US 200902388O8A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0238808 A1 Drewes et al. (43) Pub. Date: Sep. 24, 2009

(54) PROCESS FOR THE IDENTIFICATION OF (60) Provisional application No. 60/711,399, filed on Aug. NOVEL ENZYME INTERACTING 25, 2005, provisional application No. 60/782,170, COMPOUNDS filed on Mar. 14, 2006. (76) Inventors: Gerard Drewes, Heidelburg (DE); Bernhard Kuester, Heidelburg (30) Foreign Application Priority Data (DE); Ulrich Kruse, Dossenheim (DE); Carsten Hopf. Mannheim Jun. 14, 2005 (EP) ...... EP O5O12722.4 (DE); Dirk Eberhard, Mauer (DE): Marcus Bantscheff, Heidelburg Publication Classification (DE); Valerie Reader, Linton (GB); (51) Int. Cl. Manfred Raida, Singapore (SG); A638/43 (2006.01) David Middlemiss, Bishops GOIN 33/573 (2006.01) Stortford (GB) (52) U.S. Cl...... 424/94.1; 435/7.4 Correspondence Address: CLARK & ELBNG LLP (57) ABSTRACT 101 FEDERAL STREET BOSTON, MA 02110 (US) The present invention relates to methods for the characteriza tion of enzymes or of enzyme-compound complexes, wherein (21) Appl. No.: 12/002,222 the enzyme is obtained from a preparation with the help of at least one broad spectrum ligand immobilized on a (22) Filed: Dec. 14, 2007 Solid Support and wherein the enzyme is characterized by mass spectrometry. These methods are useful for the screen Related U.S. Application Data ing of non-immobilized compound libraries, selectivity pro (63) Continuation-in-part of application No. PCT/EP2006/ filing of lead compounds and mechanism of action studies in 062984, filed on Jun. 7, 2006. living cells. Patent Application Publication Sep. 24, 2009 Sheet 1 of 153 US 2009/0238808A1

Figure 1:

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Patent Application Publication Sep. 24, 2009 Sheet 2 of 153 US 2009/0238808A1

Figure 2:

Kinobeads P -626 Proteins-503

Kinases- 100 Kinases- 12

Proteins 372 Proteins- 254 Proteins 249 Kinases- 9 Kinases- 9 Kinases- 3 Patent Application Publication Sep. 24, 2009 Sheet 3 of 153 US 2009/0238808A1

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Figure 14 FAK FAK protein levels Y598 + Y599 phosphorylation dasatinib + lysate A A daSatinib + Cells

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Figure 1971

Protein binding profiles of of mixed kinase inhibitor beads (kinobeads) Protein family Subfamily Protein name Placc, no. Number of spectrum-to-seouence matches (Sugen nomenclature for Hella Placenta Jurkat K562 Ramos kinases when available, rest from IPI)

Kinase TK P00442025 200 44 81 129 423 POO3294.88 942 81 SO 788 823 Kinase TK BCR-ABL NA 208 197 5159 36 Kinase TK BLK POO306217 78 838 Kinase TTK BMX P100020899 99 4 EEE - EOEEEEEEE Kinase TK BTK EE 1539 3O8239 160110 E.1686 1908E. Kinase TK DDR1 PIOOOO1477 239 179 26 84 49 Kinase TKDDR2 P10000440986 51 Kinase TK EGFR IPO0018274 148 497 Kinase IPIOO294.250 3 162 Kinase PIOOO21287 851 241 -

Kinase P00008318POO298105 71 13026 E-E Kinase TTK Ephas PO0008290 22 3 Kinase TK Ephal IPO0016645 2 Kinase TK Ephel PIO0008315 2 16 L Kinase TK Ephb2 IPIO0021275 188274 186 28 Kinase K Eph3 IPOO289.329 57 2 Kinase TK EhB4 PIOO289342 591 1299 s 4.08 2 P00005222 5 68 1 Kinase TK FER IPOOO29263 330 271166 258 128 Kinase TK FES PIOO294344 427 L Kinase K PIOOOO5142 19 40 46 82 Kinase TK POO22O2S3 1 Kinase POO3O4578 19 K PIOOO16871 71 5 44 Kinase TK FLT3 PIOOOO5722 11 Kinase TK FLT4PIOO293565 364 12 Kinase TK IFMS PIOOO11218 64 KinaseE-E TK P00000885POO219012 100 33E. E. E.58 29 K POOO297.59 187 61 HER2/ErbB2 PIOO300384 3 Kinase TTK HER3/ErbB3 IPIOO298285 74 Kinase TK IGF1R PIO0027232 36 22 3 34 Kinase TK TK Poooo4566 1 1484 AK2 FPIOOO31016 6 46 40 Kinase TK JAK3 IPIO0219418 7 2 50 16 Kinase TK KDR PIO0021396 72 Kinase TK KIT IPOOO22296 27 140 E. LCK PIOO394952 6, 16 3818 112 810 K 18 13 23 K MET IPOO294528 102 36 K PDGFRa. Pio0027721 137 K PDGFRb IPOOO15902 13 539 3

Kinase TKK RON PIOOO30273 131 as sis as 29 K SRC iPloos28867 4739 28g 112 B SYK P100018597 576. 176203 TEC IPO0000878 L 27 32 39 430 159 TE2 (PIOO412829 151 TNK1 Pooo22633 1332 6 175

TXKEAEE POOOOO879 2 TYK2 T PO0022353 302. 21 509 227 540 YES PO0013981 1767.823 128 552 1 P00329789 74 Patent Application Publication Sep. 24, 2009 Sheet 45 of 153 US 2009/0238808A1

Figure 1972

Protein family Subfamily Protein name Pacc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest from IPI) K562 - Kinase TKL. ACTR2 IPO0015691 - 102 26 8 28 Kinase TKL ACTR2B iPIOO437565 16 23 44, 26 48 Kinase TKL. ALK PO0293271 3 T 6 Kinase TKL ALK2 (PIOOO29219 36 105 88 56 4 Kinase EAEEEEEEEETK ARAF PI00020578 37 6. 36. 33 59 BMPR1A PIO0005731 79 21 38 30 52 BMPR2 PIOO221246

BRAF IPOO303797 PIOO29218.1 PIOOO25844 POO293652 POOO26984 POOOOF841 PIOO514547 Kinase POO29702 POOO22872 Kinase POO3O6522 Kinase TK PIOO 175649 Kinase K PO)1791.89 POOOOO977 P001424.87 P00021786 P00021917 PIOO2949.38 PIOOO18182 P00102877 TKL TGFbr1 P00005733 Kinase TK TGFbr2 IPOO164934 TK ZAK IPOO329.638 IPIOO149094 45 P00020258 12 190 10 168 PIOO294842 41 82 123 82 7 IPIO0217024 32 38 B 51 3 Kinase STE LOK IPO0304742 T- 1 - T - 18

Kinase T STE MAP2K1 PIO0219604 14 3 L 1022

MAP2K2MAP2Ka EE-2EEPOOO24674 11

MAP2K5 MAP3K1 PIOOO12318 19 12 103 280872 MAP3K2 MAP3K3 PIOO181703 17 70 55' 39. 27 Kinase STE MAP3K5 PIOO412433 27 47 5, 98 Kinase TSTE MAP3K6 P10041822 9 LL4 Kinase ISTE MAP3K7 PIOO412740 4 Kinase ISTE MST2 PIOO411984 2 10 Kinase STE MST4 IPO02.92827 2L LD Kinase STE PAK4 IPO0014068 192 163. 116 105 105 Kinase STE PAK5 PIOOOO1814 . . . . . 2 Kinase ISTE SLK PO0022827 28 4 28 28 9 E. S. SS-E-319 49 6 Kinase STE TAO2 PIOO465168 I 42 57 81 11 86 Kinase ISTE TAO3 IPIOO410485 11 26 55 44 13 Kinase STE ZC17HGK PIO0219800 25 2 2. Kinase STE ZC2TNK POO145805 4 49 Kinase CK1 CK1a Poo448798 34 13 63 134 62 Kinase CK1 CK1d P0001102 5 5 2 27 44 Kinase CK1 ICKe EP0002729 45 21 68 13 59 CK12CK11 POO4S5058p00297,767 244 EE 39 42 16 67 72 Kinase AGCIBARK1 P0001.2497 2 Kinase AGC BARK2 EP00019926 1 Kinase AGC MSK Poo335101 7 5 2. Kinase AGC MSK2 P00022536 56 37 18 20 Patent Application Publication Sep. 24, 2009 Sheet 46 of 153 US 2009/0238808A1

Figure 1973

Protein family Subfamily Protein name Placc.no. Number of specturn-to-sequence matches (Sugen nomenclature for kinases when available, rest from IPI) Hella or r kinase AGC PDK1 Poooo2538 13056 146 107 222 AGC PKCa POO3854.49 12 114 78 15 41 AGC PKCb IPOO2196.28 27 165 E. Kinase AGC PKC IPOO329236 34 44 15 40 82 Kinase AGC PKCh PIOO184572 2 Kinase AGC PKC P00029.196 5 163 98 65 Kinase AGC IPKG IPOO436355 67 Kinase AGC PKN1 POO412672 7 39 18 13 Kinase AGC PKN2 PIO0002804 16 - Kinase AGC PKN3 P00413780 33 kinase AGC Rock1 Plooo22542 5 2 Kinase AGC ROCK2 PO0307155 20 kinase AGCRSKIPOo300321153 33 Kinase AGC RSK2 POOO2O898 S5 39 73 61 45 Kinase AGC RSK3 P00477982 211 63 197. 301 196 Kinase AGC RSK4 IPOOOO7123 13 764 434 383 Kinase CAMK AMPKa2 IPIOO307755 36 Kinase CAMK BRSK IPIOO 148020 13 12 Kinase CAMK BRSK2 Poo339265 32 Kinase Pool170508 1 12 71 Kinase POOSSOOSS 4. S 7 Kinase POO2.21305 3. 5 12 Kinase CAMK PI00430291 290 490 564 19 4369 Kinase CAMK CaMK2g PIOO169392 702 1030, 1868 533 631 Kinase CAMK CaMK4 P100430411 9 8 Kinase CAMK CaMLCK POo3O4648 5 4 Kinase CAMK CASK Plooo?4726 3 2 Kinase CAMK POOO23SS4 3 5 Kinase POO423156 5 Kinase POOO14934 1 Kinase P00219072 1 E Kinase CAMK MAPKAPK2 Pooo26054 4. Kinase CAMK IMAPKAPK5 PIO0160672 2 Kinase CAMK IMARK1 PIOO185037 28 Kinase CAMK MARK2 iPIOO555838 383 40 317 290 331 CAMK POO183118 190 49. 184 179 194 Kinase CAMK PIOOO64797 58 38 10 CAMK P000064.71 42 63 37 37 POO3O4048 6 Kinase CAMK PHKg2 IPO0012891 12 L 421 Kinase CAMK PIM1 Pooooso 14 11 Kinase CAMK PKD2 IPO0009334 18 1938 30 70 Kinase CAMK IPOOO15538 5 2 54 IPOO465291 29 15 115 261 252 Kinase P00657.720 62 11s 15e 219 722 Kinase CAMK P00025879 100 8 Kinase CAMK STK33 IPO0302351 6 8 13 25 IPOOO31881 249 180 163. 170 PIOOO23503 2 is 4

EPIOOO23.529PIOOO23530 25230 125 7 48210 83 Kinase CMGC 10 Kinase CMGC CLK1 P00028061 kinase CMGC CLK2 iPoooz8071 a 30 Kinase CMGC CLK3 IPO0298896 Kinase ICMGC CRK7 IPIO0021175 15 8 Kinase CMGC DYRK1A PIOOO14344 2 Kinase CMGC DYRK1B Pooooo352 1 EMS-E-EErk2 POOOO3479 1086 66 Kinase CMGC Erks P0000343 - Kinase ICMGC Erk5 PIO0219601 L Kinase CMGC Ekit IPIO0165955 1 Patent Application Publication Sep. 24, 2009 Sheet 47 of 153 US 2009/0238808A1

Figure 1914

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-Sequence matches (Sugen nomenclature for Hella Placenta Jurkat K562 kinases when available, rest from (PI) Kinase CMGC eskea POO292228 782 245 Kinase CMGC GSK3B PO0216190 538 39 SOO 568 379 Kinase CMGC PIO0414744 5 8 Kinase CMGC PIOO181855 9 8 Kinase CMGC NK1 PIO0024672 Kinase CMGC POO303550 Kinase CMGC Pooo23547 1 Kinase CMGC POOO08237 90 134 45 Kinase CMGC PO0002857 1084 969 1002 1407 Kinase CMGC 38 POOO19473 14 26 8 Kinase CMGC PCTARE2 POO376955 6 Kinase Atypical P001835.08 Kinase Atypical ADCK1 P00412099 Kinase Atypical AOCK3 POO176469 Kinase Atwoical ADCK4 POO647707 9 Kinase Atypical POO298.306 Kinase Atypical ATR P00412298 11 a Kinase Atypical ATA6sBCRMK1 P00004497 64 Kinase Atypical BRD2 POOO14414 Kinase Atypical BRD3 IPOOO 14266 11 Kinase Atypical BRD4. IPOO44O727 33 142 Kinase Atypical DNAPK POO296337 3 2 1799 Kinase Atwoical FRAP POO513678 237 2 191 Kinase Atypical PDHK P00655704 Kinase Atypical PDHK3 P00014849 Atypical TRRAP P00069084 7 Kinase TF1 TF 1b. P00438229 5 Kinase Non-SUGEN BMPR2 SF POOO27376 Kinase Non-SUGEN CK1 POo383.161 Kinase NO-SUGEN CK2P POO643723 Kinase Non-SUGEN P00396447.2 PO0396447 Kinase Non-SUGEN OC440332 POO455277 Fl Kinase Non-SUGEN MKNK2 POOS56585 - Kinase Non-SUGEN RP 11.535K183 PO0217264 SMARTO CASEIN 2122i KNASE, DELTA Kinase Non-SUGEN SOFORM. PIOO234463 SMARTO INTEGRAL MEMBRANE Kinase Non-SUGEN GLYCOPROTEINGP210P POOO17837 SMARO MOGEN Kinase Non-SUGEN ACTIVA IPIOOO8748 Kinase Non-SUGEN SPFH1 IPIOOOO7940 Kinase Non-SUGEN SPFH2 P00026942 Kinase Non-SUGEN TFGSE2- POO294619 EE3 Kinase Other P00298977 21 Kinase Other IPOO298.940 688 126 Kinase Other Aurs IPOO176642 174 - 148 Kinase.EEEEEE Other CaMKK IPIOO166909 E.62 E. E.18

Kinase. Other CK2a1 PIOOO6613 48 12 45 Kinase Other CK2a2 IPO0020602 93 102 68 1 KinaseE SEOther SEEFused EIPO0235407 10 H 3 E.Kinase. OtherE. E.GCN2 E.PIOO163851 E.102 E.20 345E. 147 231 Kinase Other HR PIO0328149 58 I 40 Kinase other KKa P00005104 Kinase Other KKe. T POOO29045 155 13 135 Kinase other MPSK1 (PIOO306833 21 12 10 Kinase Other MYT1 IPOo384765 5867 Kinase other NEK1 P100552585 19 18 Kinase other INEK2 PI00021331 81 T 67 Kinase. Other NEK6 P10039666.2 6 to Kinase Other NEK9 IPO0301609 227 2 71132 i56855 3.4.32:9i1i3O1i12 g4.Ž172: Patent Application Publication Sep. 24, 2009 Sheet 48 of 153 US 2009/0238808A1

Figure 1915

Protein family Subfamily Protein name PacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for K562 Ramos kinases when available, rest from IPI)

Kinase POOO21248 - - - Kinase PCO40344 38 22 27 45

Kinase PCO166578 Kinase POO2936.13 1483 848 POO151170 1 79 30 495 135 Lipid Kinase . . PIK3C2b PI00292056 72 40 Lipid Kinase - PIK3Cb PIOOO31388 3 lipid Kinase. PIK3Cd P002984.10 Lipid Kinase - PIK3Cig IPCO292690 13 Lipid Kinase I. PK4Ca P100070943 24 8 41 14 Lipid Kinase PIP5K2AP1000096886 7 12 Lipid Kinase T - PP5K2B P100216470 2 Lipid Kinase - PIP5K2C P100152303 66 1 8, 20 SIMILAR TO PHOSPHONOSTIDE-3- Lipid Kase KNASE, CASS 2, AL PO006O352 Sugar kinase - FRAT1 Pooo23762 1 Sugar kinase - HK1 POO220665 7 3 Sugar kinase - THK2 PIO01028643 Sugar kinase - HKDC1 Poo414612 RT Sugar kinase - PFKL POO220617 13 22 12 19 14 PFKM POO4651.79 7 4. Sugar kinase P000097.90 36 39 24 17

Nucleotide kinase - P 00215901

Nucleotide kinase POO2995.3 Nucleotide kinase Nucleotide kinase PIOO604590 Nucleotide kinase POO29924 Nucleotide kinase POO337439 Nucleotide kinase POOO65671 Other kinase C2 of 124 PIOOO13004 Other kinase NAGK PIOO296.526 Other kinase PANK4 POOO18946 Other kinase PGK1 POO169383 Other kinase PIOO294.578 PIOO657689 POO64304 6 P00478231 PIOOOOOO41 PIOOO17342

P00018882 3 SMILAR TOADP RBOSYATION FACTOR 4 o Enzyme GTPase H. SAPIENS P00013078 1 Enzyme Helicase ASCC3L-1 P00420014 11 6 10 5 Enzyme Helicase BA1 P00328343 2 Enzyme Helicase IBTAF1 PIOOO24802 7 Enzyme Helicase ICHD8 OIPIO0719073 8 6 5 48 Enzyme Helicase DDX1 PIOO293655 7 3 7 3 Enzyme Helicase DDX3YOPIO0215637 22 7 8 3 2 Enzyme Helicase DDX5 PIOOO17617 19 13 5 13 Enzyme Helicase DDX17 PIO0651677 4 1 6 10 10 Enzyme Helicase DDX20 IPIO0005904 11 3 10 Enzyme Helicase DDX39 PO06444.31 4 Enzyme Helicase DDX46 PIO0329791 3 2 Enzyme Helicase DDX48 PO0009328 T 3 Helicase DHX9 P00215638 1 Enzyme Helicase DHX15 DP100177366 6 EEEEEEEEEEnzyme Helicase EF4A1 PIO0386604 || 3 EEEEEEEEEEnzyme Helicase ERCC2 PIOOO29728 Enzyme Helicase ERCC3 PIOO291364 10 Enzyme Helicase G3BP PIOOO12442 9 Enzyme Helicase GTF2F2 OPIOO477686 5 Patent Application Publication Sep. 24, 2009 Sheet 49 of 153 US 2009/0238808A1

Figure 1976

Protein family Subfamily Protein name IP acC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Placenta Jurkat kinases when available, rest from PI) Enzyme Helicase LBA Ploogo7684 7 18 Enzyme Helicase SSRUWB1 -E;P00021187 5 4 Enzyme Helicasehelicase SKW22 PIOO647217POOOO904 EEE 8 EEESAEEEEEEEEEnzyme Helicase SMARCA4 POO293.426 4 Enzyme helicaseHelicase EEEXRCC6 P0064.47 12 115 5 6 2 7

Ezyme Hydrolase 40057 PIOO412206 5 4.

