APP (amyloid-beta precursor protein) is a single-pass type I membrane glycoprotein of the APP family. At the neuronal surface the full-length protein acts as an adhesion and receptor-like molecule: copper-dependent trans-dimerization of its E1 and E2 ectodomains between neighbouring cells promotes synapse formation, and the protein supports neurite outgrowth and axonogenesis, partly by binding heparin and other extracellular matrix components. APP traffics from the ER and Golgi to the plasma membrane and is internalized into endosomes. Sequential cleavage by alpha- or beta-secretase and gamma-secretase releases a soluble ectodomain, amyloid-beta peptides and a cytoplasmic intracellular domain (AICD). Kunitz-domain isoforms (APP751/770) inhibit serine proteases. Amyloid-beta peptides bind copper and zinc and aggregate into oligomers and fibrils that activate glia and impair synaptic plasticity. The cytoplasmic tail normally carries a YENPTY motif that binds PTB-domain adaptors such as FE65/APBB1 and X11/APBA and mediates clathrin-dependent endocytosis. Horse A0A3Q2IKB0 is the Ensembl-canonical gene model of horse APP: a 768-residue KPI-containing, OX-2-lacking (APP751-like) ectodomain with a human-identical amyloid-beta region, but with an unrelated C-terminal tail after human Glu738 that lacks the YENPTY motif, which other horse APP transcripts retain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001774 microglial cell activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Microglial cell activation, transferred by Ensembl Compara from human IGI rows. Reason: This is an effect of amyloid-beta peptides (the donor rows are mostly IGI or IMP studies in APP-mutant transgenic mice or with applied peptide) rather than a physiological function of full-length APP. The horse amyloid-beta 1-42 sequence is identical to human, so the peptide property transfers, but it is pathological and peripheral; kept as non-core. Supporting Evidence: file:human/APP/APP-uniprot.txt brain and elicit inflammatory responses. PMID:22198949 TLR2 deficiency reduced AΞ²42-triggered inflammatory activation but enhanced AΞ² phagocytosis in cultured microglia and macrophages |
| GO:0002265 astrocyte activation involved in immune response | IEA GO_REF:0000107 | UNDECIDED | Summary: Astrocyte activation involved in immune response (Compara from human IGI). Reason: Amyloid-beta acts on glia, so an astrocyte role is plausible, but the only donor (human IGI, PMID:23152628) is cached abstract-only and its abstract concerns LRP1-mediated amyloid-beta clearance by brain vascular smooth muscle cells; it does not mention astrocytes. The human UniProt record names mononuclear phagocytes, not astrocytes. No quotable evidence for astrocyte activation was found, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0004866 endopeptidase inhibitor activity | IEA GO_REF:0000104 | TOO GENERAL | Summary: Endopeptidase inhibitor activity (UniRule). True for this KPI-containing model, but the informative child serine-type endopeptidase inhibitor activity is accepted in this review. Reason: GO:0004867 serine-type endopeptidase inhibitor activity is accepted here and entails this term. Supporting Evidence: file:human/APP/APP-uniprot.txt isoforms that contain the BPTI domain possess protease inhibitor file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 291-341: 51 of 51 residues aligned, 51 identical |
| GO:0004867 serine-type endopeptidase inhibitor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Serine-type endopeptidase inhibitor activity (combined IEA from InterPro Kunitz/BPTI signatures, UniRule and Compara). The Kunitz domain of A0A3Q2IKB0 is 51/51 identical to human APP. Reason: KPI-containing APP isoforms inhibit serine proteases (human IDA, PMID:10652580; protease nexin-II). The activity is isoform-dependent (absent from APP695) but this gene model contains the Kunitz exon, and Kunitz/BPTI membership is itself good evidence for the activity. Supporting Evidence: file:human/APP/APP-uniprot.txt isoforms that contain the BPTI domain possess protease inhibitor file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 291-341: 51 of 51 residues aligned, 51 identical PMID:10652580 which is a potent inhibitor of matrix metalloproteinases and serine proteinases |
| GO:0005102 signaling receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Signaling receptor binding (IBA from PAINT node PTN002749606, APP orthologs). Reason: APP and its fragments bind several cell-surface receptors (human IPI rows); PAINT curators placed this term at the vertebrate APP ortholog node PTN002749606, which contains this horse protein (PANTHER SF7). The receptor-binding regions are in the ectodomain and amyloid-beta, both conserved in this model. Supporting Evidence: file:interpro/panther/PTHR23103/PTHR23103-review.yaml Vertebrate APP orthologs (Euteleostomi speciation node PTN002749606), including human APP, |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Signaling receptor binding (Compara from human IPI). Reason: APP and its fragments bind several cell-surface receptors (human IPI rows); PAINT curators placed this term at the vertebrate APP ortholog node PTN002749606, which contains this horse protein (PANTHER SF7). The receptor-binding regions are in the ectodomain and amyloid-beta, both conserved in this model. Supporting Evidence: file:human/APP/APP-uniprot.txt [Amyloid-beta protein 42]: Interacts with FPR2. PMID:19849849 Here, we show that CD74, the invariant chain of class II major histocompatibility complex, interacts with APP PMID:19849849 it also serves as a receptor for macrophage migration inhibitory factor |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Extracellular region (combined IEA). The soluble ectodomain (sAPP) and amyloid-beta peptides are released extracellularly. Reason: Experimentally established for the human cleavage products; the alpha/beta-secretase cleavage region and amyloid-beta are conserved in this model. Supporting