General Information of Binding Target of SBP (BTS) (ID: ST00126)
BTS Name
Amyloid-beta precursor protein
Synonyms
APP; ABPP; APPI; Alzheimer disease amyloid protein; Amyloid precursor protein; Amyloid-beta A4 protein; Cerebral vascular amyloid peptide; CVAP; PreA4; Protease nexin-II; PN-II
BTS Type
Protein
Family
APP family
Gene Name
APP
Organism
Homo sapiens (Human)
Function
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. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. 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 Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.; Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.; Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.; The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.; N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
UniProt ID
P05067
UniProt Entry
A4_HUMAN
PFam
PF10515 ; PF12924 ; PF12925 ; PF02177 ; PF03494 ; PF00014
Gene ID
351
Sequence
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
Sequence Length
770
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Affibody anti-Abeta Z(SYM73) Research binder Kd: 0.34 nM Alzheimer disease [ICD-11: 8A20]
SBP Info
[1]
DARPin anti-Abeta D23 Research Inhibitor Kd: 159 nM Alzheimer disease [ICD-11: 8A20]
SBP Info
[2]
scFv anti-Abeta A4 Research Inhibitor N.A. Alzheimer disease [ICD-11: 8A20]
SBP Info
[3]
scFv anti-Abeta c23.5 Research Binder N.A. Alzheimer disease [ICD-11: 8A20]
SBP Info
[4]
scFv anti-Abeta E1 Research Inhibitor N.A. Alzheimer disease [ICD-11: 8A20]
SBP Info
[3]
scFv anti-Abeta42 scFv-12B4 Research Inhibitor Kd: 3.0 nM Alzheimers disease (AD) [ICD-11: 8A20]
SBP Info
[5]
scFv anti-Abeta42 scFv-C Research Inhibitor Kd: 2.0 nM Alzheimers disease (AD) [ICD-11: 8A20]
SBP Info
[5]
scFv anti-Abeta42 scFv-S Research Inhibitor Kd: 3.9 nM Alzheimers disease (AD) [ICD-11: 8A20]
SBP Info
[5]
References
1 Construction and Validation of a New Na?ve Sequestrin Library for Directed Evolution of Binders against Aggregation-Prone Peptides. Int J Mol Sci. 2023 Jan 3;24(1):836.
2 Amyloid- peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease. J Biol Chem. 2014 Sep 26;289(39):27080-27089.
3 Anti-oligomeric Abeta single-chain variable domain antibody blocks Abeta-induced toxicity against human neuroblastoma cells. J Mol Biol. 2008 Dec 26;384(4):917-28.
4 Promoting alpha-secretase cleavage of beta-amyloid with engineered proteolytic antibody fragments. Biotechnol Prog. Jul-Aug 2009;25(4):1054-63.
5 Mechanism Exploration of Amyloid--42 Disaggregation by Single-Chain Variable Fragments of Alzheimer's Disease Therapeutic Antibodies. Int J Mol Sci. 2023 May 6;24(9):8371.