Ezyme Hydrolase ABHD3 PIOOO 12409 2

Enzyme Hydrolase ACAD10 IPOO418639 1 2 s EnzymeEEEEEEEEEEEEEE Hydrolase ACO8 POO2982O2 3 Enzyme Hydrolase ACY12 POO217852 EEEEEEEEEEEEEEEnzyme Hydrolase ACYP2 IPO0216461 1 1.3 Enzyme Hydrolase ADAM12 IPOO415037 41 Enzyme Hydrolase ADAM17 P00288894 10 Enzyme Hydrolase ADAMTS14 IPOO219598 1 Enzyme Hydrolase ADAMTS4 P00374068 3 Enzyme Hydrolase AFG3L2 P100001091 6 6 6 8 Enzyme Hydrolase AHCY POO646823 - 2 9 12 Enzyme Hydrolase AHCY1 Pools2938 5 2 Enzyme Hydrolase ACDA POOO1086 3

PO0337741 3. 3 5 5 E.enzyme E.Hydrolase EECSCARF4 EEEP00215918 O E E s - Enzyme Hydrolase ARG1 POo398768 2 EEEEEEEEEEEEEEEnzyme Hydrolase ASAH1 POO418446 12 Enzyme Hydrolase ATG48 IPOO554458 2

EEEEEEEEEEEEEEEnzyme Hydrolase C1727 IPOO470.478 28 2O 221 168 Enzyme hydrolase CAPN2 IPOO289758 7 3 EEEEEEEEEEEEEnzyme Hydrolase CAPNS POOO25084 2 3 5 EEEEEEEEEEnzyme Hydrolase CASP3 POO29240 2 1 1 1 Enzyme Hydrolase EAECCT8 POO3O2925 114 6 7 7 1016 Enzyme Hydrolase CDC42 Poo385447 3 4 7 Enzyme Hydrolase CDC91L1 PIO0026044 3 4 Enzyme Hydrolase COG8 P00007060 1 Enzyme Hydrolase CPD PO0027078 4 Enzyme Hydrolase CTSB Ploo295741 5 3 2 Enzyme Hydrolase ICTSC PIO0022810 || 1 || || 3 Enzyme Hydrolase CTSD POOO 1229 11 26 7 3 Enzyme Hydrolase ICTSZ IPIO0002745 4 5 Enzyme Hydrolase DFFA 1 EnzymeEEEEEEEEEEEE Hydrolase DLG IPIOO218729 3 Enzyme Hydrolase DNM1 IPIOO413140 1 Enzyme Hydrolase DNPEP IPIOOO15856 5 Enzyme Hydrolase DPP4 IPO0018953 10 Enzyme Hydrolase DPYSL2 P001.06642 21 6 Enzyme Hydrolase DUSP3 PIOOO18671 Enzyme Hydrolase DUSP12 PooDO9210 2 Enzyme Hydrolase EFTUD2 IPIOOO03519 1 4D Patent Application Publication Sep. 24, 2009 Sheet 50 of 153 US 2009/0238808A1

Figure 1977

Protein family Subfamily Protein name Placc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Placenta Jurkat K562 kinases when available, rest from IPI) Enzyme Hydrolase EHD1 poozsa a 5 Enzyme Hydrolase EHD2 Pool100980 T 3 Enzyme Hydroese EML Piossos | a Enzyme Hydrolase ENDOD1 Ploooo 1952 2 PIOO477535 Enzyme Hydrolase ExOSC4 PIOO218310 Enzyme Hydrolase FEN POOO26215 3 Enzyme Hydrolase FLJ1115FLJ25084 POO305010POO 102281 EEE Enzyme Hydrolase FUCA1 PIOO299.026 2 E Hydrolase GAA P00293O88 4 Hydrolase GALC POOOO8790 42 Hydrolase P00011454 14 19 12 19 2 Hydrolase IPOO296635 - E

Hydrolase P00328170 9 Hydrolase P004651.84 4 Hydrolase PIOO328744 2 Hydrolase GNA13 IPOO290928 2 Hydrolase GNA2 Poo46512 5 12 Hydrolase GNAI3 Pooz20578 T 2 Enzyme Hydrolase HAGH POOOo3933 T 4 Enzyme Hydrolase POO152692 E.Enzyme E.Hydrolase E. POO647O65POOOO9931 - Hydrolase P004.PIOO239.077 19802 EEE10 10 8 Hydrolase POOOOO335 T 3 Hydrolase HM13 Ploo220687 Hydrolase HP Poosa. 1737 6 Enzyme Hydrolase HPR P006O7707 2 Enzyme Hydrolase CHRSP12 POO005038 1. POOOO1663 14 PO0645392 Hydrolase INPP5D POO3292.13 4. Hydrolase INPP1 POOO16932 265

PIOO647246 144. TPA Pl00018783 3 KATNA1 - 2 KIAAO195 3 5 33 1 T TO 4

Enzyme Hydrolase LOC134147 PIOO383.046 10 Enzyme Hydrolase LOC221955 2EE

Enzyme Hydrolase LOC283871 POO177008 OC285148 POO41994 Enzyme Hydrolase LRAPLYPLA1 IPOOOO7321P00465261 EE1 7 Enzyme Hydrolase LYPLA2 IPO0027032 4 10 4 5 Enzyme Hydrolase LYZ P00019038 3 3 Enzyme Hydrolase MACF 1 EPIOO432363 67 11 Enzyme Hydrolase MCM2 PIOO184330 4 Enzyme Hydrolase MCM3 PIOOO13214 4 17 11 10 Enzyme Hydrolase MCM4 PIOOO18349 4 1 1 Enzyme Hydrolase MCM5 PIO0018350 10 14 17 13 Enzyme Hydrolase MCM6 ICP00031517 3 4 1 Enzyme Hydrolase MCM7 PO0299904 9 15 7. 13 Enzyme Hydrolase MDN1, PIOO167941 202 18 225 201 MICROSOMAL SIGNAL Hydrolase SUBUNI. PIOO104128 Enzyme... Hydrolase... EraMSH6 POo384456... 25I T 6 36 Enzyme Hydrolase INDUFS3 (PIOO174190 2 1 2 Enzyme Hydrolase NIT IPO.0456664 2 Enzyme Hydrolase NPEPPS PIO0026216 3 5 Enzyme Hydrolase NRD1 PI0024.3221 IPOOOO9662 Patent Application Publication Sep. 24, 2009 Sheet 51 of 153 US 2009/0238808A1

Figure 1978

Protein family Subfamily Protein name Pacc.no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Placenta Jurkat K582 Ramos kinases when available, rest from PI) Enzyme ... Hydrolase INTE POO640818 12 Enzyme Hydrolase NUDT1 POOOO4392 3. 10

Enzyme HydrolaseHwdolase SEENUDT18 EEEPIOO217911 8 10 4.2 Enzyme Hydrolase OPA PIOO107753PIOO 107753 37 18 Ezyme Hydrolase OTUB1 E.P00000581 5 6 Hydrolase OTUB1 (PIOO409750 2 Enzyme Hydrolase PAFAH1B2 P00026546 1 PAPPA PIOO409750 EEE

PGLS PIOOO29997 5 6 Enzyme Hydrolase PGPEP1 IPO0020539 1 Enzyme hydrolase PGS PIOO465308 Enzyme Hydrolase PIGT PO0100030 2 Enzyme Hydrolase PLCG2 PIO0329185 33 Enzyme Hydrolase IPLD3 PIO0328243 I 6 Enzyme Hydrolase PMPCA IPOO166749 1 EnzymeEEEEEEEEEEEEEE Hydrolase PMPCB PO0289535 3 Eenzyme - EHydrolase - EPPA1 - EEEPIOOO15018 3. Enzyme Hydrolase PPPCA P00027423 Enzyme Hydrolase PPPCB DPIO0218236 11 3 3 Enzyme Hydrolase PPP2CA POOOO8380 7 7 5 8 27 Enzyme Hydrolase PPP3CB EEEEEEEE Enzyme Hydrolase PP6C IPO0012970 9. 1 7 5 s Enzyme Hydrolase PRKAB1 POO220409 88 168 143 123 PROTEASOME BETA2 Enzyme. Hydrolase. FRAGMENT).. ." IoTPOO555,590 I 1I I I Enzyme HwdrolaseHydrolase EEEEEEEEEEPSAR Pooos0545 1 1 12 Enzyme Hydrolase PSMA2 IPOO2 19622 3. EnzymeE-ESMA Hydrolase PSMA3 EPOO4-19249 H2 Enzyme Hydrolase PSMAS IPIOO291922 3 7 EEEEEEEEEEEEEEEnzyme Hydrolase IPSMA6 PIOOO29623 3 5 4 2 EEEMEEEEEEEEEEnzyme Hwdolase PSM31 IPOOO25019 8 3 Enzyme Hydrolase PSMB3 POOO28004 - a EnzymeEEEME, Hydrolase PSMB4 OPIOO555956ESE 1 2 . . ... 3 Enzyme Hydrolase PSM5 PIOO383971 1 EnzymeEEE Hydrolase ESMEPSMB6 HEPIO0000811 - 2 191 2. Enzyme Hydrolase PSMB8 IPOOOOO783 1 4. Enzyme Hydrolase PSMB9 PIOOO00787 - FIFIF Enzyme Hydrolase PSMC2 PIOO021435 3 2 Enzyme Hydrolase PSMC6 IPOOO21928 s Enzyme Hydrolase PT-T 9 a Enzyme Hydrolase T. 2

Enzyme Hydrolase Enzyme Hydrolase 2 4 15 Enzyme Hydrolase CPCT T 11 Enzyme Hydrolase - I - Enzyme Hydrolase T TO Enzyme hydrolase RAB48 Patent Application Publication Sep. 24, 2009 Sheet 52 of 153 US 2009/0238808A1

Figure 1919

Protein family Subfamily Protein name Pacc.no. Number of spectrum-to-sequence matches (Sugen nomenclature for ea Placenta Jurkat K562 Ranos kinases when available, rest from IPI)

Hydrolase O Pogso 3 Hydrolase POOO16339 8 4. 6 Hydrolase POO217943 7 Hydrolase IPIOOO16342 P00020436 4 3 PIOO29 1928 10 FF10 6 IPIOO556060 4 3

PIOOO16381 5 Hydrolase POOO27981 Hydrolase POO55,5566 PIOOO 10270 8 POO549205 7 5 IPIOo328319 3 4 PIOO031755 1 PIOoo 17412 Enzyme Hydrolase Plooo31521 4 1 Enzyme Hydrolase P0007381 PIOO477805 || | | | aSe P002991.03 2 POOOOO104 1 POO642211 RP11-125A73 POO158296 4. P00020418 Plooo15954 PIOO385214 7 3 Hydrolase P002 19436 Ploog0684o P00183171 7. 2 2 3 P00472939 1 8 3 4 POO300299 4

P00001922 4 A-PP2C EEEEEPOO69326 TGM3 POO3OO376 P00020530 1 POO549189 3 - Enzyrne P00418497 4 3 7 9 Hydrolase P0065852 19 10 P00298237 1 TP2 PIOO640197 HAH Enzyme Hydrolase TYSND1 IPIOO30324 Enzyme Hydrolase UCHL3 P10001 1250 - Enzyme Hydrolase POOO24664 3. Enzyme Hydrolase POOOO3965 - 3 enzyme Hydrolase POO221012 14 17 6. 40 PIOO184533 P00000728 Enzyme Hydrolase USP22 P10000365 5 Enzyme Hydrolase USP24 (PIOO398505 6 35 P00297,593 3 8 5

PIOO100151 1 p 100045946 P00215979 8 Enzyme somerase P 2 Enzyme somerase POOO24782 somerase P 00011416 19 10 3 Enzyme somerase ERP29 P00024911 3 7 FKBP2 P00002535 2 FKBP4 PIO0219005 4 EE PIO0009885 somerase

Enzyme somerase IDI OO220014 O0549.569

Enzyme somerase LSS somerase lsonerase P4HB 52271371g.72Éf2O 84. Patent Application Publication Sep. 24, 2009 Sheet 53 of 153 US 2009/0238808A1

Figure 19/10

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Placentaukat K562 Ranos

kinases when available, rest from IP)

Enzyme somerase PDA4 POOOO9904 17 8 1 1 Enzyme somerase PDIA5 PIO0031479 2 Enzyme somerase PEC PIOO63984.1 8 somerase PGAM PIO05497.25 4 10 4 7 someraseSomerase POO217872POOO301.16 2 SEE Somerase PIN PO0013723 2 Enzyme somerase PPA P00480.133 32 24 53 56 PPB IPO0646304 4 41 9 13 17 Enzyme somerase p POOO26519 --- 2 2 PPH IPOOOO7346 3. 4. somerase PPL Pooooto19 6 2 Enzyme somerase PTGESPP3 POO297858POOO32473 EEE1 2 El Enzyme somerase PTGES3 PIOOO15029 4 2 7 3 somerase POOO26513 2 SMAROYO NOSO 1-PHOSPHATE somerase SYNTHASEA1 POO14538s 1 somerase SRR POOO3O328 1 Enzyme somerase TP1 IPIOO465028 23 32 4 17 18 Ligase 37.316 PIOOOS2839 3

Elzyre Lidase ACACAAARS IPOOO27442PIOO396015 26 HEE15 32 Enzyme Ligase ACSL3 IPIOOO31397 a 7 5

Enzyme LigaseLiaase ACSS2ACSM3 IPIOO297635PIOO549564 6 HEE Enzyme Ligase IANAPC2 IPIO0002549 12 15 37 Enzyme Ligase ANAPC4 POOOO2551 19 17 18 O Enzyme Liaase ANAPC5 PIOOOO8247 51 25 16 33 Enzyme Ligase T. ANAPC10 IPOO007088 8 9 13 Enzyme Ligase ANAPC11 PO4O1969 Enzyme Ligase APPBP1 IPOO646350 1 ASNS P00554777 Enzyme Lidase C20orf129 IPOO4801.03 3 3 4 Enzyme Ligase ICBLB IPIOO292856 s Enyne Lidase CDC23 IPO.0005322 24 28 26 26 Enzyme Ligase SES.CTPS2 IEEEIPOO514016 3 - 2 - 1 Enzyme Ligase DARS OPIOO216951 13 10 97 EDO1ELOVL5 EIPOO556024 4 - 4 3 Enzyme Ligase EPRS P00013452 111 4 32 52 50 Enzyme LigaseLiaase FARSAFARSLB IPOOO31820IPOO300074 1 4. EEE6 15 Enzyme lidase FBXO2 IPOO479583 1 Enzyme Ligase FBXW11 IPIOO465280P00328796 EH12 11 194 Enzyme ligase GCM P00010090 5 2 1 Enzyme Ligase HECTD3 PIOO456642 1 Enzyme Ligase. HIP2 OP00021370 1 Enzyme Ligase HUWE1 POO456919 35 4 22 7 29 POO307092 16 17 2 IP100103994 13 a 21 13 IP100014213 || | | | 1 POO166395 8 9 E.2 21 20 221 PIOO412253 2 2 14 8 P00291646 6 3 P00289776 is 12 19 PIO0306689 1 Ploogososo | a Patent Application Publication Sep. 24, 2009 Sheet 54 of 153 US 2009/0238808A1

Figure 19711

Protein family Subfamily Protein name Placc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Placentaukat kinases when available, rest from IPI)

O idase PARs2 TPossgoos Enzyme E.iqase PPL2 POO27324 Enzyme Ligase PRPS POO719564 Enzyme Ligase PRPS2 P007 18888 Enzyme OARS POOO26665 1 5 E n2 e RARS POOOO4.860 Enzyme idase RARSL POO549566 E zyme igase RBAF600 POC64304 E Zyte i a se RNF5 EPOOO12608 Enzyme Ligase SLC27A4 POC412147 Enzyme Ligase SUCG1 P00295625 Enzyme Ligase SUCG2 POOO96066 Enzyme Liaase TARS POO3296.33 Enzyme Ligase TARSL1 POO6O4527 Enzyme licase TrAF7 P00395631 7 Enzyme Ligase UBE1 POO645078 i2g 11 117 Enzyme ligase UBE2C P000 13002 8;3 Enzyme Ligase UBE2G2 POOOO142 12O Enzyme Ligase UEE2 POO450472 3 Enzyme licase UBE21 PO477999 24 3 Enzy Ligase UBE23 POO655957 Enzyme Liaase UBE26 P00329563 10 EEE10 11 2 1 POOO22597 3 Enzyme Liaase UBE2N IPOOOO3949 POO3f6844 ... 2 Enzyme Ligase UBE2O IPOOO2837 Enzyme Ligase BE22 POOO 1996 Enzyme licase UBE3A P00011609 licase UBE4A IPOOO28957 Ligase UBR1 POO217405 ligase UBR2 POO2174O7 Enzyme Ligase UCH P00018352 Enzyme Ligase WARS POOOOO873 1 Ligase WARS IPOO2954.00 5: Enzyme Ilyase ACO2 POOO17855 Lyase AAD IPOO44.2121 lyase ALDOA POO485439 Enzyme Lyase C1725 POOO32575 Enzyme lyase CA1 P00215983 Enzyme lyase CA2 IPOO218414 Enzyme wase CBS POO219849 E 2 Ea3 lyase CTH POOO31557 H 7:53 Enzyme lyase ECHS1 POCO24993 He wase ENO PIOO4S5248 18 4 Enzyme lyase FASN IPOOO26781 1 36 Lyase FECH POO554589 Enzyme Lyase FH POO296053 8 is Enzyme wase GMDS POOO3O2O7 Enzyme Lyase HADHA POOO31522 2 11 Enzyme lyase HADHB P00022793 4. 2 Enzyme Lyase HCCS POOO23406 wase HMGC POO293564 lyase KDNS220 EPOCO33429 wase TC4S P00004509 a - Motor - dynein DYNC11 004f7531 3. Motor - dynein DYNC12 POO30272 2 Motor - dyneir DYNLL2 IPOOO19329 2s s5 Motor - dynein DYNRB1 P00412497 Motor - dynein 4.3t; DYNLRB2 P001781.88 Motor - dynein Motor - dynein PIOO639982 EE ; Motor - kinesin Motor-kinesin 2 F Motor - kinesin KFSB 10 Enzyme Motor-kinesin KF21A 1 P Enzyme Motor - kinesin KFC 1 MYL4 POO386712 MY6 POO473069 EE H Patent Application Publication Sep. 24, 2009 Sheet 55 of 153 US 2009/0238808A1

Figure 19/12

Protein family Subfamily Protein name IPI acc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Placenta Jurkat K562 Ramos kinases when available, rest from IP) MYL9 Poo220278 3 Enzyme Motor-myosin MYO9B Ploogaso47 7 Enzyme Motor - myosin MYO15B POO3O8532 3 SMILAR TOMYOSIN REGULATORY LIGHT Motor - myosin CHAIN-LIKE. POOO87597 Zy ZWre Motor - other SMC1L1 P00291939 L 1 ZWe Oxydoreductase ACAD8 POO446874 T - 1 Zyre Oxydoreductase ACAD9 IPOO152981 - 2yre Oxydoreductase ACADS Pooo27701 Oxydoreductase ACADV IPO0028031 5 19 Oxydoreductase POO296907 - Oxydoreductase IPIO0020226 81 425 16S 132 41 i Oxydoreductase PIOO413641 12 4 Zyre PIOO641279 1 IPIOOOO6663 Oxydoreductase ALDH3A2 (PIOO394758 9 Zy Oxydoreductase ALDH7A1 IPIOO22 1234 2 Oxydoreductase ALDH18A1 TPOO008982 5 9 Oxydoreductase AOC3 P00004457 5 Oxydoreductase BDH1 EP00025341 5 9 Oxydoreductase BLVRB PO021990 10 8 Enzyme Oxydoreductase ICBR1 P00295386 7 11 3 Enzyme Oxydoreductase CBR4 P00384297 L 2 CPOX PIOOO93057 18 5 1 Enzyme Oxydoreductase CYB5R1 P00470674 11 Oxydoreductase CYB5R3 POO32841S. -

Oxydoreductase CYCS PIOO465315 4.