Evidence: file:human/APP/APP-uniprot.txt APP is released into the extracellular space and the C-terminal is file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 672-713: 42 of 42 residues aligned, 42 identical |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Nucleus (SubCell mapping of an ARBA-derived location). In human and mouse, the gamma-secretase-released AICD fragment enters the nucleus together with FE65/APBB1. Reason: Nuclear localization belongs to the AICD fragment, not to full-length APP, and depends on the C-terminal YENPTY motif that recruits FE65/APBB1. A0A3Q2IKB0 has an unrelated C-terminal tail after human Glu738 and lacks YENPTY, so this gene model cannot make the nuclear-targeted AICD. Other horse APP transcripts (F6XKR3, A0A3Q2HIF9) do retain the motif. Supporting Evidence: file:human/APP/APP-uniprot.txt translocated to the nucleus through association with APBB1 (Fe65) file:HORSE/APP/APP-bioinformatics/compare_horse_models_output.txt motifs absent: OX-2 exon (MSQSLLKT); AICD Thr site VTPEER; YENPTY file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 724-770: 42 of 47 residues aligned, 20 identical |
| GO:0005641 nuclear envelope lumen | IEA GO_REF:0000107 | UNDECIDED | Summary: Nuclear envelope lumen (Compara from human IDA, PMID:21989385). Reason: Single-study location; the perinuclear space is continuous with the ER lumen that a transiting type I membrane protein passes through, so plausible but not characteristic. The donor paper (PMID:21989385) is cached abstract-only and its abstract does not mention this compartment, and the human UniProt record gives no curated nuclear-envelope location, so no independent evidence could be quoted; left undecided rather than supported by the ortholog annotation listing. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasm (Compara from human EXP, PMID:11544248, which localized the gamma-CTF/AICD to cytoplasm and nuclei). Reason: Fragment location; full-length APP is membrane-integrated. A cytoplasmic C-terminal fragment can still be produced from this model, although its tail is aberrant. Supporting Evidence: file:human/APP/APP-uniprot.txt Located to both the cytoplasm and nuclei of neurons. |
| GO:0005768 endosome | IEA GO_REF:0000107 | ACCEPT | Summary: Endosome (Compara from human IDA). Reason: APP is internalized from the cell surface into endosomes, where amyloidogenic processing occurs; core trafficking compartment. Supporting Evidence: file:human/APP/APP-uniprot.txt surface protein that rapidly becomes internalized via clathrin-coated |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Early endosome (IBA, PTN002749606). Reason: Human APP is in early endosomes (EXP, PMID:20580937); PAINT placed this term at the APP ortholog node PTN002749606, which contains this protein. Supporting Evidence: file:interpro/panther/PTHR23103/PTHR23103-review.yaml Vertebrate APP orthologs (Euteleostomi speciation node PTN002749606), including human APP, |
| GO:0005769 early endosome | IEA GO_REF:0000120 | ACCEPT | Summary: Early endosome (combined IEA). Reason: Human APP is in early endosomes (EXP, PMID:20580937); PAINT placed this term at the APP ortholog node PTN002749606, which contains this protein. Supporting Evidence: file:human/APP/APP-uniprot.txt Early endosome {ECO:0000269|PubMed:20580937}. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000120 | ACCEPT | Summary: Endoplasmic reticulum (combined IEA). Immature APP is N-glycosylated in the ER. Reason: Biosynthetic compartment of a type I membrane glycoprotein; experimentally observed for human APP and C83. Supporting Evidence: file:human/APP/APP-uniprot.txt During maturation, the immature APP (N-glycosylated in the endoplasmic |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi apparatus (IBA, PTN002749606). Reason: APP matures in the Golgi (O-glycosylation, sulfation) and is retained in the TGN by SORL1; PAINT placed this term at the APP ortholog node PTN002749606. Supporting Evidence: file:interpro/panther/PTHR23103/PTHR23103-review.yaml Vertebrate APP orthologs (Euteleostomi speciation node PTN002749606), including human APP, |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | ACCEPT | Summary: Golgi apparatus (combined IEA). Reason: APP matures in the Golgi (O-glycosylation, sulfation) and is retained in the TGN by SORL1; PAINT placed this term at the APP ortholog node PTN002749606. Supporting Evidence: file:human/APP/APP-uniprot.txt During maturation, the immature APP (N-glycosylated in the endoplasmic |
| GO:0005798 Golgi-associated vesicle | IEA GO_REF:0000104 | ACCEPT | Summary: Golgi-associated vesicle (UniRule). APP leaves the late Golgi in secretory transport vesicles (mouse IDA, PMID:23931995). Reason: Consistent with the documented post-Golgi transport of APP. Supporting Evidence: file:human/APP/APP-uniprot.txt secretory transport vesicles leaving the late Golgi compartment and PMID:23931995 APP is conveyed in Golgi-derived vesicles |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane (IBA, PTN002749606). Reason: Single-pass type I cell-surface protein (human EXP); PAINT placed this term at the APP ortholog node PTN002749606. The signal peptide, ectodomain and transmembrane segment are conserved in this model. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. file:interpro/panther/PTHR23103/PTHR23103-review.yaml Vertebrate APP orthologs (Euteleostomi speciation node PTN002749606), including human APP, |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane (combined IEA). Reason: Single-pass type I cell-surface protein (human EXP); PAINT placed this term at the APP ortholog node PTN002749606. The signal peptide, ectodomain and transmembrane segment are conserved in this model. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Clathrin-coated pit (SubCell mapping). Human APP is internalized via clathrin-coated pits (PMID:20580937). Reason: True of the horse APP gene, but in human APP the YENPxY motif mediates clathrin-mediated endocytosis, and A0A3Q2IKB0 lacks it because of its aberrant C-terminal tail. Internalization of this particular model is therefore uncertain; kept as non-core rather than accepted. Supporting Evidence: file:human/APP/APP-uniprot.txt surface protein that rapidly becomes internalized via clathrin-coated file:human/APP/APP-uniprot.txt clathrin-mediated endocytosis. file:HORSE/APP/APP-bioinformatics/compare_horse_models_output.txt motifs absent: OX-2 exon (MSQSLLKT); AICD Thr site VTPEER; YENPTY |
