Panther Pathway: P00004 The presenilin gamma-secretase complex (consisting of presenilin, nicastrin, Aph-1 and Pen-2) has been demonstrated to cleave several single-transmembrane proteins within the membrane domain, including the amyloid precursor protein, Notch, ErbB4, E-cadherin, Nectin-1alpha, and CD44. This cleavage only occurs sequentially after an inital cleavage on the extracellular side of the transmembrane domain by an alternate enzyme. Cleavage of APP by gamma-secretase after beta-secretase cleavage yields Abeta, the backbone of senile plaques in Alzheimer's disease, and an intracellular fragment capable of nuclear translocation and subsequent effects on gene transcription. Similarly, presenilin-mediated cleavage of Notch and ErbB4 yield intracellular fragments capable of signal transduction. Medline=12142279 Medline=12834808 Medline=14598312 PMID: 12142279 PMID: 12834808 PMID: 14598312 4.0 s38 PROTEIN p14 s83 PROTEIN p38 s85 PROTEIN p38 s85 PROTEIN p39 s102 PROTEIN p49 s102 PROTEIN p48 s151 PROTEIN p12 s151 PROTEIN p11 s151 PROTEIN p13 s151 PROTEIN p78 s151 PROTEIN p79 s171 PROTEIN p15 s171 PROTEIN p39 s173 PROTEIN p17 s173 PROTEIN p39 s174 PROTEIN p20 s174 PROTEIN p39 s176 PROTEIN p20 s176 PROTEIN p39 s177 PROTEIN p20 s177 PROTEIN p39 s177 PROTEIN p66 s14 PROTEIN p2 s14 PROTEIN p3 s21 PROTEIN p2 s21 PROTEIN p7 s94 PROTEIN p40 s94 PROTEIN p41 s94 PROTEIN p42 s94 PROTEIN p43 s94 PROTEIN p44 s120 PROTEIN p49 s120 PROTEIN p48 s120 PROTEIN p43 s120 PROTEIN p44 s120 PROTEIN p41 s120 PROTEIN p42 s120 PROTEIN p40 s253 PROTEIN p52 s258 PROTEIN p88 s258 PROTEIN p87 s261 PROTEIN p12 s261 PROTEIN p11 s261 PROTEIN p13 s261 PROTEIN p78 s261 PROTEIN p79 s83 PROTEIN p39 Long Name: Notch intracellular domain Synonym: Synonym not specified Accession: P00122 s38 PROTEIN p5 s253 PROTEIN p41 SQUARE_CLOSEUP_NORTH OVAL OVAL SQUARE_CLOSEUP_NORTHWEST inactive inactive active inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive active inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active Wilson Christina SRI International Neuron Golgi Endoplasmic reticulum Nucleus Long Name: Notch Synonym: Synonym not specified Accession: P00176 transmembrane PROTEIN p1 Long Name: Furin Synonym: Synonym not specified Accession: P00157 inside PROTEIN p4 Long Name: Notch intracellular domain Synonym: Synonym not specified Accession: P00122 inside PROTEIN p5 Long Name: TNF-alpha converting enzyme Synonym: ADAM17,alpha-secretase Accession: P00147 inside PROTEIN p8 Long Name: Notch intracellular domain Synonym: Synonym not specified Accession: P00122 inside PROTEIN p5 Long Name: CBF1 Su1 and Lag1 Synonym: Synonym not specified Accession: P00158 inside PROTEIN p14 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05013 Heterodimer Member Info: NICD#PROTEIN#Notch intracellular domain#P00122##;CSL#PROTEIN#CBF1 Su1 and Lag1#P00158## inside COMPLEX Complex_br_(CSL/NICD) Long Name: Gene transcription Synonym: Synonym not specified Accession: U02081 inside PHENOTYPE Gene_br_transcription Long Name: V-erb-a erythroblastic leukemia viral oncogene homolog 4 Synonym: HER4 Accession: P00128 transmembrane PROTEIN p22 Long Name: Cell surface glycoprotein 44 Synonym: Synonym not specified