10 TRUE 24.8 19.5 NA NA NA NA NA NA P25440 BRD2,KIAA9001,RING3 NA p14-ARF 8951936 8878159 SHC1 events in R-HSA- R-HSA- P01112,P01 NA 1 2 TRUE NA FALSE TRUE TRUE 22 TRUE 33.5454545 19.5 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,EGF NA ERBB2 signaling 1250196 1227986 133 Adenylate cyclase R-HSA- R-HSA- NA 1 NA FALSE NA FALSE FALSE FALSE 14 TRUE 18.4285714 20 NA NA NA Q08462 ADCY2,KIAA1060 NA NA NA NA inhibitory pathway 170670 112040

Adenylate cyclase R-HSA- R-HSA- NA 1 NA FALSE NA FALSE FALSE FALSE 14 TRUE 18.4285714 20 NA NA NA Q08462 ADCY2,KIAA1060 NA NA NA NA inhibitory pathway 170670 997269

Constitutive Signaling by R-HSA- R-HSA- CD80,CD28LG,CD28LG1, P01133,P06 1 1 3 FALSE NA FALSE FALSE FALSE 71 TRUE 26.7323944 20 P12931 SRC,SRC1 SRC P33681 NA EGF,LCK,IRS2 LCK Aberrant PI3K in 2219530 2219528 LAB7 239,Q9Y4H2 Cancer DAG and IP3 R-HSA- R-HSA- R-HSA- 1 NA NA FALSE FALSE FALSE FALSE 33 TRUE 22.9090909 20 Q14643 ITPR1,INSP3R1 NA NA NA NA NA NA NA signaling 1489509 9006925 111997 Downstream R-HSA- R-HSA- P12931,P42 SRC,SRC1,STAT5A,STAT 2 1 1 TRUE NA FALSE TRUE TRUE 29 TRUE 33.3448276 20 SRC P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA signal transduction 186763 186797 229 5

Erythropoietin R-HSA- R-HSA- 1 NA 1 TRUE NA FALSE TRUE TRUE 7 TRUE 20 20 P42229 STAT5A,STAT5 NA NA NA NA Q9Y4H2 IRS2 NA activates STAT5 9027283 9006335 G alpha (z) R-HSA- R-HSA- A5PLK6,Q04 RGSL1,RGSL,RGSL2,PRK NA 1 2 FALSE NA FALSE FALSE FALSE 47 TRUE 19.9148936 20 NA NA NA Q08462 ADCY2,KIAA1060 NA PRKCQ signalling events 418597 388396 759 CQ,PRKCT GRB2 events in R-HSA- R-HSA- P01112,P01 NA 1 2 TRUE NA FALSE TRUE TRUE 16 TRUE 38.0625 20 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,EGF NA ERBB2 signaling 1963640 1227986 133 Negative R-HSA- R-HSA- R-HSA- regulation of the 1 NA 1 TRUE TRUE TRUE TRUE 106 TRUE 26.5943396 20 Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 199418 1257604 6811558 PI3K/AKT network Recognition of DNA damage by R-HSA- R-HSA- DTL,CDT2,CDW1,DCAF2, PCNA-containing 1 NA 1 FALSE NA FALSE FALSE FALSE 31 TRUE 41.6129032 20 Q13619 CUL4A NA NA NA NA Q9NZJ0 NA 110314 73893 L2DTL,RAMP replication complex HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H RUNX1 regulates 4/H,H4FH;,HIST1H4I,H4/ genes involved in P62805,Q9 Q04759,Q9 PRKCQ,PRKCT,PRMT1,H R-HSA- R-HSA- M,H4FM;,HIST1H4J,H4/E megakaryocyte 3 NA 3 FALSE NA FALSE FALSE FALSE 67 TRUE 22.8059701 20 UPQ9,Q9UP NA NA NA NA 9873,Q9UP MT2,HRMT1L2,IR1B4,T PRKCQ 8936459 8878171 ,H4FE;,HIST1H4K,H4/D,H differentiation and S6 Q9 NRC6B,KIAA1093 4FD;,HIST1H4L,H4/K,H4F platelet function K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, TNRC6B,KIAA1093,SETD 1B,KIAA1076,KMT2G,SE T1B

SHC1 events in R-HSA- R-HSA- NA 1 1 TRUE NA FALSE TRUE TRUE 14 TRUE 40.7857143 20 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA ERBB4 signaling 1250347 1236394 R-HSA- R-HSA- Signaling by Leptin 1 NA 1 FALSE NA FALSE FALSE FALSE 11 TRUE 20.9090909 20 P42229 STAT5A,STAT5 NA NA NA NA Q9Y4H2 IRS2 NA 2586552 162582 P01112,P06 HRAS,HRAS1,LCK,FES,FP Signaling by SCF- R-HSA- R-HSA- R-HSA- 1 1 4 FALSE TRUE TRUE TRUE 43 TRUE 28.4186047 20 P42229 STAT5A,STAT5 NA P01112 HRAS,HRAS1 NA 239,P07332, S,PTPRU,FMI,PCP2,PTPR LCK,FES KIT 1433557 9006934 1433559 Q92729 O

Toll Like Receptor R-HSA- R-HSA- R-HSA- P17213,Q8I BPI,SFTPA1,COLEC4,PSA O00206,P17 2 NA 3 FALSE TRUE TRUE TRUE 126 TRUE 29.1111111 20 NA NA NA NA TLR4,BPI,LBP NA 4 (TLR4) Cascade 166016 168898 166020 WL2 P,SFTP1,SFTPA,SFTPA1B 213,P18428

Transcription- Coupled R-HSA- R-HSA- R-HSA- P18074,Q03 ERCC2,XPD,XPDC,ERCC6, Nucleotide 1 1 2 FALSE TRUE TRUE TRUE 78 TRUE 31.8589744 20 Q13619 CUL4A NA Q9UNP9 PPIE,CYP33 NA NA 6781827 5696398 6781823 468 CSB Excision Repair (TC- NER) Transcription- Coupled R-HSA- R-HSA- R-HSA- P18074,Q03 ERCC2,XPD,XPDC,ERCC6, Nucleotide 1 1 2 FALSE TRUE TRUE TRUE 78 TRUE 31.8589744 20 Q13619 CUL4A NA Q9UNP9 PPIE,CYP33 NA NA 6781827 5696398 6782135 468 CSB Excision Repair (TC- NER) Transcription- Coupled R-HSA- R-HSA- R-HSA- P18074,Q03 ERCC2,XPD,XPDC,ERCC6, Nucleotide 1 1 2 FALSE TRUE TRUE TRUE 78 TRUE 31.8589744 20 Q13619 CUL4A NA Q9UNP9 PPIE,CYP33 NA NA 6781827 5696398 6782210 468 CSB Excision Repair (TC- NER) Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 1963642 Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 8863795 Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 1251932 Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 1963640 Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE FALSE FALSE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 1306955 Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 6785631 Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 1250196 Signaling by R-HSA- R-HSA- R-HSA- 1 NA 1 FALSE TRUE TRUE TRUE 50 TRUE 42.34 20.5 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA ERBB2 1227986 9006934 8847993 TRAF6 mediated R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 24 TRUE 24.4166667 20.5 NA NA NA NA NA NA O95786 DDX58 NA NF-kB activation 933542 168928 Activation of IRF3/IRF7 R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 17 TRUE 61.9411765 21 NA NA NA NA NA NA O00206 TLR4 NA mediated by 936964 937061 TBK1/IKK epsilon

Adenylate cyclase R-HSA- R-HSA- NA 1 NA FALSE NA FALSE FALSE FALSE 10 TRUE 20.3 21 NA NA NA Q08462 ADCY2,KIAA1060 NA NA NA NA activating pathway 170660 112040

Dual Incision in GG- R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 41 TRUE 37.9512195 21 Q13619 CUL4A NA NA NA NA P18074 ERCC2,XPD,XPDC NA NER 5696400 5696399

PI5P, PP2A and R-HSA- R-HSA- CD80,CD28LG,CD28LG1, P01133,P06 IER3 Regulate 1 1 3 TRUE NA FALSE TRUE TRUE 99 TRUE 27.2525253 21 P12931 SRC,SRC1 SRC P33681 NA EGF,LCK,IRS2 LCK 6811558 199418 LAB7 239,Q9Y4H2 PI3K/AKT Signaling

Regulation of KIT R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 16 TRUE 30.25 21 NA NA NA NA NA NA P06239 LCK LCK signaling 1433559 1433557 TRIF-mediated R-HSA- R-HSA- O00206,Q1 programmed cell NA NA 2 FALSE NA FALSE FALSE FALSE 9 TRUE 19.8888889 21 NA NA NA NA NA NA TLR4,CASP8,MCH5 NA 2562578 937061 4790 death VEGFR2 mediated R-HSA- R-HSA- 1 1 1 TRUE NA FALSE TRUE TRUE 19 TRUE 31.8947368 21 Q14643 ITPR1,INSP3R1 NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA cell proliferation 5218921 4420097 Regulation of TP53 R-HSA- R-HSA- 1 1 1 FALSE NA FALSE FALSE FALSE 2 TRUE 21.5 21.5 P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA Expression 6804754 6806003 TLR3-mediated TICAM1- R-HSA- R-HSA- dependent NA NA 1 FALSE NA FALSE FALSE FALSE 6 TRUE 20 21.5 NA NA NA NA NA NA Q14790 CASP8,MCH5 NA 9013957 168164 programmed cell death R-HSA- R-HSA- PKA activation 1 1 NA TRUE NA FALSE TRUE TRUE 17 TRUE 26.2941176 22 P22612 PRKACG NA Q08462 ADCY2,KIAA1060 NA NA NA NA 163615 111931 PKA activation in R-HSA- R-HSA- glucagon 1 1 NA TRUE NA FALSE TRUE TRUE 17 TRUE 23.7647059 22 P22612 PRKACG NA Q08462 ADCY2,KIAA1060 NA NA NA NA 164378 163359 signalling PKA-mediated R-HSA- R-HSA- R-HSA- phosphorylation of 1 NA NA FALSE TRUE TRUE TRUE 19 TRUE 26.3684211 22 P22612 PRKACG NA NA NA NA NA NA NA 111931 111933 163615 CREB R-HSA- R-HSA- R-HSA- Signalling to RAS NA 1 1 FALSE TRUE TRUE TRUE 20 TRUE 33.45 22 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 167044 187687 171007

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H Activation of 4E,H4/J,H4FJ;,HIST1H4F, anterior HOX H4/C,H4FC;,HIST1H4H,H genes in hindbrain R-HSA- R-HSA- 1 1 NA FALSE NA FALSE FALSE FALSE 91 TRUE 22.8351648 23 P62805 4/H,H4FH;,HIST1H4I,H4/ NA Q92600 CNOT9,RCD1,RQCD1 NA NA NA NA development 5617472 5619507 M,H4FM;,HIST1H4J,H4/E during early ,H4FE;,HIST1H4K,H4/D,H embryogenesis 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

CD28 co- R-HSA- R-HSA- R-HSA- CD80,CD28LG,CD28LG1, NA 1 1 FALSE TRUE TRUE TRUE 33 TRUE 28.4848485 23 NA NA NA P33681 NA P06239 LCK LCK stimulation 389356 388841 389359 LAB7 CD28 co- R-HSA- R-HSA- R-HSA- CD80,CD28LG,CD28LG1, NA 1 1 FALSE TRUE TRUE TRUE 33 TRUE 28.4848485 23 NA NA NA P33681 NA P06239 LCK LCK stimulation 389356 388841 389357 LAB7