| GO:0007165 signal transduction | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Signal transduction, inferred by GO_REF:0000108 from the receptor ligand activity row. Reason: Generic process derived from a fragment (amyloid-beta) ligand activity; true in a broad sense but uninformative and peripheral. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. |
| GO:0007409 axonogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: Axonogenesis (IBA from APP-family node PTN000559854, seeded by mouse App and zebrafish appb). Reason: Neuronal betaPP contributes to axonogenesis (mouse knockout neurons, PMID:9390996). PAINT placed the term at the APP-family node, so it is inherited across APP/APLP orthologs; this horse protein sits inside that clade (PANTHER SF7). Core physiological function of the full-length protein. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. PMID:9390996 cell-associated neuronal betaPP contributes to neuron viability, axonogenesis, and arborization PMID:9390996 hippocampal neurons from betaPP-deficient mice had diminished viability and retarded neurite development |
| GO:0007417 central nervous system development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Central nervous system development (IBA, PTN000559854). Reason: Broad developmental process inherited across the APP family (based in part on APP/APLP compound knockout phenotypes); the informative processes are axonogenesis and synapse organization. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. |
| GO:0007611 learning or memory | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Learning or memory (combined IEA incl. ARBA; donor human IGI rows from transgenic mouse studies). Reason: Learning and memory are organism-level behavioural readouts of APP-mutant or APP-overexpressing transgenic mice and of amyloid-beta toxicity. They show that APP and its peptides influence behaviour, not that APP performs a step of learning; this is a downstream phenotype rather than process participation. Supporting Evidence: PMID:15457210 Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in spatial learning/memory PMID:20445063 The AD transgenic mice with intact PrP(C) expression exhibit deficits in spatial learning and memory. |
| GO:0007612 learning | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Learning (Compara from human IMP, PMID:11140684, a Tg2576 mouse learning deficit study). Reason: Learning and memory are organism-level behavioural readouts of APP-mutant or APP-overexpressing transgenic mice and of amyloid-beta toxicity. They show that APP and its peptides influence behaviour, not that APP performs a step of learning; this is a downstream phenotype rather than process participation. Supporting Evidence: PMID:11140684 Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits |
| GO:0008201 heparin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Heparin binding (InterPro heparin-binding domain signatures and UniRule). Reason: The E1 GFLD and E2 domains bind heparin/heparan sulfate; E2 is 192/192 identical to human in this model and heparin-binding domain membership is good support. Supporting Evidence: file:human/APP/APP-uniprot.txt extracellular matrix such as heparin and collagen I and IV. file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 374-565: 192 of 192 residues aligned, 192 identical |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000107 | UNDECIDED | Summary: Negative regulation of cell population proliferation (Compara from a single human IDA study). Reason: The only donor is a human IDA (assigned by UniProt) citing PMID:22944668, whose cached abstract-only text is about antimicrobial activity and membrane disruption by aggregates of human islet amyloid polypeptide (IAPP, amylin). It never mentions APP or amyloid-beta and contains no proliferation assay, and killing bacteria would not be a regulatory role in the proliferation of the organism's own cells in any case. Unless the full text also assays amyloid-beta, the upstream row is on the wrong gene product or keyed to the wrong paper; this is recorded as a source defect. Nothing else supports an antiproliferative role of APP, so the transferred row is left undecided. |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: Cell surface (IBA, PTN002749606). Reason: Cell-surface location of the full-length protein (and of amyloid-beta bound to the cell surface); PAINT placed the term at the APP ortholog node PTN002749606. Supporting Evidence: file:interpro/panther/PTHR23103/PTHR23103-review.yaml Vertebrate APP orthologs (Euteleostomi speciation node PTN002749606), including human APP, |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: Cell surface (combined IEA). Reason: Cell-surface location of the full-length protein (and of amyloid-beta bound to the cell surface); PAINT placed the term at the APP ortholog node PTN002749606. Supporting Evidence: file:human/APP/APP-uniprot.txt surface protein that rapidly becomes internalized via clathrin-coated |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of gene expression (Compara from human IGI rows; amyloid-beta-induced expression changes in glia). Reason: The donor (human IGI, PMID:22198949) is cached abstract-only. Its abstract shows TLR2-dependent inflammatory activation of microglia by Abeta42 and a shift from M1 to M2 activation, but it names no gene whose expression goes up or down, so neither this positive row nor the negative-regulation row (GO:0010629) can be checked against the available