Poster Authors: Martin Lee Miller, Søren Brunak, Lars Juhl Jensen, Michael B

A Sequence-Specificity Atlas of the Kinase World CK1 family

NEK2 Negative Atypical S TGFbR2 S D F T EIF2AK2 YS SY A EE S F EDDETDG S DTTYGA 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 L I M S TR FWMW VS W G LT Y H T 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 E S R CK1gamma3 CK1gamma1 CK1gamma2 R K T TS DE CK1epsilon S CK1alpha2 NND QRN S KKS M CQ

CK1alpha

0 1 2 3 4 5 6 7 O -6 -5 -4 -3 -2 -1 T CK1delta -7 V D KRT R D E RL D R SEL T PTTS LD T S S L S SK LM PLP LS E E P A E K RG LDLF Y G V N G GR L I A T LV VAY TT TTBK2 KR I T RVFS I RE KA TDD RS KQ KM D EE G G BUBR1 TTBK1 VRK2 VRK1 N RE P D SgK396 VRK3 MPKRT F NFNMGPM SgK196 P I GMVHG KYL I MEL SgK493 Positive

0 SgK110 Haspin S BUB1 -7 -6 -5 -4 -3 -2 -1 SgK069 +3 +4 +5 +6 +7 +1 +2 SgK223 SgK269

Wnk2 Wnk4 Wnk3

NRBP1 ATM/ATR NRBP2 Wnk1 SCYL2 SCYL1 SCYL3 PIK3R4 Slob SgK424 SgK307 PINK1 SBK SgK496 MOS TBCK PBK CYGF CDC7 CYGD HSER NEK1 ANPb Proline NEK5 ANPa ILK NEK3 BMPR2 NEK11NEK4 MISR2 TGFbR2 ACTR2 NEK2 ACTR2B ALK2 NEK9 ALK1 NEK8 BMPR1B NEK6 BMPR1A NEK10NEK7 ALK7 TGFbR1 ALK4 AAK1 MLKL IRAK4 S S MPSK1 BIKE IRAK2 E Q EIF2AK2 S D G S E IRAK1 ES A S PS I SS GAK TQL PL SQ DL Syk family S VP Tec family P D E IRAK3 EphB3 L T GCN2 1 TESK2

0 PEK TESK1 -7 -6 -5 -4 -3 -2 -1

S +1 +2 +3 +4 +5 +6 +7 Q LIMK1 Wee1B LIMK2 mTOR LRRK2 HRI LRRK1 Wee1 RIPK1 MYT1 RIPK3 RNAseL RIPK2 IRE1 ANKRD3 IRE2 SgK288 KSR2 SgK071 KSR1 D E V L P KIS ARAF EV P S D R TTK E D D R VE AD VS A EE D DG V SSDDE EY NP R BRAF D V L E M ATPVD CLIK1LCLIK1 S EES E YE L LEE QLT EN PD E A L D T I SP NQ DG ANSS D DEE S DLL MS G PS P K A SD TEN T NGLKND D RAF1 LMP N MN P KS DV E E T A TM ED R D PP NQP ESEQ P N A S S TSE R D H Q T I GH F M L S P VT TT S HH498 E

V 0 SS T G P PRPK 0

S 0 1 2 3 4 5 6 7

E R G S P -7 -6 -5 -4 -3 -2 -1 RQP SS L -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 MAP3K7 2 +1 +2 +3 +4 +5 +6 +7 +7 S RA AlphaK1 +1 +2 +3 +4 +5 +6 F I FL N S DG PVVTCPV R PL V TTDF Q D VFT ZAK GRQRG D R GD AlphaK2 PM K YPAFP DNEGP I F E I F NLKLVTK ET I KL DLK Y Y FGGHYGH F I KKGV I Y MAP3K13