TP53,P53,HIST1H4A,H4/ A,H4FA;,HIST1H4B,H4/I, H4FI;,HIST1H4C,H4/G,H4 FG;,HIST1H4D,H4/B,H4F B;,HIST1H4E,H4/J,H4FJ;, DNA HIST1H4F,H4/C,H4FC;,HI Damage/Telomere R-HSA- R-HSA- R-HSA- P04637,P62 ST1H4H,H4/H,H4FH;,HIS 3 1 1 FALSE TRUE TRUE TRUE 61 TRUE 22.2459016 23 NA P04637 TP53,P53 NA P04637 TP53,P53 NA Stress Induced 2559586 2559583 2559584 805,Q13315 T1H4I,H4/M,H4FM;,HIST Senescence 1H4J,H4/E,H4FE;,HIST1H 4K,H4/D,H4FD;,HIST1H4 L,H4/K,H4FK;,HIST2H4A, H4/N,H4F2,H4FN,HIST2 H4;,HIST2H4B,H4/O,H4F O;,HIST4H4,ATM

A9QM74,O7 KPNA7,FLNB,FLN1L,FLN ISG15 antiviral R-HSA- R-HSA- O95786,P35 DDX58,NUP214,CAIN,CA 4 NA 2 FALSE NA FALSE FALSE FALSE 75 TRUE 28.1866667 23 5369,P3891 3,TABP,TAP,EIF4A3,DDX NA NA NA NA NA mechanism 1169408 1169410 658 N,KIAA0023 9,Q99567 48,KIAA0111,NUP88

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE FALSE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 166016 937039 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168188 445989 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE TRUE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168179 445989 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168188 937042 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE TRUE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 166016 445989 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE FALSE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168179 937042 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE FALSE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168179 450294 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE FALSE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 166016 937042 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168188 937039 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE FALSE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168179 937039 membrane

MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE FALSE TRUE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 166016 450294 membrane MyD88:MAL(TIRAP ) cascade initiated R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 95 TRUE 33.8526316 23 NA NA NA NA NA NA O00206 TLR4 NA on plasma 166058 168188 450294 membrane

Negative R-HSA- R-HSA- R-HSA- regulation of NA 1 1 TRUE FALSE TRUE TRUE 40 TRUE 45.075 23 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 5675221 5673001 5674499 MAPK pathway NOD1/2 Signaling R-HSA- R-HSA- Q14790,Q9 CASP8,MCH5,NOD1,CAR 1 NA 2 FALSE NA FALSE FALSE FALSE 31 TRUE 22 23 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA NA Pathway 168638 168643 Y239 D4 TP53,P53,AKT2,MTOR,F O75604,P04 P04637,P31 Regulation of TP53 R-HSA- R-HSA- USP2,UBP41,TP53,P53,A RAP,FRAP1,FRAP2,RAFT 4 1 4 FALSE NA FALSE FALSE FALSE 36 TRUE 43.1944444 23 637,Q13315 NA P04637 TP53,P53 NA 751,P42345, AKT2 Degradation 6804757 6806003 TM,AKT3,PKBG 1,RAPT1,DAXX,BING2,D ,Q9Y243 Q9UER7 AP6 Toll Like Receptor R-HSA- R-HSA- R-HSA- SFTPA1,COLEC4,PSAP,SF TLR1:TLR2 1 NA NA FALSE TRUE TRUE TRUE 95 TRUE 33.8526316 23 Q8IWL2 NA NA NA NA NA NA NA 168179 181438 166058 TP1,SFTPA,SFTPA1B Cascade R-HSA- R-HSA- Activation of AKT2 NA NA 1 TRUE NA FALSE TRUE TRUE 4 TRUE 26 23.5 NA NA NA NA NA NA P31751 AKT2 AKT2 165158 109704 Erythropoietin activates R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 7 TRUE 22.2857143 24 NA NA NA NA NA NA Q9Y4H2 IRS2 NA Phospholipase C 9027277 9006335 gamma (PLCG) IKK complex R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB recruitment 1 NA 1 FALSE NA FALSE FALSE FALSE 23 TRUE 55.9130435 24 P51668 NA NA NA NA O00206 TLR4 NA 937041 937061 CH5,UBCH5A mediated by RIP1 Vasopressin regulates renal R-HSA- R-HSA- water 1 1 1 FALSE NA FALSE FALSE FALSE 43 TRUE 22.372093 24 P22612 PRKACG NA Q08462 ADCY2,KIAA1060 NA P55087 AQP4 NA 432040 445717 homeostasis via Aquaporins CD28 dependent R-HSA- R-HSA- CD80,CD28LG,CD28LG1, NA 1 1 TRUE NA FALSE TRUE TRUE 12 TRUE 30.1666667 25 NA NA NA P33681 NA P06239 LCK LCK Vav1 pathway 389359 389356 LAB7 Glucagon-like Peptide-1 (GLP1) R-HSA- R-HSA- P22612,Q14 2 NA NA TRUE NA FALSE TRUE TRUE 42 TRUE 22.5 25 PRKACG,ITPR1,INSP3R1 NA NA NA NA NA NA NA regulates insulin 381676 422356 643 secretion

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 TRUE FALSE TRUE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168142 937039 plasma membrane

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 TRUE TRUE TRUE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168142 445989 plasma membrane

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 FALSE TRUE TRUE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168176 445989 plasma membrane

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 TRUE FALSE TRUE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168142 937042 plasma membrane

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 TRUE FALSE TRUE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168142 450294 plasma membrane

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 FALSE FALSE FALSE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168176 450294 plasma membrane

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 FALSE FALSE FALSE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168176 937039 plasma membrane

MyD88 cascade R-HSA- R-HSA- R-HSA- initiated on NA NA 1 FALSE FALSE FALSE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 975871 168176 937042 plasma membrane

R-HSA- R-HSA- p38MAPK events NA 1 1 TRUE NA FALSE TRUE TRUE 13 TRUE 32.2307692 25 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 171007 167044 PECAM1 R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 12 TRUE 31.3333333 25 NA NA NA NA NA NA P06239 LCK LCK interactions 210990 202733 R-HSA- R-HSA- RSK activation NA NA 1 TRUE NA FALSE TRUE TRUE 6 TRUE 30.8333333 25 NA NA NA NA NA NA Q9UK32 RPS6KA6,RSK4 RPS6KA6 444257 442742 Toll Like Receptor R-HSA- R-HSA- R-HSA- 10 (TLR10) NA NA 1 FALSE TRUE TRUE TRUE 85 TRUE 36.0588235 25 NA NA NA NA NA NA Q9BXR5 TLR10,UNQ315/PRO358 NA 168142 168898 975871 Cascade UBE2D1,SFT,UBC5A,UB CH5,UBCH5A,HIST1H4A, H4/A,H4FA;,HIST1H4B,H 4/I,H4FI;,HIST1H4C,H4/ G,H4FG;,HIST1H4D,H4/B ,H4FB;,HIST1H4E,H4/J,H Senescence- 4FJ;,HIST1H4F,H4/C,H4F Associated R-HSA- R-HSA- P51668,P62 2 1 NA FALSE NA FALSE FALSE FALSE 80 TRUE 34.6875 26 C;,HIST1H4H,H4/H,H4FH; NA Q9UJX4 ANAPC5,APC5 NA NA NA NA Secretory 2559582 2559583 805 ,HIST1H4I,H4/M,H4FM;, Phenotype (SASP) HIST1H4J,H4/E,H4FE;,HI ST1H4K,H4/D,H4FD;,HIS T1H4L,H4/K,H4FK;,HIST2 H4A,H4/N,H4F2,H4FN,HI ST2H4;,HIST2H4B,H4/O, H4FO;,HIST4H4 R-HSA- R-HSA- PDE3B signalling NA NA 1 FALSE NA FALSE FALSE FALSE 2 TRUE 26.5 26.5 NA NA NA NA NA NA P31751 AKT2 AKT2 165160 109703 Dual incision in TC- R-HSA- R-HSA- P18074,Q03 ERCC2,XPD,XPDC,ERCC6, 1 1 2 TRUE NA FALSE TRUE TRUE 65 TRUE 36.7384615 27 Q13619 CUL4A NA Q9UNP9 PPIE,CYP33 NA NA NER 6782135 6781827 468 CSB R-HSA- R-HSA- R-HSA- P04637,P25 TP53,P53,PSMA1,HC2,N P04637,P61 TP53,P53,PSME3,PSMD2 G2/M Checkpoints 2 1 3 FALSE TRUE TRUE TRUE 151 TRUE 39.7682119 27 PSMA1 P04637 TP53,P53 NA PSMD2 69481 69620 69473 786 U,PROS30,PSC2 289,Q13200 ,TRAP2

R-HSA- R-HSA- R-HSA- P04637,P25 TP53,P53,PSMA1,HC2,N P04637,P61 TP53,P53,PSME3,PSMD2 G2/M Checkpoints 2 1 3 FALSE TRUE TRUE TRUE 151 TRUE 39.7682119 27 PSMA1 P04637 TP53,P53 NA PSMD2 69481 69620 176187 786 U,PROS30,PSC2 289,Q13200 ,TRAP2

R-HSA- R-HSA- R-HSA- P04637,P25 TP53,P53,PSMA1,HC2,N P04637,P61 TP53,P53,PSME3,PSMD2 G2/M Checkpoints 2 1 3 FALSE FALSE FALSE TRUE 151 TRUE 39.7682119 27 PSMA1 P04637 TP53,P53 NA PSMD2 69481 69620 69478 786 U,PROS30,PSC2 289,Q13200 ,TRAP2

Glucagon signaling R-HSA- R-HSA- R-HSA- in metabolic NA 1 NA FALSE TRUE TRUE TRUE 33 TRUE 25.6666667 27 NA NA NA Q08462 ADCY2,KIAA1060 NA NA NA NA 163359 163685 164378 regulation

PPP1R12A,MBS,MYPT1, RHO GTPases R-HSA- R-HSA- R-HSA- O14974,P31 1 NA 3 FALSE TRUE TRUE TRUE 63 TRUE 23.5238095 27 Q16513 PKN2,PRK2,PRKCL2 PKN2 NA NA NA SFN,HME1,MYH14,KIAA NA activate PKNs 5625740 195258 5625886 947,Q7Z406 2034,FP17425 Translesion R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 19 TRUE 57.5263158 27 NA NA NA NA NA NA P55072 VCP NA Synthesis by POLH 110320 110313 Adrenaline,noradr R-HSA- R-HSA- CACNA1C,CACH2,CACN2, CACNA1D,CACH3,CACN4 enaline inhibits 1 NA 1 TRUE NA FALSE TRUE TRUE 28 TRUE 23.25 27.5 Q13936 NA NA NA NA Q01668 NA 400042 422356 CACNL1A1,CCHL1A1 ,CACNL1A2,CCHL1A2 insulin secretion

JNK (c-Jun kinases) phosphorylation and activation R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 18 TRUE 27.4444444 27.5 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA mediated by 450321 450294 activated human TAK1

Erythropoietin activates R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 12 TRUE 26.75 28 NA NA NA NA NA NA Q9Y4H2 IRS2 NA Phosphoinositide-3- 9027276 9006335 kinase (PI3K) PI3K/AKT R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 9 TRUE 33.1111111 28 NA NA NA NA NA NA Q9Y4H2 IRS2 NA activation 198203 187037 TRAF6-mediated induction of TAK1 R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 17 TRUE 65.7647059 28 NA NA NA NA NA NA O00206 TLR4 NA complex within 937072 937061 TLR4 complex IRAK2 mediated activation of TAK1 R-HSA- R-HSA- complex upon NA NA 1 FALSE NA FALSE FALSE FALSE 16 TRUE 69.5 28.5 NA NA NA NA NA NA O00206 TLR4 NA 975163 975138 TLR7/8 or 9 stimulation RNA Polymerase I R-HSA- R-HSA- P18074,Q9H ERCC2,XPD,XPDC,POLR1 NA NA 2 FALSE NA FALSE FALSE FALSE 30 TRUE 25.0666667 28.5 NA NA NA NA NA NA NA Promoter Escape 73772 73854 9Y6 B TICAM1,TRAF6- dependent R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 16 TRUE 69.5 28.5 NA NA NA NA NA NA O00206 TLR4 NA induction of TAK1 9014325 168164 complex activated TAK1 R-HSA- R-HSA- mediates p38 1 NA 1 FALSE NA FALSE FALSE FALSE 19 TRUE 28.1578947 29 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA 450302 450294 MAPK activation CREB phosphorylation R-HSA- R-HSA- through the 1 NA NA FALSE NA FALSE FALSE FALSE 8 TRUE 29.875 29 P22612 PRKACG NA NA NA NA NA NA NA 442720 438064 activation of Adenylate Cyclase Downregulation of R-HSA- R-HSA- ERBB2:ERBB3 1 NA 1 TRUE NA FALSE TRUE TRUE 13 TRUE 76.6153846 29 Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 1358803 8863795 signaling Gap-filling DNA repair synthesis R-HSA- R-HSA- P18074,Q03 ERCC2,XPD,XPDC,ERCC6, 1 1 2 TRUE NA FALSE TRUE TRUE 64 TRUE 37.40625 29 Q13619 CUL4A NA Q9UNP9 PPIE,CYP33 NA NA and ligation in TC- 6782210 6781827 468 CSB NER R-HSA- R-HSA- R-HSA- P07205,P22 P05062,Q9B ALDOB,ALDB,ADPGK,PS Glycolysis 2 NA 2 FALSE TRUE TRUE TRUE 71 TRUE 19.4225352 29 PGK2,PGKB,PRKACG NA NA NA NA NA 70171 70326 170822 612 RR6 EC0260