text. One sentence cannot support both directions, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | UNDECIDED | Summary: Negative regulation of gene expression (Compara from human IGI rows). Reason: The donor (human IGI, PMID:22198949) is cached abstract-only. Its abstract shows TLR2-dependent inflammatory activation of microglia by Abeta42 and a shift from M1 to M2 activation, but it names no gene whose expression goes up or down, so neither this negative row nor the positive-regulation row (GO:0010628) can be checked against the available text. One sentence cannot support both directions, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | TOO GENERAL | Summary: Endomembrane system (ARBA). Reason: More specific endomembrane compartments (ER, Golgi apparatus, early endosome, Golgi-associated vesicle) are accepted in this review. Supporting Evidence: file:human/APP/APP-uniprot.txt During maturation, the immature APP (N-glycosylated in the endoplasmic |
| GO:0014005 microglia development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Microglia development (Compara from human IGI, PMID:22198949). Reason: The single human donor (IGI, PMID:22198949) measures Abeta42-triggered inflammatory activation of microglia through TLR2. Activation is already captured by the microglial cell activation row; amyloid-beta does not take part in the development of microglia. Supporting Evidence: PMID:22198949 TLR2 deficiency reduced AΞ²42-triggered inflammatory activation but enhanced AΞ² phagocytosis in cultured microglia and macrophages |
| GO:0016020 membrane | IEA GO_REF:0000120 | TOO GENERAL | Summary: Membrane (InterPro/UniRule). Reason: Uninformative parent of the accepted plasma membrane and endomembrane locations. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Enzyme binding (Compara from human IPI, e.g. ADAM19 and secretases). Reason: True: human APP binds enzymes, including the gamma-secretase catalytic subunit PSEN1 (directly, PMID:30630874) and insulin-degrading enzyme IDE (PMID:17051221), but enzyme binding is an uninformative term. The Compara donor (PMID:17112471) is cached abstract-only and reports ADAM19 alpha-secretase cleavage of APP, a processing outcome rather than a binding assay, so it is not cited. Supporting Evidence: file:human/APP/APP-uniprot.txt Interacts (via transmembrane region) with PSEN1; the interaction is direct (PubMed:30630874). file:human/APP/APP-uniprot.txt Interacts with IDE (PubMed:17051221). |
| GO:0030425 dendrite | IEA GO_REF:0000107 | ACCEPT | Summary: Dendrite (Compara from human IDA, PMID:24012003). Reason: Neuronal compartment consistent with APP's synaptic adhesion role. Supporting Evidence: PMID:23931995 dendritic APP/BACE-1-containing vesicles are largely segregated in physiologic states |
| GO:0030426 growth cone | IEA GO_REF:0000044 | ACCEPT | Summary: Growth cone (SubCell mapping). Human and rat APP are in growth cones (PMID:10341243, PMID:12843239). Reason: Consistent with APP's role in neurite growth. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. PMID:12843239 FE65 and APP localize in vitro and in vivo to the most motile regions of neurons, the growth cones |
| GO:0030546 signaling receptor activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Signaling receptor activator activity (IBA, PTN002749606, seeded by mouse App and human APP). Reason: PAINT placed this activity at the vertebrate APP ortholog node containing this protein. APP products activate receptors (e.g. amyloid-beta at FPR2, mouse IDA PMID:11316806; the sAPP ectodomain on neuronal receptors). Accepted as the general receptor-activating activity of APP and its cleavage products. Supporting Evidence: file:interpro/panther/PTHR23103/PTHR23103-review.yaml Vertebrate APP orthologs (Euteleostomi speciation node PTN002749606), including human APP, PMID:11316806 Amyloid-beta, the pathologic protein in Alzheimer's disease, induces chemotaxis and production of reactive oxygen species in phagocytic cells |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic vesicle (SubCell mapping). Reason: Most human APP is in intracellular vesicles (PMID:20580937). Supporting Evidence: file:human/APP/APP-uniprot.txt surface protein that rapidly becomes internalized via clathrin-coated |
| GO:0031901 early endosome membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Early endosome membrane (Compara from human IDA, PMID:16174740). Reason: Human APP is in early endosomes (curated UniProt location, PMID:20580937) and is a single-pass type I membrane protein, so its early-endosome pool is in the organelle membrane. The Compara donor (PMID:16174740) is cached abstract-only and says only endosomal and Golgi compartments, so it is not cited. Supporting Evidence: file:human/APP/APP-uniprot.txt Early endosome {ECO:0000269|PubMed:20580937}. file:human/APP/APP-uniprot.txt Single-pass type I membrane protein |
| GO:0032224 positive regulation of synaptic transmission, cholinergic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of synaptic transmission, cholinergic (Compara from human IDA, PMID:33239400; amyloid-beta acting on nicotinic receptors). Reason: Fragment (amyloid-beta) activity; non-core. Supporting Evidence: file:human/APP/APP-uniprot.txt Amyloid-beta protein 42 binds CHRNA7 in hippocampal neurons. PMID:33239400 We used single-channel electrophysiology to show that oAΞ²42 activates both homomeric Ξ±7- and heteromeric Ξ±7Ξ²2-nAChR subtypes |