0 P eEF2K

-7 -6 -5 -4 -3 -2 -1 T +4 +5 +6 +7 +1 +2 +3 MAP3K10 Chak1 MLK4 DNAPK AlphaK3Chak2 MAP3K9 EphA4 Abl family MAP3K11 ATR FAK mTORATM PYK2 TRRAP Syk ZAP70 DNAPKSMG1 EphA10 PDHK3 CK1 EphB6 E PDHK1 EphA1 T S SS AP AT D Q BCKDK EphA2 P Q ET L QS L E V LF I D S S FP T L EE S AS PD EphA8 V LF V G G D I G D Q Q AE SK R P G G AHQ PDHK4 V V T E V SVGP DV AP D L S V Q I MGG L G I NG A P R K D E G TTK VT N N SN F A R EP A H NQ GM E EphB4 Y YY DG VG LS S TE LF T Q I K G V S P VP I T LQG T PDHK2 C YNFH P A P Q C 0 T EphB3 0 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 +1 +2 +3 +4 +5 +6 +7 ADCK1 EphB1 +1 +2 +3 +4 +5 +6 +7 ADCK5 EphB2 Y ADCK3 EphA7 ADCK4 EphA6 ADCK2 EphA4 EphA3 PDGFRY family Lck Brd3 EphA5 TIF1gammaBrd2 CTK Brd4 Csk TIF1alphaBrdT Fer Fes CaMKIIβ TIF1beta Abl2 Abl RIOK1 BMX V V RIOK3 EEE I I L PIKK BTK DDE I V GQ I D SSSD FDF T A V PPPS Y E EE E NN TTP MEM D DEF RIOK2 EEST T YP DGGLE G T E L N YW NEK ITK PP Y L Y 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 Tec -7 -6 -5 -4 -3 -2 -1 S TXK Srm FD Brk M I K K Q VS I F I F FRQL M M Y MK LELK FRK W SY RKN YTTW CaMKIdelta FLT3/CSF1R/Kit

0 1 2 3 4 5 6 7 Y BLK Y -7 -6 -5 -4 -3 -2 -1 T CaMKIalpha CaMKIgamma Lck HCK CaMKIbeta Lyn CaMKIIα/δ Fgr CaMKIV Fyn VACAMKL Src S DY NL E PSKH2 Yes D N E DP S E RES VI YKR S N NAR E EG S KV GETQ Tie1 V I NV A I S A V TY G DT TDDLS PSKH1 D DN D SR AF P F G TAHF ERWQ N VKL D FTL K DCAMKL1 LNSS QK EFPPK F Tie2 I HMLFR I FLMHH G 0

DCAMKL2 -7 -6 -5 -4 -3 -2 -1 +1 +2 PDGFRalpha +3 +4 +5 +6 +7 T A L SQ LDT S RR A F Q DCAMKL3 PDGFRbeta S FLPRD V S G Y CaMKIIgamma SE KQ I TKL D REK R R SVAK TEE Atypical R AQQP R LL SY I S LP D S R G K FLT3 K M H S P K I HY T I I EK

0 CaMKIIbeta

-7 -6 -5 -4 -3 -2 -1 CSF1R +1 +2 +3 +4 +5 +6 +7 CaMKIIalpha Kit CaMKIIdelta FLT4 JAK2/JAK3 MAPKAPK family KDR CASK Src FLT1 PHKg1 Ret PHKg2 FGFR4 RSK3 2 FGFR1 RSK2 2 FGFR3 P L P RSK1 2 FGFR2 DL TSD L SD SSLADK YK VPSG A A AV DE T SL VP L I L TV I S S RSK4 2 CCK4 PHSSQA I PTKFTD L Q P A R E R H V E HA P L H I G P T TEE FD P VW P L R T PPT T S E LS I EQ SE K NLR P P SSA GG TP G MEKD SS P V A A I KK YG E I F I K GA RK V SE TP FSAA TDQKSP MSK2 2 Lmr3 RRGPDGE R L VE L V MRVET T E GT T R R QT P G 0 V NP DGG N N DE I L K LL FG E -7 -6 -5 -4 -3 -2 -1 +7 T MSK1 2 Lmr1 +1 +2 +3 +4 +5 +6 0

