##gff-version 3 P08592 UniProtKB Signal peptide 1 17 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Chain 18 770 . . . ID=PRO_0000000159;Note=Amyloid-beta precursor protein P08592 UniProtKB Chain 18 687 . . . ID=PRO_0000000160;Note=Soluble APP-alpha;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Chain 18 671 . . . ID=PRO_0000000161;Note=Soluble APP-beta;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08592 UniProtKB Chain 18 286 . . . ID=PRO_0000381971;Note=N-APP;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Chain 672 770 . . . ID=PRO_0000000162;Note=C99;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08592 UniProtKB Chain 672 713 . . . ID=PRO_0000000163;Note=Amyloid-beta protein 42;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Chain 672 711 . . . ID=PRO_0000000164;Note=Amyloid-beta protein 40;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Chain 688 770 . . . ID=PRO_0000000165;Note=C83;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Peptide 688 713 . . . ID=PRO_0000000166;Note=P3(42);Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Peptide 688 711 . . . ID=PRO_0000000167;Note=P3(40);Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Chain 691 770 . . . ID=PRO_0000384579;Note=C80 P08592 UniProtKB Chain 712 770 . . . ID=PRO_0000000168;Note=Gamma-secretase C-terminal fragment 59 P08592 UniProtKB Chain 714 770 . . . ID=PRO_0000000169;Note=Gamma-secretase C-terminal fragment 57 P08592 UniProtKB Chain 721 770 . . . ID=PRO_0000000170;Note=Gamma-secretase C-terminal fragment 50 P08592 UniProtKB Chain 740 770 . . . ID=PRO_0000000171;Note=C31;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Topological domain 18 701 . . . Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305 P08592 UniProtKB Transmembrane 702 722 . . . Note=Helical;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Topological domain 723 770 . . . Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 P08592 UniProtKB Domain 28 189 . . . Note=E1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Domain 291 341 . . . Note=BPTI/Kunitz inhibitor;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P08592 UniProtKB Domain 374 565 . . . Note=E2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01218 P08592 UniProtKB Region 28 123 . . . Note=GFLD subdomain;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Region 131 189 . . . Note=CuBD subdomain;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Region 135 155 . . . Note=Copper-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Region 181 188 . . . Note=Zinc-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Region 196 283 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P08592 UniProtKB Region 391 423 . . . Note=Heparin-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Region 491 522 . . . Note=Heparin-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Region 523 540 . . . Note=Collagen-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Region 695 722 . . . Note=Interaction with PSEN1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Region 732 751 . . . Note=Interaction with G(o)-alpha P08592 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 P08592 UniProtKB Motif 344 365 . . . Note=OX-2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Motif 724 734 . . . Note=Basolateral sorting signal;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Motif 757 762 . . . Note=YENPXY motif%3B contains endocytosis signal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Compositional bias 196 210 . . . Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P08592 UniProtKB Compositional bias 225 263 . . . Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P08592 UniProtKB Compositional bias 267 283 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P08592 UniProtKB Binding site 96 110 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Binding site 147 147 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Binding site 151 151 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Binding site 168 168 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Binding site 183 183 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Binding site 186 186 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Binding site 187 187 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Binding site 677 677 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Binding site 677 677 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Binding site 685 685 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Binding site 685 685 . . . Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 170 170 . . . Note=Required for Cu(2+) reduction;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Site 197 198 . . . Note=Cleavage%3B by caspases;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 219 220 . . . Note=Cleavage%3B by caspases;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 301 302 . . . Note=Reactive bond;Ontology_term=ECO:0000250;evidence=ECO:0000250 P08592 UniProtKB Site 671 672 . . . Note=Cleavage%3B by beta-secretase;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 678 679 . . . Note=Cleavage%3B by ACE;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 687 688 . . . Note=Cleavage%3B by alpha-secretase;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:26479776;Dbxref=PMID:26479776 P08592 UniProtKB Site 690 691 . . . Note=Cleavage%3B by theta-secretase;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:26479776;Dbxref=PMID:26479776 