| GO:0032722 positive regulation of chemokine production | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of chemokine production (Compara from human IGI rows in amyloid-beta/APP-transgenic models). Reason: Amyloid-beta is pro-inflammatory, but the only donor (human IGI, PMID:22406537) is cached abstract-only and its abstract reports that a RAGE blocker suppresses microglial activation and the neuroinflammatory response without naming any chemokine. The cytokine-specific evidence is presumably in the full text, which could not be read, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0032731 positive regulation of interleukin-1 beta production | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of interleukin-1 beta production (Compara from human IGI rows in amyloid-beta/APP-transgenic models). Reason: Amyloid-beta is pro-inflammatory, but the only donor (human IGI, PMID:22406537) is cached abstract-only and its abstract reports that a RAGE blocker suppresses microglial activation and the neuroinflammatory response without naming interleukin-1 beta. The human UniProt line on inflammatory responses is generic. The cytokine-specific evidence is presumably in the full text, which could not be read, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of interleukin-6 production (Compara from human IGI rows in amyloid-beta/APP-transgenic models). Reason: Amyloid-beta is pro-inflammatory, but the only donor (human IGI, PMID:22406537) is cached abstract-only and its abstract reports that a RAGE blocker suppresses microglial activation and the neuroinflammatory response without naming interleukin-6. The cytokine-specific evidence is presumably in the full text, which could not be read, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of tumor necrosis factor production (Compara from human IGI rows in amyloid-beta/APP-transgenic models). Reason: Amyloid-beta is pro-inflammatory, but the only donor (human IGI, PMID:22198949) is cached abstract-only and its abstract reports TLR2-dependent inflammatory activation of microglia without naming tumor necrosis factor. The cytokine-specific evidence is presumably in the full text, which could not be read, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Identical protein binding (Compara from human IPI). APP homodimerizes through E1 and E2, and amyloid-beta self-associates. Reason: Homodimerization is a characterized, functionally relevant property (trans-dimerization drives synaptogenesis); the E1 and E2 dimerization regions are conserved in this model. Supporting Evidence: file:human/APP/APP-uniprot.txt Homodimerizes; dimerization is PMID:25122912 copper binding to the GFLD of APP is required for APP cis- / trans -directed dimerization and APP synaptogenic function |
| GO:0043005 neuron projection | IEA GO_REF:0000117 | TOO GENERAL | Summary: Neuron projection (ARBA). Reason: More specific neuronal compartments (growth cone, dendrite, dendritic spine) are retained in this review. Supporting Evidence: file:human/APP/APP-uniprot.txt Cell projection, growth cone {ECO:0000269|PubMed:10341243}. |
| GO:0043197 dendritic spine | IEA GO_REF:0000107 | UNDECIDED | Summary: Dendritic spine (Compara from human IDA, PMID:11988176). Reason: Dendritic APP is documented (accepted dendrite row, PMID:23931995), but that evidence does not distinguish spines from shafts. The only donor for the spine-specific location is a human IDA citing PMID:11988176, whose cached abstract-only text concerns the acid-sensing ion channel ASIC and does not mention APP. The sub-dendritic location cannot be checked, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0043198 dendritic shaft | IEA GO_REF:0000107 | UNDECIDED | Summary: Dendritic shaft (Compara from human IDA, PMID:11988176). Reason: Dendritic APP is documented (accepted dendrite row, PMID:23931995), but that evidence does not distinguish shafts from spines. The only donor for the shaft-specific location is a human IDA citing PMID:11988176, whose cached abstract-only text concerns the acid-sensing ion channel ASIC and does not mention APP. The sub-dendritic location cannot be checked, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | ACCEPT | Summary: Perikaryon (SubCell mapping). Human and rat APP in perikarya (PMID:10341243). Reason: Experimentally supported neuronal location. Supporting Evidence: PMID:10341243 APP was detected mostly in the cell body and in growth cones file:human/APP/APP-uniprot.txt Perikaryon {ECO:0000269|PubMed:10341243}. |
| GO:0043235 signaling receptor complex | IEA GO_REF:0000107 | UNDECIDED | Summary: Signaling receptor complex (Compara from human IDA, PMID:23382219). Reason: The donor (human IDA, PMID:23382219) is cached in full. It is a structural study of cargo recognition by the PX-FERM sorting nexins SNX17, SNX27 and SNX31, in which APP appears only as a previously identified SNX17 cargo; nothing in it places APP in a signalling receptor complex, and no other cached source does. This is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | ACCEPT | Summary: Membrane raft (IBA, PTN002749606). Reason: Human APP partitions into lipid rafts (IDA); PAINT placed the term at the APP ortholog node PTN002749606. Supporting Evidence: file:interpro/panther/PTHR23103/PTHR23103-review.yaml Vertebrate APP orthologs (Euteleostomi speciation node PTN002749606), including human APP, |
| GO:0045121 membrane raft | IEA GO_REF:0000107 | ACCEPT | Summary: Membrane raft (Compara from human IDA). Reason: Amyloid-beta binds GPC1 in lipid rafts (curated human UniProt function), and PAINT placed this term at the APP ortholog node PTN002749606. The Compara donor (PMID:24499793) is cached abstract-only and mentions raft-associated proteins only as a hypothesis, so it is not cited. Supporting Evidence: file:human/APP/APP-uniprot.txt Also binds GPC1 in lipid rafts. |
| GO:0045202 synapse | IEA GO_REF:0000107 | ACCEPT | Summary: Synapse (Compara from human IDA, PMID:11988176). Reason: Consistent with APP's synaptic adhesion and synaptogenic functions. Supporting Evidence: file:human/APP/APP-uniprot.txt molecules on neighboring cells promotes synaptogenesis PMID:12843239 APP and FE65 interact in nerve terminals |
