UniProtKB - Q29149 (A4_URSMA)
Amyloid-beta A4 protein
APP
Functioni
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 11 | Copper or zincBy similarity | 1 | |
Metal bindingi | 15 | Copper or zincBy similarity | 1 | |
Metal bindingi | 18 | Copper or zincBy similarity | 1 | |
Metal bindingi | 19 | Copper or zincBy similarity | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- nervous system development Source: InterPro
Keywordsi
Ligand | Copper, Metal-binding, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Amyloid-beta A4 proteinAlternative name(s): ABPP Short name: APP Alzheimer disease amyloid A4 protein homolog Amyloid precursor proteinCurated Amyloid-beta precursor proteinCurated 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 | Ursus maritimus (Polar bear) (Thalarctos maritimus) |
Taxonomic identifieri | 29073 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Ursidae › Ursus |
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-SubCell
- 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 – 33 | ExtracellularSequence analysisAdd BLAST | ›33 | |
Transmembranei | 34 – 57 | HelicalSequence analysisAdd BLAST | 24 |
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_0000226244 | ‹1 – ›57 | Amyloid-beta A4 proteinAdd BLAST | ›57 | |
ChainiPRO_0000000191 | ‹1 – 5 | Soluble APP-betaBy similarity | ›5 | |
ChainiPRO_0000000192 | 6 – ›57 | CTF-alphaBy similarityAdd BLAST | ›52 | |
ChainiPRO_0000000193 | 6 – 47 | Amyloid-beta protein 42By similarityAdd BLAST | 42 | |
ChainiPRO_0000000194 | 6 – 45 | Amyloid-beta protein 40By similarityAdd BLAST | 40 | |
ChainiPRO_0000000195 | 46 – ›57 | Gamma-secretase C-terminal fragment 59By similarityAdd BLAST | ›12 | |
ChainiPRO_0000000196 | 48 – ›57 | Gamma-secretase C-terminal fragment 57By similarity | ›10 |
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).
By similarityFamily & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixFamily 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 |
(1+)i Sequence
Sequence statusi: Fragment.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
SEVKMDAEFR HDSGYEVHHQ KLVFFAEDVG SNKGAIIGLM VGGVVIATVI
VITLVML
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A384CZS1 | A0A384CZS1_URSMA | Amyloid-beta A4 protein | APP | 735 | Annotation score: | ||
A0A384CYX7 | A0A384CYX7_URSMA | Amyloid-beta A4 protein | APP | 660 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Non-terminal residuei | 1 | 1 | ||
Non-terminal residuei | 57 | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X56128 mRNA Translation: CAA39593.1 |
PIRi | B60045 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X56128 mRNA Translation: CAA39593.1 |
PIRi | B60045 |
3D structure databases
SMRi | Q29149 |
ModBasei | Search... |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | A4_URSMA | |
Accessioni | Q29149Primary (citable) accession number: Q29149 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1997 | |
Last modified: | October 7, 2020 | |
This is version 93 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