-7 -6 -5 -4 -3 -2 -1 S +1 +2 +3 +4 +5 +6 +7 Lmr2 Y Mnk2 Mnk1 SuRTK106 PKD family MAPKAPK2 Tyk2 2 MAPKAPK3 JAK1 2 EGFR MAPKAPK5 JAK2 2 JAK3 2 PKD3 TK TNK2 PKD1 TNK1 S PKD2 Tyk2 CHK2 JAK1 LV V F MARK2 E F F K MM JAK3 I YA LKKK VF F DPE V A RQ L M E L P A EM FA V EDI LP V I I DND V I L MARK1 V F I V I Y P Y S H H YP N SS W WWW JAK2 NPST TYY TMM GWY I M TTT RC MMY G P T W 0 1 2 3 4 5 6 7 MARK3 0 1 2 3 4 5 6 7

-7 -6 -5 -4 -3 -2 -1 ErbB3 MARK4 ErbB4 -7 -6 -5 -4 -3 -2 -1 SIK ErbB2 CHK2 QIK EGFR Met family QSK RYK Y NuaK1 Ron NuaK2 CAMK Met BRSK2 Sky BRSK1 Axl S Mer AMPKa1 Ros V L AMPKa2 DEE V T AD PPPPA T I Q I SVHLGDN D G M S ALK YD VR T I NTS R Y R I S A SMT TY T E A S Y N F S FR MELK M L QV N DQ S MN L GAE S CV Y A VR L Y TE H D RC K M A MC F ERC L H C S KSP L L L W HK WW RM D MFEKN P Y H LTK PQTPKM K H R HUNK HS N I L THNGY V 0 1 2 3 4 5 6 7 STE 0 -7 -6 -5 -4 -3 -2 -1

R T -7 -6 -5 -4 -3 -2 -1 IRR +2 +3 +4 +5 +6 +7 CHK1 +1 LKB1 InsR Y SSTK IGF1R AMPK subfamily DDR2 TSSK3 DDR1 InsR/IGF1R TSSK1 ROR1 TSSK2 ROR2 TSSK4 Musk NIM1 TRKA S SNRK TRKB Pim1 M Pim3 TRKC L Pim2 R SLK D R H I R L E ND SP D G ME G S GE MS I NGK LE DPP ANPYSVK 0 1 2 3 4 5 6 7 PASK S KK E I A P R T G EG T V L

-7 -6 -5 -4 -3 -2 -1 LOK T S

Trb2 0

MAP4K1 -7 -6 -5 -4 -3 -2 -1 Trb1 MAP4K2 Y +1 +2 +3 +4 +5 +6 +7 LKB1 Trb3 KHS2 MAP4K5 SgK495 MYO3A SgK085 MYO3B caMLCK NRK skMLCK TNIK smMLCKTTN MAP4K6 MAP4K4 I DAPK1 TAO3 WF CMGC F YYLV PWTR T AGC CM DAPK3 S P TAO1 M A W C

0 1 2 3 4 5 6 7 DAPK2 TAO2 -7 -6 -5 -4 -3 -2 -1 PKC DRAK2 MAP3K MST1 T DRAK1 MST2 YSK1 TNIK SLK Pim1 Pim2 Obscn 2 SPEG 2 MST3 MST4 SPEG 1 PAK2 ObscnTrad 1 CDK Trio PAK1 PAK3 STK33 PAK6 S PAK4 S ULK1 PAK5 LRRR R R ULK2 R M OSR1 P YG K H W Y WN MKP RH H G W Q K Y LKR G H H Y H H S N K N H R R RN P WI NS HKK Y K D Q NHK R ULK3 T T C T KF FG H R N Q STLK3 S S CTST R QT I T N Y RN W K NW R K R N P KK K KK G H RQ SRHY