| GO:0045821 positive regulation of glycolysis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of glycolysis (Compara from human IGI, PMID:29061364). Reason: Single-study metabolic effect in an amyloid model; non-core. Supporting Evidence: PMID:29061364 revealed genotype-related increases in glycolysis, accompanied by increased PFKFB3 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of transcription by RNA polymerase II (Compara from human IGI and mouse rows). In other species the AICD, bound to FE65/APBB1-KAT5, promotes transcription. Reason: AICD-dependent transcriptional activation requires the FE65-binding YENPTY region of the cytoplasmic tail, which A0A3Q2IKB0 lacks (its tail diverges completely after human Glu738). The claim may hold for other horse APP transcripts, but not for this gene model. Supporting Evidence: file:human/APP/APP-uniprot.txt transcription activation through binding to APBB1-KAT5 file:HORSE/APP/APP-bioinformatics/compare_horse_models_output.txt motifs absent: OX-2 exon (MSQSLLKT); AICD Thr site VTPEER; YENPTY |
| GO:0046330 positive regulation of JNK cascade | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of JNK cascade (Compara from human IGI). Reason: The only donor (human IGI, PMID:23921129) is cached abstract-only; its abstract reports FcgammaRIIb-mediated ER stress, caspase-12 activation, inhibition of long-term potentiation and memory impairment by amyloid-beta, but does not mention JNK. No cached source states that APP or amyloid-beta activates the JNK cascade (the human record reports binding of the JNK scaffold MAPK8IP1, which is not activation), so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0046914 transition metal ion binding | IEA GO_REF:0000002 | MODIFY | Summary: Transition metal ion binding (InterPro2GO from the copper-binding domain signatures). Reason: Correct but general. The E1 copper-binding subdomain is conserved (157/162 identical over E1, no substitution at the His147/His151/Tyr168 copper ligands) and the GFLD copper site drives dimerization; copper ion binding is the specific supported child. Zinc binding by the ectodomain and amyloid-beta is also documented (rat EXP). Proposed replacements: copper ion binding zinc ion binding Supporting Evidence: file:human/APP/APP-uniprot.txt The GFLD subdomain binds Cu(2+) ions; this promotes PMID:25122912 copper ion bound with high affinity to an extended hairpin loop at the dimerization interface |
| GO:0048018 receptor ligand activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Receptor ligand activity (Compara from human IDA; amyloid-beta and sAPP acting on receptors). Reason: Describes cleavage products (amyloid-beta, sAPP) acting as ligands; the general receptor-activating activity is accepted as signaling receptor activator activity. Supporting Evidence: PMID:22198949 demonstrate a direct interaction between TLR2 and the aggregated 42-aa form of human AΞ² (AΞ²42) |
| GO:0048143 astrocyte activation | IEA GO_REF:0000107 | UNDECIDED | Summary: Astrocyte activation (Compara from human IGI). Reason: Amyloid-beta acts on glia, so an astrocyte role is plausible, but the only donor (human IGI, PMID:15457210) is cached abstract-only and its abstract reports RAGE-dependent neuronal and behavioural effects of amyloid-beta in transgenic mice without mentioning astrocytes. The human UniProt record names mononuclear phagocytes, not astrocytes. No quotable evidence for astrocyte activation was found, so this is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0048169 regulation of long-term neuronal synaptic plasticity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of long-term neuronal synaptic plasticity (Compara from human IGI). Reason: This is an effect of amyloid-beta peptides (the donor rows are mostly IGI or IMP studies in APP-mutant transgenic mice or with applied peptide) rather than a physiological function of full-length APP. The horse amyloid-beta 1-42 sequence is identical to human, so the peptide property transfers, but it is pathological and peripheral; kept as non-core. Supporting Evidence: PMID:23921129 Fcgr2b deficiency ameliorated AΞ²-induced inhibition of long-term potentiation |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (Compara from human and mouse IDA). Reason: Supported vesicular/TGN distribution, but a descriptive rather than characteristic location. Supporting Evidence: file:human/APP/APP-uniprot.txt Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions. |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of inflammatory response (Compara from human IMP). Reason: This is an effect of amyloid-beta peptides (the donor rows are mostly IGI or IMP studies in APP-mutant transgenic mice or with applied peptide) rather than a physiological function of full-length APP. The horse amyloid-beta 1-42 sequence is identical to human, so the peptide property transfers, but it is pathological and peripheral; kept as non-core. Supporting Evidence: file:human/APP/APP-uniprot.txt brain and elicit inflammatory responses. PMID:29961672 BACE1 is required for the cleavage of amyloid precursor protein (APP) to generate AΞ², which stimulates the nuclear transcription factor ΞΊB (NF-ΞΊB) signaling, leading to the secretion of inflammatory cytokines. |
| GO:0050808 synapse organization | IEA GO_REF:0000107 | ACCEPT | Summary: Synapse organization (Compara from human IGI rows). Reason: Trans-dimerization of the APP ectodomain between neighbouring cells promotes synaptogenesis; the E1 copper site and E2 domain required for this are conserved in this model. Supporting Evidence: file:human/APP/APP-uniprot.txt molecules on neighboring cells promotes synaptogenesis PMID:25122912 APP potently promotes synaptogenesis depending on copper binding to the GFLD PMID:19726636 expression of APP in HEK293 cells potently promotes synaptogenesis in contacting axons |
| GO:0050850 positive regulation of calcium-mediated signaling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of calcium-mediated signaling (Compara from human IGI). Reason: This is an effect of amyloid-beta peptides (the donor rows are mostly IGI or IMP studies in APP-mutant transgenic mice or with applied peptide) rather than a physiological function of full-length APP. The horse amyloid-beta 1-42 sequence is identical to human, so the peptide property transfers, but it is pathological and peripheral; kept as non-core. Supporting Evidence: PMID:22500019 AΞ²1-42 and human amylin (hAmylin) increase cytosolic cAMP and Ca(2+) |