NEP/NS2 Interacts R-HSA- R-HSA- P62826,Q99 RAN,ARA24,OK/SW- NUP214,CAIN,CAN,KIAA with the Cellular 2 NA 1 FALSE NA FALSE FALSE FALSE 37 TRUE 27.1891892 29 NA NA NA NA P35658 NA 168333 168274 567 cl.81,NUP88 0023 Export Machinery

NS1 Mediated R-HSA- R-HSA- R-HSA- A9QM74,Q9 NUP214,CAIN,CAN,KIAA Effects on Host 2 NA 1 FALSE FALSE FALSE FALSE 41 TRUE 23.4878049 29 KPNA7,NUP88 NA NA NA NA P35658 NA 168276 168253 168305 9567 0023 Pathways NS1 Mediated R-HSA- R-HSA- R-HSA- A9QM74,Q9 NUP214,CAIN,CAN,KIAA Effects on Host 2 NA 1 FALSE FALSE FALSE FALSE 41 TRUE 23.4878049 29 KPNA7,NUP88 NA NA NA NA P35658 NA 168276 168253 168315 9567 0023 Pathways NS1 Mediated R-HSA- R-HSA- R-HSA- A9QM74,Q9 NUP214,CAIN,CAN,KIAA Effects on Host 2 NA 1 FALSE FALSE FALSE FALSE 41 TRUE 23.4878049 29 KPNA7,NUP88 NA NA NA NA P35658 NA 168276 168253 169131 9567 0023 Pathways Nuclear import of R-HSA- R-HSA- P62826,Q99 RAN,ARA24,OK/SW- NUP214,CAIN,CAN,KIAA 2 NA 1 FALSE NA FALSE FALSE FALSE 33 TRUE 27.7272727 29 NA NA NA NA P35658 NA Rev protein 180746 177243 567 cl.81,NUP88 0023 Nuclear Pore R-HSA- R-HSA- NEK9,KIAA1995,NEK8,N NUP214,CAIN,CAN,KIAA Complex (NPC) 1 1 1 FALSE NA FALSE FALSE FALSE 35 TRUE 27.9714286 29 Q99567 NUP88 NA Q8TD19 NA P35658 NA 3301854 2980766 ERCC 0023 Disassembly Platelet R-HSA- R-HSA- sensitization by 1 NA NA TRUE NA FALSE TRUE TRUE 17 TRUE 34.4117647 29 P09769 FGR,SRC2 FGR NA NA NA NA NA NA 432142 418346 LDL R-HSA- R-HSA- RAF activation NA 1 1 TRUE NA FALSE TRUE TRUE 25 TRUE 35.68 29 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 5673000 5673001

Regulation of Glucokinase by R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA 1 NA 1 TRUE NA FALSE TRUE TRUE 31 TRUE 28.8387097 29 Q99567 NUP88 NA NA NA NA P35658 NA Glucokinase 170822 70171 0023 Regulatory Protein

Rev-mediated R-HSA- R-HSA- P62826,Q99 RAN,ARA24,OK/SW- NUP214,CAIN,CAN,KIAA nuclear export of 2 NA 1 FALSE NA FALSE FALSE FALSE 35 TRUE 26.8571429 29 NA NA NA NA P35658 NA 165054 177243 567 cl.81,NUP88 0023 HIV RNA Rev-mediated R-HSA- R-HSA- P62826,Q99 RAN,ARA24,OK/SW- NUP214,CAIN,CAN,KIAA nuclear export of 2 NA 1 FALSE NA FALSE FALSE FALSE 35 TRUE 26.8571429 29 NA NA NA NA P35658 NA 165054 162599 567 cl.81,NUP88 0023 HIV RNA R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA snRNP Assembly 1 NA 1 FALSE NA FALSE FALSE FALSE 52 TRUE 19.7307692 29 Q99567 NUP88 NA NA NA NA P35658 NA 191859 194441 0023 HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, SUMOylation of H4/C,H4FC;,HIST1H4H,H chromatin R-HSA- R-HSA- P62805,Q99 4/H,H4FH;,HIST1H4I,H4/ P35658,Q01 NUP214,CAIN,CAN,KIAA 2 NA 2 FALSE NA FALSE FALSE FALSE 57 TRUE 21.4912281 29 NA NA NA NA NA organization 4551638 3108232 567 M,H4FM;,HIST1H4J,H4/E 826 0023,SATB1 proteins ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, NUP88 SUMOylation of R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA DNA replication 1 NA 1 FALSE NA FALSE FALSE FALSE 45 TRUE 23.6222222 29 Q99567 NUP88 NA NA NA NA P35658 NA 4615885 3108232 0023 proteins SUMOylation of NUP214,CAIN,CAN,KIAA R-HSA- R-HSA- P35658,Q9Y RNA binding 1 NA 2 FALSE NA FALSE FALSE FALSE 46 TRUE 23.2173913 29 Q99567 NUP88 NA NA NA NA 0023,NOP58,NOL5,NOP NA 4570464 3108232 2X3 proteins 5,HSPC120 SUMOylation of R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA SUMOylation 1 NA 1 FALSE NA FALSE FALSE FALSE 34 TRUE 28.3235294 29 Q99567 NUP88 NA NA NA NA P35658 NA 4085377 3108232 0023 proteins SUMOylation of R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA ubiquitinylation 1 NA 1 FALSE NA FALSE FALSE FALSE 38 TRUE 26.1578947 29 Q99567 NUP88 NA NA NA NA P35658 NA 3232142 3108232 0023 proteins TAK1 activates NFkB by R-HSA- R-HSA- phosphorylation 1 NA 1 TRUE NA FALSE TRUE TRUE 28 TRUE 29.0357143 29 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA 445989 166058 and activation of IKKs complex TAK1 activates NFkB by R-HSA- R-HSA- phosphorylation 1 NA 1 FALSE NA FALSE FALSE TRUE 28 TRUE 29.0357143 29 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA 445989 168164 and activation of IKKs complex TAK1 activates NFkB by R-HSA- R-HSA- phosphorylation 1 NA 1 FALSE NA FALSE FALSE TRUE 28 TRUE 29.0357143 29 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA 445989 975138 and activation of IKKs complex TAK1 activates NFkB by R-HSA- R-HSA- phosphorylation 1 NA 1 TRUE NA FALSE TRUE TRUE 28 TRUE 29.0357143 29 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA 445989 975871 and activation of IKKs complex TAK1 activates NFkB by R-HSA- R-HSA- phosphorylation 1 NA 1 FALSE NA FALSE FALSE TRUE 28 TRUE 29.0357143 29 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA 445989 937061 and activation of IKKs complex TAK1 activates NFkB by R-HSA- R-HSA- phosphorylation 1 NA 1 TRUE NA FALSE TRUE TRUE 28 TRUE 29.0357143 29 Q9HC29 NOD2,CARD15,IBD1 NA NA NA NA Q9Y239 NOD1,CARD4 NA 445989 9020702 and activation of IKKs complex Transport of Mature mRNA P35658,Q10 NUP214,CAIN,CAN,KIAA R-HSA- R-HSA- Derived from an 1 NA 3 FALSE NA FALSE FALSE FALSE 41 TRUE 25 29 Q99567 NUP88 NA NA NA NA 570,Q9UKF 0023,CPSF1,CPSF160,CP NA 159231 159234 Intronless 6 SF3,CPSF73 Transcript Transport of Ribonucleoprotein R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA 1 NA 1 FALSE NA FALSE FALSE FALSE 36 TRUE 27.4166667 29 Q99567 NUP88 NA NA NA NA P35658 NA s into the Host 168271 168255 0023 Nucleus Transport of the R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA SLBP Dependant 1 NA 1 FALSE NA FALSE FALSE FALSE 35 TRUE 28.0857143 29 Q99567 NUP88 NA NA NA NA P35658 NA 159230 159234 0023 Mature mRNA Transport of the R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA SLBP independent 1 NA 1 FALSE NA FALSE FALSE FALSE 34 TRUE 28.7941176 29 Q99567 NUP88 NA NA NA NA P35658 NA 159227 159234 0023 Mature mRNA Vpr-mediated R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA nuclear import of 1 NA 1 FALSE NA FALSE FALSE FALSE 39 TRUE 26 29 Q99567 NUP88 NA NA NA NA P35658 NA 180910 176033 0023 PICs

IRS-related events R-HSA- R-HSA- R-HSA- P08069,Q9Y NA NA 2 FALSE TRUE TRUE TRUE 52 TRUE 33.0576923 29.5 NA NA NA NA NA NA IGF1R,IRS2 IGF1R triggered by IGF1R 2428928 2428924 112399 4H2

R-HSA- R-HSA- R-HSA- PI3K Cascade NA NA 1 TRUE FALSE TRUE TRUE 44 TRUE 32.1136364 29.5 NA NA NA NA NA NA Q9Y4H2 IRS2 NA 109704 112399 109703 R-HSA- R-HSA- R-HSA- PI3K Cascade NA NA 1 TRUE TRUE TRUE TRUE 44 TRUE 32.1136364 29.5 NA NA NA NA NA NA Q9Y4H2 IRS2 NA 109704 112399 165158 Signaling by Type 1 Insulin-like R-HSA- R-HSA- R-HSA- O75339,P08 CILP,UNQ602/PRO1188, 1 NA 2 FALSE FALSE FALSE FALSE 54 TRUE 32.6666667 29.5 O75339 CILP,UNQ602/PRO1188 NA NA NA NA IGF1R Growth Factor 1 2404192 9006934 2428924 069 IGF1R Receptor (IGF1R) Viral Messenger R-HSA- R-HSA- NUP214,CAIN,CAN,KIAA 1 NA 1 FALSE NA FALSE FALSE FALSE 48 TRUE 34.5833333 29.5 Q99567 NUP88 NA NA NA NA P35658 NA RNA Synthesis 168325 168273 0023 Activation of G protein gated R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 25 TRUE 19.2 30 NA NA NA NA NA NA P48544 KCNJ5,GIRK4 NA Potassium 1296041 1296059 channels Inhibition of voltage gated R-HSA- R-HSA- Ca2+ channels via NA NA 1 FALSE NA FALSE FALSE FALSE 25 TRUE 19.2 30 NA NA NA NA NA NA P48544 KCNJ5,GIRK4 NA 997272 991365 Gbeta/gamma subunits HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, Formation of the H4/C,H4FC;,HIST1H4H,H SMARCA4,BAF190A,BR beta-catenin:TCF R-HSA- R-HSA- R-HSA- P51532,Q9H 1 NA 2 TRUE TRUE TRUE TRUE 61 TRUE 23.8196721 31 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA G1,SNF2B,SNF2L4,TCF7 NA transactivating 201722 201681 4411364 CS4 M,H4FM;,HIST1H4J,H4/E L1,TCF3 complex ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