P08592 UniProtKB Site 706 706 . . . Note=Susceptible to oxidation;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 711 712 . . . Note=Cleavage%3B by gamma-secretase%3B site 1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:26479776;Dbxref=PMID:26479776 P08592 UniProtKB Site 713 714 . . . Note=Cleavage%3B by gamma-secretase%3B site 2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 720 721 . . . Note=Cleavage%3B by gamma-secretase%3B site 3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Site 739 740 . . . Note=Cleavage%3B by a caspase;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Modified residue 198 198 . . . Note=Phosphoserine%3B by CK2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Modified residue 206 206 . . . Note=Phosphoserine%3B by CK1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Modified residue 217 217 . . . Note=Sulfotyrosine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08592 UniProtKB Modified residue 262 262 . . . Note=Sulfotyrosine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08592 UniProtKB Modified residue 336 336 . . . Note=Sulfotyrosine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08592 UniProtKB Modified residue 441 441 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:22673903;Dbxref=PMID:22673903 P08592 UniProtKB Modified residue 497 497 . . . Note=Phosphotyrosine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P05067 P08592 UniProtKB Modified residue 729 729 . . . Note=Phosphothreonine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:9085254;Dbxref=PMID:9085254 P08592 UniProtKB Modified residue 730 730 . . . Note=Phosphoserine%3B by APP-kinase I;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10329382,ECO:0000269|PubMed:9085254;Dbxref=PMID:10329382,PMID:9085254 P08592 UniProtKB Modified residue 743 743 . . . Note=Phosphothreonine%3B by CDK5 and MAPK10;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10936190,ECO:0000269|PubMed:9085254;Dbxref=PMID:10936190,PMID:9085254 P08592 UniProtKB Modified residue 757 757 . . . Note=Phosphotyrosine%3B by ABL1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P12023 P08592 UniProtKB Glycosylation 542 542 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08592 UniProtKB Glycosylation 571 571 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08592 UniProtKB Glycosylation 656 656 . . . Note=O-linked (Xyl...) (chondroitin sulfate) serine%3B in L-APP isoforms P08592 UniProtKB Disulfide bond 38 62 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Disulfide bond 73 117 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Disulfide bond 98 105 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Disulfide bond 133 187 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Disulfide bond 144 174 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Disulfide bond 158 186 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01217 P08592 UniProtKB Disulfide bond 291 341 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P08592 UniProtKB Disulfide bond 300 324 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P08592 UniProtKB Disulfide bond 316 337 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00031 P08592 UniProtKB Cross-link 763 763 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22847417;Dbxref=PMID:22847417 P08592 UniProtKB Alternative sequence 289 289 . . . ID=VSP_000015;Note=In isoform APP695. E->V;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:2900758;Dbxref=PMID:2900758 P08592 UniProtKB Alternative sequence 290 364 . . . ID=VSP_000016;Note=In isoform APP695. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:2900758;Dbxref=PMID:2900758 P08592 UniProtKB Mutagenesis 656 656 . . . Note=No chondroitin sulfate linkage to isoform L-APP733. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:7737970;Dbxref=PMID:7737970 P08592 UniProtKB Mutagenesis 704 704 . . . Note=Little oxidized neuronal proteins. Scarce amyloid-beta protein 42 aggregation. No neurotoxicity. G->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11959460;Dbxref=PMID:11959460 P08592 UniProtKB Mutagenesis 732 733 . . . Note=Almost complete loss of binding to GNAO1. No inhibition of GTPase activity. HH->GL%2CGP;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10024358;Dbxref=PMID:10024358 P08592 UniProtKB Mutagenesis 743 743 . . . Note=No effect on neurite growth and maturation. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10341243;Dbxref=PMID:10341243 P08592 UniProtKB Mutagenesis 743 743 . . . Note=Inhibits neurite growth and maturation. T->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10341243;Dbxref=PMID:10341243 P08592 UniProtKB Mutagenesis 757 757 . . . Note=No DBB1 binding. Y->G;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:9930726;Dbxref=PMID:9930726 P08592 UniProtKB Mutagenesis 759 759 . . . Note=Some DBB1 binding. N->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:9930726;Dbxref=PMID:9930726 P08592 UniProtKB Mutagenesis 762 762 . . . Note=Some DBB1 binding. Y->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:9930726;Dbxref=PMID:9930726 P08592 UniProtKB Mutagenesis 763 763 . . . Note=Loss of ubiquitination. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22847417;Dbxref=PMID:22847417 P08592 UniProtKB Turn 674 676 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2LI9 P08592 UniProtKB Turn 679 686 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1NMJ P08592 UniProtKB Helix 687 695 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1NMJ