The amyloid precursor protein can be cleaved by multiple enzymes. Sequential cleavage by alpha-secretase (TACE, ADAM10 or MDC9) followed by gamma-secretase (presenilin complex) results in the formation of benign p3. By contrast, cleavage by beta-secretase (BACE) followed by gamma-secretase cleavage produces amyloid-beta, a fragment which assembles into senile plaques in Alzheimer's disease patients' brains. Medline=10806097 Medline=11484003 Medline=11520976 Medline=12142279 Medline=14598312 4.0 s156 PROTEIN p17 s156 PROTEIN p39 s161 PROTEIN p20 s161 PROTEIN p39 s180 PROTEIN p20 s180 PROTEIN p39 s180 PROTEIN p66 s217 PROTEIN p20 s217 PROTEIN p39 s220 PROTEIN p75 s220 PROTEIN p76 s253 PROTEIN p12 s253 PROTEIN p11 s253 PROTEIN p13 s253 PROTEIN p78 s253 PROTEIN p79 s191 PROTEIN p70 s191 PROTEIN p19 s254 PROTEIN p12 s254 PROTEIN p11 s254 PROTEIN p13 s254 PROTEIN p78 s254 PROTEIN p79 s154 PROTEIN p15 s154 PROTEIN p39 s165 PROTEIN p60 s165 PROTEIN p15 s213 PROTEIN p15 s213 PROTEIN p75 s213 PROTEIN p76 s222 PROTEIN p60 s222 PROTEIN p15 s260 PROTEIN p12 s260 PROTEIN p11 s260 PROTEIN p13 s260 PROTEIN p78 s260 PROTEIN p79 SQUARE_CLOSEUP_NORTH OVAL OVAL OVAL OVAL OVAL inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active active active active inactive inactive active inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive active 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 inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active Neuron Golgi Lysosome Vesicle Nucleus Long Name: Furin Synonym: Synonym not specified Accession: P00105 inside PROTEIN p4 Long Name: TNF-alpha converting enzyme Synonym: ADAM17,alpha-secretase Accession: P00092 inside PROTEIN p8 Long Name: Gene transcription Synonym: Synonym not specified Accession: U02059 inside PHENOTYPE Gene_br_transcription Long Name: Amino terminal fragment of amyloid precursor protein Synonym: Synonym not specified Accession: P00104 inside PROTEIN p16 Long Name: Amyloid precursor binding protein, family B Synonym: Rir Accession: P00087 inside PROTEIN p39 Long Name: Long Name: Ca2+ Synonym: Synonym not specified Accession: U05008 inside ION Ca_super_2+_endsuper Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05000 Heterodimer Member Info: Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00087#Rir#;C99#PROTEIN#Carboxy-terminal 99 amino acids of amyloid precursor protein#P00106## transmembrane COMPLEX Complex_br_(C99/Fe65) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05007 Heterodimer Member Info: AICD#PROTEIN#Amyloid precursor protein intracellular domain#P00080##;Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00087#Rir# inside COMPLEX Complex_br_(AICD/Fe65) Long Name: Amyloid precursor binding protein, family A Synonym: D9S411E,MINT1 Accession: P00084 inside PROTEIN p60 Long Name: Amyloid precursor protein alpha ectodomain Synonym: Synonym not specified Accession: P00097 inside PROTEIN p61 Long Name: Carboxy-terminal 83 amino acids of amyloid precursor protein Synonym: Synonym not specified Accession: P00100 innerSurface PROTEIN p62 Long Name: meltrin gamma Synonym: ADAM9 Accession: P00090 inside PROTEIN p63 Long Name: A disintegrase and metalloprotease 10 Synonym: Synonym not specified Accession: P00108 inside PROTEIN p64 Long Name: p3 Synonym: Synonym not specified Accession: P00086 inside PROTEIN p65 Long Name: Amyloid precursor protein intracellular domain Synonym: Synonym not specified Accession: P00080 inside PROTEIN p20 Long Name: HIV-1 Tat interactive protein, 60kDa Synonym: HTATIP1,PLIP,TIP,TIP60,cPLA2 Accession: P00093 inside PROTEIN p66 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U04999 