G beta:gamma R-HSA- R-HSA- signalling through 1 NA 1 FALSE NA FALSE FALSE FALSE 25 TRUE 28.24 31 Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 392451 397795 PI3Kgamma Inhibition of Signaling by R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 2 TRUE 31.5 31.5 NA NA NA NA NA NA P01133 EGF NA Overexpressed 5638303 5638302 EGFR PLCG1 events in R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 4 TRUE 30.5 31.5 NA NA NA NA NA NA P01133 EGF NA ERBB2 signaling 1251932 1227986 CTLA4 inhibitory R-HSA- R-HSA- CD80,CD28LG,CD28LG1, P06239,P31 1 1 2 FALSE NA FALSE FALSE FALSE 21 TRUE 38.3809524 32 Q9Y243 AKT3,PKBG NA P33681 NA LCK,AKT2 LCK,AKT2 signaling 389513 388841 LAB7 751

Formation of HIV elongation R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, NA NA 2 TRUE NA FALSE TRUE TRUE 48 TRUE 30.2708333 32 NA NA NA NA NA NA NA complex in the 167152 167172 615 RD,RDBP absence of HIV Tat

Formation of HIV- 1 elongation R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, complex NA NA 2 TRUE NA FALSE TRUE TRUE 47 TRUE 30.5531915 32 NA NA NA NA NA NA NA 167200 167246 615 RD,RDBP containing HIV-1 Tat Formation of TC- R-HSA- R-HSA- P18074,Q03 ERCC2,XPD,XPDC,ERCC6, NER Pre-Incision 1 1 3 TRUE NA FALSE TRUE TRUE 53 TRUE 37.8867925 32 Q13619 CUL4A NA Q9UNP9 PPIE,CYP33 NA NA 6781823 6781827 468,Q92905 CSB,COPS5,CSN5,JAB1 Complex HIV Transcription R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C 1 NA 3 TRUE NA FALSE TRUE TRUE 47 TRUE 27.7446809 32 Q8IZX4 TAF1L NA NA NA NA NA Initiation 167161 167172 1X5,Q8IZX4 IF150,TAF2B,TAF1L

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H Meiotic R-HSA- R-HSA- P62805,Q13 4/H,H4FH;,HIST1H4I,H4/ P38398,Q9B 2 NA 2 FALSE NA FALSE FALSE FALSE 56 TRUE 25.3214286 32 NA NA NA NA BRCA1,RNF53,TEX15 NA recombination 912446 1500620 315 M,H4FM;,HIST1H4J,H4/E XT5 ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, ATM

DNMT1,AIM,CXXC9,DN MT,HIST1H4A,H4/A,H4F A;,HIST1H4B,H4/I,H4FI;, HIST1H4C,H4/G,H4FG;,H IST1H4D,H4/B,H4FB;,HIS T1H4E,H4/J,H4FJ;,HIST1 NoRC negatively H4F,H4/C,H4FC;,HIST1H R-HSA- R-HSA- P26358,P62 P18074,Q9H ERCC2,XPD,XPDC,POLR1 regulates rRNA 2 NA 2 FALSE NA FALSE FALSE FALSE 77 TRUE 25.1688312 32 4H,H4/H,H4FH;,HIST1H4I NA NA NA NA NA 427413 5250941 805 9Y6 B expression ,H4/M,H4FM;,HIST1H4J, H4/E,H4FE;,HIST1H4K,H 4/D,H4FD;,HIST1H4L,H4/ K,H4FK;,HIST2H4A,H4/N, H4F2,H4FN,HIST2H4;,HI ST2H4B,H4/O,H4FO;,HIS T4H4 RNA Polymerase II R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C HIV Promoter 1 NA 3 TRUE NA FALSE TRUE TRUE 47 TRUE 27.7446809 32 Q8IZX4 TAF1L NA NA NA NA NA 167162 167172 1X5,Q8IZX4 IF150,TAF2B,TAF1L Escape RNA Polymerase II R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C 1 NA 3 TRUE NA FALSE TRUE TRUE 47 TRUE 27.7446809 32 Q8IZX4 TAF1L NA NA NA NA NA Promoter Escape 73776 76042 1X5,Q8IZX4 IF150,TAF2B,TAF1L RNA Polymerase II R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C Transcription 1 NA 3 TRUE NA FALSE TRUE TRUE 47 TRUE 27.7446809 32 Q8IZX4 TAF1L NA NA NA NA NA 75953 76042 1X5,Q8IZX4 IF150,TAF2B,TAF1L Initiation RNA Polymerase II Transcription R-HSA- R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C Initiation And 1 NA 3 FALSE TRUE TRUE TRUE 47 TRUE 27.7446809 32 Q8IZX4 TAF1L NA NA NA NA NA 76042 73857 73776 1X5,Q8IZX4 IF150,TAF2B,TAF1L Promoter Clearance RNA Polymerase II Transcription R-HSA- R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C Initiation And 1 NA 3 FALSE TRUE TRUE TRUE 47 TRUE 27.7446809 32 Q8IZX4 TAF1L NA NA NA NA NA 76042 73857 75953 1X5,Q8IZX4 IF150,TAF2B,TAF1L Promoter Clearance RNA Polymerase II Transcription Pre- R-HSA- R-HSA- P18074,Q6P ERCC2,XPD,XPDC,TAF2,C 1 NA 3 FALSE NA FALSE FALSE FALSE 47 TRUE 27.7446809 32 Q8IZX4 TAF1L NA NA NA NA NA Initiation And 73779 73857 1X5,Q8IZX4 IF150,TAF2B,TAF1L Promoter Opening Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 25 TRUE 35.36 32 NA NA NA NA NA NA Q9Y4H2 IRS2 NA Erythropoietin 9006335 162582 9027283 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 25 TRUE 35.36 32 NA NA NA NA NA NA Q9Y4H2 IRS2 NA Erythropoietin 9006335 162582 9027277 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 25 TRUE 35.36 32 NA NA NA NA NA NA Q9Y4H2 IRS2 NA Erythropoietin 9006335 162582 9027284 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 25 TRUE 35.36 32 NA NA NA NA NA NA Q9Y4H2 IRS2 NA Erythropoietin 9006335 162582 9027276 Tat-mediated R-HSA- R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, elongation of the NA NA 2 FALSE TRUE TRUE TRUE 47 TRUE 30.5531915 32 NA NA NA NA NA NA NA 167246 167169 167200 615 RD,RDBP HIV-1 transcript Insulin receptor R-HSA- R-HSA- R-HSA- NA 1 1 FALSE TRUE TRUE TRUE 54 TRUE 35.4259259 32.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA signalling cascade 74751 74752 74713 Insulin receptor R-HSA- R-HSA- R-HSA- NA 1 1 FALSE TRUE TRUE TRUE 54 TRUE 35.4259259 32.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA signalling cascade 74751 74752 112399 Insulin receptor R-HSA- R-HSA- R-HSA- NA 1 1 FALSE TRUE TRUE TRUE 54 TRUE 35.4259259 32.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA signalling cascade 74751 74752 74749 IRS-mediated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE TRUE TRUE TRUE 48 TRUE 35.4166667 32.5 NA NA NA NA NA NA Q9Y4H2 IRS2 NA signalling 112399 74751 112412 IRS-mediated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE TRUE TRUE TRUE 48 TRUE 35.4166667 32.5 NA NA NA NA NA NA Q9Y4H2 IRS2 NA signalling 112399 2428928 109704 IRS-mediated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE TRUE TRUE TRUE 48 TRUE 35.4166667 32.5 NA NA NA NA NA NA Q9Y4H2 IRS2 NA signalling 112399 74751 109704 IRS-mediated R-HSA- R-HSA- R-HSA- NA NA 1 TRUE TRUE TRUE TRUE 48 TRUE 35.4166667 32.5 NA NA NA NA NA NA Q9Y4H2 IRS2 NA signalling 112399 2428928 112412

SF3B1,SAP155,HIST1H4 A,H4/A,H4FA;,HIST1H4B ,H4/I,H4FI;,HIST1H4C,H4 /G,H4FG;,HIST1H4D,H4/ B,H4FB;,HIST1H4E,H4/J, B-WICH complex H4FJ;,HIST1H4F,H4/C,H4 positively R-HSA- R-HSA- O75533,P62 FC;,HIST1H4H,H4/H,H4F Q03468,Q9 2 NA 2 FALSE NA FALSE FALSE FALSE 60 TRUE 27.2166667 33 NA NA NA NA ERCC6,CSB,POLR1B NA regulates rRNA 5250924 5250913 805 H;,HIST1H4I,H4/M,H4FM H9Y6 expression ;,HIST1H4J,H4/E,H4FE;,H IST1H4K,H4/D,H4FD;,HIS T1H4L,H4/K,H4FK;,HIST2 H4A,H4/N,H4F2,H4FN,HI ST2H4;,HIST2H4B,H4/O, H4FO;,HIST4H4

HRAS,HRAS1,FGFR1,BF P01112,P11 GFR,CEK,FGFBR,FLG,FL Signaling by R-HSA- R-HSA- R-HSA- O95684,P39 FGFR1OP,FOP,CUX1,CU 2 1 4 FALSE FALSE FALSE FALSE 38 TRUE 32.7105263 33 NA P01112 HRAS,HRAS1 NA 362,P39880, T2,HBGFR,CUX1,CUTL1, FGFR1 FGFR1 in disease 5655302 1226099 1839124 880 TL1 Q9UBW7 ZMYM2,FIM,RAMP,ZNF 198 Erythropoietin R-HSA- R-HSA- P01112,Q9Y NA 1 2 TRUE NA FALSE TRUE TRUE 14 TRUE 40.9285714 33.5 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,IRS2 NA activates RAS 9027284 9006335 4H2 CD209 (DC-SIGN) R-HSA- R-HSA- P22612,P32 P01112,Q01 2 1 2 FALSE NA FALSE FALSE FALSE 21 TRUE 33.047619 34 PRKACG,ICAM3 NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,RELB NA signaling 5621575 5621481 942 201 HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, ERCC6 (CSB) and H4/C,H4FC;,HIST1H4H,H EHMT2 (G9a) R-HSA- R-HSA- 1 NA 1 FALSE NA FALSE FALSE FALSE 46 TRUE 27.3043478 34 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA Q03468 ERCC6,CSB NA positively regulate 427389 5250913 M,H4FM;,HIST1H4J,H4/E rRNA expression ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

PKA-mediated phosphorylation of R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 5 TRUE 25.2 34 P22612 PRKACG NA NA NA NA NA NA NA key metabolic 163358 163685 factors R-HSA- R-HSA- Signal attenuation NA NA 1 TRUE NA FALSE TRUE TRUE 10 TRUE 42.8 34 NA NA NA NA NA NA Q9Y4H2 IRS2 NA 74749 74751 HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H Transcriptional 4/H,H4FH;,HIST1H4I,H4/ R-HSA- R-HSA- P62805,P62 NUP214,CAIN,CAN,KIAA regulation by 3 NA 1 FALSE NA FALSE FALSE FALSE 75 TRUE 35.2533333 34 M,H4FM;,HIST1H4J,H4/E NA NA NA NA P35658 NA 5578749 211000 826,Q99567 0023 small RNAs ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4, RAN,ARA24,OK/SW- cl.81,NUP88 EGFR interacts with R-HSA- R-HSA- NA NA 1 TRUE NA FALSE TRUE TRUE 3 TRUE 34.3333333 35 NA NA NA NA NA NA P01133 EGF NA phospholipase C- 212718 177929 gamma R-HSA- R-HSA- GAB1 signalosome 1 NA 1 TRUE NA FALSE TRUE TRUE 11 TRUE 44 35 P12931 SRC,SRC1 SRC NA NA NA P01133 EGF NA 180292 177929

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H RNA Polymerase I R-HSA- R-HSA- P18074,Q9H ERCC2,XPD,XPDC,POLR1 1 NA 2 FALSE NA FALSE FALSE FALSE 59 TRUE 31 35 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA NA Chain Elongation 73777 73864 9Y6 B M,H4FM;,HIST1H4J,H4/E ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