Accession: P00145 transmembrane PROTEIN p27 Long Name: Membrane metalloprotease Synonym: Synonym not specified Accession: P00141 inside PROTEIN p31 Long Name: Low-density lipoprotein receptor-related protein Synonym: Synonym not specified Accession: P00150 transmembrane PROTEIN p34 Long Name: LRP N-terminal fragment Synonym: Synonym not specified Accession: P00169 inside PROTEIN p35 Long Name: Erb-B4 N-terminal fragment Synonym: Synonym not specified Accession: P00148 inside PROTEIN p23 Long Name: Erb-B4 C-terminal fragment Synonym: Synonym not specified Accession: P00163 transmembrane PROTEIN p24 Long Name: LRP C-terminal fragment Synonym: Synonym not specified Accession: P00112 transmembrane PROTEIN p36 Long Name: LRP transmembrane fragment Synonym: Synonym not specified Accession: P00152 transmembrane PROTEIN p37 Long Name: LRP intracellular fragment Synonym: Synonym not specified Accession: P00173 inside PROTEIN p38 Long Name: Amyloid precursor binding protein, family B Synonym: Rir Accession: P00126 inside PROTEIN p39 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05025 Heterodimer Member Info: Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00126#Rir#;LRP intracellular fragment#PROTEIN#LRP intracellular fragment#P00173## inside COMPLEX Complex_br_(LRP_br_intracellular_br_fragment/Fe65) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05021 Heterodimer Member Info: Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00126#Rir#;LRP intracellular fragment#PROTEIN#LRP intracellular fragment#P00173## inside COMPLEX Complex_br_(LRP_br_intracellular_br_fragment/Fe65) Long Name: E-cadherin N-terminal fragment Synonym: Synonym not specified Accession: P00165 inside PROTEIN p46 Long Name: E-cadherin C-terminal fragment Synonym: Synonym not specified Accession: P00117 transmembrane PROTEIN p47 Long Name: gamma-catenin Synonym: Synonym not specified Accession: P00153 inside PROTEIN p42 Long Name: alpha-catenin Synonym: Synonym not specified Accession: P00133 inside PROTEIN p43 Long Name: actin Synonym: Synonym not specified Accession: P00114 inside PROTEIN p44 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05012 Heterodimer Member Info: Afadin#PROTEIN#Afadin#P00146##;Nectin 1alpha#PROTEIN#Nectin 1alpha#P00160## transmembrane COMPLEX Complex_br_(Nectin 1_alpha_/Afadin) Long Name: a153_degraded Synonym: Synonym not specified Accession: U02079 inside DEGRADED a153_degraded Long Name: Proteasome Synonym: Synonym not specified Accession: P00161 inside PROTEIN p50 Long Name: Presenilin Synonym: Synonym not specified Accession: P00129 inside PROTEIN p10 Long Name: Glycogen synthase kinase 3beta Synonym: Synonym not specified Accession: P00175 inside PROTEIN p51 Long Name: T-cell factor/lymphoid enhancer factor Synonym: T-cell-specific transcription factor 1 Accession: P00143 inside PROTEIN p52 Long Name: Ire-1 Synonym: Synonym not specified Accession: P00144 transmembrane PROTEIN p54 Long Name: Ire-1 Synonym: Synonym not specified Accession: P00144 transmembrane PROTEIN p54 Long Name: Unfolded protein Synonym: Synonym not specified Accession: P00116 inside PROTEIN p55 Long Name: Ire-1 N-terminal fragment Synonym: Synonym not specified Accession: P00110 transmembrane PROTEIN p56 Long Name: Ire-1 C-terminal fragment Synonym: Synonym not specified Accession: P00125 transmembrane PROTEIN p57 Long Name: Tripartite motif-containing protein 3 Synonym: BERP,RNF22,RNF97 Accession: P00131 inside PROTEIN p58 Long Name: Capacitative calcium channels Synonym: Synonym not specified Accession: P00124 transmembrane PROTEIN p59 Long Name: Long Name: Ca2+ Synonym: Synonym not specified Accession: U05026 inside ION Ca_super_2+_endsuper Long Name: Long Name: Ca2+ Synonym: Synonym not specified Accession: U05026 inside ION Ca_super_2+_endsuper Long Name: Presenilin Synonym: Synonym not specified Accession: P00129 inside PROTEIN p10 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05016 Heterodimer Member Info: Nicastrin#PROTEIN#Nicastrin#P00115##;Presenilin N-terminal fragment#PROTEIN#Presenilin N-terminal fragment#P00140##;Pen-2#PROTEIN#Presenilin enhancer 2#P00149##;Presenilin C-terminal fragment#PROTEIN#Presenilin C-terminal fragment#P00155##;Aph-1#PROTEIN#Anterior pharynx defective-1#P00170## transmembrane COMPLEX Complex_br_(Nicastrin/Aph-1/_br_Pen-2/Presenilin_br_N-terminal_br_fragment/_br_Presenilin_br_C-terminal_br_fragment) Long Name: Presenilin enhancer 2 Synonym: Synonym not specified Accession: P00149 transmembrane PROTEIN p13 Long Name: Nicastrin Synonym: Synonym not specified Accession: P00115 transmembrane PROTEIN p12 Long Name: Anterior pharynx defective-1 Synonym: Synonym not specified Accession: P00170 transmembrane PROTEIN p11 Long Name: Presenilin N-terminal fragment Synonym: Synonym not specified Accession: P00140 inside PROTEIN p78 Long Name: Presenilin C-terminal fragment Synonym: Synonym not specified Accession: P00155 transmembrane PROTEIN p79 Long Name: Presenilin Synonym: Synonym not specified Accession: P00129 transmembrane PROTEIN p10 Long Name: Beta-amyloid cleavage enzyme Synonym: Asp2,memapsin-2 Accession: P00172 transmembrane PROTEIN p60 Long Name: amyloid precursor protein Synonym: Synonym not specified Accession: P00127 transmembrane PROTEIN p15 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05014 Heterodimer Member Info: Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00126#Rir#;APP#PROTEIN#amyloid precursor protein#P00127## transmembrane COMPLEX Complex_br_(APP/Fe65) Long Name: Beta-amyloid cleavage enzyme Synonym: Asp2,memapsin-2 Accession: P00172 inside PROTEIN p60 Long Name: Amyloid precursor protein beta-ectodomain Synonym: Synonym not specified Accession: P00151 inside PROTEIN p16 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05018 Heterodimer Member Info: C99#PROTEIN#Carboxy-terminal 99 amino acids of amyloid precursor protein#P00111##;Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00126#Rir# transmembrane COMPLEX Complex_br_(C99/Fe65) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05015 Heterodimer Member Info: Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00126#Rir#;AICD#PROTEIN#AICD#P00166## inside COMPLEX Complex_br_(AICD/Fe65) Long Name: Beta-amyloid Synonym: Synonym not specified Accession: P00136 inside PROTEIN p19 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05019 Heterodimer Member