Oxydoreductase CYP22 POOO19411 2 Oxydoreductase CYP11A1 PIOO295771 43 CYP19A1 P004,65065 21 - Enzyme oxydoreductase CYTOCHROME C. PIOO465315 2 8 1 Enzyme Oxydoreductase DCXR PIOO448095 4 1 6 Enzyme Oxydoreductase DECR1 P100003482 LSU4 Enzyme Oxydoreductase DECR2 PIOOO1090 10 7 Enzyme Oxydoreductase DHCR7 PI00294.501 37 2 8 5 26 Enzyme Oxydoreductase DHRS1. PIO0065063 1 Enzyme Oxydoreductase DHRS2 PIOO376377 3 Enzyme Oxydoreductase DHRS7B POO550165 Enzyme Oxydoreductase IDLD POOO15911 1 L7L4 DNAC10 POO293260 11 16 24 36 47 Enzyme Oxydoreductase POO479733 3 4 Enzyme Oxydoreductase POOO 10810 Enzyme Oxydo?eductase PO0556451 3. 4 Enzyme FADS1FADS2 EHPOO183786 is Enzyme Oxydoreductase FDFT IPO0020944 3 3 5. 7 Enzyme Oxydoreductase FDX1 P00019326 3 Enzyme Oxydoreductase FN1 IPOo339227 85 LIL Enzyme Oxydoreductase FWT1 IPO0029015 3 Enzyme Oxydoreductase (G6PD IPO.0216008 || 7 || 10 Enzyme Oxydoreductase GAPDH POO219018 I 46 46 - 28 32 41 Oxydoreductase GCDH (PIOO024317T 4 4 7 Enzyme Oxydoreductase GLUD1 IPOOO16801 3. Enzyme Oxydoreductase GPD2 IPOOO17895 17 6 Oxydoreductase GSR PIOOO16862 3 4 3 8 Oxydoreductase GSTO1 IPIO0019755 3 Oxydoreductase HADH2 DP0007726 5 16 7 4 24 Oxydoreductase HBADH POO479966 T 5 Oxydoreductase HMOX1 IPO0215893 Oxydoreductase HMOX2 P00026824 5 4 6 3 POOf 19246 47 POOO19872 15 Oxydoreductase HSD17B12 IPOO007676 8 6 7 Oxydoreductase HSDL2 PIOO414384 4 3 2. Patent Application Publication Sep. 24, 2009 Sheet 56 of 153 US 2009/0238808A1

Figure 19713

Protein family Subfamily Protein name Placc, no. Number of spectrum-to-Sequence matches (Sugen nomenclature for Hella Pacerta kinases when awailable, rest from IPI) E zyme OxydoreductaseO O DH1 Po27223 H1 2 Enzyme Oxydoreductase DH2 PO0011107 Enzyme Oxydoreductase D3A P00030702 E Zyte POO177674.1 POO177674 MD1A P00479.179 Enzyme Oxydoreductase OHA POO217966 a Enzyme Oxydoreductase LHB POO21921.7 8 s 4.32 E 2. e Oxydoreductase OHC P00554498 Enzyme Oxydoreductase POO217056 Enzyme Oxydoreductase MAOA IPOOOO8483

Enzyme MDH2 PE00291OO6 10 9 Enzyme POOO5995S 1 P00479793 T Enzyme P00071334 F- - 2 Enzyme Oxydoreductase POOOO8495 Enzyme Oxydoreductase ND5 PIOOOO8511 -- Enzyme NDUFA4 PIOOO 11770 Enzyme Oxydoreductase NDUFAS IPOO412545 4. Enzyme POO219034 Enzyme Oxydoreductase NDUFA11 IPOO329301 Enzyme POOOO59ss Enzyme Oxydoreductase NDUFA13 POO219685 Enzyme Oxydoreductase NDUFB5 POO220059P00013459 - E Enzyme Oxydoreductase NDUFB9 P00255052 E. P00479905 Enzyme Oxydoreductase NDUFB11 IPIOO473450 1 Enzyme Oxydoreductase SEEENDUFS7 PO0807749 -4 Enzyme Oxydoreductase SES-E-NoUFS8 PI000 10845 F Enzyme Oxydoreductase NOS3 POO2 1884.5 E. Egg Enzyme Oxydoreductase NOO1 POOO12O69 43 38 Enzyme Oxydoreductase NOO2 pCO2 19129 4641 136 Enzyme Oxydoreductase P4HA1 POOOO9923 5 11 Enzyme Oxydoreductase PDCD8 POOOOO690 17 8 Enzyme Oxydoreductase PDHA1 POO306301 41 16 48 51

Enzyme Oxydoreductase PGD P00219525 6

PNPO P00018272 1 Enzyme Oxydoreductase POR PIOO470467 E. E. 12 Enzyme Oxydoreductase PYCR1 Hal a Enzyme Oxydoreductase YCRL PIOO646105 2 PYRROLINE 5 CARBOXYLATE Enzyme Oxydoreductase REDUCTASE PO470s O 2 RDH10 PO0218086 - Enzyme Oxydoreductase RDH11 POO339384 19 Enzyme Oxydoreductase RDh3 PIOO301.204 Enzyme Oxydoreductase FIFF Enzyme Oxydoreductase RRM1 PIOOO13871 9 5 8 Enzyme oxydoreductase RRM2 PIO0011118 7 Enzyme Oxydoreductase SC4MOLRRM2B E. E. E. Enzyme Oxydoreductase SDHA POO305166 15 19, 13 25 Enzyme Oxydoreductase SDHB PIOO294911 3 3 7 Enzyme Oxydoreductase SEPx1. PIO0654889 1 Enzymein loosa,Oxydoreductase C.""Ports PIOO176698 3.4.35832

3

Enzyme Oxydoreductase SPR DPIOOO17469 Enzyme Oxydoreductase ISCRDL IPIOOO09634

Enzyme Oxydoreductase SRD5A2L PIOOOO2344 8 Enzyme Oxydoreductase TXN PIO0216298 16 9. 14 15 11 Patent Application Publication Sep. 24, 2009 Sheet 57 of 153 US 2009/0238808A1

Figure 19714

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest from IPI) Enzyme oxydoreductase txndo Ploogossars----- 2 2.72s. 11 Enzyme Oxydoreductase TXNDC12 Pooo26328 3 6 Enzyme oxydoreductase TXN1 iPIOO6420327 10 Enzyme Oxydoreductase TXNRD1 Poo554786 2 4 3 T Enzyme oxydoreductase IUGDH POOO31420 4 3 7 Enzyme Oxydoreductase IVKORC1 IPOO644735 1 Enzyme Oxydoreductase YWHAB P00216318 28, 27 41 49 86 Enzyme Peptidase MESTIP100298947 Ig Enzyme DPeroxidase CAT IPOO465436 4 7 9 Enzyme Peroxidase IGPx1 Ploo293975 a Enzyme Peroxidase IGPx4 P00304314 T 4 Enzyme Peroxidase GPX7 P100045798 || 5 | Enzyme Peroxidase MGST3 IPOO639812 1 13 T 2 3 Enzyme Peroxidase PRDxi Pooooo874 10846 5o 4g Peroxidase PRDX2 Pooo27350 21 6 6 Enzyme Peroxidase PRDX3 PIO0024919 19 7 7 12 Enzyme Peroxidase PRDX4PRDX5 EEEIPIOOO24915 2:3 EEE6 1. Enzyme PeroxidaseE EPTGS1 - EPIOO298.267 BE 25 EE- 4 1. Enzyme Peroxidase SAPS PIOO402008 7 12 67 Enzyme Peroxidase SAPS2 Poo414872 1 Enzyme Peroxidase SAPS3 P007 19725 5 T 5 EngineEnzyrne Phospholipase LP- " PoosaPIOO385212 Enzyme Protease ICOCIPIO00223944 Enzyme Protease C7 | Poo296608T. T. 2 E.Enzyme E.Protease E.C8B E.PIOO294395 137 - R Enzyme Protease C8G IPOOO 126 6 SIMLAR TO TRANSMEMBRANE PROTEASE, SERINE 3 Protease SER IPIOOO23802 Enzyme Transferase AASDHPPT Poo250297 2 2 Enzyme Transferase ACAA2 PIOOOO1539 2 Transferase IPIOOO30363 10 Transferase ACAT2 IP100291419 || 2 | | | Enzyme Transferase AGPAT1 IPOoo 1914 3 4 Enzyme Transferase AGPAT2 Poo464993 2 1 Enzyme Transferase AGPAT5 PIO0028491 1 Enzyme Transferase AGPS PIOO010349 2 2 3 Enzyme Transferase AKAP2 P00032064 3 Enzyme Transferase ALG1 PIOO54976 3 4 Enzyme Transferase ALG3 PIOO178700 3 5 T 1 6 Enzyme Transferase ALG10 (PIOO 105827 4 7 6 15 Enzyme Transferase ANP32A PO0025849 18 11 23 5, 14 Enzyme Transferase ANP32B iPoooo7423 14 3 19 11 g Enzyme Transferase ANP32C P00018262 2 Enzyme Transferase IASMTL PIO0003119 3 Enzyme Transferase AYTL2 P00171626 3 2 1 Enzyme Transferase BAT2D-1 (PIOO083708 2 Enzyme Transferase BCAT1 (PIOO382412 5 11. Enzyme Transferase BGN PO0010790 3 T Transferase C20orf38 P00640240 3 Enzyme Transferase C21orf2 (PIOO414362. 3 T T. T. 13 Enzyme Transferase CDS2 P00032150 5 1 Enzyme Transferase CEPT1 P0000575 T 3 Enzyme Transferase CHSY1 EP0032914 3 Enzyme Transferase CINP PIOOO13263 Enzyme Transferase CKB PIO0022977 2 5 Enzyme Transferase CMAS Poo303158 Enzyme Transferase COASY P0018482 3 Enzyme Transferase COMMD3 PIOOO15773 3 Enzyme Transferase COMT P000.11284 5 1o Patent Application Publication Sep. 24, 2009 Sheet 58 of 153 US 2009/0238808A1

Figure 19/15

Protein family Subfamily Protein name Pacc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Placenta Jurkat K562 Ramos kinases when available, rest from Pl) nzyme fra - O Zyre nzylte zyme DAD1 nyre Transferase ZWe ransferase POOO12119 51 ransferase CTN5 ransferase DOST POO297084 34. ransferase HPS POOO26829 ransferase KFZP588AO522 POOO22300 7.Z ransferase POO604707 7 8 1 ransferase LAfTN P00031519 92 ransferase OO54278 n ransferase OWS POO647062 ransferase LOV6 POOO31695 4. 3:32 29 ransferase 13A POO297.550 44 Enzyleeeee ransferase B P00025039 s Transferase POO 10405 Enzyme Transferase POO220299 Enzyme Transferase POOO31023 Enzyme Transferase F10774 POO3OO127 1 Transferase F21901 P0388852 Enzyme Transferase FN3K POOO23729 3 Enzyme Transferase FN3KRP POOO99986 163 22 Enzyme Transferase FNA PIOOO26813 Enzyme Transferase FU8 PO0004668 Enzyme Transferase GALNT2 IPIOOOO4669 2 Enzyme Transferase GFPT1 P00217952 6 21 L7 Enzyme Transferase GNPATTP00005677 Enzyme Transferase GOT2 iPIOOO18206 7 2 Enzyme Transferase GSTM3 PIOO246975 T 7 3 Enzyme Transferase GSTP PO0219757. 23 6 12 17 Enzyme Transferase HAT1 P00024719 1 3 2 Enzyme Transferase HRMTL2 3. 9. Enzyme Transferase HRMT13 POO 103026 4 HS2ST1 POO54989 3 Enzyme Transferase POO337307 3 Transferase CMT IPOOO31458 Transferase VB POO554541 4 Transferase TV1 PIOOO11916 Transferase LRRC1 PIOO427739 Transferase RRC47 PIO0170935 4 2 Transferase RRC59 PI00396321 14 8 4 7 8 Enzyme Transferase RRC2 PO383439 2 Enzyme Transferase LUM EP00020986 3 L. Enzyme Transferase IMAPKAP P100028.195 2 Enzyme Transferase MAT2A PIO0010157 T 3 3 - 5 Enzyme Transferase MGC5297 PIOOO31696 3 Enzyme Transferase MGMT P00028618 7 6 Enzyme Transferase MGST1 IPO0021805 T 4 Enzyme Transferase MMAB IPO0029665 1 POO3O4895 H Enzyme Transferase MPP1 Poo215610 s Enzyme Transferase MTAP POOO11876 69 12 Enzyme Transferase MULK POOO19353 a 7 Enzyme Transferase MYBBP1A P00607584 T POO329692 3 2 Enzyme Transferase INP P100017672 Enzyme POO374294 Enzyme Transferase OACT5 P00306419 Enzyme Transferase OAT PO0022334 Enzyme Transferase OGT POO005780 Enzyme Transferase OTTHUMP00000042411, P00552282 Enzyme Transferase PARP, PIOO449049 Enzyme Transferase PARP4 PIOO296909 Enzyme Transferase PCMT1 POO41 1680 Enzyme Transferase PCNA POOO2700 39235 Patent Application Publication Sep. 24, 2009 Sheet 59 of 153 US 2009/0238808A1

Figure 19/16

Protein family Subfamily Protein name Pacc.no. Number of spectrum-to-secuence matches (Sugen nomenclature for kinases when available, rest from IPI) Enzyme Transferase PCY1A Plooggaezg 4 2 Enzyme Transferase PDHX PIOO298423 25 711 .44 Enzyme Transferase PHKA1 Poo216725 26 Enzyme Transferase PHKA2 T T PO0004237 59 18 3 70 Enzyme Transferase PIGH POO005263 2 3 2 2 Enzyme Transferase PIK3AP1 IPOO419050 1 EnzymeE EEM-ESETransferase PNMT IP100003466 21st 2 EEnzyme EEEEEEEE-2Transferase POLR1D PIOOO32439 1 POLR2E PIOO29.1093 EEEEEEEEEnzyme Transferase POLR2H POOO03309 5 - 2S 2 - 3 EEEEEEOEransferase PRKAG1 P004.13318 194 128 268as 249a 2152 EnzymeEEE-IEEE, Transferase PTDSS1 IPIC0010746 10 8 7 26i. E.Enzyme E.Transferase E.RABGGTB E.P00295849 E. 3 Enzyme Transferase RCSD1 Poo514815 2 Enzyme Transferase IRLTPR PIOO456628 3 Enzyme Transferase RNMT IPOO410657 T 1 Enzyme Transferase RPN POOO25874 15 38 32 13 22 Enzyme Transferase RPN2 IPIOO301271 11 11 2 9 Enzyme Transferase RSU IPO0643346 75 39 82 8 16 Enzyme Transferase SCAP PO0289536 14 Enzyme Transferase SHMT2 IPIOOOO2520 | | | | 7 EEEEEEEEEEEEEEESIMILAR TO ATP SYNTHASE GAMMA CHAIN, Enzyme Transferase MTOCHONorA POO244574 3. Enzyme Transferase SKB1 PIOO441473 2 - Enzyme Transferase SNRPA1 POO183920 Enzyme Transferase SPTLC1 DP00432425 2 7 EEEEEEEEEEEEEEEEEnzyme Transferase SRP72 IPO0215888 1 3 1 2 E-HEEnzyme Transferase SHESTT3B E;P100152377 E 5 E9 - 4 EEEEEEEEEE2 90 27 45 E.Enzyme E.Transferase E.TJP2 EEEEEPO0003843 2 4 38 Enzyme Transferase TKT P100021716 a 13 3 11 4 EnzymeEEEEEEEEEEEEEE Transferase TROVE2 P00019450 1 1 5 EEEEnzyme Transferase ETYMS EPIOO221108 3 - E - F-I-E Enzyme Transferase UBAD1 P00002468 2 Enzyme Transferase IUBOX5 P00074719 5 Enzyme Transferase UGCGL1 P00024466 15 25 25 6 17 EnzymeEEEEEE Transferase WFS1 EEEEEEP00008711 5 Transferase ZDHHC17 P004 10687 1 EEEEEEEEEEEEEEEEEnzyme Transferase ZDHHC18 IPOO183979 2 Enzyme Glucosidase PRKCSH PIO0026154 39 3 5 Enzyme Phosphatase DCD POO027547 7106 4 8 Enzyme Phosphatase PTPN22 P00298016 5 Enzyme Phosphatase TENC1 IPOO550368 24 Enzyme Phosphodiesterase APEX1 PIOO215911 11 Enzyme Phosphodiesterase ENPP1 PIOO1843 5 Enzyme Phosphodiesterase MGC5139 PIOO414629 51 33 Enzyme Phosphodiesterase PDE2A PIO0655740 4 3 Enzyme Phosphodiesterase PDE4A P00020973 32T Enzyme Phosphodiesterase PDE6D PIOOO1516 5 13 5 4 3

Enzyme Phosphodiesterase PDE7A PO0217833 1 Patent Application Publication Sep. 24, 2009 Sheet 60 of 153 US 2009/0238808A1

Figure 19/17

Protein family Subfamily Protein name PacC. no. Number of spectrum-to-secuence matches (Sugen nomenclature for HeLa Placenta Jurkat K562 Ranos kinases when available, rest from IPI) Enzy the Phosphodiesterase PDE7B POS1990.1 of 2 Enzyme Phosphodiesterase PDE10A P00215786 307 S2 Enzyme Phosphodiesterase SAMH)1 Poo2947ag 2 1 Enzyme Phosphodiesterase UNC119 POOO13262 5428 Enzyme Ubiquitinylation ANAPC1 P00033907 93 Enzyme Ubiquitinylation ANAPC7 IPOOOO8248 23 13 12 22 Enzyme || 1 Enzyme Enzyme Ubiquitinylation FBXO45 POO1744.38 Enzyme Ubiquitinylation PSMD1 POO299608 Enzyme Ubicuitinylation PSM3 P00011603 1. Efzyme Enzyme Enzyme Enzyme PSMD11 POOO5598 Enzyme Ubiquitinylation PSMD12 PO185374 3 E zyme UbiquitinylationA PSMD13 P003.75380 Poteins CRYABcRae roseOOO2369 Proteins OER2cera leasePIOo3O4264 Heat Shock Proteins OER3 P00430.407 Heat Shock Proteins D-1 P002985.47 1 Proteins DNAA POOO12535 272 1 Heat Shock Proteins DNAB2 POOO15948 Heat Shock Proteins DNABS POOO24523 Heat Shock

Proteins HSPA1A POOS14377 1 1 S 4 S 3. 4.