AKT-mediated R-HSA- R-HSA- inactivation of 1 NA 1 TRUE NA FALSE TRUE TRUE 4 TRUE 30.25 35.5 Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 211163 210745 FOXO1A Formation of the R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, Early Elongation NA NA 2 TRUE NA FALSE TRUE TRUE 33 TRUE 36.8787879 36 NA NA NA NA NA NA NA 113418 75955 615 RD,RDBP Complex Formation of the HIV-1 Early R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, NA NA 2 FALSE NA FALSE FALSE FALSE 33 TRUE 36.8787879 36 NA NA NA NA NA NA NA Elongation 167158 167169 615 RD,RDBP Complex DNMT1,AIM,CXXC9,DN MT,HIST1H4A,H4/A,H4F A;,HIST1H4B,H4/I,H4FI;, HIST1H4C,H4/G,H4FG;,H IST1H4D,H4/B,H4FB;,HIS T1H4E,H4/J,H4FJ;,HIST1 H4F,H4/C,H4FC;,HIST1H PRC2 methylates R-HSA- R-HSA- P26358,P62 2 NA NA FALSE NA FALSE FALSE FALSE 42 TRUE 27.6428571 36 4H,H4/H,H4FH;,HIST1H4I NA NA NA NA NA NA NA histones and DNA 212300 212165 805 ,H4/M,H4FM;,HIST1H4J, H4/E,H4FE;,HIST1H4K,H 4/D,H4FD;,HIST1H4L,H4/ K,H4FK;,HIST2H4A,H4/N, H4F2,H4FN,HIST2H4;,HI ST2H4B,H4/O,H4FO;,HIS T4H4

KLK2,HIST1H4A,H4/A,H4 FA;,HIST1H4B,H4/I,H4FI; ,HIST1H4C,H4/G,H4FG;, HIST1H4D,H4/B,H4FB;,H Activated PKN1 IST1H4E,H4/J,H4FJ;,HIST stimulates 1H4F,H4/C,H4FC;,HIST1 transcription of AR R-HSA- R-HSA- P20151,P62 H4H,H4/H,H4FH;,HIST1H (androgen 2 NA NA TRUE NA FALSE TRUE TRUE 36 TRUE 31.4722222 37 NA NA NA NA NA NA NA 5625886 5625740 805 4I,H4/M,H4FM;,HIST1H4 receptor) J,H4/E,H4FE;,HIST1H4K, regulated genes H4/D,H4FD;,HIST1H4L,H KLK2 and KLK3 4/K,H4FK;,HIST2H4A,H4/ N,H4F2,H4FN,HIST2H4;, HIST2H4B,H4/O,H4FO;,H IST4H4

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, Condensation of H4/C,H4FC;,HIST1H4H,H R-HSA- R-HSA- SMC2,CAPE,SMC2L1,PR Prophase 1 1 NA FALSE NA FALSE FALSE FALSE 43 TRUE 28.5348837 37 P62805 4/H,H4FH;,HIST1H4I,H4/ NA O95347 NA NA NA NA 2299718 68875 O0324 Chromosomes M,H4FM;,HIST1H4J,H4/E ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

DNMT1,AIM,CXXC9,DN MT,HIST1H4A,H4/A,H4F A;,HIST1H4B,H4/I,H4FI;, HIST1H4C,H4/G,H4FG;,H IST1H4D,H4/B,H4FB;,HIS T1H4E,H4/J,H4FJ;,HIST1 H4F,H4/C,H4FC;,HIST1H R-HSA- R-HSA- P26358,P62 DNA methylation 2 NA NA FALSE NA FALSE FALSE FALSE 34 TRUE 32.0588235 37 4H,H4/H,H4FH;,HIST1H4I NA NA NA NA NA NA NA 5334118 212165 805 ,H4/M,H4FM;,HIST1H4J, H4/E,H4FE;,HIST1H4K,H 4/D,H4FD;,HIST1H4L,H4/ K,H4FK;,HIST2H4A,H4/N, H4F2,H4FN,HIST2H4;,HI ST2H4B,H4/O,H4FO;,HIS T4H4 R-HSA- R-HSA- mRNA Capping NA NA 1 FALSE NA FALSE FALSE FALSE 29 TRUE 38.6896552 37 NA NA NA NA NA NA P18074 ERCC2,XPD,XPDC NA 72086 8953854

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H Packaging Of R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 33 TRUE 30.6363636 37 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA NA NA NA Telomere Ends 171306 157579 M,H4FM;,HIST1H4J,H4/E ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4 RNA Pol II CTD phosphorylation R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 27 TRUE 39.1111111 37 NA NA NA NA NA NA P18074 ERCC2,XPD,XPDC NA and interaction 77075 73857 with CE RNA Pol II CTD phosphorylation R-HSA- R-HSA- and interaction NA NA 1 TRUE NA FALSE TRUE TRUE 27 TRUE 39.1111111 37 NA NA NA NA NA NA P18074 ERCC2,XPD,XPDC NA 167160 167172 with CE during HIV infection

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, H4/C,H4FC;,HIST1H4H,H RNA Polymerase I R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 32 TRUE 35.875 37 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA NA NA NA Promoter Opening 73728 73854 M,H4FM;,HIST1H4J,H4/E ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

HIST1H4A,H4/A,H4FA;,H IST1H4B,H4/I,H4FI;,HIST 1H4C,H4/G,H4FG;,HIST1 H4D,H4/B,H4FB;,HIST1H 4E,H4/J,H4FJ;,HIST1H4F, SIRT1 negatively H4/C,H4FC;,HIST1H4H,H R-HSA- R-HSA- regulates rRNA 1 NA NA FALSE NA FALSE FALSE FALSE 37 TRUE 30.6756757 37 P62805 4/H,H4FH;,HIST1H4I,H4/ NA NA NA NA NA NA NA 427359 5250941 expression M,H4FM;,HIST1H4J,H4/E ,H4FE;,HIST1H4K,H4/D,H 4FD;,HIST1H4L,H4/K,H4F K;,HIST2H4A,H4/N,H4F2, H4FN,HIST2H4;,HIST2H4 B,H4/O,H4FO;,HIST4H4