Info: Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00126#Rir#;AICD#PROTEIN#AICD#P00166## inside COMPLEX Complex_br_(AICD/Fe65) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05009 Heterodimer Member Info: Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00126#Rir#;Tip60#PROTEIN#HIV-1 Tat interactive protein, 60kDa#P00137#HTATIP1|PLIP|TIP|TIP60|cPLA2#;AICD#PROTEIN#AICD#P00166## inside COMPLEX Complex_br_(AICD/Fe65/_br_Tip60) Long Name: HIV-1 Tat interactive protein, 60kDa Synonym: HTATIP1,PLIP,TIP,TIP60,cPLA2 Accession: P00137 inside PROTEIN p66 Long Name: CD44 N-terminal fragment Synonym: Synonym not specified Accession: P00174 inside PROTEIN p29 Long Name: CD44 C-terminal fragment Synonym: Synonym not specified Accession: P00123 transmembrane PROTEIN p30 Long Name: Notch N-terminal fragment Synonym: Synonym not specified Accession: P00171 inside PROTEIN p2 Long Name: Notch transmembrane fragment Synonym: Synonym not specified Accession: P00135 transmembrane PROTEIN p6 Long Name: Notch C-terminal fragment Synonym: Synonym not specified Accession: P00120 transmembrane PROTEIN p3 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05020 Heterodimer Member Info: Notch C-terminal fragment#PROTEIN#Notch C-terminal fragment#P00120##;Notch N-terminal fragment#PROTEIN#Notch N-terminal fragment#P00171## transmembrane COMPLEX Complex_br_(Notch_br_N-terminal_br_fragment/Notch_br_C-terminal_br_fragment) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05023 Heterodimer Member Info: Notch N-terminal fragment#PROTEIN#Notch N-terminal fragment#P00171##;Notch extracellular fragment#PROTEIN#Notch extracellular fragment#P00179## inside COMPLEX Complex_br_(Notch_br_N-terminal_br_fragment/Notch_br_extracellular_br_fragment) Long Name: CD44 intracellular fragment Synonym: Synonym not specified Accession: P00121 inside PROTEIN p33 Long Name: CD44 intracellular fragment Synonym: Synonym not specified Accession: P00121 inside PROTEIN p33 Long Name: Erb-B4 transmembrane fragment Synonym: Synonym not specified Accession: P00113 transmembrane PROTEIN p26 Long Name: Erb-B4 intracellular fragment Synonym: Synonym not specified Accession: P00138 inside PROTEIN p25 Long Name: Erb-B4 intracellular fragment Synonym: Synonym not specified Accession: P00138 inside PROTEIN p25 Long Name: Notch fragment Synonym: Synonym not specified Accession: P00154 transmembrane PROTEIN p9 Long Name: Afadin Synonym: Synonym not specified Accession: P00146 inside PROTEIN p48 Long Name: E-cadherin Synonym: Synonym not specified Accession: P00118 inside PROTEIN p40 Long Name: Matrix metalloprotease Synonym: Synonym not specified Accession: P00130 inside PROTEIN p80 Long Name: E-cadherin intracellular fragment Synonym: Synonym not specified Accession: P00168 inside PROTEIN p81 Long Name: Nectin 1alpha N-terminal fragment Synonym: Synonym not specified Accession: P00164 inside PROTEIN p83 Long Name: Nectin 1alpha C-terminal fragment Synonym: Synonym not specified Accession: P00177 transmembrane PROTEIN p84 Long Name: Membrane metalloprotease Synonym: Synonym not specified Accession: P00141 inside PROTEIN p31 Long Name: TNF-alpha converting enzyme Synonym: ADAM17,alpha-secretase Accession: P00147 inside PROTEIN p8 Long Name: Nectin 1alpha intracellular fragment Synonym: Synonym not specified Accession: P00159 inside PROTEIN p85 Long Name: Nectin 1alpha transmembrane fragment Synonym: Synonym not specified Accession: P00134 transmembrane PROTEIN p86 Long Name: Nectin 1alpha intracellular fragment Synonym: Synonym not specified Accession: P00159 inside PROTEIN p85 Long Name: CD44 transmembrane fragment Synonym: Synonym not specified Accession: P00167 transmembrane PROTEIN p32 Long Name: E-cadherin transmembrane fragment Synonym: Synonym not specified Accession: P00139 transmembrane PROTEIN p82 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05011 Heterodimer Member Info: actin#PROTEIN#actin#P00114##;E-cadherin#PROTEIN#E-cadherin#P00118##;alphacatenin#PROTEIN#alpha-catenin#P00133##;gammacatenin#PROTEIN#gamma-catenin#P00153##;beta-catenin#PROTEIN#beta-catenin#P00156## transmembrane COMPLEX Complex_br_(E-cadherin/_beta_-catenin/_br__gamma_catenin/_alpha_catenin/_br_actin) Long Name: beta-catenin Synonym: Synonym not specified Accession: P00156 inside PROTEIN p41 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05017 Heterodimer Member Info: actin#PROTEIN#actin#P00114##;E-cadherin#PROTEIN#E-cadherin#P00118##;alphacatenin#PROTEIN#alpha-catenin#P00133##;Afadin#PROTEIN#Afadin#P00146##;gammacatenin#PROTEIN#gamma-catenin#P00153##;beta-catenin#PROTEIN#beta-catenin#P00156##;Nectin 1alpha#PROTEIN#Nectin 1alpha#P00160## transmembrane COMPLEX Complex_br_(Nectin 1_alpha_/Afadin/_br__alpha_catenin/actin/_br__beta_-catenin/_gamma_catenin/_br_E-cadherin) Long Name: beta-catenin Synonym: Synonym not specified Accession: P00156 inside PROTEIN p41 Long Name: beta-catenin Synonym: Synonym not specified Accession: P00156 inside PROTEIN p41 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05022 Heterodimer Member Info: TCF/LEF#PROTEIN#T-cell factor/lymphoid enhancer factor#P00143#T-cell-specific transcription factor 1#;beta-catenin#PROTEIN#beta-catenin#P00156## inside COMPLEX Complex_br_(_beta_-catenin/TCF/_br_LEF) Long Name: beta-catenin Synonym: Synonym not specified Accession: P00156 inside PROTEIN p41 Long Name: Frizzled Synonym: Synonym not specified Accession: P00119 transmembrane PROTEIN p87 Long Name: Wingless-type protein Synonym: INT1L1,IRP Accession: P00142 inside PROTEIN p88 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05010 Heterodimer Member Info: Frizzled#PROTEIN#Frizzled#P00119##;Wnt#PROTEIN#Wingless-type protein#P00142#INT1L1|IRP# transmembrane COMPLEX Complex_br_(Wnt/Frizzled) Long Name: Dishevelled Synonym: Synonym not specified Accession: P00132 inside PROTEIN p89 Long Name: Ire-1 C-terminal fragment Synonym: Synonym not specified Accession: P00125 inside PROTEIN p57 Long Name: Pro-BACE-1 Synonym: Synonym not specified Accession: P00162 transmembrane PROTEIN p73 Long Name: BACE-1 pro-domain Synonym: Synonym not specified Accession: P00178 inside PROTEIN p74 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05024 Heterodimer Member Info: Nicastrin#PROTEIN#Nicastrin#P00115##;Presenilin N-terminal fragment#PROTEIN#Presenilin N-terminal fragment#P00140##;Pen-2#PROTEIN#Presenilin enhancer 2#P00149##;Presenilin C-terminal fragment#PROTEIN#Presenilin C-terminal