| GO:0051246 regulation of protein metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Regulation of protein metabolic process (ARBA). Reason: Uninformative over-generalization from a machine-learned rule; no specific APP activity corresponds to it. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. |
| GO:0051247 positive regulation of protein metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of protein metabolic process (Compara from human IMP/rat IDA, PMID:11404397, amyloid-beta activating MAPK via alpha7 nAChR). Reason: Very broad term for an indirect effect of amyloid-beta. Supporting Evidence: PMID:11404397 Abeta peptide 1-42 (Abeta42) couples to the mitogen-activated protein kinase (MAPK) cascade via alpha7 nicotinic acetylcholine receptors |
| GO:0051425 PTB domain binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: PTB domain binding (Compara from human IPI, PMID:12805363). In human APP the C-terminal YENPTY motif binds PTB/PID adaptors (FE65/APBB, X11/APBA, DAB1, SHC1). Reason: PTB/PID binding requires the YENPTY motif. A0A3Q2IKB0 lacks it: its cytoplasmic tail diverges from all other vertebrate APPs after human Glu738 (20/47 identical over human 724-770), and four other horse APP transcripts that keep the conserved tail exist. This is a true function of the horse APP gene, but this gene model cannot do it; the problem is the Ensembl canonical model, not the ortholog transfer. Supporting Evidence: file:human/APP/APP-uniprot.txt Binds, via its C-terminus, to the PID domain of several file:human/APP/APP-uniprot.txt containing proteins which bind APP require the YENPTY motif for full file:HORSE/APP/APP-bioinformatics/compare_horse_models_output.txt motifs absent: OX-2 exon (MSQSLLKT); AICD Thr site VTPEER; YENPTY file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 724-770: 42 of 47 residues aligned, 20 identical |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of ERK1 and ERK2 cascade (Compara from human IGI). Reason: This is an effect of amyloid-beta peptides (the donor rows are mostly IGI or IMP studies in APP-mutant transgenic mice or with applied peptide) rather than a physiological function of full-length APP. The horse amyloid-beta 1-42 sequence is identical to human, so the peptide property transfers, but it is pathological and peripheral; kept as non-core. Supporting Evidence: PMID:11404397 early AD etiology involves chronic activation of the ERK MAPK cascade as a consequence of elevated AΞ² binding to and activating this signaling cascade via Ξ±7 nAChRs |
| GO:0098815 modulation of excitatory postsynaptic potential | IEA GO_REF:0000107 | UNDECIDED | Summary: Modulation of excitatory postsynaptic potential (Compara from human IGI). Reason: The only donor (human IGI, PMID:20974225) is cached abstract-only; its abstract measures agonist-enhanced long-term potentiation and alpha7 nAChR ligand binding in APPswe/PS1dE9 hippocampal slices but reports no excitatory postsynaptic potential measurement. This is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:0099503 secretory vesicle | IEA GO_REF:0000117 | ACCEPT | Summary: Secretory vesicle (ARBA). Reason: APP accumulates in secretory transport vesicles leaving the late Golgi (curated UniProt text for human APP). Supporting Evidence: file:human/APP/APP-uniprot.txt secretory transport vesicles leaving the late Golgi compartment and |
| GO:0106003 amyloid-beta complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Amyloid-beta complex (Compara from human IDA). Reason: Assemblies of the amyloid-beta peptide, a cleavage product; the horse peptide is identical to human. Pathological fragment property, non-core. Supporting Evidence: file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 672-713: 42 of 42 residues aligned, 42 identical PMID:26138908 The aggregation of AΞ² leads to diverse oligomeric states |
| GO:0120283 protein serine/threonine kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein serine/threonine kinase binding (Compara from human IPI, PMID:24305806). Reason: True for human APP, but the kinase interactions characterized for APP centre on the cytoplasmic tail around Thr743 (Thr668 in APP695), which is absent from this gene model; low-information binding term kept as non-core. Supporting Evidence: file:human/APP/APP-uniprot.txt Interacts with LRRK2 (PubMed:28720718). file:HORSE/APP/APP-bioinformatics/compare_horse_models_output.txt motifs absent: OX-2 exon (MSQSLLKT); AICD Thr site VTPEER; YENPTY |
| GO:0140677 molecular function activator activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Molecular function activator activity (ARBA). Reason: Uninformative high-level term from a machine-learned rule. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. |
| GO:0150003 regulation of spontaneous synaptic transmission | IEA GO_REF:0000107 | UNDECIDED | Summary: Regulation of spontaneous synaptic transmission (Compara from human IGI). Reason: The only donor (human IGI, PMID:15457210) is cached abstract-only; its abstract reports spatial learning and memory and markers of synaptic plasticity in mutant-APP/RAGE transgenic mice, with no measurement of spontaneous synaptic transmission. This is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:1900272 negative regulation of long-term synaptic potentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of long-term synaptic potentiation (Compara from human IGI). Reason: This is an effect of amyloid-beta peptides (the donor rows are mostly IGI or IMP studies in APP-mutant transgenic mice or with applied peptide) rather than a physiological function of full-length APP. The horse amyloid-beta 1-42 sequence is identical to human, so the peptide property transfers, but it is pathological and peripheral; kept as non-core. Supporting Evidence: PMID:23921129 Fcgr2b deficiency ameliorated AΞ²-induced inhibition of long-term potentiation |