WR W AKQ 0 1 2 3 4 5 6 7 HQ S G ULK4 STLK5 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 T T STLK6 Fused MAP2K5 MAPK MAP2K1 PKCbeta MAP2K2 PAK4 PAK2 PKCalpha MAP2K7 T MAP2K4 T MAP2K6 PKCgammaPKCeta MAP2K3 PKCepsilon MAP3K8 PKCtheta MAP3K14 PKCdelta GCN2 2 PKCzeta PKC family SGK family PKN1 MAP3K4 PKCiota MAP3K6 PKN2 MAP3K7 S PKN3 R W MAP3K5 I A RK C HH V LY SGK3 MYW W F SYR Y ST I K K R MAP3K1 Q SF S S W Y L SY P G FVL R V W SGK1 MAP3K8 2 RNHS C R 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7

-7 -6 -5 -4 -3 -2 -1 T SGK2 -7 -6 -5 -4 -3 -2 -1 R MAP3K3 R S MAP3K2 T D PKBbeta CK2alpha S C A P S A S RSK1 CK2a2 G P S MAP2K3/4/6/7 MST1 AS S N S PKBalpha Polo MST4 P T V T G DR R LT ANPE CDK10 TQ A A M LVV S RSK2 S A S GSRE N R EF R V SDQ I N D W T PITSLRE RR LG LL AE RSK3 S RP K K K KSR N G N VQ L R G I L HG YRK I SS S KS L PKBgamma CDK9 T T RSK4 0 0 -7 -6 R-5 -4 -3 -2 -1 CRK7 -7 -6 -5 -4 -3 -2 -1 +2 +3 +4 +5 +6 +7 +1 +1 +2 +3 +4 +5 +6 +7 CHED R CDK7 RSK5 p70S6Kbp70S6K CDK11 CDK8 MSK2GRK5 1 CDK6 E A GRK4 CDK4 T Y A T M CDK5 S V V R GRK6 TSDDMTG V TWYR PKB family p70S6K subfamily RSK family GRK7 CDK1 MR SVT D PA R A E C P K CDK3 RDG LV GV T M C T GRK1 Y R AQ K W G DY W V LTE F MV Y D N CDK2 G L RFKVA Y AAPW WG R H DKD L N C K QKMS P R E S W K KSR GRK2 PFTAIRE1 A W G K L TWM GD A W K RR H E ND A M NR YQR TP M T RT M E STM HA NNH YKK G VG Q LES SL G H CI P A M P R CY RG I P L HY N GRK3 PFTAIRE2 Q G Q T VHSY I LT I MDSYK I M R S R PCTAIRE3 0 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1

PCTAIRE1 -7 -6 -5 -4 -3 -2 -1 MRCKa PCTAIRE2 +1 +2 +3 +4 +5 +6 +7 MRCKb CCRK MAPK6 DMPK2 MAPK4 T DMPK1 MAPK15 ROCK2 NDR1 MAPK1 S ROCK1 MAPK3 NDR2CRIK MAPK7 NLK S MAPK9 F P LATS2 MAPK10 CK2 family T W RS MAPK8 T S E RSR S G R R R P LATS1 I K H SRG G V N S F Y R GS R SEK S MAPK13 P K S P A L G RDL LG WL DKA L ED MAPK12 S HN H C RRG WKM DP PF VN TKS Y N E LD EG S E K T M QRYS T LQSAK D P MAST4 MAPK14 Y KS R K H YLKQPT N I MAST1 MAPK11 CDKL5 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 0 MAST2 CDKL1 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 R T -7 -6 -5 -4 -3 -2 -1 S CDKL4 R +1 +2 +3 +4 +5 +6 +7 MAST3 CDKL2 CDKL3 MASTLYANK1 GSK3beta T GSK3alpha MOK R YANK2 ICK MAK YANK3 PRP4 SRPK1 SRPK2 MSSK1 RSKL2 CLK3 SgK494 CLK2 RSKL1 CLK1 CLK4 HIPK4 HIPK3

DYRK1B HIPK2 DYRK3 DYRK1A HIPK1

DYRK2 DYRK4 ROCK family PRKX DMPK family PKA family GRK subfamily PRKY PKAbeta PDK1 PLK2 PKAalpha PLK3 CDK2/CDK3 PLK1 PLK4 E TBK1 DE TLK1 TLK2 D ED EE PKAgamma E S DSD S S E E G S ESEEE G DDE S DD G GSSD AuroraB S T PKG2cGKIIPKG1cGKI AuroraC AuroraA ST IKKbeta 0 -4 -3 -2 -1 -7 -6 -5