Activated NTRK3 R-HSA- R-HSA- signals through 1 NA NA TRUE NA FALSE TRUE TRUE 6 TRUE 38.8333333 40.5 P12931 SRC,SRC1 SRC NA NA NA NA NA NA 9603381 9034015 PI3K R-HSA- R-HSA- Tie2 Signaling NA 1 1 TRUE NA FALSE TRUE TRUE 18 TRUE 39.6111111 41 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 210993 202733 PSMA1,HC2,NU,PROS30 ,PSC2,HIST1H4A,H4/A,H 4FA;,HIST1H4B,H4/I,H4F I;,HIST1H4C,H4/G,H4FG; ,HIST1H4D,H4/B,H4FB;, RUNX1 regulates HIST1H4E,H4/J,H4FJ;,HIS transcription of T1H4F,H4/C,H4FC;,HIST1 R-HSA- R-HSA- P25786,P62 P15923,P61 TCF3,BHLHB21,E2A,ITF1 genes involved in 2 NA 3 FALSE NA FALSE FALSE FALSE 99 TRUE 55.5353535 42 H4H,H4/H,H4FH;,HIST1H PSMA1 NA NA NA PSMD2 8939236 8878171 805 289,Q13200 ,PSME3,PSMD2,TRAP2 differentiation of 4I,H4/M,H4FM;,HIST1H4 HSCs J,H4/E,H4FE;,HIST1H4K, H4/D,H4FD;,HIST1H4L,H 4/K,H4FK;,HIST2H4A,H4/ N,H4F2,H4FN,HIST2H4;, HIST2H4B,H4/O,H4FO;,H IST4H4 MAP3K8 (TPL2)- dependent R-HSA- R-HSA- BTRC,BTRCP,FBW1A,FB 1 NA NA FALSE NA FALSE FALSE TRUE 16 TRUE 77.0625 43 Q9Y297 NA NA NA NA NA NA NA MAPK1/3 5684264 450294 XW1A activation MAP3K8 (TPL2)- dependent R-HSA- R-HSA- BTRC,BTRCP,FBW1A,FB 1 NA NA TRUE NA FALSE TRUE TRUE 16 TRUE 77.0625 43 Q9Y297 NA NA NA NA NA NA NA MAPK1/3 5684264 9020702 XW1A activation Constitutive R-HSA- R-HSA- P01112,P01 Signaling by NA 1 2 FALSE NA FALSE FALSE FALSE 15 TRUE 50.0666667 44 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,EGF NA 5637810 5637812 133 EGFRvIII FRS-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 23 TRUE 45.9130435 44 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA FGFR1 signaling 5654693 5654687 FRS-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 25 TRUE 44.92 44 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA FGFR2 signaling 5654700 5654696 MET activates RAS R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 11 TRUE 43.8181818 44 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA signaling 8851805 6806834 SHC-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 21 TRUE 47.5714286 44 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA cascade:FGFR1 5654688 5654687 SHC-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 23 TRUE 46.3478261 44 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA cascade:FGFR2 5654699 5654696 Signaling by R-HSA- R-HSA- FGFR1,BFGFR,CEK,FGF activated point NA NA 1 FALSE NA FALSE FALSE FALSE 11 TRUE 42.5454545 44 NA NA NA NA NA NA P11362 FGFR1 1839122 1839124 BR,FLG,FLT2,HBGFR mutants of FGFR1 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 17 TRUE 43.3529412 44 NA NA NA NA NA NA Q16827 PTPRO,GLEPP1,PTPU2 NA NTRK3 (TRKC) 9034015 166520 9603505 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 17 TRUE 43.3529412 44 NA NA NA NA NA NA Q16827 PTPRO,GLEPP1,PTPU2 NA NTRK3 (TRKC) 9034015 166520 9603381 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE TRUE TRUE TRUE 17 TRUE 43.3529412 44 NA NA NA NA NA NA Q16827 PTPRO,GLEPP1,PTPU2 NA NTRK3 (TRKC) 9034015 166520 9034864 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 17 TRUE 43.3529412 44 NA NA NA NA NA NA Q16827 PTPRO,GLEPP1,PTPU2 NA NTRK3 (TRKC) 9034015 166520 9034013 Signaling by R-HSA- R-HSA- R-HSA- NA NA 1 FALSE FALSE FALSE TRUE 17 TRUE 43.3529412 44 NA NA NA NA NA NA Q16827 PTPRO,GLEPP1,PTPU2 NA NTRK3 (TRKC) 9034015 166520 9034793 FRS-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 22 TRUE 46.2272727 44.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA FGFR4 signaling 5654712 5654716 SHC-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 20 TRUE 48 44.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA cascade:FGFR4 5654719 5654716 FRS-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 20 TRUE 49.4 45 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA FGFR3 signaling 5654706 5654708 SHC-mediated R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 18 TRUE 51.7222222 45 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA cascade:FGFR3 5654704 5654708 Signaling by R-HSA- R-HSA- R-HSA- FGFR3 point NA 1 1 FALSE FALSE FALSE FALSE 22 TRUE 50.8636364 45 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 8853338 5655332 2033514 mutants in cancer Abortive elongation of HIV- R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE 23 TRUE 38.3913043 46 NA NA NA NA NA NA P18615 NELFE,RD,RDBP NA 1 transcript in the 167242 167169 absence of Tat Signaling by R-HSA- R-HSA- R-HSA- NA 1 1 FALSE FALSE FALSE FALSE 43 TRUE 46.7674419 46 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA FGFR2 in disease 5655253 1226099 1839126 PSMA1,HC2,NU,PROS30 Interleukin-1 R-HSA- R-HSA- R-HSA- P25786,Q9H ,PSC2,NOD2,CARD15,IB P61289,Q13 PSME3,PSMD2,TRAP2,N 3 NA 3 FALSE TRUE TRUE TRUE 102 TRUE 53.2843137 49 PSMA1 NA NA NA PSMD2 signaling 9020702 446652 5684264 C29,Q9Y297 D1,BTRC,BTRCP,FBW1A, 200,Q9Y239 OD1,CARD4 FBXW1A PSMA1,HC2,NU,PROS30 Interleukin-1 R-HSA- R-HSA- R-HSA- P25786,Q9H ,PSC2,NOD2,CARD15,IB P61289,Q13 PSME3,PSMD2,TRAP2,N 3 NA 3 FALSE TRUE TRUE TRUE 102 TRUE 53.2843137 49 PSMA1 NA NA NA PSMD2 signaling 9020702 446652 445989 C29,Q9Y297 D1,BTRC,BTRCP,FBW1A, 200,Q9Y239 OD1,CARD4 FBXW1A InlA-mediated entry of Listeria R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE 10 TRUE 91.9 50.5 P12931 SRC,SRC1 SRC NA NA NA NA NA NA monocytogenes 8876493 8876384 into host cells PSME3,PSMD2,TRAP2,T TNFR2 non- R-HSA- R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 NFSF13B,BAFF,BLYS,TA canonical NF-kB 1 NA 3 FALSE TRUE TRUE TRUE 101 TRUE 45.6831683 52 P25786 PSMA1 NA NA NA PSMD2 5668541 1280215 5676590 ,PSC2 200,Q9Y275 LL1,TNFSF20,ZTNF4,UN pathway Q401/PRO738 PSME3,PSMD2,TRAP2,T TNFR2 non- R-HSA- R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 NFSF13B,BAFF,BLYS,TA canonical NF-kB 1 NA 3 FALSE TRUE TRUE TRUE 101 TRUE 45.6831683 52 P25786 PSMA1 NA NA NA PSMD2 5668541 1280215 5676594 ,PSC2 200,Q9Y275 LL1,TNFSF20,ZTNF4,UN pathway Q401/PRO738 PSME3,PSMD2,TRAP2,T TNFR2 non- R-HSA- R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 NFSF13B,BAFF,BLYS,TA canonical NF-kB 1 NA 3 FALSE TRUE TRUE TRUE 101 TRUE 45.6831683 52 P25786 PSMA1 NA NA NA PSMD2 5668541 1280215 5669034 ,PSC2 200,Q9Y275 LL1,TNFSF20,ZTNF4,UN pathway Q401/PRO738 PSMA1,HC2,NU,PROS30 P04234,P06 ,PSC2,UBE2D1,SFT,UBC CD3D,T3D,LCK,PSME3,P Downstream TCR R-HSA- R-HSA- P25786,P51 239,P61289, LCK,PRKCQ, 3 NA 5 FALSE NA FALSE FALSE FALSE 104 TRUE 51.4423077 52.5 5A,UBCH5,UBCH5A,BTR PSMA1 NA NA NA RKCQ,PRKCT,PSMD2,TR signaling 202424 202403 668,Q9Y297 Q04759,Q1 PSMD2 C,BTRCP,FBW1A,FBXW1 AP2 3200 A P10070,P22 GLI2,THP,PRKACG,PTCH Hedgehog 'off' R-HSA- R-HSA- R-HSA- 612,Q13635 1,PTCH,KIF7,UNQ340/P 5 1 NA FALSE TRUE TRUE TRUE 100 TRUE 49.26 52.5 NA Q08462 ADCY2,KIAA1060 NA NA NA NA state 5610787 5358351 5610783 ,Q2M1P5,Q RO539,IFT140,KIAA0590 96RY7 ,WDTC2 P10070,P22 GLI2,THP,PRKACG,PTCH Hedgehog 'off' R-HSA- R-HSA- R-HSA- 612,Q13635 1,PTCH,KIF7,UNQ340/P 5 1 NA FALSE TRUE TRUE TRUE 100 TRUE 49.26 52.5 NA Q08462 ADCY2,KIAA1060 NA NA NA NA state 5610787 5358351 5610785 ,Q2M1P5,Q RO539,IFT140,KIAA0590 96RY7 ,WDTC2 P10070,P22 GLI2,THP,PRKACG,PTCH Hedgehog 'off' R-HSA- R-HSA- R-HSA- 612,Q13635 1,PTCH,KIF7,UNQ340/P 5 1 NA FALSE TRUE TRUE TRUE 100 TRUE 49.26 52.5 NA Q08462 ADCY2,KIAA1060 NA NA NA NA state 5610787 5358351 5610780 ,Q2M1P5,Q RO539,IFT140,KIAA0590 96RY7 ,WDTC2 Activated NTRK2 R-HSA- R-HSA- signals through NA 1 1 FALSE NA FALSE FALSE FALSE 11 TRUE 46.9090909 62 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 9028731 9006115 FRS2 and FRS3 PSMA1,HC2,NU,PROS30 ,PSC2,UBE2D1,SFT,UBC CLEC7A (Dectin-1) R-HSA- R-HSA- R-HSA- P25786,P51 P61289,Q13 3 NA 2 FALSE TRUE TRUE TRUE 100 TRUE 53.43 63 5A,UBCH5,UBCH5A,BTR PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 signaling 5607764 5621481 5660668 668,Q9Y297 200 C,BTRCP,FBW1A,FBXW1 A PSMA1,HC2,NU,PROS30 ,PSC2,UBE2D1,SFT,UBC CLEC7A (Dectin-1) R-HSA- R-HSA- R-HSA- P25786,P51 P61289,Q13 3 NA 2 FALSE TRUE TRUE TRUE 100 TRUE 53.43 63 5A,UBCH5,UBCH5A,BTR PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 signaling 5607764 5621481 5607763 668,Q9Y297 200 C,BTRCP,FBW1A,FBXW1 A PSMA1,HC2,NU,PROS30 ,PSC2,UBE2D1,SFT,UBC CLEC7A (Dectin-1) R-HSA- R-HSA- R-HSA- P25786,P51 P61289,Q13 3 NA 2 FALSE TRUE TRUE TRUE 100 TRUE 53.43 63 5A,UBCH5,UBCH5A,BTR PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 signaling 5607764 5621481 5607761 668,Q9Y297 200 C,BTRCP,FBW1A,FBXW1 A Constitutive Signaling by R-HSA- R-HSA- P01112,P01 Ligand-Responsive NA 1 2 FALSE NA FALSE FALSE FALSE 19 TRUE 81.7368421 65 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,EGF NA 1236382 5637815 133 EGFR Cancer Variants Signaling by R-HSA- R-HSA- R-HSA- NA 1 1 FALSE FALSE FALSE FALSE 11 TRUE 58.0909091 65 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA FGFR4 in disease 5655291 1226099 1839128 Signaling by R-HSA- R-HSA- FGFR3 fusions in NA 1 1 FALSE NA FALSE FALSE FALSE 10 TRUE 60.2 67.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 8853334 5655332 cancer P22612,P25 PRKACG,PSMA1,HC2,NU P55895,P61 MAPK6/MAPK4 R-HSA- R-HSA- RAG2,PSME3,PSMD2,TR 3 NA 4 FALSE NA FALSE FALSE FALSE 94 TRUE 50.8297872 69 786,Q9UPQ ,PROS30,PSC2,TNRC6B, PSMA1 NA NA NA 289,Q13200 PSMD2 signaling 5687128 5683057 AP2,TNRC6B,KIAA1093 9 KIAA1093 ,Q9UPQ9 PSMA1,HC2,NU,PROS30 R-HSA- R-HSA- P25786,P85 P61289,Q13 PSME3,PSMD2,TRAP2,M UCH proteinases 3 NA 3 FALSE NA FALSE FALSE FALSE 96 TRUE 47.9479167 69 ,PSC2,FOXK1,MNF,FOXK PSMA1 NA NA NA PSMD2 5689603 5688426 037,Q01167 200,Q96EZ8 CRS1,INO80Q,MSP58 2,ILF,ILF1 Activated NTRK2 R-HSA- R-HSA- signals through NA 1 1 FALSE NA FALSE FALSE FALSE 9 TRUE 51 70 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 9026519 9006115 RAS Activation of RAS R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 5 TRUE 45.4 70 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA in B cells 1169092 1168372 EGFR R-HSA- R-HSA- Transactivation by NA 1 1 FALSE NA FALSE FALSE FALSE 9 TRUE 54.3333333 70 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 2179392 881907 Gastrin SHC-related events R-HSA- R-HSA- P01112,P08 NA 1 2 FALSE NA FALSE FALSE FALSE 9 TRUE 49.7777778 70 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,IGF1R IGF1R triggered by IGF1R 2428933 2428924 069

Activated NTRK3 R-HSA- R-HSA- signals through NA 1 1 TRUE NA FALSE TRUE TRUE 8 TRUE 55.5 70.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA 9034864 9034015 RAS RAS signaling downstream of R-HSA- R-HSA- NA 1 1 FALSE NA FALSE FALSE FALSE 4 TRUE 55 70.5 NA NA NA P01112 HRAS,HRAS1 NA P01112 HRAS,HRAS1 NA NF1 loss-of- 6802953 6802957 function variants SHC1 events in R-HSA- R-HSA- P01112,P01 NA 1 2 TRUE NA FALSE TRUE TRUE 8 TRUE 61.75 70.5 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,EGF NA EGFR signaling 180336 177929 133 GRB2 events in R-HSA- R-HSA- P01112,P01 NA 1 2 TRUE NA FALSE TRUE TRUE 7 TRUE 64.2857143 71 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,EGF NA EGFR signaling 179812 177929 133 SOS-mediated R-HSA- R-HSA- P01112,Q9Y NA 1 2 TRUE NA FALSE TRUE TRUE 7 TRUE 61.5714286 71 NA NA NA P01112 HRAS,HRAS1 NA HRAS,HRAS1,IRS2 NA signalling 112412 112399 4H2 R-HSA- R-HSA- R-HSA- PCP/CE pathway NA NA 1 FALSE TRUE TRUE TRUE 92 TRUE 50.5434783 72 NA NA NA NA NA NA O14641 DVL2 NA 4086400 3858494 5140745 R-HSA- R-HSA- R-HSA- PCP/CE pathway NA NA 1 FALSE TRUE TRUE TRUE 92 TRUE 50.5434783 72 NA NA NA NA NA NA O14641 DVL2 NA 4086400 3858494 4608870 R-HSA- R-HSA- R-HSA- PCP/CE pathway NA NA 1 FALSE TRUE TRUE TRUE 92 TRUE 50.5434783 72 NA NA NA NA NA NA O14641 DVL2 NA 4086400 3858494 5099900 PSMA1,HC2,NU,PROS30 Activation of NF- R-HSA- R-HSA- P25786,Q9Y P61289,Q13 2 NA 2 FALSE NA FALSE FALSE FALSE 67 TRUE 69.8208955 75 ,PSC2,BTRC,BTRCP,FBW PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 kappaB in B cells 1169091 1168372 297 200 1A,FBXW1A APC/C:Cdc20 mediated R-HSA- R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE FALSE FALSE TRUE 75 TRUE 62.0933333 75 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA degradation of 176409 176814 179419 CH5,UBCH5A mitotic proteins APC/C:Cdc20 mediated R-HSA- R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE TRUE TRUE TRUE 75 TRUE 62.0933333 75 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA degradation of 176409 176814 174154 CH5,UBCH5A mitotic proteins APC/C:Cdc20 mediated R-HSA- R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE TRUE TRUE TRUE 75 TRUE 62.0933333 75 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA degradation of 176409 176814 174048 CH5,UBCH5A mitotic proteins APC/C:Cdc20 PSMA1,HC2,NU,PROS30 mediated R-HSA- R-HSA- P25786,P51 P61289,Q13 2 1 2 TRUE NA FALSE TRUE TRUE 67 TRUE 67.119403 75 ,PSC2,UBE2D1,SFT,UBC PSMA1 Q9UJX4 ANAPC5,APC5 NA PSME3,PSMD2,TRAP2 PSMD2 degradation of 174154 176409 668 200 5A,UBCH5,UBCH5A Securin APC/C:Cdh1 mediated degradation of PSMA1,HC2,NU,PROS30 Cdc20 and other R-HSA- R-HSA- P25786,P51 P61289,Q13 2 1 2 FALSE NA FALSE FALSE FALSE 72 TRUE 63.4305556 75 ,PSC2,UBE2D1,SFT,UBC PSMA1 Q9UJX4 ANAPC5,APC5 NA PSME3,PSMD2,TRAP2 PSMD2 APC/C:Cdh1 174178 174143 668 200 5A,UBCH5,UBCH5A targeted proteins in late mitosis/early G1 Asymmetric O14641,P61 R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 DVL2,PSME3,PSMD2,TR localization of PCP 1 NA 4 TRUE NA FALSE TRUE TRUE 64 TRUE 66.90625 75 P25786 PSMA1 NA NA NA 289,Q13200 PSMD2 4608870 4086400 ,PSC2 AP2,PRICKLE1,RILP proteins ,Q96MT3