fragment#P00155##;Aph-1#PROTEIN#Anterior pharynx defective-1#P00170## transmembrane COMPLEX Complex_br_(Nicastrin/Aph-1/_br_Pen-2/Presenilin_br_N-terminal_br_fragment/_br_Presenilin_br_C-terminal_br_fragment) TRUNCATION 0.4794800108527697,-0.014745608757711803 a1 a3 a2 a4 HETERODIMER_ASSOCIATION 0.0981895055481945,0.350068058501526 a2 a3 a19 TRUNCATION 0.7886319400019043,-0.18816099307190814 a24 a28 a23 a251 TRUNCATION -0.07163158946297576,0.6418265018965692 a19 a26 a24 a27 HETERODIMER_ASSOCIATION 0.5731728095410276,0.417678185140554 a36 a37 a46 TRUNCATION -0.008889937849106744,0.5000786720163628 a58 a59 a60 a61 TRUNCATION 0.40037660768848404,0.12387550628863542 a60 a63 a62 a251 TRUNCATION -0.08897950252273645,0.5929245620458001 a66 a68 a69 a70 TRUNCATION 0.569579535536576,8.097967410132245E-4 0.3740135769837787,0.14213365279177692 a69 a71 a72 a251 TRUNCATION 0.5925062243952866,-1.556549217065495E-4 -0.21401741505890404,0.7377212452336188 a75 a76 a77 a78 TRUNCATION 0.32994087002395567,0.1246345591629483 a77 a79 a80 a251 HETERODIMER_ASSOCIATION 0.5471431362765031,0.3642022856201734 a83 a80 a86 TRUNCATION 0.3651593114611522,0.22615034292442004 a97 a99 a100 a226 DISSOCIATION 0.09332055595747968,6.834177360488525E-4 -0.18191368436744426,0.7261493026434387 a97 a103 a104 a106 a105 STATE_TRANSITION 0.5034635908711755,-0.0019774725843824115 a103 a152 a162 STATE_TRANSITION a152 a153 a158 STATE_TRANSITION a153 a154 a155 STATE_TRANSITION a168 a169 a170 TRUNCATION 0.06100755034765855,0.3925523824915391 a169 a172 a173 a183 STATE_TRANSITION a177 a178 a250 TRANSPORT 0.6537080433755982,1.1102230246251565E-15 a180 a181 sa143 TRUNCATION 0.5530513724958186,-0.007122507122507948 a198 a196 a195 a4 TRUNCATION 0.5091130283024561,0.012968111566520335 a190 a188 a189 HETERODIMER_ASSOCIATION 0.8114574678135327,0.3263655609884646 a189 a188 a186 a185 a187 a184 HETERODIMER_ASSOCIATION 0.0033884394419043673,0.37089146832375963 a206 a207 a208 TRUNCATION 0.03772490067374523,0.5713155795437759 a211 a214 a212 a251 TRUNCATION 0.6210370629018875,-3.5923252626934854E-4 0.004057676571008972,0.49025837824618357 a208 a210 a211 a209 HETERODIMER_ASSOCIATION 0.5067335334444358,0.4973518178749923 a217 a215 a216 TRUNCATION 0.6367205551128592,0.002412426726632777 a100 a228 a227 a251 HETERODIMER_ASSOCIATION -1.0310401982193858,1.0096050501096467 a97 a110 a151 TRUNCATION 0.2681417747493917,0.3573494558592669 a151 a231 a230 a233 a234 TRUNCATION 0.18891555175700603,0.2771221634178147 a231 a235 a236 a251 DISSOCIATION 0.15499853344100245,-0.003353252673399254 0.29875823768759346,0.17759214173022286 a151 a221 a224 a222 a220 a225 a103 HETERODIMER_ASSOCIATION 1.7512632948779583E-4,0.4078087292955601 a164 a166 a242 HETERODIMER_ASSOCIATION 0.5120862619928843,0.301883019622494 a244 a243 a247 STATE_TRANSITION a249 a248 a247 TRANSPORT a173 a250 TRANSPORT a23 a36 TRANSPORT a212 a215 TRANSPORT a62 a65 TRANSPORT a72 a74 TRANSPORT a86 a88 TRANSPORT a235 a239 TRANSPORT a103 a164 TRANSPORT a184 a251 STATE_TRANSITION a162 sa142 a248 STATE_TRANSITION a179 sa143 a183 MODULATION a178 a47 MODULATION a65 a47 MODULATION a216 a47 MODULATION a46 a47 MODULATION a74 a47 MODULATION a88 a47 MODULATION a239 a47 MODULATION a242 a47