Proteins HSPA2 P00007702 3 2 6

Proteins HSPA4 POOOO2966 3 1 Heat Shock Proteins SPAA POO2954.85 Heat Shock Proteins -SPA6 POO339269

Proteins HSPA8 POOOO386.5 334 9 332 20 2 heat Shock ed Proteins POOO25512 1. Heat Shock Proteins P00022433 Heat Shock to Proteins POO382470 82 5 Heat Shock to Proteins HSPCB POO414676 72 1 Heat Shock Proteins HSPD1 POO472102 4. A. 1 Heat Shock Proteins HSPE1 POO220382

Proteins HSPH1 P0051.4983

Proteins POO3851.49 Proteins SERPINH1 POOO3240

Proteins SMARTO 60 KDA HEA SHOCKPROTEIN, Proteins MTOCHONOR POO41304.8 SOO24.2 Heat Shock SEMI AR TO CDC37 roser, Proteins HOMOLOG. POO25927 Patent Application Publication Sep. 24, 2009 Sheet 61 o f 153 US 2009/0238808A1

Figure 19/18

Protein family Subfamily Protein name Placc, no. Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Placenta Jurkat

kinases when available, rest from PI)

SMARTOhEAT SHOCK Heat Shock 7OK PROTEN 93 Proteins MORTALIN-2 POOO96692 SMARTO HEAT SHOCK Heat Shock OKD PROTEINBINDING Proteins PROTE P00107552 SMARTO HEAT SHOCK Heat Shock COGNATE 71 KDA Proteins PROTEIN. IPO.0258.419 1 Heat Shock Proteins 1 Heat Shock Proteins TOR1A p00477,657 heat Shock Proteins p10040 1264 Heat Shock Proteins ER orotein folding IPOOO2O984 2

Heat Shock Proteins ER protein folding ORMOL1 POOOO9364 2 Heat Shock Proteins ERR protein folding ORMD2 poof 701 Heat Shock Proteins ORMD3 OO66066

ACY POOO21290 1 ism

ism POO296441 ADK PIOO29.0279 61 301

Nucleic acid bindino Purine metado ism APR POO218693

AC IPOO2894.99

Nucleic acid binding Purine metabolism POOO25273 5 16 14

Nucleic acid binding Purine metabolisrn POOO29079 18 Nucleic acid binding Purine metabolism POO513722 2 3 Nucleic acid bindina Purine metabolism IMPOH2 . P00291510 Nucleic acid binding Purine metabolism MTHFD1 P00218342 2

N ucleic acid birding Purine metabolism 2 Nucleic acid binding Purine metabolism NME-NME2 |Poosasso 19 18

Nucleicl acid binding Purine metabolism NME3 PIOOO 12315 4. 51

N C lessNucleic acid elemenbindi laics P00217223 Nu cleic acid bindi Purine metabolist pAS POOOO4534 5237 Nucleic acid birdi Purine metabolism POOO295.34

Nu POO414323

N cleic acid bindi Pyrimidine metabolism CAD POO3O1263 479 1228

Nu cleic acid bindi

Nu cleic acid bindi Nu cleic acid bindi

Nucleiccleic acid bindibindino Pyrimidine metabolism Patent Application Publication Sep. 24, 2009 Sheet 62 of 153 US 2009/0238808A1

Figure 19/19

Protein family Subfamily Protein name Placc, no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Placenta Jurkat K562 Ramos kinases when available, rest from PI)

Nucleic acid binding Receptor activit ARF3 POO2597 8 a 7

Nucleic acid binding Ribosomal protein 20 KDA PROTEIN. POO478310

40S ribOSOMA PROTEIN Nucleic acid bindino Ribosoma protein S23. EPOO218606 2 Nucleic acid binding Ribosoma protein ARL6P POOO14232 Nucleic acid binding Ribosomal protein EIF2A PIOOO12462 Nucleic acid binding Ribosomal protein ETF P0042919.1 Nucleic acid bindic Ribosomal protein GADD45A POOO29.104 Nucleic acid bindino Ribosomal protein GADD45B P00307805 Nucleic acid binding Ribosomal protein GB4BP POOO1O 105 Nucleic acid binding Ribosomal protein LOC3885.19 P00450975

POO376564 Nucleic acid binding Ribosomal protein OC391701 Nucleic acid binding Ribosomal LOC40.1016 P004. 19880 4.

Nucleic acid binding Ribosomal protein OC441112 POOOO8527 2 Nucleic acid binding Ribosomal protein OC441912 Nucleic acid binding Ribosomal protein MRP12 POOOO5537 Nucleic acid binding Ribosomal protein MRPL14 P004. 18290 1

Nucleic acid binding Ribosomalprotein MRPL32 POOO11077 Nucleic acid birding Ribosomal protein MRP49 POO555553

Nucleic acid binding Ribosoma protein Nucleic acid bindino Ribosomal protein MRPS11to P00010244 Nucleic acid binding Ribosomal protein POO46518.5 Nucleic acid binding Ribosomal MRPS21 IPOOO14812

Nucleic acid binding Ribosomal NAG POO333.913 PREDCTE: SMARTO

Ribosonal ReOSOMAL PROTEN L7. POOO18680 Ribosomal RP-11 posters | | | | |

Nucleic acid bindina Ribosomal protein RPL18 P00215719

Nucleic acid binding RPL22 POO219153 Nucleic acid binding Ribosomal protein RP23 IPOOO10153 Nucleic acid binding Ribosomal protein RPL30 POO219 156 Patent Application Publication Sep. 24, 2009 Sheet 63 of 153 US 2009/0238808A1

Figure 19/20

Protein family Subfamily Protein name Placc.no. Number of spectrum-to-Sequence matches (Sugen nomenclature for K562 kinases when available, rest from IPI)

Nucleic acid binding Ribosomalorotein RP-38 POO215790

Nucleic acid binding Ribosonal protein RPPO POOO08530 EEE2 2 Nucleic acid binding Ribosomal protein RPLP2 POOOO8529 8 Nucleic acid binding Ribosonal protein RPS3 POO455589 EEE15 10 5 Nucleic acid binding Ribosonal protein RPS4X Po0217030 13 1 Nucleic acid binding Ribosomal RPS5 POOOO8433 6 5 1 1

Nucleic acid binding Ribosomal protein RPS8 P OO26587

Nucleic acid bindira Ribosomal protein RPS9 IPOO221088 1 Nucleic acid binding Ribosoma protein RPS10 00454,704 3 2 s Nucleic acid bindir Ribosomalorotein RPS11 OOO25091 3 7

Nucleic acid bindic Ribosomal protein 00013917 Nucleic acid bindina Ribosoma protein RPS12 0044922

Nucleic acid binding Ribosomal protein OO221089 3 3 5 s

Nucleic acid bindina Ribosomal protein RPS1.4 OOO26271 8 5 2 8

Nucleic acid binding Ribosomal protein POO221091 2 7 eic acid bindina Ribosomal protein RPS17 POO4.4603 s

eic acid binding Ribosomal protein RPS18 POOO13296 3 8

eic acid bindir Ribosoma protein RPS19 POO25780 6. 2 11 7 Nucleic acid binding Ribosomal protein RPS2O PIOOO2493 2 5 Nuc eic acid binding Ribosomal protein RPS21 POO387084 E.5

Nucleic acid binding Ribosomal protein RPS25 PIOOO12750 as Nuc Ribosomal protein RPS26p 10 p001766.96 Nucleic acid binding Ribosomal protein IPOO22109s eic acid binding Ribosoma protein P00422085 5

Nucleic acid binding Ribosomal protein RPS27A POO387164 14 a 72 Nucleicc acid binding Ribosomal protein RS28 P00556589 3

Nuc POO553164. 2 S SMARTO 40S Ribosomala protein- RBOSOMA PROTEN S12.IPOO414922 4. SMARTO 60SACDIC RBOSOMAPROTENP1 H. SA POOO59481 SMARTO DJ75305.2 (NOVEL PROTEINSIMLAR tORP POO414447 Nucleic acid binding ropeanRibosomal protein EF"PROTEIN 9. logoso,POO140907 seeNucleic acid bindinoalone. Ribosomal protein ENE"PROTEIN 31. lootersPOO181443 Patent Application Publication Sep. 24, 2009 Sheet 64 of 153 US 2009/0238808A1

Figure 19/21

Protein family Subfamily Protein name Placc, no. Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Placentaluka K562 Ramos kinases when available, rest

from IPI)

O SIMILAR TORBOSOMA O PROTEIN S10 (H. Nucleic acid binding Ribosomal protein SAPIENS). POOO37555 Nucleicendo acid binding Ribosomal protein SMARPROTEINS27. TORBOSOMA POO451483 SIMILARTO RIBOSOMA E. Nucleic acid binding Ribosomal protein PROENS29. POOSOs99 SIMIAR TORBOSOMAL Nucleic acid binding Ribosomal protein PROTEN. POOO95888 21 Nucleic acid binding Ribosonal protein POO328348 Nucleic acid binding Transcription factor AFF1 POO396310 4.1 48 4.9 1 7 Nucleic acid binding Transcription factor POOOO4344 106 5 O 4.5

Nucleic acid binding Transcription factor AP PIOOO10460 1 2

Nucleic acid binding Transcription factor POO3O8845

Nucleic acid bindinatranscription factor CBL POOO27269

Nuc eic acid binding ranscription factor POOOO9958

Nuc eic acid binding Transcription factor EDF1 OOO2570

Nuc eic acid binding Transcription factor POOO23467 4

Nuc eic acid binding transcription factor FMN2 POO464953 eic acid binding Transcription factor

eic acid binding Transcription factor G10

eic acid binding Transcription factor POOO17450 Nucleic acid binding Transcription factor GTF2H1 POOO3O380

3 H 53. 6 1 Nucleic acid bindina Transcription factor GTF2H4 POOO16839

Nucleic acid binding Transcription factor GTF2 PIOOO54042 1 1 Nucleic acid bindira Transcription factor GTF3C3 P00015806 Nucleic acid binding Transcription factor HCFC1 PIOOO19848 Nucleic acid binding Transcription factor HCLS1 POOO2856 13 Transcription factor E5 Nucleic acid binding HDAC1 PIOOO13774 1

Nucleic acid binding Transcription factor Nucleic acid binding Transcription factor HDAC6 P00005711 1 1 2

Nucleic acid binding transcription factor HDAC10 P000 12439 19 15 1 1 Nucleic acid bindina Transcriptionrena factor PROTEINHMG-IIHMG-Y.HIGHMOBILITY GROUP POO177716 Nucleic acid bindireTranscription factor HMGAt PIOO1797.00 Nucleic acid binding Transcription factor HMGB2 POO219097 Patent Application Publication Sep. 24, 2009 Sheet 65 of 153 US 2009/0238808A1

Figure 19/22

Protein family Subfamily Protein name Placc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Placenta K562 Ramos kinases when available, rest from IPI)

Nucleic acid binding Transcription factor HNRPD P00028888 a Nucleic acid binding Transcription factor HSD17B8 POO64 1330 Nucleic acid bindina Transcription factor HSPCO16 P00006378

Nucleic acid binding Transcription factor P00002335 1 2 5 1 Nucleic acid binding Transcription factor to leone

Nucleic acid binding Transcription factor POOOO3443 Nucleic acid binding Transcription factor POO4, 18313 2 Nucleic acid binding Transcript POO289982 Nucleic acid binding Transcription factor POOO26224 Nucleic acid binding Transcription factor kiores POOOO8575 5 Nucleic acid bindira Transcription factor knic POOOO1458 1O a Nucleic acid binding Transcription factor Kua POO397947 Nucleic acid binding Transcription factor LASS2 POO305304 3 Nucleic acid binding Transcription factor ASS2 P0047210

Transcription factor OC440719 P00455474 Transcription factor IPOOO31018

Transcription factor P00007021

Nucleic acid binding Transcription factor MMS 19 POO5445 15 Nucleic acid bindina Transcription factor OOO3287 a

Nucleic acid binding Transcription factor Nucleic acid binding Transcription factor PBXIP1 PogosoH

elene ?econ lease I | | | |

Nucleic acid binding Transcription factor PFDN5 P00015361 3 a Nucleic acid binding Transcription factor PHB POOO17334 46 41 as a Nucleic acid binding Transcription factor PHF5A POOOO5511

Nucleic acid binding transcription factor PHOX2A P00024171

Nucleic acid binding transcription factor PR IPOOO12575 Nucleic acid binding transcription factor POU2AF1 POO293727 | | | | | Patent Application Publication Sep. 24, 2009 Sheet 66 of 153 US 2009/0238808A1

Figure 19/23

Protein family Subfamily Protein name Pacc.no. Number of spectrum-to-secuence matches (Sugen nomenclature for Hella Placenta Jurkat K562 Ramos kinases when available, rest from Pl) Nucleic acid binding Transcription factor PPARGC1B PIOO152517 | | | Nucleic acid bindina Transcription factor PSMC3 IPIOOO18398

N ucleic acid binding Transcription factor PURA p00023591 3 Nucleic acid binding Transcription factor RB1 POO3O2829

ucleic acid binding Transcription factor RNF20 PCO251559 Nucleic acid binding Transcription factor RPAP1 POO402657

NucleicuCl acid bindinranscription factor RTF1 POO303832 Nucleic acid binding Transcription factor RUNX1 IP0028943 Nucleic acid binding Transcription factor SAP18 POOO11698 Nucleic acid binding Transcription factor SFRS2 POOOO5978 Nucleic acid binding Transcription factor SMAD POOO19549 3.E. Nucleic acid binding Transcription factor SMARCC1 POO23.4252 -262 Nucleic acid binding Transcription factor SMARCC2 PO0216047 H1 Nucleic acid binding Transcription factor Nucleic acid binding Transcription factor STAT3 P00298887 E. s Nucleic acid binding Transcription factor STAT5A POOO30.783 13 13

Nucleic acid binding Transcription factor SUB1 PO0221222 32 1. s Nucleic acid binding Transcription factor SUPT4H1 P00442.913

Nucleic acid binding transcription factor SUPTSH P00298058

cleic acid binding Transcription factor SUPT6 P00456.681 2 Nucleic acid binding Transcription factor SUPT16 POOO26970

cleic acid binding Transcription factor TAROBP POOO25815 cleic acid binding Transcription factor TBR1 POOOO3421 cleic acid binding TFAM IPOOO2O928

N l cleic acid binding Transcription factor TFCP2 IPOOO37599

Nucleic acid binding Transcription factor TAL1 POOOO5615 1 1 ucleic acid binding RFP cleic acid binding RM22

Nucleic acid binding RM25 13 Nucleic acid binding RP1 Nucleic acid binding RP13 Nucleic acid binding UBTF Nucleic acid binding Transcription factor WARS Patent Application Publication Sep. 24, 2009 Sheet 67 of 153 US 2009/0238808A1

Figure 19/24

Protein family Subfamily Protein name Placc, no. Number of spectrum-to-sequence matches (Sugen nomenclature for Placenta Jurka K562 Ramos

kinases when available, rest from IPI)

Nucleic acid binding WDR39 P OOOO8791

Nucleic acid binding YEATS4 P OOOO8536 81 Nucleic acid binding Transcription factor Nucleic acid binding Transcription factor ZNF265 p 0.0029.400 Nucleic acid binding Transcription factor ZNF277 p OO479533

Nucleic acid binding Translation factor BZW1 PPO0556167 Nucleic acid bindic Translation factor POOO22305

Nucleic acid bindic EEFA1 P004.72724 3

Nucleic acid binding Translation factor EEFA2 POOO14424d 3

Nucleic acid binding Translation factor EEF1B2 POO178440 3.

Nucleic acid binding Translation factor EF1D POOO23048 4.

Nucleic acid binding Trans ation factor EEFG POOOOO875 2 O

Nucleic acid binding Translation factor EEF2 PIOO186290 3 1

Nucleic acid binding Translation factor EF1 POOO15077

Nucleic acid binding Translation actor EF1AY POO719092

- 85

O

Nucleic acid binding Translation factor 7 Nucleic acid binding Translation factor EF3S4 P0029.0480

Nucleic acid birding Translation factor EIF3S5 POO24O909

Nucleic acid binding Translation factor EIF3S5 POO654777 Nucleic acid binding translation factor EIF3S6 POOO13068 Nucleic acid binding translation factor EIF3S7 POOOO6181 Nucleic acid binding Translation factor EF3S8 POOO16910 Nucleic acid binding Translation factor EIF3S9 P007 19752 Nucleic acid bindina Translation factor EIF3S10 POOO29O2

Nucleic acid binding Translation factor EIF3S12 elee Iran loan

elsea liras, leone See alree lars lone Patent Application Publication Sep. 24, 2009 Sheet 68 of 153 US 2009/0238808A1

Figure 19/25

Protein family Subfamily Protein name IP acc.no. Number of spectrum-to-sequence matches (Sugen northenclature for rea Placerta Jurkat K562 Ramos kinases when available, rest from IP) Nucleic acid binding Translation factor EIF5A2 P00376005 E. Nucleic acid binding Translation factor EF5B IPOO29925.4 28 EUKARYOTC TRANSATON ELONGATION FACTOR 1 Nucleic acid binding Translation factor APHA IPOO513808 Nucleic acid binding Translation factor GCN11 POOOO159 Nucleic acid binding Translation factor GSPT1 POO28829 Nucleic acid binding Translation factor KIAAOS64 POOO24.425 Nucleic acid binding Translation factor LOC143244 POO218084 Nucleic acid binding Translation factor PABPC1 POOOO8524 Nucleic acid binding translation factor TCEA1 POO333215 | | | | | Nucleic acid binding translation factor CEA2 PIOO472949 Nucleic acid binding Translation factor TUFM P00027107 Nucleic acid binding Translation factor P00014263 Nucleic acid binding Translation factor POO444371

Nucleic acid binding Other Nucleic acid binding Other

Nucleic acid bindinal Other Nucleic acid bindinaOther enerolone s see nealone P00072955 see alone POO305031 31 seen alone POO333010 1. secreenealone PIOO180954 2 secondalone IPOO419531

Nucleic acid binding. Other POOOO7818 Nucleic acid binding Other CSPG4 POOO19157 needle necessalone 12 1 5 1 771 elona eelone necessalone

elona 2 Nucleic acid bindin Other Patent Application Publication Sep. 24, 2009 Sheet 69 of 153 US 2009/0238808A1

Figure 19/26

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Pacentaukat K562 kinases when available, rest

from IPI)

3

Nucleic acid binding Other HIST1H1B POO217468 8 Nucleic acid binding Other HIST1H1C PIOO217.465 26

2 11 See alone listen leone 3 neederalone lastate lose Nucleic acid binding HIST4H4 poser I 3

Nucleic acid binding HMGB3 POO217477 3 30 Nucleic acid binding HMGN2 P004.78470

2

1

1

20 1 2

Nucleic acid binding PO0644055 2 Nucleic acid bindic P00025054 31a 22a 2.2

Nucleic acid binding

3 see alone lineu, leogen 4. Nucleicas acid binding.alone Other EXP O16170, "poisogoPOO180730 Nucleic acid binding FITM3 5

Nucleic acid binding Other P100003262.1 a 3 see alone knee less

Nucleic acid binding LIME1 IPOOS53175

Nucleic acid binding one RPPRC PO0329745 15 1 3 1 Nucleic acid binding LRRFP1 PIOO656067

Nucleic acid binding MCM3AP POOO28954

Nucleic acid binding MCTS1 IPOO6454.46 2 Nucleic acid binding NACA IPOOO23748 Patent Application Publication Sep. 24, 2009 Sheet 70 of 153 US 2009/0238808A1

Figure 19/27

Protein family Subfamily Protein name Placc.no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hea Placenta Jurkat kinases when available, rest from IPI)

Nucleic acid binding NCK2 POO3O8531

Nucleic acid binding Other NC POOSO462O Nucleic acid binding Other NHP2.1 POO026167

Nucleic acid binding NOA2 POOO41325 Nucleic acid binding NOC1 POO216654 3O3 Nucleic acid binding NOM1 OOa5593

3

Nucleic acid binding PLCG1 OOO16736

Nucleic acid binding POLDP3 POO44O688 3 Nucleic acid bindic POM12 P00032358 Nucleic acid binding PPP4C P00012833 Nucleic acid binding PRPFS9 POO383823

Nucleic acid binding PSPC1 POO 103525 Nucleic acid binding PTRF PO176903

Nucleic acid binding PUM POOO32355

Nucleic acid bindric RAB2 POOO31169

Nucleic acid binding RAB8A OOO2848

Nucleic acid binding. Other POOOOF866

Nucleic acid bindina Other P00007755 1

necessalone lee logo eace eneralone RBM17 PIOO176706 RBM25 P00004273

Nucleic acid binding RNPC2 POO16350s Nucleic acid binding SAR1B POOOO2149 Nucleic acid binding POOO17451

