Molecule Information

General Information of the Molecule (ID: Mol02117)

• Name: Amyloid-beta precursor protein (APP) ,Homo sapiens
• Synonyms: Amyloid-beta precursor protein (APP) (ABPP) (APPI) (Alzheimer disease amyloid A4 protein homolog) (Alzheimer disease amyloid protein) (Amyloid precursor protein) (Amyloid-beta (A4) precursor protein) (Amyloid-beta A4 protein) (Cerebral vascular amyloid peptide) (CVAP) (PreA4) (Protease nexin-II) (PN-II) [Cleaved into: N-APP; Soluble APP-alpha (S-APP-alpha); Soluble APP-beta (S-APP-beta); C99 (Beta-secretase C-terminal fragment) (Beta-CTF); Amyloid-beta protein 42 (Abeta42) (Beta-APP42); Amyloid-beta protein 40 (Abeta40) (Beta-APP40); C83 (Alpha-secretase C-terminal fragment) (Alpha-CTF); P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59 (Amyloid intracellular domain 59) (AICD-59) (AID(59)) (Gamma-CTF(59)); Gamma-secretase C-terminal fragment 57 (Amyloid intracellular domain 57) (AICD-57) (AID(57)) (Gamma-CTF(57)); Gamma-secretase C-terminal fragment 50 (Amyloid intracellular domain 50) (AICD-50) (AID(50)) (Gamma-CTF(50)); C31]; APP; A4; AD1
• Molecule Type: Protein
• Gene Name: APP
• Gene ID: 351
• Location: Chromosome 21: 25,880,550-26,171,128 reverse strand
• Sequence:
  MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
  TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
  EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
  GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
  EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
  RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
  PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
  KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
  QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
  MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
  KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
  IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
  VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
• 3D-structure: PDB ID: 8KF4; Classification: Protein fibril; Method: Electron microscopy; Resolution: 3.00 Å
• 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. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. 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.
• Uniprot ID: A4_HUMAN
• Ensembl ID: ENSG00000142192
• HGNC ID: HGNC:620

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Tacrine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Alzheimer's disease [ICD-11: 8A20.0] [1]

• Sensitive Disease: Alzheimer's disease [ICD-11: 8A20.0]
• Sensitive Drug: Tacrine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: By using tacrine to target the active catalytic site (CAS), the tacrine-based MTDLs can act on both CAS and peripheral anion site (PAS) of AChE to serve as a dual-site AChE inhibitor. Additionally, the tacrine-based MTDLs can also be designed on the basis of other theories of AD, for example, introducing functional moieties to modulate the formation of beta-amyloid (Abeta), oxidation resistance, or metal chelation.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 08

Alzheimer's disease [ICD-11: 8A20]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Entorhinal cortex
• The Specified Disease: Alzheimer's disease
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.60E-02; Fold-change: -7.24E-02; Z-score: -3.10E-01

References

• Ref 1: Multi-Target Drug Design of Anti-Alzheimer's Disease based on Tacrine .Mini Rev Med Chem. 2021;21(15):2039-2064. doi: 10.2174/1389557521666210212151127. 10.2174/1389557521666210212151127