IKKalpha +1 +2 +3 +4 +5 +6 +7 T IKKepsilon KR RR V CaMKKbeta S Y P S S R SR S CaMKKalpha RKSY G SS EM S I S VRMP D R DY T G S E GP RGVAR F S T GF T I YG S Q N QQ F T S S G K Q V D V G ASHL L GN S R ED D AV T GK R D D S PE CDK1 S E E T G V G AV NGEK FS P CDK4/CDK6 K T Q K Q A T D Q Q T K ER G D R KP F AS RS DE V S QS PAQTL I D L V T N E S P SE E TN LNVYVK K LL P P LG T K R T CLK family MAPK14 SR

R 0 R P T

0 PLK1 AuroraA LR L G T S P

L -7 -6 -5 -4 -3 -2 -1

0 1 2 3 4 5 6 7 S S AR 0 S P LL -7 -6 -5 -4 -3 -2 -1 S TA +1 +2 +3 +4 +5 +6 +7 P H R -7 -6 -5 -4 -3 -2 -1 +1 +2 +3 +4 +5 +6 +7 G -7 -6 -5 -4 -3 -2 -1 LSS G Q P E H

S +1 +2 +3 +4 +5 +6 +7 0

-7 -6 -5 -4 -3 -2 -1 T +1 +2 +4 +5 +6 +7 T P +3

PKGcGK family PDK1 JNK subfamily S S S S R S P R PAG RY PM P A VVAR R DA LS SS V N T R R LA Q A L A Q V N R F L V P H T S R F A S R P M H AYE I T L KK L A S HN S S ESP P Q T I K P P L E V QK N F EP K S LAS L L L P P P R H RSHN G K S SPS S KSET KP P R D HPG S S I A K E K P L G TRL Q L P L S K LV N QESQR AQAL SE K T L G EE T D PNPV S K L H I Y I M Y I I YKK PL SES S D PP TAS GL KAPQ I S TGL QLR AL KKSCR H L G PPD Q PSK VL EQS TV I GQEL V

S K A G K Q 0 KE DS P TK Q T VD T L L K M V 0 D N NT R N K N T I T K G K -7 -6 -5 -4 -3 -2 -1 V E E SG T R L FG G FNN R -7 -6 -5 -4 -3 -2 -1 R H R F +1 +2 +3 +4 +5 +6 +7 +1 +2 +3 +4 +5 +6 +7 P T R 0 0 0 1 2 3 4 5 6 7 T S 0 1 2 3 4 5 6 7 -4 -2 -1 -7 -6 -5 -3 -6 -7 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 -7 -5 -4 -3 -2 -1 -6 +1 +2 +3 +4 +5 +6 +7 +1 +2 +3 +4 +5 +6 +7 S TP P R T C D TS FY G PE R T Y A V T S R T EA S AS I DT Q S LSFT SSP T RKPK AS AP F D AAF R H GA E A L L GK SV S Q TEPS A VG RS ET A E E G FV I D AK VGV AAPV P G EGKCN QRNG SSLTAR QTE P AK P M D R L K E H RR I HA Q A L K L LG S GSK3 subfamily TS N A A ICK S L N L G Q ES D S MM N K S VL KHG R N Q LHSKV Q AuroraB/AuroraC L CDK5 F GHY I I G S CDK7 N L VR N I Y I Y R TLK1/TLK2 LP I PA P T T S S PA A E S D G AP S P ST A S