Nucleic acid binding SF3B1 IPOOO26089 O Patent Application Publication Sep. 24, 2009 Sheet 71 of 153 US 2009/0238808A1

Figure 19/28

Protein family Subfamily Protein name IP acc, no. Number of spectrum-to sequence matches (Sugen nomenclature for Placenta Jurkat Ramos kinases when available, rest

from IPI)

Nucleic acid binding SF3B2 POO221 10s 2

Nucleic acid binding. Other SF3B14 IPOOO32827 5 Nucleic acid binding Other SFRS6 POOO12345 2 Nucleic acid binding SHANK2 POO220490 17 Nucleic acid binding Other PROTEIN. POO1851.97

Nucleic acid binding Other SNRPF POO22528

Nucleic acid binding. Other SRP14 POO293434 3

Nucleic acid binding Other 5

Nucleic acid binding 3

Nucleic acid binding 3 7

Nucleic acid binding. Other POOOO9032

Nucleic acid binding Other POOO29744 1

SYNCRIP POOO18140

THOC2 POO158615

1

Other TSN P000 18768

POO55.0503 1

POO306290 9 2 3 28 3 O O1243.133 54O7O3.3.227O Nucleic acid binding ZNF706 POO183657 2 1 2 2 Nucleic acid binding ZWCH PCO329679 14-3-3 zeta human 53 111 26 P004727.7g FIFIF1 AP3M1 TH Cytoskeleton ARCN1 EEIPOO298520 2 5 Cytoskeleton ARPC5ARPCB EEP00645266 T TO5 Cytoskeleton ARPC5 Poso.445g 1 1 Protein bindi Cytoskeleton BASP1 IPIOO299.024 5 Protein binding cytoskeleton ICEP192 PIOO456708 9 1 1 17 Protein binding Cytoskeleton CKAP4 PO1438 3 Protein binding cytoskeleton CLTA IPOOO14587 2 1 2 Protein binding Cytoskeleton CLTB DP0004589 4 Protein binding Cytoskeleton COPZ1 IPIOO032851 T3 Protein binding Cytoskeleton CSRP PIOO442073 B - Protein binding Cytoskeleton CSRP2 PIO0002824 FT-H Protein binding cytoskeleton CYFP1 DPIOO644231 40 89 Protein binding Cytoskeleton CYFIP2 PIO0655548 2212333 8 29

IPIOO167909P00001466 7 - E 2 a g Protein binding Cytoskeleton HSPG2 PIO0024284 E.is 13 Patent Application Publication Sep. 24, 2009 Sheet 72 of 153 US 2009/0238808A1

Figure 19/29

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Placenta Jurkat kinases when available, rest from IPI) Protein binding Cytoskeleton PIO00373672 P00037367 3 Protein binding Cytoskeleton IPOO 105140. 1 P00105140 1 Protein binding Cytoskeleton P00332047.2GA1 IPOOPOO332047 106698 EEE2 Protein binding Cytoskeleton LMNB1 PIO0217975 3 MNB2 P00009771 3 Cytoskeleton MAP4OC387805 P00005162POO398,171 EEE7 Cytoskeleton MAP4 P0041 1375 3 FIF Protein binding Cytoskeleton NCKAP1 POOSO4736 Protein binding Cytoske NPM POOS49248 PAXLLNWARIANT Protein binding Cytoskeleton O05.55917 Protein binding Cytoskeleton PN1 P00216691 1 22 Protein binding Cytoskeleton PFN2 P00107555 s Protein binding PSTP2 IPOO170554

Protein binding Cytoskeleton RBOSOMA PROEN S11. POOOf8131 Protein bindind TAGN2 PO0647915 5 5 Protein binding Cytoskeleton BCD POOO30774 Protein binding Cytoskeleton TLN1 POO298.994 155 Protein bindino TUBA1 POOOO7750 FIF Protein binding Cytoskeleton TBAS POO387.144. 179 221 17 Protein binding Cytoskeleton TBAL3 P00015671 Protein binding Cytoskeleton TUB3 P00011654 103 308 217 152 Protein binding Cytoskeleton TUBB2A POOO13475 1 5 Protein binding TUBB3 POO152453 : Protein binding Cytoskeleton TUBB4 POO655896 2 11 24. 3.O Protein bindic TUBB6 POOO34283 Protein binding TUBGCP2 P100029.705 5 Protein binding Cytoskeleton TUBGCP3 P00033516 :49 C Protein binding TUBGCP5 POOO45492 4.2; Protein binding P00478003 1 5 Protein inding Enzyme inhibitor A: M POOO3222O Protein binding Enzyme inhibitor AHRR P00025277 4 1 8 E.Ea4.11 POOO22.426 F4FH Enzyme inhibitor ANGPTL3 P00004957 Enzyme inhibitor ANP32E POO165393 Protein binding Enzyme inhibitor ANXA1 POO218918 278 2 4 PO418169 1 Protein binding Enzyme inhibitor ANXA3ANXA5 P00024095P100329.801. ---18 POC204 189 5 POO218095 2 Protein bindino Enzyme inhibitor BRCS POO299635 1 Protein binding enzyme inhibitor C3 POO164623 1, 2 POO719024 19|| Enzyme inhibitor C5 P00032291 4 Enzyme inhibitor CNO1 POO166010 2 7 1 O 1 3. Protein binding Enzyme inhibitor COL6A3 P00022200 7 2 Enzyme inhibitor CSTB P00021828 2 9

1 13 102 68 71 Enzyme inhibitor GBP1 POOO19143 Enzyme inhibitor TH1 PIOO2925.30 2 Enzyme inhibitor TH4 POO294193 29 1 PIOOO32328 18 Enzyme inhibitor NF1 P002995 12 1 Protein binding Enzyme inhibitor PPP2R1A P00419307 3. Protein inding Enzyme inhibitor PPP2R2A PIOO332511 Protein binding Enzyme inhibitor PPP4R2 PIOO 103654

e PROTEIN PHOSPHATASE 4 Protein bindic Enzyme inhibitor REGULATORY SUBUNIT 2. PIOOO67514 Patent Application Publication Sep. 24, 2009 Sheet 73 of 153 US 2009/0238808A1

Figure 19/30

Protein family Subfamily Protein name Placc.no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hea Placenta Jurkat K562 Ranos kinases when available, rest from IPI) Protein binding Enzyme inhibitor RNH1 E 1 Protein binding Enzyme inhibitor SE1 PIOOOO2790 2 2 Protein binding Enzyme inhibitor SE IPIO0072377 T 7 3 4 || 8 Protein binding Enzyme inhibitor SET IPIOO301.311 2 4 2 Protein binding Enzyme inhibitor STS-1 POO154910 62 1st as Protein binding Enzyme inhibitor FP2 IPOOOO9198 18 Protein binding Enzyme inhibitor TMP2 Pooo27166 3 Protein binding Enzyme inhibitor TIMP3 PIO0218247 3 T Protein binding Enzyme inhibitor TRAF1 POOO11549 2E 26 Protein binding GTPase regulator ABR POOO30389 2 Protein binding GTPase requlator ARFGEF1 IPIO000288 3 3 10 Protein binding GTPase regulator ARFGEF2 PIO0002186 42 12 26 GTPase regulator ARHGDA P0003815 3 GTPase regulator ARHGDB Poooo3817 1 3. 1 3 Protein binding GTPase requlator ARHGEF2 PIO0643259 1 GTPase requator ARHGEF18 PO79437 - I - Protein binding GTPase redulator CEND1 POO29241 41 2 7 Protein binding GTPase regulator CENTD2 . PIOO646915 6 Protein binding GTPase regulator CEND3 PIOO103380 48 Protein binding GTPase regulator DNMBP IPOO470926P0014025 2EFHF Protein binding GTPase regulator DOCK2 T POOO22449 56 13 30 Protein binding GTPase regulator DOCK8EIF2B EEEEEEPOO221300 2 1 Protein biding GTPase regulator EIF2B4 P00220232 GTPase regulator EIF2B5 Pooo118983 Protein binding GTPase regulator EPS3L1 P003.01250 7 Protein binding GTPase regulator EVI5L PIOO060473 1 3 4. GTPase recuator E-- Protein binding GTPase regulator GAPVD1 OO292.753 GTPase regulator GB POO54994 7 3. is Protein binding EGTPase regulator GD2 POOO314S1 5 Protein binding GTPase regulator GNB1 PIOOO26268 3 2 2. GTPase regulator GNB1 PO17339 2 : GTPase regulator GNB2 POOOO3348 s 3 Protein binding GTPase reculator GNB4 IPOOO12451 4 GTPase regulator 3 GTPase regulator CGAP1 71 7 9 20 GTPase regulator QGAP2 55 3 7 Protein bindin GTPase regulator KIAA 1244 4 || | | GTPase regulator Loc8agazipios992122 105 Protein binding GTPase reculator RAB3-GAP50 IPOO554590 4. GTPase regulator RANBP2 IPOO221325 9 3 2 Protein bindic GTPase regulator RANBPO POOO39864 1 . .

Protein binding GTPase regulator IRANGAP1 P004 1570 Fl Protein bindino GTPase regulator RAP1GDS1 IPOO60759 Protein binding GTPase regu ator Protein binding GTPase reu ator RCC1 POOOO661 13 Protein binding GTPase regulator pOOO247 10 GTPase regulator POOO14454 GTPase regulator TC) POO164610 3 Protein binding GTPase regulator TBC1D15 PIOO154645 GTPase regulator WAV POOO1696 Protein binding GTPase regulator IVAV3 - IPOO299753 Protein binding GTPase regulator IWAS IPOOOO1545 - :3. Kinase regulatory Protein binding subunit ASG PIOOO22431 Kinase regulatory 5352 Protein binding subunit 68 153 13S 129 Patent Application Publication Sep. 24, 2009 Sheet 74 of 153 US 2009/0238808A1

Figure 19/31

Protein family Subfamily Frotein name Placc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest from PI) K562 -

Protein binding subunit CABLES1 IPOO291427 22 3

Protein binding subunit CABLES2 POOO30512 2

Protein binding subunit CABLES2 POO552732 Protein binding subunitR" loonCCNH locatesPOOO21305 10 5 9 Protein binding R"subunit CCNon pos,POOO28541 2 1 2 5 Protein binding issubunit equato, CDC1s POOO22091 24 3 1 Protein binding subunitis equato, CDC26 P0069387 Kinase regulatory Protein binding subunit POO2.94575 35 1 Kinase regul atory Protein binding subunit CDK5R1 POOO 14316

9ss Kinase regul atory Protein binding subunit CDKN2A P00001560 Kinase regulatory Protein binding subunit CKS1B IPOOO1504 Kinase regulatory Protein binding Subunit CSNK2B PIOOO10865 1 3 1 O 1 13 Kinase regulatory Protein binding Subunit GMFG PIOOO28414

PeneoProtei binding SubunitKinase regulatory KBKAP PIOO293735 25 1 pense Kinase regulatory Protein ordic subunit MAD POO 103536 atory Protein binding Subunit MAP2K1R1 IPOOO3O919 atory Protein binding subunit PAG1 POOO2O4S4 12 27 atory

Protein binding subunit PK3R1 POOO21448 S Kinase regu atory Protein inding subunit P00011736 1 9 Kinase regulatory Protein bincino subunit POOO13905 5 s 3 3. 5 Kinase regu Protein binding subunit P00005367 1 2 1 3.

Kinase regulatory Protein binding subunit PRKAR1A PIOOO21831 Kinase regulatory Protein binding subunit Rictor P00455500 14 Kinase regulatory Protein birdi subunit SFN POOO3890 Kinase regu atory Protein binding subunit BKBP1 POOOO6084 190 11 5 15 s Kinase regulatory Protein binding subunit YWHAG IPOO220642 3. Kinase regu Protein bindic subunit YWHAH P00216319 9 2 4

Protein binding Receptor binding ARTS-1 OPIOO165949 EEEEEEEEEEEEProtein binding Receptor binding BD PIOO420084

Protein binding Receptor binding BOBST2 IEEEPIOOO2S241 2 1. 14O8287 EAEEEProtein bring Receptor binding CD74 E.P00022933 Protein binding Receptor binding CMTMs POOO158O1 Fl Protein binding Receptor binding 11 CSH2 P00025785

Protein birdic Receptor binding CNNB1 P0007292 10 Patent Application Publication Sep. 24, 2009 Sheet 75 of 153 US 2009/0238808A1

Figure 19/32

Protein family Subfamily Protein name Pacc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Placerta KS62 Ramos kinases when available, rest from IPI) Receptor binding DAPH1 Pooo30876 10 1 12 Receptor binding DOK POOO15287 4 12 g Receptor bindic DOK2 EPOOO22602 2 2 34 Receptor bindino Protein binding Receptor binding p004 101.77 1 Protein binding Receptor binding POO334282 Protein binding Receptor binding POO154603 17 Receptor binding POo396967 3 Protein binding Receptor binding FYBTPOOO730 93 Protein binding Receptor binding GABARAPL2 IPO0026358 4 2 Receptor binding GLG1 2 8 2 Protein binding Receptor binding GNB21 POO64 950 7 4 3. 6 Receptor binding GP PIO0027497 2 2 Protein binding Receptor binding IGRB2 EPOOO21327 T6 6 152 7 Protein binding Receptor binding HDGF PIO051427 4

JAG2 POOO32416 -F eleaseProtein binding Receptor binding KL rolePIOO295265 29 EEE Protein binding Receptor binding LAMA2 IPIOO2 18725 3 POO6468O2 90 Protein binding Receptor binding P0029.3276 173 363 285 251 242 Protein binding Receptor binding P00514912 14 9 17 22 Protein binding Receptor bindino POOO28065 1 Protein binding Receptor binding P11 IPIOO006995 6 Protein binding Receptor binding PDGFC TPIO0099977 1 Receptor binding PSMC5 POOO23919 3. 1 A Receptor birdino REEP5 P00024670 REEP6 POOS46963 3 Protein binding Receptor binding RETN IPOOOO6988 1 Protein binding Receptor binding SCYE POO006252 9 3 SNW1 POOO 3830 Protein bindic Receptor binding SR P000271.75 3 6 Protein binding Receptor binding TGFB IPIO0018219 6 ME1 P00009976 Receptor binding OLLP IPOO654582 2 Protein binding Receptor binding TRA1 POOO27230 14 77 Protein binding Receptor binding TRAP EPIO0030275 4 3 4 Protein binding Receptor binding TRIP6 PIOO301561 T L 1 Protein binding Receptor binding TXLNA POO470779 - 7 9 11 4 Proteinbinding Receptor binding YARS Pooooo74 4 Protein binding Enzyme activatof ALOX5AP EPIO0022975 2 Protein binding Enzyme activator ARL1 PIOO219518 4 2 ... 6 Protein binding Enzyme activator CACYBP. EPIOO395627 15 18 19 10 Protein binding Enzyme activator DBNLCPIOO101968 10 I L 2.

Enzyme activator FZR1 PIOO383919 12 7 5 H4 Protein binding Enzyme activator MRCL3 IPIOO220573 5 Protein binding Enzyme activator PAA IPOO550517 2 3 4 Protein binding Enzyme activator PSME1 IPIOO4797.22 177 18 10 26 Enzyme activator PSME2 IPIOO384051 - 9 7 14 7 22 Enzyme activator PSME3PYCARD PIOO2PIOOOO1699 19445 SE - 3 1 Protein binding Enzyme activator RFC1 IPIOo375358 2 Protein binding Enzyme activator TIFA POO514147 4 P00098880.1 IPIO0098880 1 Proteinase inhibitor SERPINA1SERPINB1 PIOOO27444 8 28 EE

IPOOO22204 16 EEEEEEEEEEEEEEProtein binding Proteinase inhibitor SERPINB6 IPIOO413451 6 2 Protein binding Proteinase inhibitor SERPINB9 PIOOO32139 8 11 16 Patent Application Publication Sep. 24, 2009 Sheet 76 of 153 US 2009/0238808A1

Figure 19/33

Protein family Subfamily Protein name IP acc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for K562 kinases when available, rest from IPI) O - O 3 Protein binding Proteinase inhibitor SERPNB12 IEEEP00032179 SEE4 Protein binding Other XTP3PA IEEEEEEEPlooo33025 4, 2 3 110 Protein binding Other 40787 P00019376 1 Protein binding Other 42248 PO0030877 2 2 2 3 EEEAEEEEEEACA2 POO640698 43 3 s 3 Protein binding Other 36 3 35 124 99 Protein birding Other ACTL6A POOOO3627 1 4 3 Protein binding Other AEEE - Protein bindingbindina Other ADRMACTR3 POoo33030POOO28091 EEEE3 Protein binding Other AEEEEEEEEAKAP8L Ploo2974ss 4 5 s 3 Protein binding other ALB PIO0022434 12 441 7 L8 EEEANEEEEEEEProtein binding Other ANKRD28 P00477505 10 15 1 Protein binding Other ANKRD44 P00395999 9 5 7 Protein binding Other AP1B1 POO328257 - G - E AP1M POOO325s 3. Protein binding Other AP2B1 Protein bindino Other AP5 PO0555572 2 Protein binding Other ARFs PIO0215920 4 3 Protein binding Other ARMC8 POO332835 Protein binding Other P0055481 7 2 3 Protein binding Other ASF1A p0O292188. 2 2 POOOO6904 - Protein bindir Other BAG2 POOOOO643 7 5 9 5 Protein binding Other BAX IPOO444945 L5 Protein bindingbirding Other BETBRC2 E--P0001348 32 10 8 Other BRC3 P00013409 2 68

Other BUB3 PIOOO13468 7 5

IPOO514682 1 C1orf73 POO550858 4. 1 POOO 14230 3 3 7 Other Coff32 POO5493.89

EEE,Protein binding Other C15orf23 IEEE IPOO294680 1 H S Protein binding Other C20orf18 P00010266 11 IPOO102070 19 26 15 Protein binding Other CALD1 PIOOO 14516 59 Protein binding Other CALM2 IPO.0075248. 7 9 9, 17 8 Protein binding. Other CAND1 IPOO100160 L 10 19 28 10 23 Protein binding other CAP1 OPIOO639931 - 7 4 Protein binding other CAPG IPO0027341 - 1 1 Proteinbinding other ICAPZA1 OPIO0005969 4 12 9 5 11 Protein binding Other ICAPZA2 IPO0026182POO2 18782 B6 23 IPOO3O4409 3 Protein binding. Other ICAV Poooo9236 4 Protein binding other CBX3 PIOO297579 2 4 2 3 Protein binding other ICCNA2 PIO0022865 26 T12 11 Protein binding Other CCNB1 PIOO294696 51 45 92 12 Protein binding other CCNB2 Poo28266 35 36 Protein binding Other ICCND3 Pooo25817 3 6 Protein binding Other CCNE2 P100014085 L 1 Protein binding other ICCNK PIOO431127 7 4 5 6 Protein binding other ICCNT1 IPO0030247 57 45 83 - 111 Protein binding other CCNT2P00030313 23 126 Protein binding other CCT2 PIOO297.779 1o 8 13 11 5 Protein binding Other ICCT3 IPIOO553185 10 2 12 14 30 Patent Application Publication Sep. 24, 2009 Sheet 77 of 153 US 2009/0238808A1

Figure 19/34

Protein family Subfamily Protein name Pacc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Placerta Jurkat K562 kinases when available, rest from IPI) Protein binding IPOO3O2927 Protein binding POOO 1072O 8 13 19 Protein binding IPOOO27826 Protein binding IPOOO18465 18 17 Protein birding P00013122P00000190 EEE5. 3 19 21 Protein binding other CDC45L POOO25695 2 CDC73 IPIOO3OO659 5 514 Other CDH1 PIOOO25861 2 Protein binding Other CEP57 IPOO465200 3 Protein binding Other ch-TOG DPIOOO28275 4 12 Protein binding Other T. CHCHD2 T POOOO7673 2 5 4 Protein binding Other TCHCHD6 PIOOO31622 6 T 7 2 Protein binding other CIB1 IPOOO 1845 2 1 Proteinbinding other cKAP1 IPIOO293126 1 Protein binding other CTC POoo24067534.133 38 45 Protein binding. Other CNAP1 DPIOO299524 7 16 POO152s2 8 7 4 25 Protein bindino PO0216682 2 Protein binding PIOO149849 1 1 1 Protein binding COG5 POO3770SO 2 Protein binding COG7 IPOO164005 7 5 A. CO6A1 PIO0291136 EGEEEEEEEEEEEEEEEProtein iriding Other COL14A1 IPIOO1761.93 53 Protein binding other CORO-1A PO00101.33 T. 6 5 Protein binding other COROC POOO08453 1 8 Protein binding. Other CPSF1 POOO26219 13 15. 3 15 Protein binding other CPSF3 P00063404 Protein binding other CTNNA POO47336 9 8 CTNND1 POO182540 7

P00062884 11 4 IPIO0014310 9 Protein inding P00014311 Protein binding P00014312 9 1 4 Protein inding P00337800 LT 5 Protein inding IP10002891 1 Protein binding P00029485 7 18 14 Protein indic P00027014 2 1 Protein binding other DEPDC6 P00290560 3 Protein binding Other DIABLO PIOO008418 2 4 g. Other OKFZPS64AO22 PROTEIN POO384.679 | | | | | Protein binding other DMX PO0294728 6 Protein binding other DNAA2 PIOOO32406 7 4 6 8 Other ONAA5ONAA3 IPIOO294610POO41336s E. E. E.

