UniProtKB - Q28053 (A4_BOVIN)
Amyloid-beta precursor protein
APP
Functioni
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions (By similarity).
Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb (By similarity).
Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP (By similarity).
Inhibits G(o)-alpha ATPase activity (By similarity).
Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity).
By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (By similarity).
May be involved in copper homeostasis/oxidative stress through copper ion reduction (By similarity).
In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-mediated low-density lipoprotein oxidation (By similarity).
Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and mitochondrial dysfunction in cultured cortical neurons. Provides Cu2+ ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1 (By similarity).
By similarityGO - Biological processi
- cognition Source: UniProtKB
- nervous system development Source: InterPro
Names & Taxonomyi
Protein namesi | Recommended name: Amyloid-beta precursor proteinBy similarityAlternative name(s): ABPP Short name: APPBy similarity Alzheimer disease amyloid A4 protein homolog Amyloid precursor proteinCurated Amyloid-beta (A4) precursor proteinBy similarity Amyloid-beta A4 protein Cleaved into the following 6 chains: Alternative name(s): Beta-APP42 Alternative name(s): Beta-APP40 Alternative name(s): Gamma-CTF(59) Alternative name(s): Gamma-CTF(57) |
Gene namesi | Name:APP |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein By similarity
Endosome
- Early endosome By similarity
Other locations
- Membrane By similarity; Single-pass type I membrane protein By similarity
- Perikaryon By similarity
- growth cone By similarity
- clathrin-coated pit By similarity
- Cytoplasmic vesicle By similarity
Note: Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface.By similarity
Extracellular region or secreted
- Secreted By similarity
Other locations
- Cell surface By similarity
Note: Associates with FPR2 at the cell surface and the complex is then rapidly internalized.By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
- Nucleus By similarity
Note: Located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). In dopaminergic neurons, the phosphorylated form is localized to the nucleus (By similarity).By similarity
Endosome
- early endosome Source: UniProtKB
- recycling endosome Source: UniProtKB
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Nucleus
- nucleus Source: UniProtKB-SubCell
Plasma Membrane
- clathrin-coated pit Source: UniProtKB-SubCell
Other locations
- cell surface Source: UniProtKB-SubCell
- Golgi-associated vesicle Source: UniProtKB
- growth cone Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-KW
- perikaryon Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | ‹1 – 34 | ExtracellularSequence analysisAdd BLAST | ›34 | |
Transmembranei | 35 – 58 | HelicalSequence analysisAdd BLAST | 24 | |
Topological domaini | 59 | CytoplasmicSequence analysis | ›1 |
Keywords - Cellular componenti
Amyloid, Cell membrane, Cell projection, Coated pit, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus, SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000000064 | ‹1 – 6 | Soluble APP-betaBy similarity | ›6 | |
ChainiPRO_0000000065 | 7 – ›59 | CTF-alphaBy similarityAdd BLAST | ›53 | |
ChainiPRO_0000000066 | 7 – 48 | Amyloid-beta protein 42By similarityAdd BLAST | 42 | |
ChainiPRO_0000000067 | 7 – 46 | Amyloid-beta protein 40By similarityAdd BLAST | 40 | |
ChainiPRO_0000000068 | 47 – ›59 | Gamma-secretase C-terminal fragment 59By similarityAdd BLAST | ›13 | |
ChainiPRO_0000000069 | 49 – ›59 | Gamma-secretase C-terminal fragment 57By similarityAdd BLAST | ›11 |
Proteomic databases
PaxDbi | Q28053 |
Interactioni
Subunit structurei
Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity).
Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif.
Also interacts with GPCR-like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity).
Interacts, through a C-terminal domain, with GNAO1.
Interacts with CPEB1, ANKS1B, TNFRSF21 and AGER (By similarity).
Interacts with ITM2B.
Interacts with ITM2C.
Interacts with IDE. Can form homodimers; dimerization is enhanced in the presence of Cu2+ ions. Can form homodimers; this is promoted by heparin binding (By similarity).
Interacts with SORL1 (via N-terminal ectodomain); this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (By similarity).
Interacts with PLD3 (By similarity).
Interacts with VDAC1 (By similarity).
Interacts with NSG1; could regulate APP processing (By similarity). Amyloid-beta protein 42 interacts with FPR2 (By similarity).
Interacts with LRRK2 (By similarity).
Interacts (via cytoplasmic domain) with KIF5B (By similarity).
Interacts (via C-terminus) with APBB2/FE65L1 (via C-terminus) (By similarity).
Interacts (via intracellular domain) with APBB3 (By similarity).
By similarityProtein-protein interaction databases
STRINGi | 9913.ENSBTAP00000045951 |
Structurei
3D structure databases
BMRBi | Q28053 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3540, Eukaryota |
HOGENOMi | CLU_014607_2_1_1 |
InParanoidi | Q28053 |
OrthoDBi | 953529at2759 |
Family and domain databases
Gene3Di | 4.10.230.10, 1 hit |
InterProi | View protein in InterPro IPR008155, Amyloid_glyco IPR013803, Amyloid_glyco_Abeta IPR037071, Amyloid_glyco_Abeta_sf IPR028866, APP |
PANTHERi | PTHR23103, PTHR23103, 1 hit PTHR23103:SF7, PTHR23103:SF7, 1 hit |
Pfami | View protein in Pfam PF03494, Beta-APP, 1 hit |
PRINTSi | PR00204, BETAAMYLOID |
i Sequence
Sequence statusi: Fragment.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
ISEVKMDAEF RHDSGYEVHH QKLVFFAEDV GSNKGAIIGL MVGGVVIATV
IVITLVMLK
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Non-terminal residuei | 1 | 1 | ||
Non-terminal residuei | 59 | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X56124 mRNA Translation: CAA39589.1 X56126 mRNA Translation: CAA39591.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X56124 mRNA Translation: CAA39589.1 X56126 mRNA Translation: CAA39591.1 |
3D structure databases
BMRBi | Q28053 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000045951 |
Proteomic databases
PaxDbi | Q28053 |
Phylogenomic databases
eggNOGi | KOG3540, Eukaryota |
HOGENOMi | CLU_014607_2_1_1 |
InParanoidi | Q28053 |
OrthoDBi | 953529at2759 |
Family and domain databases
Gene3Di | 4.10.230.10, 1 hit |
InterProi | View protein in InterPro IPR008155, Amyloid_glyco IPR013803, Amyloid_glyco_Abeta IPR037071, Amyloid_glyco_Abeta_sf IPR028866, APP |
PANTHERi | PTHR23103, PTHR23103, 1 hit PTHR23103:SF7, PTHR23103:SF7, 1 hit |
Pfami | View protein in Pfam PF03494, Beta-APP, 1 hit |
PRINTSi | PR00204, BETAAMYLOID |
MobiDBi | Search... |
Entry informationi
Entry namei | A4_BOVIN | |
Accessioni | Q28053Primary (citable) accession number: Q28053 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 129 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families