0 E S0 EPS V L -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 +1 +2 +3 +4 +5 +6 +7 +1 +2 +3 +4 +5 +6 +7

T0 -7 -6 -5 -4 -3 -2 -1 P+1 +2 +3 +4 +5 +6 +7 S MAPK1/3/7/NLK G S A K GA P G P L P L S KPG S R VV KT AR R I K A S Q AE S R S R SAT VW S S A G SC LA C A P S P P K E V P Y R R SV F T N V E I D V V G L KK V T TP HY FGFR3 T G VT PG R VT AH V T S FGFR2 TNVS L NS T L S PP GPPDA KS DV QK K TQ E E Q R S S G S ES T SP T SQ Y L D I AP S VA Q I ST AL F I RLS I P A D LY V EPL V R K F TQ R E L R P F N ST R S SP A Q F G A Q V RDWH DS T D G PS V S S PV P EP G R N N GS E M TS P A LLLL AA Q Q K L P T A P P TV D AR P EK N Q RN H H TrkC I RN SDTN R KQA PE G GHP R P H Q E LKS L ML E H L CVG G PR T EK S PM F N H K NS R K S K P F R H G HRN Y I SKV T T W R S R G I LL SK Q L G H M GC D W L I L K K EphB2 FGFR1 Y I Y I HGK KHKKYML RK

TrkB 0 0 1 2 3 4 5 6 7 FGFR4 T0 0 1 2 3 4 5 6 7 R T -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 T 0 -7 -6 -5 -4 -3 -2 -1 +1 +2 +3 +4 +5 +6 +7 +1 +2 +3 +4 +5 +6 +7 -7 -6 -5 -4 -3 -2 -1 -7 -6 -5 -4 -3 -2 -1 T T EphB1 TrkA FLT1/VEGFR1 +1 +2 +3 +4 +5 +6 +7 EphA5 KDR/VEGFR2 T Fms/CSFR MuSK ROR2ROR1 P EphB3 Ret Kit EphA3 DDR2 Mer The DDR1 Tyro3/ Human Kinome FLT4 EphA4 Axl Sky PDGFRα S FLT3 P IRR L EphA6 IGF1R PDGFRβ A P PT S S GSL GPPSS InsR S S S S S S PS A P Yes EphB4 Met EGFR HER2/ErbB2