DNAB6DNAB11 IPOOOO8454.P00556073 El H DNAB12 POOO14400 E. a Protein bindic DNAC7 PO329629 11 DNAC12 PI00029149 3 L Other DNAC14 PIOO396326 3 3 s 2 Protein inding Other DNAJC9 PIO0304306 5 1 4 2 Other DPT PIOO292130 2 Protein binding Other DRG1 PI00031836 1 Protein binding other DRM PO0004970 5 23 Protein binding other DSC1 - IPO0336975 2 3 Protein binding Other IDSG1 IPO0025753 22 20 22 17 9

Protein inding DSP IPIO0013933 81 63. 28 40 55 DSTN P00473014 15 3 4 6 Protein binding DYSF P00020210 55 Protein binding Other IEEF1E1 PIO0003588 3 2 11 7 Protein binding Other EFS (IPIO0011652 19 Protein binding Other EIF3S6P P100465233 12 2 6 4 20 Protein binding Other ELAVL1 PO0301936 Patent Application Publication Sep. 24, 2009 Sheet 78 of 153 US 2009/0238808A1

Figure 19/35

Protein family Subfamily Protein name IP acc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Placenta Jurkat K562 Ramos kinases when available, rest

from PI) Protein binding other ELMo1P100219532 2s. 4 7 Protein binding Other ENGEMD P00017567POOO32003 2 EEET Protein binding Other EPB412 PIOOO15973 2 Othe EPB413ERGC1 POOO32230PIOOD22887 7 248 6 EE10 Other EWL POO21824.5 2 PIOOOO984 38 31 Protein binding Othe POO33596 2 Protein binding Other FANCA P00006170 3 5 10 Protein binding.binding Other FANCD2 POOO7508P00171291 - E1 Protein binding Other FGA P00021885 Protein binding other T FGBT IPOO298497 10 Protein binding Other FBP P0002443 32 4 26 IEEEEEEEEEPOOOO7052 2 4. 2 Protein binding Other F12529 POO550821 2 1 Protein binding Other FL14668 POO303722 4 2 2 POOOO7929 EEEE Protein inding Other FLNB POO178352POO28.933a 29, 36 341 P000274.38 4 Protein binding other TFLOT2 PIO0386741 4 P0026O715POO1631.87 27 EEE29 21 Protein binding other FXR1 IPO0016249.5 6 GP2 POO37563 El SEE Protein binding Other GEMIN5 PIOO2.91783 21 1 2 14 2 Protein bindino Other GEMIN7 PIOOOO3027 2 Protein binding other GMCL1 P00063669 11 || 8 Protein bindic Other GOGB1 10 15 13 Protein binding Other GRPELT IPOOO29557 2 Protein inding Other HAX1 IPF000 10440 3 9 EGEProtein binding SEother - E.HBXIP E.PIOOO12831 E.H.1 Other HRP5 POO455153 1 1 2 Protein binding other HIST3H2A (PIOO219037 7 17 5 11 12 Other HNRPA P00215965 8 9 5 POO396378 3 12 2 2 POO21 S592 6 P00003881 4 || 6 11 16 Other PIOO216746 15 51 4. ; : Other HSPA93 POOOO7765 186 2O 46 127 75 Protein binding other HSPBP1 PIOO100748 I 4 7 HSPC152 POO 106374 IGFBP1 PIOOO31086 Protein binding other IGHA1 PIOO430842 1 POO178926

1 Protein binding Other NCENP P00024970 27 45 37 38 Other INT1 POO175295 9 5 4 Protein binding. Other ISGF3G IPOOO94740 17 IPOOOO303 P00014319 EEEE,28 9. 15 17 Protein binding other KBTBD7 PIOO383044 Protein binding Other KEAP PIOO106502 3 2 15 Protein binding other KAA0174 P100024660 4 Protein binding other IKA604 PIOO177381 4 1 2 Patent Application Publication Sep. 24, 2009 Sheet 79 of 153 US 2009/0238808A1

Figure 19/36

Protein family Subfamily Protein name Placc, no. Number of spectrum-to-secuence matches (Sugen nomenclature for kinases when available, rest from IPI) K562 s

Protein binding KAAS98 POO3O4676 3

Protein binding KH23 POOO62213 | | | 10 | 1 Protein binding AMB P00013976 OT 1 T TO Protein binding AMC1 P00298281 9 Protein binding Other AT2 iPIO0395993 4 Protein binding Other CP1 IPIOOO10471 9 29 10 35 Protein binding N7C P00019997 4 3 3 5 Protein binding MNA P100021405 2 6 6 Protein binding OC149329 P00554749 12 24 15 27 107 Protein binding OC39.1039 IP100457307 31 11 2g 17 Protein binding Other SM8 Protein binding Other SM14A

Protein binding Other LUZP5 Protein binding Other MAD21 Protein inding MAD22 Protein binding other Magmas PIO0218463 1 2 3 Protein binding Other IMAGOH POO641469 1 LL Protein binding other IMAPRE POOO17596 - 4 4 Protein binding. Other MARCKS PIOO219301 19 L Protein binding other MARCKSL1. IPOO641 181 1 Protein binding Other IMGC52010 POO219006 4 MG12 Ploooog73o 5 3 MNAT1 POO29470 se as 87 72 MSH2 POOO17303 6 Protein binding other IMTPN Pool179589 1 2 3. PIOO154778 2 1 Protein inding POOO195O2 139 10 59 47 58 Protein bidi POO397.526 32 2 3 13

Protein bindingbiding PO378344POOO2O5O1 18 1 -- Protein binding Other MYO1C IPOOO10418 - H Protein binding Other MYO1F POO414576 I. I. 3 Protein binding Other NAP1L1 P00023860 - 3 1 Protein binding NAP14 P100017763 5 Protein inding NCBP1 (PIOOO19380 L 3 8 1 Protein binding. Other NCBP2 P00183500 L86 Protein binding Other NCKAP1 EP004O9684 22 7 86 Protein binding Other NID1 PIO0026944 3LO Protein binding Other NIFE14 PIOOO13293 3 2 2 Proteinbirding Other NOMO1 P00465432 3 1 Protein binding other NONO PIO0304596 12 5 8L 12 POO29277 6 48 5 S

Protein bindingbindic Other NUP205 POO171542POO472675 EEEEEE78 21 101 Protein indin Other NUP210 POO29,755 2 g is Protein binding NXT1 PIOOOO7605 1 - Protein binding Other PABPNPARWA POOO18983 45 161. --- Protein binding Other PARWB PIOO382605 7 Protein binding Other PARWG PIOOOO5512 3S Protein binding PIOOO6610 28 40 20 15 62 Protein inding PIOO216689 12 Protein binding Other PCDH9 P0040962s 5 Protein binding Other PDCD6P PIOO246058 s 9 4

Protein binding Other PEF 5 Protein binding Other PEX3 PIO0010232 1 Protein binding otherOther PFDN2PEX 18 . . . EHPIO0006052 - 2 2 2 6 5 Protein binding IOther PHKB IPO0218571 41 17 12 - 16 24 Protein binding other PIP P100022974 3 7 3 2 2. Protein binding Other - IPKP1 HP00071509 3 2 3 2 Protein binding Other IPLEC1 IPO0014898 || || 9 19 37 59 Protein binding other PLEKHCC IPO0000856 O 6 Protein bindic Other POTE2 IPOO455547 T 1 Protein binding other PRPF8 IPOOOO7928 8 33 Protein binding Other PRPF40A P00337387 5 6 3 Patent Application Publication Sep. 24, 2009 Sheet 80 of 153 US 2009/0238808A1

Figure 19/37

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest from Pl) Protein binding other PSMD2 IPOOO 12268 22 8 6 12 9 Protein binding Other PSMD9 P100010860 2 4 4 6 Protein binding Other PTBP1 P00183626 9 14 3 8 11 PURB P00045051 1 Protein binding Other PXN P00220031 15 2 Protein bindino RAB1A P00005719 14 6 7. Protein binding Other RAB3 P00102897 8 6 14, 7 10 Protein binding other RAE P000 19733 TT Protein binding. Other RA14 IPOO292953 1 Protein bindino Other RAP1A POOO15148 6 4. 3 Other RASSF2 P0041417g 6 Protein binding Other RASSF5 POO332633 7 3 Protein binding other RBBP5 P00021035 1 1 2 Protein binding Other RBL1 PIOOOO5139 3. 4 Protein binding Other RBL2 PIOo3O4028 15 6 8 Protein binding Other IRBMXL1 PO0304692 2 Other RBX1 POOOO3386 7 9 9

Other ROXRCO-8 PIOO376317 1312 EE Protein binding Other REPS PIO0337532 25 T 10 Protein binding Other RGS19 PO002808 7 Protein bindinobinding Other RNF7RRAS2 E.PIOO012512 : 1 E 2I 22 Protein bindic Other RN4 PIO0021766 1 Protein binding Other SAMSN1 PIO0185526 4 Protein binding. Other ISCC-1 12 POo303063 2 20 8 Protein binding other SDC1 IPIOooo2441 g Protein binding other SDFR1 POoo 18311 1 Protein binding. Other SERBP1 IPIOO410693 T 10 3 5 57 Protein binding Other SERF2 P00024781 3 8 Other SERF2 P00335001 -- a Protein binding SF3B3 IPOO300371 14 22 14 17 Protein binding Other SF3B4 P00017339 1 Protein binding other SFPQ Plooo10740 22 21 23 30 Other SFRS3SFRS1 IP100010204PO0218591 2 S- Protein bindino Other SFRS7 IP100003377 2 Protein binding Other SGTA IPO0013949 2 Protein binding Other SH2D A POO032401 2 Other SH3BGRLSH2)2A IPOO220388PIOOO25318 - 2 1 - Other SHANK2 P006.43662 8 Other SHC1 IPIOOO21326 20 Protein binding Other SAHBP1 IPO0069750 6 2 14 SMILAR TO U2 SMALL NUCLEAR Protein binding Other RBONUCLEOPROTEINB. POO550235 2 Protein binding Other SP1 PIOOO24281 3 1 Protein binding Other SKP1A POO163974 6 6 6 10 Other SMC2L1 PO0007927 7 16 4' 35 Other SMC4L1 PIOO411559 26 41 2, 26 Protein binding other SMCHD1 P00465022 3 Protein binding Other SMN1 P00003394 4 1 5 Protein binding Other SMNDC1 PIOOO251.76 2 3 Protein binding Other SNAP23 PIOOO 10438 4 4 8 Protein bindino Other SNAPAP P100018331 2 Protein binding other SNRPA POOO12382 2 Protein binding Other SNRPB PIOO329512 4 Protein binding Other SNRPB2 (PIOOO29267 1 2 4 3 Protein binding Other SNRPD PO0302850 3 2 6 4 Protein binding Other SNRPD2 PIO0017963 7 4 9 16 13 Protein binding Other SNRPD3 PO0017964 3 3 4 5 8 Protein binding Other SNRPE P00029266 3 Protein binding other SNRPG PIOOO16572 Protein bindin EEEEEEEPIOOOO9505 17 Patent Application Publication Sep. 24, 2009 Sheet 81 of 153 US 2009/0238808A1

Figure 19/38

Protein family Subfamily Protein name IP acC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Pacerta Jurkat K562 Ramos kinases when available, rest from IPI) SNX1 Poo183530 5 3 Protein binding Other SNX22 P00307039 13 Protein binding Other SPTAN1 IPOO478292 131 34 SPTBN1 P0000564 5 72 106 Protein binding Other SOSM1 P1001794.73 4 T EASProtein binding E.Other S.SSRP1 P00009235P00005154 19 2 2 2 Protein binding other STMN1 IPOO479997 - 5 18, 7 EASEProtein bindino EOther SESTRN4 PO0103521P0000306 8 1 EASEProtein binding EOther - SEESTX18 P00027194PIO0029730 2 1 Other SUMO2 P00140827 2 Protein binding Other SYMPK P00028344 1 3 7 SYNE1 P0386444 9 Protein binding Other SYNE2 (PIOO239406 26 Protein binding. Other SYWN1 PIOO166996 3 4 8 Protein binding other TAGLN P00216138 57 Protein binding Other TBCA PO0217236 4 2 5 Protein binding Other TCEB1 IPO0300341 8 8 5 7 Protein binding. Other TCEB2 IPOO410162 4 L5 - 6 16 Protein binding Other TCL1A PO0178749 13 Protein binding Other TCP1 Poo?90566 11 5, 8, 1o 12 Protein binding Other THOC4 Poo328840 11 24 3 24 TMEM4 POO443909 1 MPO POOO3O131 1 Other MPO POO216230 2 7 POO237449 -H Protein binding TNKSBP1 P00304589 4 Protein binding TNS1 IPIO0307545 4 Protein binding TP52 IEEE 1 2 Protein binding TPD522 POO399265 3

Protein binding TPM POO21839 1. 19 9 Protein binding PM PIOO44.2122 8 Protein binding TPM2 PIOO220709 3 Other TPM4 PIOO2 16975 28 4 Other TRAF3 IPIOO2974.73 4 Protein binding other TRAF5 IPIOOOO5760 2 Protein binding other TRIM31 PIOO643935 2 LL Protein binding IOther TRIM59 PIOO432462 32 Protein binding. Other TRIM65 OP1004-19451 2 2 Protein binding IOther U2AF1 PIOO619914 6 4 3 - 5 Protein binding other UBAP2L P00412535 2 11 Protein binding . Other URP2 POo397834 1 1 - 1 Protein binding other UTRN POOOO9329 31 21 Protein binding other UTRN Poo514575 4 6 Protein binding other IVAMP3 POO514389 3 Protein binding Other IVASP IPIOO301.058 4 Protein binding other IWBP1 PIOO334159 2 Protein binding Other IVIL2 IPIOO479359 4 53 5 Protein binding. Other IVIM POD418471 7 24 Protein binding. Other IVPS28 IPIO0328913 4 3 3 Protein binding Other TVPS35 POOO18931. 1 6 3D 5 Protein binding other IWF PIO0023014 7 Protein binding. Other WASF2 IPOO472164 5 14 4 EEE SEEEEEEEEEEEE7 4 Protein binding other WDR5 Ploooos492 153 Protein binding. Other WDR68 IPIO0006754 8 2 15 17 Protein binding. Other XPO5 IPOO640703 51 5 47 52 41 Protein binding other YWHAE PIOOOOO816 123 72 99 150 80 Protein binding. Other YWHAQ. LIPIOOO1846 30 19 57 68 T 89 Protein binding other YWHAZ Poo 180776 538 3 116 Protein binding. Other ZMYM1 IPIOO643628 2 protein binding other ZNF294 Pool15593 4668 31 Protein binding other ZNF313 IPOO032955 5 Protein binding. Other ZNF364 POO337608 1 Patent Applicati on Publication Sep. 24, 2009 Sheet 82 of 153 US 2009/0238808A1

Figure 19/39

Protein family Subfamily Protein name Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Placenta K562 Ramos kinases when available, rest from IPI) Protein binding other ZNF598 Ploog28.737 1 Protein binding Other ZW10 PIOoo 1631 2 3 9 E. Transporter Amine SLC1A5 P000 19472 2 6 Transporter Amine SLC7A Pooo27728 Transporter Amine SLC7A8 PI00296.114 TransporterEEASE: Amine SLC7A11 EEEPIOoo 10474 3913 2. Transporter SLC25A22 PIOOOO3004 3 3. E4 Transporter SLC38A1 POOO23030 1 | 1 Transporter TAP2 IPIOo328112PIO0328112 3 2 6 11 Transporter EBP POOOO8599 2 8 Transporter lon IATP1A1 15 14 13 Transporter lon ATP1B3 IPIOOO08167 7 Transporter lon ATP2A3 POO303760 2 Transporter on ATP2B1 IPO002 1695 23 1 3

Transporter A AE IPO06O7568IP000 12490 3 3 ransporter IPIO0303476 27 12 7 15 16 P004784.10 - 18 9 9 8 8 Transporter ransporter EEEEEEEEEP000291.33 7 11 21 ransporter IPOO220487 109 7 19 raSOrter ransporter POO220300 ransporter EF ransoorter 2 1 6 7 ransporter ATP6 HUMAN P00654820 ransporter P00000425 ranSOO?ter 5 ransporter ATP6V1H IEEEP00296.191 1 2 CACNA1A - CLIC1 EEEIPIO0010896 2 7 ranSporter CLIC3 IPOOO00692 5 ransporter SEEEEEEEEECLIC5 P00027193 2 fansporter COX2 P0007510 64 6 ransporter EEE - E. ransporter COX6B1 IPIO0216085 1 ransporter - a piO er Transporter TPR P00333753 ransporter TPR2 iPIOoo31545 5 36 g is TransporterEEEEEEEEEEEEEr:r KCTD5 P00004506 2 TransporternGnSSS rtii on KCTD12 IPOOO60715 4. Transporter on MGC 15619 IPIOO53005 1 2 E:Transporterlon EAE-E MON2 Poo465246 33 34 11. 3 24 NOLA1 PIOO302176 4 TransporterE. E.lon NUP153S. IEEEIPOO292059 a1 Transporter lon SFXN3EEE IPO0329606 SIMILAR TO WOLTAGE DEPENDENT ANON Transporter SELECTIVECHAN POOO56004 3 Transporter on SLC3A2 PIOO554481 45 12 3 8 10 Transporter on SLC4A1 Pooo22361 4 Transporter SEEEEEEEESLC9A3R1 IPIOOOO3527 2 on SLC12A2 PIO0022649 6 SLC22A18 IPOO4103472 Patent Application Publication Sep. 24, 2009 Sheet 83 of 153 US 2009/0238808A1