AUF1 (hnRNP D0) R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 binds and 1 NA 2 FALSE NA FALSE FALSE FALSE 55 TRUE 77.0181818 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 450408 450531 ,PSC2 200 destabilizes mRNA

Autodegradation PSMA1,HC2,NU,PROS30 R-HSA- R-HSA- P25786,P51 P61289,Q13 of Cdh1 by 2 1 2 FALSE NA FALSE FALSE FALSE 63 TRUE 67.9047619 75 ,PSC2,UBE2D1,SFT,UBC PSMA1 Q9UJX4 ANAPC5,APC5 NA PSME3,PSMD2,TRAP2 PSMD2 174084 174143 668 200 Cdh1:APC/C 5A,UBCH5,UBCH5A Autodegradation R-HSA- R-HSA- P04637,P25 TP53,P53,PSMA1,HC2,N P04637,P61 TP53,P53,PSME3,PSMD2 of the E3 ubiquitin 3 1 3 TRUE NA FALSE TRUE TRUE 52 TRUE 81.75 75 PSMA1 P04637 TP53,P53 NA PSMD2 349425 69541 786,Q13315 U,PROS30,PSC2,ATM 289,Q13200 ,TRAP2 ligase COP1 Cdc20:Phospho- PSMA1,HC2,NU,PROS30 APC/C mediated R-HSA- R-HSA- P25786,P51 P61289,Q13 2 1 2 FALSE NA FALSE FALSE FALSE 72 TRUE 64.0972222 75 ,PSC2,UBE2D1,SFT,UBC PSMA1 Q9UJX4 ANAPC5,APC5 NA PSME3,PSMD2,TRAP2 PSMD2 degradation of 174184 179419 668 200 5A,UBCH5,UBCH5A Cyclin A CDK-mediated PSMA1,HC2,NU,PROS30 phosphorylation R-HSA- R-HSA- P25786,P51 P61289,Q13 2 1 2 FALSE NA FALSE FALSE FALSE 72 TRUE 63.8055556 75 ,PSC2,UBE2D1,SFT,UBC PSMA1 Q9UJX4 ANAPC5,APC5 NA PSME3,PSMD2,TRAP2 PSMD2 and removal of 69017 69052 668 200 5A,UBCH5,UBCH5A Cdc6 CDT1 association with the R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 1 NA 2 FALSE NA FALSE FALSE FALSE 59 TRUE 72.4067797 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 CDC6:ORC:origin 68827 68867 ,PSC2 200 complex Cross-presentation of soluble R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 exogenous 1 NA 2 FALSE NA FALSE FALSE FALSE 50 TRUE 67.78 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 1236978 1236975 ,PSC2 200 antigens (endosomes) Cyclin A:Cdk2- R-HSA- R-HSA- R-HSA- associated events 1 NA 1 FALSE TRUE TRUE TRUE 85 TRUE 55.3764706 75 Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 69656 69242 187577 at S phase entry

Dectin-1 mediated PSMA1,HC2,NU,PROS30 R-HSA- R-HSA- P25786,Q9Y P61289,Q01 PSME3,RELB,PSMD2,TR noncanonical NF- 2 NA 3 TRUE NA FALSE TRUE TRUE 62 TRUE 72.5645161 75 ,PSC2,BTRC,BTRCP,FBW PSMA1 NA NA NA PSMD2 5607761 5607764 297 201,Q13200 AP2 kB signaling 1A,FBXW1A

Defective CFTR P55072,P61 R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 VCP,PSME3,PSMD2,TRA causes cystic 1 NA 4 FALSE NA FALSE FALSE FALSE 61 TRUE 69.7213115 75 P25786 PSMA1 NA NA NA 289,Q13200 PSMD2 5678895 5619084 ,PSC2 P2,OS9 fibrosis ,Q13438 TNKS,PARP5A,PARPL,TI Degradation of R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 O95271,P61 1 NA 3 TRUE NA FALSE TRUE TRUE 55 TRUE 77.0363636 75 P25786 PSMA1 NA NA NA N1,TINF1,TNKS1,PSME3 PSMD2 AXIN 4641257 201681 ,PSC2 289,Q13200 ,PSMD2,TRAP2 Degradation of PSMA1,HC2,NU,PROS30 beta-catenin by R-HSA- R-HSA- R-HSA- P25786,Q9Y P61289,Q13 2 NA 2 FALSE FALSE FALSE TRUE 84 TRUE 59.9880952 75 ,PSC2,BTRC,BTRCP,FBW PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 the destruction 195253 195721 196299 297 200 1A,FBXW1A complex Degradation of PSMA1,HC2,NU,PROS30 beta-catenin by R-HSA- R-HSA- R-HSA- P25786,Q9Y P61289,Q13 2 NA 2 FALSE TRUE TRUE TRUE 84 TRUE 59.9880952 75 ,PSC2,BTRC,BTRCP,FBW PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 the destruction 195253 195721 4641265 297 200 1A,FBXW1A complex

Degradation of R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 O14641,P61 DVL2,PSME3,PSMD2,TR 1 NA 3 TRUE NA FALSE TRUE TRUE 57 TRUE 74.6666667 75 P25786 PSMA1 NA NA NA PSMD2 DVL 4641258 201681 ,PSC2 289,Q13200 AP2

Degradation of PRKACG,PSMA1,HC2,NU R-HSA- R-HSA- P22612,P25 P61289,Q13 GLI1 by the 3 NA 2 TRUE NA FALSE TRUE TRUE 60 TRUE 75.0833333 75 ,PROS30,PSC2,BTRC,BT PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 5610780 5610787 786,Q9Y297 200 proteasome RCP,FBW1A,FBXW1A GLI2,THP,PRKACG,PSMA Degradation of P10070,P22 R-HSA- R-HSA- 1,HC2,NU,PROS30,PSC2, P61289,Q13 GLI2 by the 4 NA 2 TRUE NA FALSE TRUE TRUE 60 TRUE 75.55 75 612,P25786, PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 5610783 5610787 BTRC,BTRCP,FBW1A,FB 200 proteasome Q9Y297 XW1A O00206,P01 891,P01892, P04439,P05 534,P10314, P10316,P13 746,P16188, P16189,P16 190,P18462, TLR4,HLA- ER-Phagosome R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 1 NA 5 FALSE NA FALSE FALSE FALSE 85 TRUE 54.2117647 75 P25786 PSMA1 NA NA NA P30443,P30 A,HLAA,PSME3,PSMD2,T PSMD2 pathway 1236974 1236975 ,PSC2 447,P30450, RAP2,SEC61A2 P30453,P30 455,P30456, P30457,P30 459,P30512, P61289,Q09 160,Q13200 ,Q9H9S3

FBXL7 down- regulates AURKA R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 during mitotic 1 NA 2 FALSE NA FALSE FALSE FALSE 55 TRUE 78.8545455 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 8854050 69275 ,PSC2 200 entry and in early mitosis GLI3 is processed PRKACG,PSMA1,HC2,NU R-HSA- R-HSA- P22612,P25 P61289,Q13 to GLI3R by the 3 NA 2 TRUE NA FALSE TRUE TRUE 60 TRUE 75.55 75 ,PROS30,PSC2,BTRC,BT PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 5610785 5610787 786,Q9Y297 200 proteasome RCP,FBW1A,FBXW1A GLI2,THP,PSMA1,HC2,N P10070,P25 Hedgehog 'on' R-HSA- R-HSA- R-HSA- U,PROS30,PSC2,PTCH1,P P61289,Q13 4 NA 2 FALSE TRUE TRUE TRUE 86 TRUE 51.7093023 75 786,Q13635 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 state 5632684 5358351 5635851 TCH,KIF7,UNQ340/PRO5 200 ,Q2M1P5 39 GLI2,THP,PSMA1,HC2,N P10070,P25 Hedgehog 'on' R-HSA- R-HSA- R-HSA- U,PROS30,PSC2,PTCH1,P P61289,Q13 4 NA 2 FALSE TRUE TRUE TRUE 86 TRUE 51.7093023 75 786,Q13635 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 state 5632684 5358351 5632681 TCH,KIF7,UNQ340/PRO5 200 ,Q2M1P5 39 GLI2,THP,PSMA1,HC2,N P10070,P25 Hedgehog 'on' R-HSA- R-HSA- R-HSA- U,PROS30,PSC2,PTCH1,P P61289,Q13 4 NA 2 FALSE TRUE TRUE TRUE 86 TRUE 51.7093023 75 786,Q13635 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 state 5632684 5358351 5635838 TCH,KIF7,UNQ340/PRO5 200 ,Q2M1P5 39 P55072,P61 Hedgehog ligand R-HSA- R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 VCP,PSME3,PSMD2,TRA 1 NA 4 FALSE FALSE FALSE FALSE 65 TRUE 66.2 75 P25786 PSMA1 NA NA NA 289,Q13200 PSMD2 biogenesis 5358346 5358351 5362798 ,PSC2 P2,OS9 ,Q13438 Hh mutants that don't undergo P55072,P61 R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 VCP,PSME3,PSMD2,TRA autocatalytic 1 NA 4 FALSE NA FALSE FALSE FALSE 56 TRUE 75.6785714 75 P25786 PSMA1 NA NA NA 289,Q13200 PSMD2 5362768 5387390 ,PSC2 P2,OS9 processing are ,Q13438 degraded by ERAD Negative R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 regulation of 1 NA 2 FALSE NA FALSE FALSE FALSE 54 TRUE 77.7037037 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 9604323 9013694 ,PSC2 200 NOTCH4 signaling NIK-- PSMA1,HC2,NU,PROS30 R-HSA- R-HSA- P25786,Q9Y P61289,Q01 PSME3,RELB,PSMD2,TR >noncanonical NF- 2 NA 3 TRUE NA FALSE TRUE TRUE 59 TRUE 75.4915254 75 ,PSC2,BTRC,BTRCP,FBW PSMA1 NA NA NA PSMD2 5676590 5668541 297 201,Q13200 AP2 kB signaling 1A,FBXW1A Orc1 removal from R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 1 NA 2 FALSE NA FALSE FALSE FALSE 71 TRUE 63.9014085 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 chromatin 68949 69052 ,PSC2 200 Oxygen-dependent proline PSMA1,HC2,NU,PROS30 R-HSA- R-HSA- P25786,P51 P61289,Q13 hydroxylation of 2 NA 2 FALSE NA FALSE FALSE FALSE 66 TRUE 66.1060606 75 ,PSC2,UBE2D1,SFT,UBC PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 1234176 1234174 668 200 Hypoxia-inducible 5A,UBCH5,UBCH5A Factor Alpha Regulation of activated PAK- 2p34 by R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 1 NA 2 FALSE NA FALSE FALSE FALSE 50 TRUE 84.1 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 proteasome 211733 169911 ,PSC2 200 mediated degradation

Regulation of APC/C activators R-HSA- R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE FALSE FALSE TRUE 80 TRUE 60.6625 75 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA between G1/S and 176408 174143 176417 CH5,UBCH5A early anaphase Regulation of APC/C activators R-HSA- R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 1 NA FALSE TRUE TRUE TRUE 80 TRUE 60.6625 75 P51668 NA Q9UJX4 ANAPC5,APC5 NA NA NA NA between G1/S and 176408 174143 174113 CH5,UBCH5A early anaphase

