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