Figure 1940

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for HeLa Placenta Jurkat kinases when available, rest from IPI) Transporter 4 Transporter SLC25A1 P002 19729 Transporter Transcoter SLC25A13 P00007084 Transporter Transporter SLC39A1 POO 100.585 Transcoter POOO29337 Transporter lo SC39A9 POOO2OO3O Transporter SC40A1 PIOooos547P00005547 4 Transporter 2 Transpotter WDAC2 IPIOOO24145 1 3.9 Transporter g Transporter r P00022463 Transporter Transporter ipiddid AEGAPOB - E.P00022229 Transporter APOE POO021842 Transporter ipid CDPT POO374969 Trasporter ioid POOO22228 Transporter 31 1 7 Transporter KAA212 isPIOO171134 i 71 Transporter L D R Transporter lipid LRP1 P00020557 - 2 3 2 Transporter 4. 2:38 A RF1 POOO59368 Transporter P00295132 i Transdotter Liipid SOR1 POOO22608 Transporter itochondrial FXC1 POOOO1538 Transporter Mitochondria POO29O827 E Transporter Mitochondria MTCH2 Poooo3833 SMARTO

Transporter Mitochondrial MTOCHONDRIALNNER MEMBRANETR MPORT rPOO5498.65 Transporter Transporter Mitochondria TMM9 w Transporter Transporter Nucleic acid SLC25A4 POOO2.289 3. Transporter Nucleic acid POOOOf 188 12 27 40 13 Transporter Nucleoporin NUP35 P003296.50 Transporter Nucleoporin POO17665 Transporter Nucleoporin NUP88 P00001738 TransporterTransporter Nucleoporin Transporter Nucleoporin Transporter Nucleoporin NUP133 POO2912CO Transporter NUP155 P00026625 Transporter Nucleoporin NUP188 POO477040 4. Transporter Nucleodorin NUP214 POO1832.94 Transporter Nucleoporin SEH POO22O609 Transporter ransporter Nucleoporin TR POOO22970 ransporter X pO 4. ransporter Nucleotide C6orf108 IP100007926 ranSoter 2 ransporter Organic acid SLC16A3 POOOO6666 Transporter Organic acid Transporter Organic acid Transporter Organic acid Transporter Peotide Transporter eptide Transporterransporter T POOS46625 Transporter APS1 POO152898 Transporter Protein AP2S PIOO219840 Transporter Protein C3orf1 PO0299387 Transporterransporter Transporter Protein s1 Transporterraster Transporter asporter IPO4 P00398009 TransporterTransporter 127 11:2 ;::17 Patent Application Publication Sep. 24, 2009 Sheet 84 of 153 US 2009/0238808A1

Figure 19/41

Protein family Subfamily Protein name Pacc. no. Number of spectrum-to-Secuence matches (Sugen nomenclature for kinases when available, rest from PI) Transporter Protein IPOs Plooootao 7 a 4 2 Transporter Protein IPO9 P100514686 g 3 12 9 13 Transporter Protein Po11 P100301 107.5 s 20 17 4 Transporter Protein IPO3 POOOO565 2 1 P0000224 3 Transporter Protein KPNA3 IPOO299.033 5 Transporter Protein KPNA4 P100012578 3 1 1 8 Transporter Protein KPNA5 PIOO413214PIOOOO1639 10 EEE12 102 POOO257f7 2 S SEC 31 POO3.75370 5 14 10 SEC61A1 PO0218466 46 19 17 SEC61B PIOO220835 6 6 7 s Transporter Protein SC25A17 POOO14440 3 Transporter Protein SORT1 PIOO217882 3 Transporter Protein STX7 P00289876 4. Transporter Protein Six12 POO329332 Transporter Protein MM23 P00007309 Transporter Protein MM44 IPOO3O8516 Transporter Protein NPO1 POOO24364 16 19 Transporter Protein TNPO2 IPOO4096.98 2 Transporter Protein TOMM20 POOO15676 3 Transporter Protein Transporter Protein 4 4 Transoorter Protein Transporter Protein XPO6 PIOO639925 12 1310 14 Transporter Protein XPO7 POO302458 10 21 27 26 g Transporter Sugar SLC2A1 POO220194 61 19 Transporter Sugar SLC2A5 P00027452 2 Transporter Sugar SLC2A14 IPOO152505 3 Transporter Sugar SLC37A4 POO217409 L1 Transporter T Trafficking TRAPPC3 POO004.324 5 2 TTR P00022432 7 Transporter Amino acid SLC43A2 POO171004 16 Transporter T. ERI Golgi SEC221. POOOO6865 12 6 9 Transporter ERI Golgi SEC23A T POO0173757 10 4 8

EEEE| HSEE. He 4. 11 5s 2 ai 26 Transporter ABCB8 PIOOO15826 PIOO291373 P00002372

O4. POO302146

POO645849 Transporter POO555812 Transporter PIOO382950 5 S

Transporter PIOOO3O809 1 334 13 3 Transporter PIOO334432 295 2 - 2 6 PIOO480.146 5 10 KIAA1012 POOO22488 EHE1 NAPA 1 Transporter. Other NAPB | | | | | 2 17 7 30 24 Transporter Other PPGB IPIOO640525 1 Transporter Other SLC33A1 IPIO0006205 1 1 1 2 6 Transporter other SNAP29 PIO0032831 1 2 1 8 5 Transporter Other SV2A (PIOO644.025 2 .

Receptor CRECEPTORBETA, PIOO397415 Receptor - B2M EPIOOOO4656 6 3 3 5 Receptor - BCAM P000024.06 4 Patent Application Publication Sep. 24, 2009 Sheet 85 of 153 US 2009/0238808A1

Figure 19742

Protein family Subfamily Protein name PlacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Placenta Jurkat K562 Ramos kinases when available, rest from IPI) Receptor BzRPPIOOO26850 2 Receptor - CD3D Poo022934 1 Receptor cD3E Plooolag23 3 Receptor - CD3G IPO0016O20 Receptor CD32 Ploo218634 8 Receptor CD38 P0000607 10 ReceptorEEEEEEEEEEE cD79A Ploooos473 1 EG - E - E - Receptor coLEC12CLDN4 IEEEPooza7616 4. - E. E. E. E. Receptor - CXCR4 P1002 16445 23 Receptor - DERL1 P0001327 3 4 6 Receptor - DOCK10DMBT1 EEEEEEEEPIOO333770 Receptor - ELOVL4 IPOOOO9295 2 Receptor . EPS15 PIO0292.134 T 7 Receptor - FBN DP100328113 2 Receptor focR2B Plooos971 | 1 || 2 E.Receptor E. E.FKBP1A E.--P00413778 3 4 E.9 6 E.4. Receptor FKBP3 IPOCO24157 2 2 Receptor GPR89 IPIOO008847 4 6 2 11 ReceptorE E- SEE--GUCY1B3 IPO0289033 - 2 EP Receptor - HLA-A IPOO472882 12 2 Receptor - HLA-B PIO0604445 4 EEEEEEEE-Receptor - HLA-B PO0646083 2 2 - Receptorrea EE"FRAGMENT). POO604470or Receptor - HLA-C PIOO472162 8 3 11 ReceptorE2 - HLA-CW3HLA-DOB (FRAGMENT). E-EPIOOO 10410 1 Receptor - IHLA-DQA1 OPIOO719648 4 Receptor HLA-DRB1 P00472236 TT 9 ReceptorEEEEEEEEEEEH - HMMR PIO0337772 11 6 10 14 Receptor E HPGD PIOO305286 54 1 4 Receptor - IGF2RCAM1 EEEEEEP00289819 4. 5 37 Receptor EA E Receptor - ITGA3ITGA1 POO472202POO29.0043 --1 Receptor - ITGA4 DP100009803 10 T 1 Receptor - ITGA5 IPO0306604 10 4 Receptor - ITGA6 PIOOO 10697 17 Receptor - ITGAL PO0219896 1 7 Receptor - ITGB1 IPO0217561 20 Receptor - ITGB2 IPIOO291792 4 SEE TGB4 IPO0027422 35 Receptor - KDELR2KDELR1 IPIC0018248PIOOO28116 EEE SHE5 Receptor - KDELR3 PO0376991 1 Receptor - LAMA5 PIOO641693 6 Receptor - ANCL1 PIO0005724 1 Receptor - LBR PIOO29235 Receptor LENG4 P00657706 9 8 1 Receptor - LEPR EPIOO472452 2 1 4 Receptor - LEPROTL1 IPIOOO29397 2 Receptor - OLGALS3BP IPIO0023673 90 5 4 15

Receptor - LRP2 IPO.0024292 7 Receptor - MRC1 P00027848 Receptor MS4A1 IPO.0007880 5 Receptor - MYD88 IPIOOOO 1062 3 T 6 Patent Application Publication Sep. 24, 2009 Sheet 86 of 153 US 2009/0238808A1

Figure 19143

Protein family Subfamily Protein name PacC. no. Number of spectrum-to-sequence matches (Sugen nomenclature for Hella Placenta Jurkat kinases when available, rest from IPI) Recentor NRP Po299594 Receptor OFM4 POOO22255 Receptor OPRS1 P00218268 Receptor PDAP1 IPIO001.3297 4 Receptor PHB2 P00027252 62 66 2 Receptor PLXNB2 Receptor PPARBP POO427522 1 Receptor PTGR Receptor PTPRC POO306325 Receptor PPRF POO4S586 Receptor PWRL4 POOO43992 E. 5 Receptor RRBP1 PIOO215743 2 Receptor RN4RL2 2 18 Receptor SEC63 P002 18922 Receptor SELS 3. Receptor ST1 Receptor SAMFSSRPR EEEEEPOO385267 1 Receptor - SRPRB PO0295098 6. 2 TFRCTACSTD2 EEEEEEPOOO22462 28 41 5 Receptor THADA P00444,843 T 68 34 23 53 EEEEEEEEEReceptor - THRAP4 Poo21943o 2 2 Receptor - THRAPG IPO0063213 2 Receptor - TMED7TNPO3 IPOO428967IPOO455125 E 4S is 14 Receptor - TOMM22 P00024976 2 Receptor TRAF2 POO2926.35 5-1 70 56 191 Receptor TRAM1 POO219111 - EEE TVB1 HUMAN P100003986 4 Lipid binding - ANXA6 P10022226 4. Lipid binding - ANXA1 P004,14320 14 EEAEEEEEEEEAP2A1 POO30457 53 Lipid binding - IAP2A2 PO0016621 23 16 44, 25 AP3B1 IPF00021129 4. 9 4.

Lipid binding APO2 IPOO220007 4. 1 1 Lipid binding - APOL3 IPOO302796 2 Lipid binding - CD48 PIOOO13831 Lipid binding - CD59 Poo011302 5 p CLU P004.00826 5 Lipid binding - EEAFABP4 POO329536P00215746 a ----- Lipid binding - FABP5 PIOOOO7797 7 9 8 12 21 Lipid binding - GPA1 IPO0021594 | | | | 1 Lipid binding - HIP1R PIO0024417 8 52 lipid bindic - M11S1 P100402233 3 Lipid binding E INCF PIO0027007 3 lipid binding - PGRMC2 P Lipid binding - PPNB IPOO395939EEE 10 Lipid binding - RUFY1 DP100465429 1 Lipid binding - SCP2 IPIO0026105 4 2 Lipid binding - ISNX9 IPO0001883 3 Lipid binding - SNX24 P100022302 2 Lipid binding - IVCP PIOO478540 30 57 44; 21 36 Sugar binding - IAPCS IPIO0022391 || || 2 | Sugar binding - BSG L T PO0218019 8 T 16 Sugar binding - CD22 IPOO295133 1 Sugar binding ICSPG2 P100009802 1 SEESALGALS7 P00219221POO292.19 4| 2 || 8 10 Sugar bindino LGALS8 PO0215644 OT TO Patent Application Publication Sep. 24, 2009 Sheet 87 of 153 US 2009/0238808A1

Figure 19744

Protein family Subfamily Protein name IP acc. no. Number of spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest from IP) K562 - sugar binding. PRG2P000 10341 4 Sugar binding - PRG3 IPIO0005778 1 L. Sugar binding - TSVEP Ploogo1288 T 6 Sugar binding : WN POO298971 3 - TO Metabolite binding Calcium CAR IPOOO2O599 2 CAPS P00465352 6 Metabolite binding Calcium CHP P002 18924 5 2 6, 9 Metabolite binding Calcium HPCAL 1 PIOO219344 T L 7 Metabolite binding Calcium P00398625 26 55 23 36 9 Metabolite binding Calcium S100A7 POO328396 1 5 Metabolite binding Calcium S100A8 PIOOOO7047 s 7 4. 10 S100A9 P00027462 7 7 2 12 Metabolite binding Calcium S100A1 P100013895 3 13 5 Metabolite binding Calcium S100A14 TPI00002141 Metabolite binding Calcium S100A16 Plooos2120 3 1 ite binding Calcium S1 OOP PIOOO17526 12 ite binding Copper SCO2 PIOOO14458 5 Metabolite binding Metal FHL P00055606 8 Metabolite binding Metal MT1G P004 13064 3 3 1 4 Metabolite binding Metal SEK IPOO428100 T 1 Metabolite binding Metal SELT IPOOO08351 4 Zinc P00006034 6 Zinc POO398576 2 Metabolite binding Zinc POO2A4212 47 16 28 11 13 IPOO2.99066 10 Metabolite binding zinc LUC7L2 IPOOOO6932 7 2 4 7 Metabolite binding zinc PRE3 POo386122 2 3 Metabolite binding Zinc PRE3 P00477800 L 4 Metabolite binding Zinc SPIRE1 Proof 1145 3 Metabolite binding Zinc POO47O896 Metabolite bindina - POO 148063 a 24- 4. Metabolite binding - SCARA5 POO3990.26 6 Metabolite binding. SEC 141 TPO0021887 2 vesicle Trafficking ER Golgi TCOG3 IPOO414858 L5 Vesicle Trafficking TER Golgi cogs IPIOO642611 5 Vesicle Trafficking ER Golgi COG8 IPIOO140201 || | | | | 6 Vesicle Trafficking ER Golgi COPG E-EEE - vesicleVesicle Trafficking ERTER Golgi LRMPOAB2 P00006158POO179438 EE-2H24 Vesicle Trafficking ER Golgi RER1 IPO0005728 10 6 Vesicle Trafficking ER Golgi RER1 IPOO54.9335 2 3 vesicle Trafficking ERT Golgi SCAMP2 P00218850 1 L ER Golgi SCAMP3 P00306382 2 Wesicle Trafficking ER I Gold SCAMP4 POOO56310 1

ERI Gold SCFD1 P00294.133POO479223 3 23 EH vesicle Trafficking ER Golgi SEC311 PIOO515103 6 Vesicle Trafficking TER Golgi SSR1 OPIOO301021 2 3 vesicle Trafficking ER Golgi SSR4 PIOO647461 3 9 3 4 9 ER Gold TMED9 Plooo23542 a 2 VesicleVEEE Trafficking ER Golgi EMETMED10 HEHPIOOO28055 5 3 1 3 Vesicle Trafficking ER Golgi TRAPPC6A POOO12211 1 Vesicle Trafficking ERT Golgi TRAPPC6BOPIOo384.047 L 1L vesicle Trafficking ER Golgi IVAMP2 IPOO477.183 1 9 Vesicle Trafficking ER Golgi IVAMP5 PIOO293756 3 WAMP8 IPOOO3091 WAPA POO374657 1 4 2 Vesicle Trafficking ERT Golgi IVAPB PIO0006211 4 Vesicle Trafficking ER Golgi IVPS13C PIOO465428 17 19 Vesicle Trafficking ER Goli WPS29 PIOO184284 1 VesicleVEEEEEEEEEEEEEE Trafficking ER Golgi IVPS33A POOO73179 1 2 Vesicle Trafficking ER Golgi IVPS37B IPO0002926 2 vesicle Trafficking ERT Golgi IWDR48 OPIOO658210 9 1 O3 Unknown . 67 KDA PROTEIN. IPO0640857 1 3 2 Unknown . 75KDA PROTEIN. PIOOO52996 1 Unknown T. 90 KDA PROTEIN. Poo479092 1 Patent Application Publication Sep. 24, 2009 Sheet 88 of 153 US 2009/0238808A1

Figure 1945

Protein family Subfamily Protein name Pacc.no. Number of spectrum-to-seauence matches (Sugen romenclature for kinases when available, rest from IPI) Unknown PIO0024143 FIFBI Unknown P00464999 Unknown PIO0020903 23 IPIO0022258 3 unknown - ARMET PIOo328748 7 5 1 4 Unknown Ataxin-10 PIO064280 1 unknown - AUP TPIOOOO1891 4 Unknown - TAYP1 IPO0382985 1 Unknown BAAP21 P0079326 unknown - BBC3 IPIOoo44436 Unknown - BC002942 POo3854956 Unknown. BOLA2 IPloogo1434 2 4 4 Unknown - 2 Unknown ONCOPROTEN PO465212 25 5 Unknown BR3BP Pool1035gg 3 3 14 Unknown - BRRN1 PO0299507 2 Unknown - c1orig5 PIO0293746 2 4 Unknown - T C or 45 T POO5149083 2 9 12 2 Unknown - Corfsa PO0023078 3 3 3 unknown - c1orf112 Pool1785124 3 Unknown - 3 2 8 Unknown - 4. 2 1 Unknown IPOO643625 2 2 Unknown P00412376 Unknown 1 Unknown - 2 Unknown - 3 Unknown - 3 3 Unknown - 5 Unknown - O - Unknown - 1 3 6 PIOO165995 2 Unknown 2 2 3 Unknown IPOo394816 8 Unknown - PIO0031564 5 4 5 - 0 Unknown - P00658145 6 9 10 7 Unknown - Poooog335 Unknown - P00306207 Unknown - P00171421 2 10 2 3 unknown P00607576 2 1 Unknown - 1 P00307547 4. 2 3. Uknown P00456750 17 Unknown - C9orf114 DP00418229 1 Unknown - c10orf57 IPOO290807 1

Unknown - c10orf64 IPO0175026 ...... 25 Unknown - C10orf64 PO0646942 76 Unknown - C10orf70 IPO.0020510 G . Unknown - C10orf104 PIO0060893 4 3 2 2 Unknown - C10orf119 IPO.0478.758 1 Unknown - C10orf137 POO183424 2 Unknown C11orf51 Pooo22312 Unknown - C11orf52 EP00059185 4 Unknown E.C13orf1 E.PIO0030959 E. E. E. E.1 Unknown - C14orf125 HPIOO329192 9 Unknown - C14orf129 (PIOOOO9374 3 2. Unknown - C14orf166 IPIOOOO6980 57 Unknown - C14orf73 IPIO0008339 - 5 Unknown - C7orf63 PIOO291010 17 50 49 15 Unknown - C18orf19 IPO0290799 4 Unknown - C18orf24 (PIOOO59912 2 Unknown - C18orf25 PIO0059687 Unknown - C18orf15 PIO0645638 CT 2 Unknown - C18orf55 PIO0306439 1 Patent Application Publication Sep. 24, 2009 Sheet 89 of 153 US 2009/0238808A1