Ron T0 Src

MLK3 -7 -6 -5 -4 -3 -2 -1

Ros +1 +2 +3 +4 +5 +6 +7 EphA7 ALK MLK1 Lyn LTK Tie2 P Tie1 HCK Fyn RYK HER4 EphA8 MLK4 CCK4/PTK7 MLK2 Lck Fgr Ack Tnk1 Tyk2 Jak1 HER3 Jak2 EphA2 Jak3 TKL TK BLK DLK Syk Zap70/SRK ANKRD3 SgK288 EphA1 PYK2/FAK2 LZK Lmr1 FAK ALK4 ITK Lmr2 C-Raf/Raf1 TGFβR1 FRK ZAK BRaf EphB6 KSR TEC Srm RIPK2 KSR2 TXK Brk Lmr3 ALK7 BTK IRAK3 IRAK1 ARaf LIMK1 BMPR1B Etk/BMX EphA10 LIMK2 TESK1 ILK BMPR1A CTK RIPK3 TSK2 TAK1 HH498 ALK1 CSK ALK2 Abl2/Arg IRAK2 ActR2 Abl Fes ActR2B Fer RIPK1 TGFβR2 STE Jak3~b LRRK2 MEKK2/MAP3K2 Jak2~b LRRK1 MISR2 MEKK3/MAP3K3 Tyk2~b SuRTK106 IRAK4 BMPR2 ASK/MAP3K5 ANPα/NPR1 MAP3K8 Jak1~b MAP3K7 ANPβ/NPR2 KHS1 MOS MST1 MST2 HPK1 KHS2 HSER SgK496 WNK1 GCK WNK3 MEKK6/MAP3K6 YSK1 Finding the Targets of the Human Kinome MST4 DYRK2 PBK MAP3K4 DYRK3 GUCY2D WNK2 STLK3 MST3 MINK/ZC3 DYRK4 NRBP2 DYRK1A NRBP1 GUCY2F MEKK1/MAP3K1 OSR1 HGK/ZC1 TNIK/ZC2 DYRK1B WNK4 NRK/ZC4 Poster authors: Martin Lee Miller, Søren Brunak, Lars Juhl Jensen, Michael B. Yaffe, Rune Linding MLKL Protein kinases are enzymes that mediate cellular decision dependent binding domains or families of closely related STRAD/STLK5 MYO3A PERK/PEK SgK307 STLK6 SLK MYO3B PKR LOK Science Signaling coordinator: Nancy R. Gough HIPK1 HIPK3 GCN2 SgK424 TAO1 SCYL3 TAO2 processes by catalyzing the addition of a negatively charged domains. is poster presents the specicities of kinases as HIPK2 SCYL1 Tpl2/COT TAO3 SCYL2 NIK PAK1 CLK4 HIPK4 PRP4 HRI PAK3 PAK4 Design and production: Lars Juhl Jensen, Rune Linding, Dave Comb, Aileen Taylor, Marcus Spiegler CLIK1 PAK2 CLK1 IRE1 PAK5/PAK7 CLK2 CLIK1L MAP2K5 IRE2 PAK6 phosphate group to protein substrates, which can subse- TBCK sequence logo plots around a phylogenetic map of the CLK3 MAP2K7 MEK1/MAP2K1 RNAseL GCN2~b MEK2/MAP2K2 Copyeditor: Harry Jach TTK MSSK1 SgK071 CMGC KIS SRPK2 MYT1 MKK3/MKK6 quently be recognized by phosphorylation-dependent human protein kinases. e height of a stack of letters SEK1/MAP2K4 SRPK1 CK2α1 Wee1 Sponsored by Cell Signaling Technology, Inc. SgK196 CK1 MAK CK2α2 CDC7 Wee1B δ PRPK TTBK1 CK1 GSK3 ICK ε β TTBK2 GSK3α MOK CK1α1 binding domains in other proteins. e human genome represents the information content of a particular position This poster accompanies the Science Signaling paper “Linear Motif Atlas for Phosphorylation-Dependent CDKL3 CK1α2 CDKL2 PINK1 SgK493 1,2* 2,3* 3 4 5 SgK269 VRK3 CK1γ2 CDKL1 SgK396 Signaling” by Martin Lee Miller, Lars Juhl Jensen, Francesca Diella, Claus Jørgensen, Michele Tinti, CDKL5 ERK7 SgK223 CDKL4 ERK4 Slob CK1γ1 encodes 518 protein kinases, which have been organized into relative to a phosphorylation site, and the height of the ERK3 SgK110 PIK3R4 CK1γ3 6 4 7 7 1 4 NLK SgK069 Bub1 Lei Li, Marilyn Hsiung, Sirlester A. Parker, Jennifer Bordeaux, Thomas Sicheritz-Ponten, Marina Olhovsky, SBK ERK5 BubR1 IKKα 4 8 9 1 2,10 6 5 ERK1/p44MAPK Haspin CK1 IKKβ VRK1 a tree that represents evolutionary relationships. e individual letters is proportional to the frequency of the Adrian Pasculescu, Jes Alexander, Stefan Knapp, Nikolaj Blom, Peer Bork, Shawn Li, Gianni Cesareni, CDK7 IKK VRK2 ERK2/p42MAPK ε PLK4 TBK1/NAK p38 PITSLRE MPSK1 4 7 8† 1,2† 4,8,11† γ JNK1 p38δ JNK2 TLK2 Tony Pawson, Benjamin E. Turk, Michael B. Yaffe, Søren Brunak, Rune Linding JNK3 CDK10 GAK TLK1 PLK3 p38β AAK1 substrate specicities of