Heterodimer Member Info: AICD#PROTEIN#Amyloid precursor protein intracellular domain#P00080##;Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00087#Rir#;Tip60#PROTEIN#HIV-1 Tat interactive protein, 60kDa#P00093#HTATIP1|PLIP|TIP|TIP60|cPLA2# inside COMPLEX Complex_br_(AICD/Fe65/_br_Tip60) Long Name: Cholesterol Synonym: Synonym not specified Accession: S01595 inside SIMPLE_MOLECULE Cholesterol Long Name: Protein kinase C Synonym: Synonym not specified Accession: P00109 inside PROTEIN p67 Long Name: Muscarinic acetylcholine receptors Synonym: Synonym not specified Accession: P00083 transmembrane PROTEIN p69 Long Name: alpha7 nicotinic acetylcholine receptor Synonym: Synonym not specified Accession: P00079 transmembrane PROTEIN p70 Long Name: Long Name: Ca2+ Synonym: Synonym not specified Accession: U05008 inside ION Ca_super_2+_endsuper Long Name: L-type calcium channels Synonym: Synonym not specified Accession: P00082 transmembrane PROTEIN p72 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U04998 Heterodimer Member Info: AICD#PROTEIN#Amyloid precursor protein intracellular domain#P00080##;Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00087#Rir# inside COMPLEX Complex_br_(AICD/Fe65) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05002 Heterodimer Member Info: Microtubule#PROTEIN#Microtubule#P00103##;kinesin#PROTEIN#kinesin#P00107## inside COMPLEX Complex_br_(kinesin/Microtubule) Long Name: Mitogen activated protein kinase Synonym: ERK Accession: P00099 inside PROTEIN p71 Long Name: a269_degraded Synonym: Synonym not specified Accession: U02060 inside DEGRADED a269_degraded Long Name: Presenilin Synonym: sel-12 Accession: P00098 inside PROTEIN p10 Long Name: Nicastrin Synonym: Synonym not specified Accession: P00095 transmembrane PROTEIN p12 Long Name: Anterior pharynx defective-1 Synonym: Synonym not specified Accession: P00091 transmembrane PROTEIN p11 Long Name: Presenilin enhancer 2 Synonym: Synonym not specified Accession: P00089 transmembrane PROTEIN p13 Long Name: Presenilin N-terminal fragment Synonym: Synonym not specified Accession: P00088 transmembrane PROTEIN p78 Long Name: Presenilin C-terminal fragment Synonym: Synonym not specified Accession: P00102 inside PROTEIN p79 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05004 Heterodimer Member Info: Presenilin N-terminal fragment#PROTEIN#Presenilin N-terminal fragment#P00088##;Pen-2#PROTEIN#Presenilin enhancer 2#P00089##;Aph-1#PROTEIN#Anterior pharynx defective-1#P00091##;Nicastrin#PROTEIN#Nicastrin#P00095##;Presenilin C-terminal fragment#PROTEIN#Presenilin C-terminal fragment#P00102## inside COMPLEX Complex_br_(Nicastrin/Aph-1/_br_Pen-2/Presenilin_br_N-terminal_br_fragment/_br_Presenilin_br_C-terminal_br_fragment) Long Name: Beta-amyloid Synonym: Abeta1-40,Abeta1-42 Accession: P00096 inside PROTEIN p19 Long Name: Beta-amyloid Synonym: Abeta1-40,Abeta1-42 Accession: P00096 inside PROTEIN p19 8 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05001 Heterodimer Member Info: alpha7 nicotinic acetylcholine receptor#PROTEIN#alpha7 nicotinic acetylcholine receptor#P00079##;Abeta#PROTEIN#Beta-amyloid#P00096#Abeta1-40|Abeta1-42# transmembrane COMPLEX Complex_br_(_alpha_7 nicotinic_br_acetylcholine_br_receptor/A_beta_) Long Name: Beta-amyloid Synonym: Abeta1-40,Abeta1-42 Accession: P00096 inside PROTEIN p19 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05003 Heterodimer Member Info: Presenilin N-terminal fragment#PROTEIN#Presenilin N-terminal fragment#P00088##;Pen-2#PROTEIN#Presenilin enhancer 2#P00089##;Aph-1#PROTEIN#Anterior pharynx