Figure 1946

Protein family Subfamily Protein name Number of spectrum-to-sequence matches (Sugen nomenclature for Placenta kinases when available, rest from IPI) Unknown - C190rf28 Pool166640 2 Unknown - C20orias POO297.121 S Unknown C20orf52 P00016048 2 Unknown - C20orfso IPO334710 2 4 Unknown C21orf70 P00027898 12 Unknown C21 of 124 PIOO642485 36 Unknown. c22orf18 PIOOO31566 4 Unknown POOOOO634POO329147 3 E - Unknown CCDC44 PIOOO1990.3 2 Unknown - CCDC56 PIO0022277 3 EEEEEEEEEEUnknown CCDC59 PIOO329594 f 1 Unknown - CCDC69 P1004 10093 4 Unknown - CCL28 PO0221002 2 Unknown CDKAL1 POOO15713 - 1 Unknown - CG-38 PO0306413 25 Unknown - CHAC2 Poo 103047 2 AIEEEEEEEEEEECHCHD4 P00177428 1 Unknown - CHMP4B P00025974 1 Unknown - CKAP2 EEEEEEE Unknow CNS1A PIOOOO4795 3 UnknownAACE - - ECOL1A1 - POOOOPOO297646 133 282 - Unknown - COMMD4 PIOO413500 - 3 Unknown - COMMD9 PIOO305212 2 Unknown - COQ7 POO294O73 3. Unknown - COX4NB P00005740 1 Unknown - CRR9 POO151358 TL1 CXof 5 POOO19994 3. Unknown - CXorf56 POO335006 1 E-TFF Unknown - CYB5B PIOO303954 1 Unknown - DKFZp586C 1924 P00031.064 2 2 3 EEEEEEEEUnknown. DKFZp667B1218 IPOO74390 8 9 5 2 10 Unknown - DOPEY2 POO29.4653 6 Unknown - DREV1 PIOO 100239 Unknown - DSCR2 PIOOO30770 1 Unknown. DYM POO296211 2 6 Unknown - E2IG5 PROTEIN PO0554692 1 1 1 Unknown - EAF1 IPIO0328258 1 Unknown - EAF2 POOO93988 6 EEEEEEEEHUnknown EFHD2 PO0060181 2 HH1 Unknown - EI24 DP00023185 3 Unknown . ELOVL.1 1 Ha 2 Unknown - EPDR1 P00657648 33 108 Unknown E EXOC1 - IPO0019427 1 1 - Unknown - EXOC4 DP00059279 2 Unknown - FADS Poo385842 1 Unknown - E OFAM32A IP00022402 | | | 3 || 5 Unknown - FAM33A POO 103149 2 Unknown. FAM36A POO 103057 2 2 2 3' 6 Unknown - FAM49A POOOO6574 3. FIF Unknown - FAM49B IPO0303318 3 Unknown - FAM53A IPO0395371 T G T 3 T 10 Unknown FAM62A P100022143 1o 10 Unknown - FAM62B IPOO409635 4 1 13 3 Unknown - FAM83A - IPO0328846 5 152 Unknown - FAM96B PIOO007024 2 4 2 2 7 Unknown - FAM98A PIOO174442 1 Patent Application Publication Sep. 24, 2009 Sheet 90 of 153 US 2009/0238808A1

Figure 19147

Protein name Placc, no. Number of spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest from IP) K562 -

-- Pootors P0002048

ER PIOOO14903

POO186732 PIOOO60574 FLJ10808 POOO23647

F12688 POOO342O1 F13910 POOOO9707 Unknown F14346 PIOO41OO94

F14803 PIO0045764 F20272 POO183938 - FLU20397 PIOO242630 F2O625 IPOOO16670 1 - FJ20699 POO550844 H FLU22555 PIOO29.1751 FJ34931 IPOO39.7879 FLJ36004 POO167858 FJ46O72 POO394.829 2 FLOTILIN 1. POO514818 - FRMD6 P0004:3622 - F POO159652. GALG PROTEIN. IPOO384413 Unknown GBAS POOO16077 3 GCET2 PIOO167003

GDF1 PIOOO19462 1 F GHTM POOO23567 - GOLGA3 POO3O5267 4. GOLGA7 POO480022

- GOLT1B PIOOOOO61 - GPSN2 POOS44037 8 29 GRAMD1A POO180434 170 20 6 129

GRAMDB POOOO8.177

Unknown GRAMD3 POO3O5868 HBLD1 IPOO376195 -5 CAP-D3 POOOOO899 HCAP-G IPOOO6495 HDOC2 IPO0386751 HDGF2 POOO 13290 HERW-FRD IPO0398.064 IPOOOOO495 H HGD1A P00176824 3. HPS6 IPOOO15505 2 HSPC138 PO002637

Ea"pooreDKFZP686E23209. PIOO470798 FLJ46024.NETCA PROTEIN P004.44177 4.21H 52;81 ECAXP 051477. PROTEN,PIOO385962

ECAXP 066O73. PROTEIN PIOOO44536

ECAXP O67264. PROTEIN IPOOO56251

XPECA 067436, PROTEIN PIOOO56985

XPECA 067755, PROTEIN PIOOO58119

ECALXP 067988. PROTEIN IPOOO58956

XPE""Poso 070964, IPOOO53.204

XPE""Poosano 074598, POOO56710 HYPOTHETICAL PROTEIN XP O77601 POOO51491 111.2O Patent Application Publicati on Sep. 24, 2009 Sheet 91. Of 153 US 2009/0238808A1

Figure 19148

Protein family Subfamily Protein name PaCC. no. Number of spectrum-to-sequence matches (Sugen omenclature for Placenta Jurkat kinases when available, rest from IPI)

XP 0891. 18. P00077192 HYPOTHETICAL proTEN Unknown XP 089347. POO102791 | | | | | HYPOTHETICAL PROTEN Unknown XP 0901.10, POOO90052 upon HYPOTHETICAL PROTEIN Unknown XP 091115. P00080641 HYPOTHETICAL PROTEN XP 092572. POOO94646 HYPOHTCAL PRON XP 093117. P00083315 3 HYPOTHETICAL PROTEIN union I XP 093525. PO0084638 | | | | | HYPOTHETICAL PROTEIN XP O94O22. IPOOO95488 HYPOTHETICAL PROTEIN XP 094.185. IP00098060

Unknown XP 0944.27. IPOOO97031 ECAHYPOTHETICApROTEN PROTEIN Unknown XP 095.377. POOO86787 HYPOTHETICAL PROTEIN Unknown XP 095701. IPOOO88092 HYPOTHETICAL PROTEN XP O96748. IPOOO78833 HYPOTHETICAL PROTEN XP 0993 13. IPOOO92745 1 HYPOTHECAL PROTEN XP 103875. POOO83209 HYPOTHETICAL PROTEIN XP 104,170. IPOOO93000 HYPOTHETICAL PROFEN Unknown XP 108488 IPOOO77790 HYPOTHETICAL PROEN Unknown XP 120423. POO150581 HYPOTHETICAL PROTEIN XP 12O656. POO151048 HYPOTHETICAL PROTEIN Unknown XP 120711. POO151187 HYPOTHETICAL PROTEN XP 121796. PIOO146153 HYPOTHETICAL PROTEIN on 1 XP 298883. PIOO259288 HYPOTHETICAL PROTEIN XP 299754. POO245792 HYPOTHETICA PROTEIN XP 303855. POO260484 1 XPESCAL 30a2S2. PROTEIN POO24.4572 | | | | | HYPOTHECA PROEN poore Unknown XP 353184. POO374663 HYPOTHECA PROTEIN. P00303912 HYPOTHETICA PROTEN. IPOO719079 | | | | | Unknown P000055.05.1 POOO40071.1 IPIOOO40071 3 FSI POOO98658.4 H2FIF Ha

IPOO154147.1 POO154147 POO157357.1 POO157357 P00179072.1 POO1790.72 POO180955.1 POO180955 POO221 136.3 POO221 136 Patent Application Publication Sep. 24, 2009 Sheet 92 of 153 US 2009/0238808A1

Figure 19149

Protein family Subfamily Protein name Placc, no. Number of spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest HeLa K562 - from IP) Unknown Ploog330811Poo333081 3| 3 || 3 Unknown . IPOo333348.1 PIO0333348 Unknown - P00335775.1 IPOO335775 5 Unknown . Plooggs487.1 IPO0396487 1 Unknown . PIOO411598.1 P10041598 1 Unknown - Poo413331.1 Poo413331 Unknown - PIOO414413.1 IPOO414413 1 Unknown occ IPIOOO18690 1 Unknown - JAGN POo329025 2 unknown - KAAo101PIOOO1447 2 Unknown - KAA013 PIOOO4149 4 1 Unknown - KAAO133 PO0028980 3 9 EGEEUnknown - KIAAO 196 - POOO2904s000291.75 4. 23 Unknown - KIAA0261 POO412441 2 KIAAO310 POO641384 30 60 Unknown KAA0368 POO157790 37 s KAAO372 POOOO5634 2 Unknown KAAO404 POO3O4928 2 KAAO406 P00011702 Eas Unknown KAAOS28 POO465142 45 8 22s Unknown KAAO883 POOO16868 3 Unknown KIAAO690 P0001186 1 1 EEEEEEEEEEEEEUnknown KAA802 PIOO411635 7 Unknown. KIAA0922 PIOOO21671 6 Unknown - KIAAO963 PIOOO24900 1 Unknown - KAA0999 PIOO440492 4 Unknown - KAA1033 POO298991 1 Unknown - KAA1414 PIOO479069 T 2. UnknownE. E.- TAEEEEEEEKAA1524 BPOO154283 8 Unknown - KAA1618 Poo242962 8. 86 65 Unknown - KAA1632 PI004.00765 4. O 7 Unknown KIAA1787 POOO642.19 1

EGUnknown -- KAA1794KAA1797 IPOO3836O7P00477345 689 409 2813 Unknown KEAA 1833 P00376747 4 - 7 7 Unknown KAA1840 PIOO 101923 4 8: 5 Unknown KAA967 PIOO182757 1 Unknown E10KTN1 EEPIOo328753 2: 19 se 2 st Unknown - LAMP2 DP00216172 I 1 Unknown - LANCl3 PIOO643639 ...... 1 Unknown - AS1L PI00641990 2 Unknown - LETM1 IPI00017592 - 2 - 1 Unknown - LGP1, PIOO427501 1 12 Unknown - LIMD2 IPO0549972 - - - - - 4 Unknown - LOC51035 PIOO396563 5 3 6 1 Unknown - LOC90580 IPIOO157215 6 3 6 9. 8 Unknown - LOC92345 PIO0063219 || 1 || | | 3 Unknown . . . . LOC11643 (PIOO465211 | | | | T 5 Unknown - LOC128977 IPIOO418459 1 Unknown. LOC12938 P00025746 27 65 UnknownEx T. EPROTENLOC203547 EHP00334343 Unknown - LOC255326 IPO.0457009 unknown LOC283377 Poo291643 1 Unknown - T. LOC284.06 P100401947 6 Unknown - LOC339766 P100216817 3 LOC388568 POO398,588 El 2 10 Unknown . LOC391352 (PIOO39719 1 1 Unknown. LOC39722 Ploog76572

Unknown -. LOC392758LOC401531 POo375167PIOO401259 HE Unknown. TILOC441454 IPO.0454810 1 Patent Application Publication Sep. 24, 2009 Sheet 93 of 153 US 2009/0238808A1

Figure 19750

Protein family Subfamily Protein name Pacc.no. Number of spectrum-to-Sequence matches (Sugen nomenclature for kinases when available, rest from IPI) K562 r

LOC441899 POO457324

LOC493856 OO166865 LOC494,150 PROTEN. POO3864.35 Unknown P00002255 LSM12 POO410324 4 Unknown - MAD1L1 P00470519 Unknown - IMAEA P006O7605 Unknown - MAGED1 DPIOO398845 Unknown - IMAPBPIP P10047441 Unknown MFSD1 PIOO152959 1 Unknown - MFSD5 PIOo3O1554 Unknown - IMGC2803 P00031526 Unknown - MGC 10993 IP10001.2251 1 Unknown - IMGC13096 P100031647 Unknown MGC33214 POO181160 Unknown MGC52424 P00177509 Unknown MGC61571 IPOO376.478 1 Unknown MGP POOO2871.4 Unknown Mitsuomin 23 P00031697

Unknown MC1SA POOO27255 Unknown MLT3 POOOOOO33 MSD2 IPOO478838 2 P004O9675 1 PIOO329.552 2

5 Unknown P00382557 2 IPOOO23161 4.

P100061531 2 POOOO6606 Unknown - MTP18 PIOo383766 Unknown - MVP P100000105 3 Unknown - NBEAL2 POO297242 3 Unknown - NCDN PO0549543 2 Unknown - INFUN IPO0022240 Unknown - NIPSNAP1 P100304435 Unknown - NOL9 IPO0002902 Unknown - NRM. T. PO0217557 Unknown - NSUN2 IPOo306369 8 Unknown - ONUDC PIOO550746 3 Unknown - NUDCD1 PIO0306398 2 Unknown - NUDCD2 PIO0103142 Unknown - NUDT161 IPO0031650 I L7 Unknown - NYREN18 PIOO37.7271 1 Unknown - OCTAD2 PIO0555902 Unknown - ODZ3 DP00398020 4 Unknown - ORF1-FL49 P00382821 Unknown - OSBP PO0024971 3 1 Unknown - PACAP P100102821 Unknown PAGE4 pOO2992.44 Unknown. PAPD P00470416 12 Unknown - PDCD10 POO298558 1 4 Unknown - PDCL2 IPOO166688 2 Unknown - PHLDA2 IPO0019551 2 Unknown - PHLDB2 PIOO410259 Unknown - PNPLA POO67613 Unknown - POPDC2 IPO03287.17 unknown PP3971. Pool170670 Unknown - POLC3 IPOO167098 2 PREOCTED: SMILARO

Unknown GOGINS P00399.155 2 Patent Application Publication Sep. 24, 2009 Sheet 94 of 153 US 2009/0238808A1

Figure 19751

Protein family Protein name PlacC. no. Number of Spectrum-to-Secuence matches (Sugen nomenclature for kinases when available, rest from PI) K562 - nknown PROSC Poco 16346 a 15 7 8 nknown PSG1 POO 63720 nknown PSG9 IPIOO293461 E nknown PTMA POOO15550 16 2 nknown PTMS POO719158 2 29 RAFT IN POOO32395 2 6 Unknown Unknown RHBDF1 IPOO290292 Unknown Unknown RHBOL7 Unknow 233 Unknown R5-1104E155 Unknow - Unknown Fl 5O Unknown Unknow Unknown RTN3 POO398795 Unknown Unknown RTN POO645947 Unknown P00304935 1 Unknown SAMM50 Unknown SAR1 E.P00021417 Unknown Unknown SF3B5 PIOOO 104.04 Unknown Unknown SFT2D2 PIOOO29002 SH2BP1 PIOOOO5625 Unknown SKE PIOO305186 Unknown SMARO BX34-P1 PIOOO63142 SMARTO 21 OPEN Unknown READING FRAME 70 OOO67466 SMAR TO COX11 (YEAST) HOMOLOG, Unknown CYTOCHROME COX POO142866 SIMIAR TO DJ604K5.1 (15 KDA SELENOPROTEIN). POOO4903 SMARTOE2F TRANSCRIPTION FACTOR LIKE PROTEN PIOO 183869 SMARTO FRG1 PROTEIN (FSHD REGION Unknown 1 PROTE IPOOO19816 SMARTO -- HYPOTHETICAL PROTEIN Unknown H. SAPENS). POOO36670 SMARO HYPOTHETICAL PROTEIN FLJ10292. POOOO4316 1 SMARTO HYPOTHETICA PRON FLJ10902 (H. SAP POOO4377O SMARTO HYPOTHETICAL PROTEN FLJ12457. P00076139 2 SMARTO HYPOTHETICA PROTEIN MGC29729, POOO47508 SIMIARTO KARYOPHERNALPHA IMPORTNALPHAS POOO97143 SMILARTO NONSYNDROMCHEARING IMPAIRMENT PROTE PIOO 106625 Patent Application Publication Sep. 24, 2009 Sheet 95 of 153 US 2009/0238808A1

Figure 1952

Protein family Subfamily Protein name Placc.no. Number of spectrum-to-seouence matches (Sugen nomenclature for kinases when available, rest from PI) K562 s SMARTO PEPTDYLPROY SOMERASEA Unknown CYCLOPHIL POOO94886 1 SMARTOPESCAOLO HOMOOG 1. POOO742.23 SMARTOPROLNE SERINE-THREONNE PhOSPHATASE PIOO1a10s SMAR TOR27-2 PROTEIN-TRYPANOSOMA CRUZ. P001s1341 5 SMARTO RETICULON PROTEIN 3 known NEUROENDOCRINE-SP P00177423 SMARTO SERNEFHREONNE Urkflown PROTENKNASEPAK2 POO1583.54 1 SIMLARTO SEROD HORMONE RECEPTOR Unknown HOMOOG - FR P00098097 SMARTO ANDEM PORE DOMAIN Unknown POTASSUM CHANNE POOO41219 1 Unknown SPBC24 PIOO168317 2 -- Uknown SPBC25 1

Unknown - SSNA1SSU72 IEEEEEEEP00023556 STARD7 IPO0024548 3 Unknown - STOMSTATP1 EEEEEEPOO219882 2 1 EE-SE-EEEUnknown STRAP P00294536 - 2 Unknown . STXBPs IPOO178314 EG-SEEEEEEEEEUnknown SURF4 P00005737 15 SYNGR2 IPIOOO3946 3 SYNGR3 P00013947 2 Ex-E P00000948 4 Unknown - TEX264TCOF1 P00006372POO298898 2EE,6 9 2 3. 19 TPRL POO180637 Unknown - T TMCO1 BPIOOO26111 4 3 Unknown - TMEM2 BPIOO170706 13 Unknown - TMEM16F PIOO151710 3 5 O EEEEEUnknown - TMEM33 PIOO299.084 11 132 123 4. 14 Unknown - TMEM38B PIOOO18237 1 1. Unknown ...... TMEM41A PIOOO63334 2 Unknown - TMEM41B PIOO555703 3 1 UnknownE. E.. E.TMEM49 E.PIOOO62469 E. Unknown TMEM50B PIOOO1046 5 EEEEEEEEEEEEEUnknown. T TMEM66 PO0604763 13 3 5 2 6 Unknown - TMEM103 PIOO107.155 1 Unknown - TMEM111 PIO0020472

Ericunknown. TMPiTMEM13. EEEPIOO470533 2 Unknown TNFAP8 PIO002762732 Unknown - TPARL PIOO307572 2 2 2 Unknown TRAM2 IPIOOO4218 Unknown - SC PIOOO22043 a Unknown - TTC7B PIGO456534 4 Patent Application Publication Sep. 24, 2009 Sheet 96 of 153 US 2009/0238808A1

Figure 19/53

Protein family Subfamily Protein name Placc.no. Number of Spectrum-to-sequence matches (Sugen nomenclature for kinases when available, rest from IPI) K562 r Unknown - Pools24 Unknown UBXD2 E.P00293946 Unknown UFC POO294.495 3

POO186099 Unknown - UNQ501 IPIOOO63130 Unknown - USMG5 PO0640630 3 Unknown - MEEEVCY POO297.427 1 EE Unknown - WBSCR19 PIOO477.590 2 Unknown WDR42A PIOO290.071 2

Unknown WOR6 PIOOO19269 1 4 Unknown - WDR62 PIOO470483 1 Unknown WIBG IPOo305092PIO0010873 H 3 Unknown - XX-Fw81657B94 IPIOOO32314 2 Unknown - YFA POO65871 3 2 2 Unknown - YF1B IPOOO63544 1 2 1 Unknown YPF5 IPOO607768 2 2 3 Unknown - YPE5 PIOO429538 2 ENG-I-ME-E.-----YRDC IPO384 180 2 Patent Application Publication Sep. 24, 2009 Sheet 97 of 153 US 2009/0238808A1

Patent Application Publication Sep. 24, 2009 Sheet 98 of 153 US 2009/0238808A1

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