Regulation of ornithine R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 1 NA 2 FALSE NA FALSE FALSE FALSE 51 TRUE 66.4705882 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 decarboxylase 350562 351202 ,PSC2 200 (ODC) O00308,O9 WWP2,TNKS,PARP5A,P Regulation of PSMA1,HC2,NU,PROS30 R-HSA- R-HSA- P25786,Q92 5271,P3175 ARPL,TIN1,TINF1,TNKS1 AKT2,PSMD PTEN stability and 3 NA 5 FALSE NA FALSE FALSE FALSE 69 TRUE 64.0869565 75 ,PSC2,USP13,ISOT3,AKT PSMA1 NA NA NA 8948751 6807070 995,Q9Y243 1,P61289,Q ,AKT2,PSME3,PSMD2,TR 2 activity 3,PKBG 13200 AP2

Regulation of RAS R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P01112,P61 HRAS,HRAS1,PSME3,PS 1 1 3 TRUE NA FALSE TRUE TRUE 68 TRUE 66.0735294 75 P25786 PSMA1 P01112 HRAS,HRAS1 NA PSMD2 by GAPs 5658442 5673001 ,PSC2 289,Q13200 MD2,TRAP2

Regulation of R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 RUNX2 expression 1 NA 2 FALSE NA FALSE FALSE FALSE 73 TRUE 62.1232877 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 8939902 8878166 ,PSC2 200 and activity Regulation of R-HSA- R-HSA- P12931,P25 SRC,SRC1,PSMA1,HC2,N P61289,Q13 RUNX3 expression 2 NA 2 FALSE NA FALSE FALSE FALSE 55 TRUE 76.6363636 75 SRC,PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 8941858 8878159 786 U,PROS30,PSC2 200 and activity SCF-beta-TrCP PSMA1,HC2,NU,PROS30 mediated R-HSA- R-HSA- P25786,Q9Y P61289,Q13 2 NA 2 TRUE NA FALSE TRUE TRUE 55 TRUE 79.2545455 75 ,PSC2,BTRC,BTRCP,FBW PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 degradation of 174113 176408 297 200 1A,FBXW1A Emi1 SCF(Skp2)- mediated R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 1 NA 2 TRUE NA FALSE TRUE TRUE 60 TRUE 71.2 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 degradation of 187577 69656 ,PSC2 200 p27/p21 SCF(Skp2)- mediated R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 1 NA 2 TRUE NA FALSE TRUE TRUE 60 TRUE 71.2 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 degradation of 187577 69202 ,PSC2 200 p27/p21 Stabilization of R-HSA- R-HSA- R-HSA- P04637,Q13 2 1 1 FALSE TRUE TRUE TRUE 57 TRUE 75.5614035 75 TP53,P53,ATM NA P04637 TP53,P53 NA P04637 TP53,P53 NA p53 69541 69563 349425 315 The role of GTSE1 P04637,P25 in G2/M R-HSA- R-HSA- TP53,P53,PSMA1,HC2,N P04637,P61 TP53,P53,PSME3,PSMD2 3 1 3 FALSE NA FALSE FALSE FALSE 60 TRUE 73.5666667 75 786,Q3ZCM PSMA1 P04637 TP53,P53 NA PSMD2 progression after 8852276 69275 U,PROS30,PSC2,TUBB8 289,Q13200 ,TRAP2 7 G2 checkpoint Ubiquitin Mediated R-HSA- R-HSA- P25786,Q13 PSMA1,HC2,NU,PROS30 P61289,Q13 Degradation of 2 NA 2 FALSE NA FALSE FALSE FALSE 53 TRUE 80.0566038 75 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 69601 69610 315 ,PSC2,ATM 200 Phosphorylated Cdc25A Ubiquitin- dependent R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 1 NA 2 FALSE NA FALSE FALSE FALSE 52 TRUE 81.4807692 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 degradation of 69229 75815 ,PSC2 200 Cyclin D1 Vif-mediated R-HSA- R-HSA- PSMA1,HC2,NU,PROS30 P61289,Q13 degradation of 1 NA 2 FALSE NA FALSE FALSE FALSE 55 TRUE 77.8 75 P25786 PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 180585 162909 ,PSC2 200 APOBEC3G Vpu mediated PSMA1,HC2,NU,PROS30 R-HSA- R-HSA- P25786,Q9Y P61289,Q13 degradation of 2 NA 2 FALSE NA FALSE FALSE FALSE 53 TRUE 81.2075472 75 ,PSC2,BTRC,BTRCP,FBW PSMA1 NA NA NA PSME3,PSMD2,TRAP2 PSMD2 180534 162909 297 200 CD4 1A,FBXW1A Activation of BAD R-HSA- R-HSA- P31751,P31 and translocation 1 NA 2 FALSE NA FALSE FALSE FALSE NA FALSE NA NA Q9Y243 AKT3,PKBG NA NA NA NA AKT2,SFN,HME1 AKT2 111447 114452 947 to mitochondria Cleavage of Q05519,Q1 Growing SRSF11,SFRS11,CPSF1,C R-HSA- R-HSA- 0570,Q8N6 Transcript in the 1 NA 5 FALSE NA FALSE FALSE FALSE NA FALSE NA NA P38919 EIF4A3,DDX48,KIAA0111 NA NA NA NA PSF160,CPSF7,THOC2,CX NA 109688 73856 84,Q8NI27, Termination orf3,CPSF3,CPSF73 Q9UKF6 Region Cleavage of the R-HSA- R-HSA- O95243,Q1 damaged NA NA 2 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA MBD4,MED1,TDG NA 110329 73928 3569 pyrimidine

Cyclin E associated R-HSA- R-HSA- R-HSA- events during 1 NA 1 FALSE FALSE FALSE TRUE NA FALSE NA NA Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 69202 69206 69200 G1/S transition

Cyclin E associated R-HSA- R-HSA- R-HSA- events during 1 NA 1 FALSE TRUE TRUE TRUE NA FALSE NA NA Q9Y243 AKT3,PKBG NA NA NA NA P31751 AKT2 AKT2 69202 69206 187577 G1/S transition

Cytosolic sensors R-HSA- R-HSA- R-HSA- of pathogen- NA NA 1 FALSE FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P78527 PRKDC,HYRC,HYRC1 NA 1834949 168249 3134963 associated DNA Cytosolic sensors R-HSA- R-HSA- R-HSA- of pathogen- NA NA 1 FALSE FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P78527 PRKDC,HYRC,HYRC1 NA 1834949 168249 1606322 associated DNA Cytosolic sensors R-HSA- R-HSA- R-HSA- of pathogen- NA NA 1 FALSE FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P78527 PRKDC,HYRC,HYRC1 NA 1834949 168249 3134975 associated DNA Cytosolic sensors R-HSA- R-HSA- R-HSA- of pathogen- NA NA 1 FALSE FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P78527 PRKDC,HYRC,HYRC1 NA 1834949 168249 1834941 associated DNA Cytosolic sensors R-HSA- R-HSA- R-HSA- of pathogen- NA NA 1 FALSE FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P78527 PRKDC,HYRC,HYRC1 NA 1834949 168249 3134973 associated DNA

Defective ABCB11 causes progressive familial intrahepatic R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE NA FALSE NA NA O95342 ABCB11,BSEP NA NA NA NA NA NA NA cholestasis 2 and 5678520 5619084 benign recurrent intrahepatic cholestasis 2

Defective ABCB4 causes progressive familial intrahepatic cholestasis 3, R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P21439 ABCB4,MDR3,PGY3 NA intrahepatic 5678771 5619084 cholestasis of pregnancy 3 and gallbladder disease 1

Defective ABCC9 causes dilated cardiomyopathy 10, familial atrial R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE NA FALSE NA NA O60706 ABCC9,SUR2 NA NA NA NA NA NA NA fibrillation 12 and 5678420 5619084 hypertrichotic osteochondrodyspl asia Defective CYP19A1 causes Aromatase R-HSA- R-HSA- CYP19A1,ARO1,CYAR,CY 1 NA NA FALSE NA FALSE FALSE FALSE NA FALSE NA NA P11511 NA NA NA NA NA NA NA excess syndrome 5579030 5579029 P19 (AEXS) Defective MOGS R-HSA- R-HSA- causes MOGS-CDG 1 NA NA FALSE NA FALSE FALSE FALSE NA FALSE NA NA Q13724 MOGS,GCS1 NA NA NA NA NA NA NA 4793954 3781860 (CDG-2b)

Defective SLC12A1 R-HSA- R-HSA- causes Bartter NA NA 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA Q13621 SLC12A1,NKCC2 NA 5619104 5619102 syndrome 1 (BS1)

Defective SLC27A4 causes ichthyosis R-HSA- R-HSA- 1 NA NA FALSE NA FALSE FALSE FALSE NA FALSE NA NA Q6P1M0 SLC27A4,ACSVL4,FATP4 NA NA NA NA NA NA NA prematurity 5619108 5619102 syndrome (IPS)

Defective SLC2A2 causes Fanconi- R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P11168 SLC2A2,GLUT2 NA Bickel syndrome 5619098 5619102 (FBS) Defective SLC6A2 R-HSA- R-HSA- SLC6A2,NAT1,NET1,SLC causes orthostatic NA NA 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P23975 NA 5619109 5619102 6A5 intolerance (OI) Essential R-HSA- R-HSA- NA NA 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P50053 KHK NA fructosuria 5657562 5663084 Formation of RNA R-HSA- R-HSA- P18074,P18 ERCC2,XPD,XPDC,NELFE, Pol II elongation NA NA 2 TRUE NA FALSE TRUE TRUE NA FALSE NA NA NA NA NA NA NA NA NA 112382 75955 615 RD,RDBP complex GRB2:SOS provides linkage to R-HSA- R-HSA- P12931,Q7Z SRC,SRC1,APBB1IP,PREL 2 1 NA TRUE NA FALSE TRUE TRUE NA FALSE NA NA SRC P02751 FN1,FN NA NA NA NA MAPK signaling for 354194 354192 5R6 1,RARP1,RIAM Integrins Hereditary R-HSA- R-HSA- fructose NA NA 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P05062 ALDOB,ALDB NA 5657560 5663084 intolerance Intestinal R-HSA- R-HSA- saccharidase NA NA 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA NA NA NA NA NA P14410 SI NA 5659898 5663084 deficiencies MPS VI - R-HSA- R-HSA- Maroteaux-Lamy 1 NA NA FALSE NA FALSE FALSE FALSE NA FALSE NA NA P15848 ARSB NA NA NA NA NA NA NA 2206285 2206281 syndrome MyD88- R-HSA- R-HSA- R-HSA- independent TLR4 NA NA 1 TRUE FALSE TRUE TRUE NA FALSE NA NA NA NA NA NA NA NA O00206 TLR4 NA 166166 166016 937061 cascade

P00451,P01 F8,F8C,SERPINA1,AAT,PI Platelet R-HSA- R-HSA- O00391,P00 QSOX1,QSCN6,UNQ252 009,P01133, ,PRO0684,PRO2209,EGF 2 1 6 FALSE NA FALSE FALSE FALSE NA FALSE NA NA NA P02751 FN1,FN NA NA degranulation 114608 76005 488 0/PRO6013,F13A1,F13A P07225,P35 ,PROS1,PROS,ACTN2,ST 609,Q15833 XBP2,UNC18B

TICAM1, RIP1- mediated IKK R-HSA- R-HSA- UBE2D1,SFT,UBC5A,UB 1 NA NA FALSE NA FALSE FALSE FALSE NA FALSE NA NA P51668 NA NA NA NA NA NA NA complex 168927 168164 CH5,UBCH5A recruitment Transcriptional R-HSA- R-HSA- activation of cell 1 1 1 FALSE NA FALSE FALSE FALSE NA FALSE NA NA P04637 TP53,P53 NA P04637 TP53,P53 NA P04637 TP53,P53 NA 69895 69560 cycle inhibitor p21