kinases are in part determined by amino acid residue in question. e serine, threonine, or CDK8 CDK11 ULK3 PLK1 p38 CAMKK1 PLK2 α CDK4 CCRK BIKE CAMKK2 BARK1/GRK2 CDK6 ULK1 BARK2/GRK3 RHOK/GRK1 Fused GRK5 CHED 1 Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Lyngby, Denmark. PFTAIRE2 SgK494 the amino acid sequence of the phosphorylation sites, and tyrosine phosphoacceptor residues are placed at the center of ULK2 ULK4 GRK7 GRK4 PFTAIRE1 CDK9 GRK6 Nek6 RSKL1 Nek10 2 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, PCTAIRE2 Nek7 SgK495 PASK PDK1 RSKL2 Nek8 MSK1 RSK1/p90RSK CRK7 LKB1 MSK2 PCTAIRE1 PCTAIRE3 CDK5 Nek9 RSK4 RSK2 comprehensively mapping the consensus sequence motif each logo plot. Closely related kinases typically have similar RSK3 2200 Copenhagen, Denmark. Nek2 Chk1 p70S6K Akt2/PKBβ AurA/Aur2 Akt1/PKB cdc2/CDK1 p70S6Kβ α Nek11 Akt3/PKBγ CDK3 SGK1 3 European Molecular Biology Laboratory, 69117 Heidelberg, Germany. CDK2 Nek4 AurB/Aur1 recognized by each kinase catalytic domain is thus crucial for substrate specicities; however, distantly related kinases may SGK3 Trb3 AurC/Aur3 PKN1/PRK1 SGK2 Pim1 Pim2 LATS1 PKG2 PKG1 PKN2/PRK2 Nek3 LATS2 4 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5. Trb2 Pim3 Trio PKN3 Nek5 Trad NDR1 PRKY PKCδ Trb1 NDR2 PKCθ Obscn~b PRKX understanding phosphorylation-mediated signaling not have divergent substrate specicities. e compass Atypical Protein Kinases YANK1 PKCη Nek1 SPEG~b MAST3 5 University of Rome, Tor Vergata, 00133 Rome, Italy. MASTL PKCε ADCK1 Obscn STK33 YANK2 PKCι YANK3 PKCζ ADCK5 SPEG PKAγ PKCγ 6 University of Western Ontario, London, Ontario, Canada N6A 5C1. ADCK3 PKAα networks. summarizes the major trends of the specicity atlas in the MAST2 ABC1 TTN PKAβ ADCK4 smMLCK ADCK2 TSSK4 ROCK1 PKCα 7 Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. HUNK ROCK2 ChaK1 PKCβ NetPhorest (http://netphorest.info) is a community center; for example, most kinases that prefer positively Chk2/Rad53 skMLCK SSTK SNRK MAST1 DMPK ChaK2 DRAK2 MAST4 NIM1 CRIK 8 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Alpha AlphaK3 DRAK1 TSSK3 PKD2/PKCμ EEF2K TSSK1 MAPKAPK2 AlphaK2 SgK085 TSSK2 CASK DMPK2 AGC resource that uses phylogenetic trees to organize data from charged residues are located in the lower le-hand part of 9 Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. AlphaK1 caMLCK PKD1 DCAMKL3 DAPK2 MAPKAPK5 DCAMKL1 DAPK3 MELK PKD3/PKCν DAPK1 DCAMKL2 MRCKβ Brd2 10 Max-Delbrück-Centre for Molecular Medicine, 13092 Berlin, Germany. VACAMKL MRCKα both in vivo and in vitro experiments to derive sequence the phylogenetic map. Brd3 MNK1 PhKγ1 MNK2 Brd Brd4 PhKγ2 PSKH1 11 Cellular & Molecular Logic Team, The Institute of Cancer Research, London SW3 6JB, UK. BrdT CaMKIIγ MAPKAPK3 PSKH2 CaMKIIβ PDHK2 BRSK2 CaMKIIα specicities for individual kinase or phosphorylation- AMPKα2 BRSK1 CaMKIIδ PDHK3 RSK4~b * These authors contributed equally to this work. AMPKα1 PDHK PDHK1 SNARK RSK1~b CaMKIV ARK5 PDHK4 MSK2~bMSK1~b BCKDK CAMK † To whom correspondence should be addressed. E-mail: [email protected] (S.B.), [email protected] (M.B.Y.), and QSK RSK3~b ATM RSK2~b ATR CaMKIβ [email protected] (R.L.) PIKK mTOR/FRAP SIK QIK DNAPK CaMKIγ SMG1 TRRAP MARK4 CaMKIα RIOK3 CaMK MARK3 Iδ RIO RIOK1 MARK1 RIOK2 MARK2

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