defective-1#P00091##;Nicastrin#PROTEIN#Nicastrin#P00095##;Presenilin C-terminal fragment#PROTEIN#Presenilin C-terminal fragment#P00102## 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: Beta-site amyloid precursor protein-cleaving enzyme Synonym: Asp2,asp-2,beta-secretase,memapsin,memapsin-2 Accession: P00101 inside PROTEIN p18 Long Name: Amyloid precursor protein Synonym: Synonym not specified Accession: P00085 transmembrane PROTEIN p15 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U04997 Heterodimer Member Info: APP#PROTEIN#Amyloid precursor protein#P00085##;Fe65#PROTEIN#Amyloid precursor binding protein, family B#P00087#Rir# transmembrane COMPLEX Complex_br_(APP/Fe65) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05005 Heterodimer Member Info: X11alpha#PROTEIN#Amyloid precursor binding protein, family A#P00084#D9S411E|MINT1#;APP#PROTEIN#Amyloid precursor protein#P00085## transmembrane COMPLEX Complex_br_(X11_alpha_/APP) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U04995 Heterodimer Member Info: APP#PROTEIN#Amyloid precursor protein#P00085##;Microtubule#PROTEIN#Microtubule#P00103##;kinesin#PROTEIN#kinesin#P00107## transmembrane COMPLEX Complex_br_(APP/kinesin/_br_Microtubule) Long Name: Amyloid precursor protein Synonym: Synonym not specified Accession: P00085 transmembrane PROTEIN p15 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05006 Heterodimer Member Info: X11alpha#PROTEIN#Amyloid precursor binding protein, family A#P00084#D9S411E|MINT1#;APP#PROTEIN#Amyloid precursor protein#P00085## transmembrane COMPLEX Complex_br_(X11_alpha_/APP) Long Name: Amyloid precursor protein Synonym: Synonym not specified Accession: P00085 transmembrane PROTEIN p15 Long Name: Beta-amyloid Synonym: Abeta1-40,Abeta1-42 Accession: P00096 inside PROTEIN p19 Long Name: Amino terminal fragment of amyloid precursor protein Synonym: Synonym not specified Accession: P00104 inside PROTEIN p16 Long Name: Carboxy-terminal 99 amino acids of amyloid precursor protein Synonym: Synonym not specified Accession: P00106 transmembrane PROTEIN p17 Long Name: BACE-1 pro-domain Synonym: Synonym not specified Accession: P00094 inside PROTEIN p74 Long Name: Pro-BACE-1 Synonym: Asp-2,Aspartyl protease 2,Memapsin Accession: P00081 transmembrane PROTEIN p73 Long Name: Beta-site amyloid precursor protein-cleaving enzyme Synonym: Asp2,asp-2,beta-secretase,memapsin,memapsin-2 Accession: P00101 inside PROTEIN p18 Long Name: Amino terminal fragment of amyloid precursor protein Synonym: Synonym not specified Accession: P00104 inside PROTEIN p16 Long Name: Carboxy-terminal 99 amino acids of amyloid precursor protein Synonym: Synonym not specified Accession: P00106 transmembrane PROTEIN p17 Long Name: Beta-site amyloid precursor protein-cleaving enzyme Synonym: Asp2,asp-2,beta-secretase,memapsin,memapsin-2 Accession: P00101 transmembrane PROTEIN p18 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U04996 Heterodimer Member Info: Presenilin N-terminal fragment#PROTEIN#Presenilin N-terminal fragment#P00088##;Pen-2#PROTEIN#Presenilin enhancer 2#P00089##;Aph-1#PROTEIN#Anterior pharynx defective-1#P00091##;Nicastrin#PROTEIN#Nicastrin#P00095##;Presenilin C-terminal fragment#PROTEIN#Presenilin C-terminal fragment#P00102## transmembrane COMPLEX Complex_br_(Nicastrin/Aph-1/_br_Pen-2/Presenilin_br_N-terminal_br_fragment/_br_Presenilin_br_C-terminal_br_fragment) TRANSPORT 0.25577562378567675,-0.006599431899104502 0.6381241230403778,0.01000072221828141 a180 a181 sa98 HETERODIMER_ASSOCIATION 0.3333333333333339,0.0 0.6666666666666714,0.0 0.3333333333333335,-1.7763568394002505E-15 0.6666666666666665,0.0 0.33333333333333304,0.33333333333333304 