##gff-version 3 P12023 UniProtKB Signal peptide 1 17 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Chain 18 770 . . . ID=PRO_0000000114;Note=Amyloid-beta precursor protein P12023 UniProtKB Chain 18 687 . . . ID=PRO_0000000115;Note=Soluble APP-alpha;Ontology_term=ECO:0000255;evidence=ECO:0000255 P12023 UniProtKB Chain 18 671 . . . ID=PRO_0000000116;Note=Soluble APP-beta;Ontology_term=ECO:0000255;evidence=ECO:0000255 P12023 UniProtKB Chain 18 286 . . . ID=PRO_0000381968;Note=N-APP;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Chain 672 770 . . . ID=PRO_0000000117;Note=C99;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Chain 672 713 . . . ID=PRO_0000000118;Note=Amyloid-beta protein 42;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Chain 672 711 . . . ID=PRO_0000000119;Note=Amyloid-beta protein 40;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Chain 688 770 . . . ID=PRO_0000000120;Note=C83;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Peptide 688 713 . . . ID=PRO_0000000121;Note=P3(42);Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Peptide 688 711 . . . ID=PRO_0000000122;Note=P3(40);Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Chain 691 770 . . . ID=PRO_0000384576;Note=C80 P12023 UniProtKB Chain 712 770 . . . ID=PRO_0000000123;Note=Gamma-secretase C-terminal fragment 59 P12023 UniProtKB Chain 714 770 . . . ID=PRO_0000000124;Note=Gamma-secretase C-terminal fragment 57 P12023 UniProtKB Chain 721 770 . . . ID=PRO_0000000125;Note=Gamma-secretase C-terminal fragment 50 P12023 UniProtKB Chain 740 770 . . . ID=PRO_0000000126;Note=C31;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Topological domain 18 701 . . . Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305 P12023 UniProtKB Transmembrane 702 722 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Topological domain 723 770 . . . Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 P12023 UniProtKB Domain 28 189 . . . Note=E1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Domain 291 341 . . . Note=BPTI/Kunitz inhibitor;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P12023 UniProtKB Domain 374 565 . . . Note=E2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01218 P12023 UniProtKB Region 28 123 . . . Note=GFLD subdomain;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Region 131 189 . . . Note=CuBD subdomain;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Region 181 188 . . . Note=Zinc-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Region 193 284 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P12023 UniProtKB Region 391 423 . . . Note=Heparin-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Region 491 522 . . . Note=Heparin-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Region 523 540 . . . Note=Collagen-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Region 695 722 . . . Note=Interaction with PSEN1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Region 732 751 . . . Note=Interaction with G(o)-alpha;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Region 756 770 . . . Note=Interaction with DAB2;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11247302;Dbxref=PMID:11247302 P12023 UniProtKB Region 756 770 . . . Note=Required for the interaction with KIF5B and for anterograde transport in axons;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Motif 344 365 . . . Note=OX-2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Motif 724 734 . . . Note=Basolateral sorting signal P12023 UniProtKB Motif 757 762 . . . Note=YENPXY motif%3B contains endocytosis signal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Compositional bias 195 210 . . . Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P12023 UniProtKB Compositional bias 225 263 . . . Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P12023 UniProtKB Compositional bias 267 284 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P12023 UniProtKB Binding site 96 110 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Binding site 147 147 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Binding site 151 151 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Binding site 168 168 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Binding site 183 183 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Binding site 186 186 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Binding site 187 187 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Binding site 677 677 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Binding site 677 677 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Binding site 685 685 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Binding site 685 685 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 170 170 . . . Note=Required for Cu(2+) reduction;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Site 197 198 . . . Note=Cleavage%3B by caspases;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 219 220 . . . Note=Cleavage%3B by caspases;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 301 302 . . . Note=Reactive bond;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Site 671 672 . . . Note=Cleavage%3B by beta-secretase;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 678 679 . . . Note=Cleavage%3B by ACE;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 687 688 . . . Note=Cleavage%3B by alpha-secretase;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P08592 P12023 UniProtKB Site 690 691 . . . Note=Cleavage%3B by theta-secretase;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P08592 P12023 UniProtKB Site 704 704 . . . Note=Implicated in free radical propagation;Ontology_term=ECO:0000250;evidence=ECO:0000250 P12023 UniProtKB Site 706 706 . . . Note=Susceptible to oxidation;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 711 712 . . . Note=Cleavage%3B by gamma-secretase%3B site 1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P08592 P12023 UniProtKB Site 713 714 . . . Note=Cleavage%3B by gamma-secretase%3B site 2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 720 721 . . . Note=Cleavage%3B by gamma-secretase%3B site 3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Site 739 740 . . . Note=Cleavage%3B by a caspase;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Modified residue 198 198 . . . Note=Phosphoserine%3B by CK2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Modified residue 206 206 . . . Note=Phosphoserine%3B by CK1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Modified residue 217 217 . . . Note=Sulfotyrosine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P12023 UniProtKB