| GO:1900273 positive regulation of long-term synaptic potentiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of long-term synaptic potentiation (Compara from human IGI, PMID:20974225). Reason: The single human donor (IGI, PMID:20974225) shows that an alpha7 nAChR agonist enhances long-term potentiation in wild-type slices but not in APPswe/PS1dE9 slices: the APP transgene blocks a potentiation, which if anything argues the opposite direction. This row also contradicts the retained negative regulation of long-term synaptic potentiation. Supporting Evidence: PMID:20974225 in the Tg mice the application of SSR180711 did not result in an increase in LTP beyond control levels |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of non-canonical NF-kappaB signal transduction (Compara from human IGI/IMP). Reason: The only donor (human IGI, PMID:15457210) is cached abstract-only; its abstract describes RAGE as a signal-transducing acceptor for amyloid-beta but does not mention NF-kappaB, let alone the non-canonical pathway. This is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:1904646 cellular response to amyloid-beta | IEA GO_REF:0000107 | UNDECIDED | Summary: Cellular response to amyloid-beta (Compara from human IDA/IGI). Reason: The donor (human IDA, PMID:29518356) is cached abstract-only; its abstract shows that TREM2 binds amyloid-beta oligomers and mediates the microglial response to them. The responding entity there is TREM2-expressing microglia, and the abstract does not show APP taking part in the response. This is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:1905606 regulation of presynapse assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of presynapse assembly (Compara from human IDA/IMP, PMID:19726636). Reason: APP is a synaptic adhesion molecule whose expression promotes presynapse formation in contacting axons, but in PMID:19726636 that activity needed both the ectodomain and the intracellular domain (the Mint1/Cask-binding tail). This gene model has the ectodomain but an aberrant intracellular tail, so the full activity may not be executed by it; kept as non-core. Supporting Evidence: PMID:19726636 requires both the extracellular and intracellular domains file:HORSE/APP/APP-bioinformatics/compare_horse_models_output.txt motifs absent: OX-2 exon (MSQSLLKT); AICD Thr site VTPEER; YENPTY PMID:19726636 These in vitro and in vivo studies identify APP as a novel synaptic adhesion molecule. |
| GO:1905908 positive regulation of amyloid fibril formation | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of amyloid fibril formation (Compara from human IMP). Reason: The only donor (human IMP, PMID:19660551) is cached abstract-only and characterises amyloid-beta monomers, dimers, oligomers and insoluble aggregates in J20 APP-transgenic mice; it does not test whether APP regulates fibril formation. Fibril formation by the peptide itself is covered by the amyloid fibril formation row. The regulatory claim is left undecided rather than supported by a quote that does not state it (2026-10-23 re-review). |
| GO:1990000 amyloid fibril formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Amyloid fibril formation (Compara from human EXP/IMP). Reason: Amyloid-beta peptides themselves assemble into fibrils, so a product of this gene does the work of the process; pathological, kept as non-core. The horse amyloid-beta 1-42 is identical to human. Supporting Evidence: file:HORSE/APP/APP-bioinformatics/alignment_output.txt human region 672-713: 42 of 42 residues aligned, 42 identical PMID:26138908 a stable, primarily disordered AΞ²1-40 oligomer 5-15 nm in diameter can form and coexist in parallel with the well-known cross-Ξ²-sheet fibrils |
| GO:1990535 neuron projection maintenance | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Neuron projection maintenance (Compara from human IGI, PMID:20445063). Reason: The single human donor (IGI, PMID:20445063) shows that in APPswe/PSen1dE9 mice the transgene causes 5-HT axonal degeneration and loss of synaptic markers, and that deleting PrP(C) rescues it. Amyloid-beta there destroys neuron projections; it is not shown to maintain them. APP's physiological support of neurite growth is captured by the accepted axonogenesis row. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. PMID:20445063 deletion of PrP(C) expression rescues 5-HT axonal degeneration, loss of synaptic markers, and early death in APPswe/PSen1DeltaE9 transgenic mice |
| GO:2000406 positive regulation of T cell migration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of T cell migration (Compara from human IMP, PMID:19660551). Reason: The single human donor (IMP, PMID:19660551) characterises amyloid-beta assembly forms in J20 transgenic mice; the cached abstract contains no T-cell migration assay. No other evidence links APP to T-cell migration, and an effect of amyloid deposits on T-cell infiltration would be an indirect disease phenotype. Supporting Evidence: PMID:19660551 These data demonstrate the presence of multiple assembly forms of Abeta throughout the life of J20 mice |
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Download this section (compressed HTML)Q: Is the C-terminal tail of the Ensembl-canonical horse APP model ENSECAT00000045461 (A0A3Q2IKB0), which lacks the conserved YENPTY motif, supported by any horse transcript evidence, or is it a gene-model artefact that should be replaced by a transcript ending in the conserved APP C-terminus (as in F6XKR3)?
Q: Which APP isoforms (APP695 versus KPI-containing APP751/770) are expressed in horse brain and peripheral tissues, and does the human-type amyloid-beta sequence lead to amyloid deposition in aged horses?
Experiment: RT-PCR or long-read sequencing of horse brain APP transcripts across the last two exons, to test whether the divergent C-terminal exon of ENSECAT00000045461 is expressed and translated.
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