a184 a83 a186 TRUNCATION 0.48662326196023287,0.011285034842922315 0.33333333333333126,-8.881784197001252E-16 0.6666666666666661,2.6645352591003757E-15 0.33333333333333437,0.3333333333333348 a188 a52 a195 a312 TRUNCATION 0.3333333333333357,-8.881784197001252E-16 0.6666666666666643,-8.881784197001252E-16 0.4677842040199014,-6.821098584239849E-4 0.9355684080398019,-0.0013642197168408643 0.6240198760029152,-0.0026668490153163305 0.3333333333333338,0.3333333333333357 a186 a49 a188 a51 a220 HETERODIMER_ASSOCIATION 0.4511239439444008,0.037118047869796555 0.4226997875661578,0.057463301999931105 0.3283297450026845,0.33980738443317016 a197 a184 a200 TRUNCATION 0.3333333333333339,-8.881784197001252E-16 0.6666666666666679,-8.881784197001252E-16 0.3333333333333339,6.661338147750939E-16 0.6666666666666661,1.5543122344752192E-15 0.3333333333333326,0.0 0.6666666666666639,0.0 0.33333333333333304,0.33333333333333437 a201 a202 a203 a27 a204 a205 TRUNCATION 0.3333333333333339,4.440892098500626E-16 0.6666666666666679,2.220446049250313E-15 0.3333333333333315,8.881784197001252E-16 0.6666666666666676,-8.881784197001252E-16 0.5231500456452665,0.05026551935176293 0.3333333333333328,0.33333333333333304 a203 a206 a208 a311 STATE_TRANSITION 0.3333333333333348,2.220446049250313E-15 0.6666666666666705,-4.440892098500626E-16 a52 a211 HETERODIMER_ASSOCIATION 0.6928241998896851,-0.018878781644792397 0.7125925856523629,-0.061851089308277096 0.1766960597613929,-0.004796872094608773 0.3533921195227885,-0.009593744189219322 0.35527844295806155,0.27383143898649687 a212 a196 a219 STATE_TRANSITION 0.2617893791614343,-2.535046599403401E-4 0.5235783564766918,-3.731945433687045E-4 a221 a222 a225 STATE_TRANSITION a223 a27 a222 STATE_TRANSITION 0.3333333333333339,-8.881784197001252E-16 0.6666666666666661,-1.7763568394002505E-15 a227 a228 a235 HETERODIMER_ASSOCIATION 0.49832784300926747,0.03546209305859449 0.6734637573081912,0.011393633573825834 0.38906181966408315,0.32106018917391665 a52 a229 a235 TRUNCATION 0.5696161786857683,-0.07265018520894273 0.28757430425741637,0.020865243562472102 0.5751486085148305,0.04173048712494065 0.3814656332418318,0.25666971670523964 a239 a240 a241 a4 TRUNCATION 0.24835367133777275,0.5615979364667147 a256 a247 a251 a318 a246 TRUNCATION 0.49705092655905236,0.02026643429314845 a251 a249 a253 a313 HETERODIMER_ASSOCIATION 0.3697010252777133,-0.02605663852452933 0.7394020505554302,-0.052113277049052886 0.3333333333333328,0.3333333333333339 a265 a268 a256 STATE_TRANSITION 0.5100894484717458,0.12666921022510458 a269 a270 TRUNCATION 0.6074257226042246,0.043626601412924515 0.5730710784518962,-0.03064890781512375 0.4847684264846439,-0.08435126780735835 0.3333333333333305,0.33333333333333215 a284 a289 a290 HETERODIMER_ASSOCIATION 0.3333333333333339,-1.7763568394002505E-15 0.6666666666666643,-1.7763568394002505E-15 0.6111356276856501,0.0813819669682132 0.3333333333333338,0.3333333333333348 a290 a289 a285 a287 a286 a310 TRUNCATION 0.6912410428981557,-0.23457275269911548 0.6332823510650201,-0.007513556397353405 0.18711800695888847,-0.031869992528861246 0.37423601391776984,-0.06373998505771539 0.394371514556612,0.3026955893298249 a333 a334 a332 a240 TRUNCATION 0.5090466829345868,0.07552446547254732 a334 a329 a336 a310 TRANSPORT 0.32717031237820837,0.010082698860244932 0.661088498958478,0.008530912690319692 a200 a269 TRANSPORT 0.30738800020220025,-0.12292180489326654 0.6407213335355331,-0.12292180489326743 a195 a196 TRANSPORT 0.6665643370428108,0.32283781729438865 0.8858496796345222,0.2893211588028659 a240 a51 TRANSPORT a310 a311 STATE_TRANSITION a236 sa98 a235 a52 MODULATION a219 a47