Modified residue 262 262 . . . Note=Sulfotyrosine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P12023 UniProtKB Modified residue 336 336 . . . Note=Sulfotyrosine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P12023 UniProtKB Modified residue 441 441 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:21183079;Dbxref=PMID:21183079 P12023 UniProtKB Modified residue 497 497 . . . Note=Phosphotyrosine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P12023 UniProtKB Modified residue 729 729 . . . Note=Phosphothreonine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P08592 P12023 UniProtKB Modified residue 730 730 . . . Note=Phosphoserine%3B by APP-kinase I;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P08592 P12023 UniProtKB Modified residue 743 743 . . . Note=Phosphothreonine%3B by CDK5 and MAPK10 and LRRK2;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28720718;Dbxref=PMID:28720718 P12023 UniProtKB Modified residue 757 757 . . . Note=Phosphotyrosine%3B by ABL1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11279131;Dbxref=PMID:11279131 P12023 UniProtKB Glycosylation 542 542 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PDB:4YN0 P12023 UniProtKB Glycosylation 571 571 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000305;evidence=ECO:0000305 P12023 UniProtKB Disulfide bond 38 62 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Disulfide bond 73 117 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Disulfide bond 98 105 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Disulfide bond 133 187 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Disulfide bond 144 174 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Disulfide bond 158 186 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P12023 UniProtKB Disulfide bond 291 341 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P12023 UniProtKB Disulfide bond 300 324 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P12023 UniProtKB Disulfide bond 316 337 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P12023 UniProtKB Cross-link 763 763 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P08592 P12023 UniProtKB Alternative sequence 289 289 . . . ID=VSP_000012;Note=In isoform APP695. E->V;Ontology_term=ECO:0000303,ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:11235921,ECO:0000303|PubMed:1756177,ECO:0000303|PubMed:3322280;Dbxref=PMID:11235921,PMID:1756177,PMID:3322280 P12023 UniProtKB Alternative sequence 290 364 . . . ID=VSP_000013;Note=In isoform APP695. Missing;Ontology_term=ECO:0000303,ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:11235921,ECO:0000303|PubMed:1756177,ECO:0000303|PubMed:3322280;Dbxref=PMID:11235921,PMID:1756177,PMID:3322280 P12023 UniProtKB Alternative sequence 346 380 . . . ID=VSP_000014;Note=In isoform APP751. Missing;Ontology_term=ECO:0000305;evidence=ECO:0000305 P12023 UniProtKB Mutagenesis 728 728 . . . Note=No effect on MAPK8IP1 binding. Y->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11517249;Dbxref=PMID:11517249 P12023 UniProtKB Mutagenesis 732 733 . . . Note=Almost complete loss of binding to G(o) alpha subunit. No inhibition of GTPase activity. HH->GL%2CGP P12023 UniProtKB Mutagenesis 743 743 . . . Note=No effect on MAPK8IP1 binding. T->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11517249;Dbxref=PMID:11517249 P12023 UniProtKB Mutagenesis 756 756 . . . Note=Greatly impairs interaction with DAB2. G->F%2CH%2CN%2CS%2CW;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11247302;Dbxref=PMID:11247302 P12023 UniProtKB Mutagenesis 756 756 . . . Note=Impairs interaction with DAB2. G->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11247302;Dbxref=PMID:11247302 P12023 UniProtKB Mutagenesis 757 757 . . . Note=Greatly promotes interaction with DAB2. Y->F;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Mutagenesis 757 757 . . . Note=Greatly impairs interaction with DAB2. Y->G%2CH%2CV;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Mutagenesis 757 757 . . . Note=No MAPK8IP1 nor APBA1 nor APBB1 nor DAB1 binding. Y->G;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Mutagenesis 757 757 . . . Note=Impairs interaction with DAB2. Y->I%2CW;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Mutagenesis 759 759 . . . Note=No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. N->A;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Mutagenesis 759 759 . . . Note=Greatly impairs interaction with DAB2. N->G%2CL%2CM%2CP;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Mutagenesis 760 760 . . . Note=Greatly impairs interaction with DAB2. P->E%2CF%2CI%2CK%2CL%2CQ%2CR%2CV%2CW%2CY;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11247302;Dbxref=PMID:11247302 P12023 UniProtKB Mutagenesis 762 762 . . . Note=No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. Y->A;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Mutagenesis 762 762 . . . Note=Greatly impairs interaction with DAB2. Y->W;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11247302,ECO:0000269|PubMed:11517249;Dbxref=PMID:11247302,PMID:11517249 P12023 UniProtKB Sequence conflict 211 211 . . . Note=G->V;Ontology_term=ECO:0000305;evidence=ECO:0000305 P12023 UniProtKB Sequence conflict 375 375 . . . Note=V->A;Ontology_term=ECO:0000305;evidence=ECO:0000305 P12023 UniProtKB Turn 47 49 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 50 53 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 56 58 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Helix 70 76 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 82 87 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 115 121 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 127 129 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 134 139 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Helix 147 160 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 164 175 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Beta strand 178 187 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7MRN P12023 UniProtKB Helix 382 419 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4YN0 P12023 UniProtKB Turn 420 422 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4YN0 P12023 UniProtKB Helix 425 481 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4YN0 P12023 UniProtKB Helix 487 518 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4YN0 P12023 UniProtKB Helix 520 550 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4YN0 P12023 UniProtKB Helix 552 581 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4YN0 P12023 UniProtKB Helix 744 753 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2ROZ