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1.C.50.1.1
Alzheimer''s disease amyloid β-protein (amino acids 1-42) (Abeta protein or AβP or Aβ42).  Aβ pores may consist of tetrameric and hexameric beta-sheet subunits (Strodel et al. 2010).  Residues 22 - 35 in the peptide binds cholesterol to form Ca2+-permeable pores (Di Scala et al. 2014).  Cholesterol promotes the insertion of Abeta in the plasma membrane, induces alpha-helical structure formation, and forces the peptide to adopt a tilted topology that favours oligomerization. Bexarotene, an amphipathic drug for the treatment of neurodegenerative diseases, competes with cholesterol for binding to Abeta and prevents oligomeric channel formation (Di Scala et al. 2014).

Accession Number:P08592
Protein Name:A4 aka ABP aka APP
Length:770
Molecular Weight:86704.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Membrane1 / Single-pass type I membrane protein2
Substrate Ca2+

Cross database links:

Genevestigator: P08592
eggNOG: roNOG06213
DIP: DIP-685N
RefSeq: NP_062161.1   
Entrez Gene ID: 54226   
Pfam: PF02177    PF10515    PF03494    PF00014   
KEGG: rno:54226   

Gene Ontology

GO:0030424 C:axon
GO:0005905 C:coated pit
GO:0005794 C:Golgi apparatus
GO:0016021 C:integral to membrane
GO:0019717 C:synaptosome
GO:0003677 F:DNA binding
GO:0008201 F:heparin binding
GO:0046872 F:metal ion binding
GO:0016504 F:peptidase activator activity
GO:0004867 F:serine-type endopeptidase inhibitor activity
GO:0008344 P:adult locomotory behavior
GO:0008088 P:axon cargo transport
GO:0016199 P:axon midline choice point recognition
GO:0007155 P:cell adhesion
GO:0006878 P:cellular copper ion homeostasis
GO:0048669 P:collateral sprouting in the absence of injury
GO:0016358 P:dendrite development
GO:0006897 P:endocytosis
GO:0030198 P:extracellular matrix organization
GO:0000085 P:G2 phase of mitotic cell cycle
GO:0006917 P:induction of apoptosis
GO:0035235 P:ionotropic glutamate receptor signaling pat...
GO:0007617 P:mating behavior
GO:0006378 P:mRNA polyadenylation
GO:0016322 P:neuron remodeling
GO:0007219 P:Notch signaling pathway
GO:0045931 P:positive regulation of mitotic cell cycle
GO:0006468 P:protein amino acid phosphorylation
GO:0007176 P:regulation of epidermal growth factor recep...
GO:0040014 P:regulation of multicellular organism growth
GO:0050803 P:regulation of synapse structure and activity
GO:0006417 P:regulation of translation
GO:0008542 P:visual learning

References (20)

[1] “Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact.”  Shivers B.D.et.al.   2900758
[2] “Amyloid beta protein precursor is possibly a heparan sulfate proteoglycan core protein.”  Schubert D.et.al.   2968652
[3] “Purification and tissue level of the beta-amyloid peptide precursor of rat brain.”  Potempska A.et.al.   1673681
[4] “The sequence of the two extra exons in rat preA4.”  Kang J.et.al.   2648331
[5] “Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch.”  Gu Y.et.al.   11483588
[6] “APP gene family. Alternative splicing generates functionally related isoforms.”  Sandbrink R.et.al.   8624099
[7] “The Alzheimer amyloid precursor proteoglycan (appican) is present in brain and is produced by astrocytes but not by neurons in primary neural cultures.”  Shioi J.et.al.   7744833
[8] “Expression of the APP gene family in brain cells, brain development and aging.”  Sandbrink R.et.al.   8996834
[9] “A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein.”  Watanabe T.et.al.   9930726
[10] “The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction.”  Brouillet E.et.al.   10024358
[11] “The beta A4 amyloid precursor protein binding to copper.”  Hesse L.et.al.   7913895
[12] “The chondroitin sulfate attachment site of appican is formed by splicing out exon 15 of the amyloid precursor gene.”  Pangalos M.N.et.al.   7737970
[13] “The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction.”  Huang X.et.al.   10386999
[14] “Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease.”  Liu S.T.et.al.   10413512
[15] “Role of glycine-33 and methionine-35 in Alzheimer's amyloid beta-peptide 1-42-associated oxidative stress and neurotoxicity.”  Kanski J.et.al.   11959460
[16] “The cytoplasmic domain of Alzheimer's amyloid precursor protein is phosphorylated at Thr654, Ser655, and Thr668 in adult rat brain and cultured cells.”  Oishi M.et.al.   9085254
[17] “Phosphorylation of the cytoplasmic domain of Alzheimer's beta-amyloid precursor protein at Ser655 by a novel protein kinase.”  Isohara T.et.al.   10329382
[18] “Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation.”  Ando K.et.al.   10341243
[19] “Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5.”  Iijima K.et.al.   10936190
[20] “Appican, the proteoglycan form of the amyloid precursor protein, contains chondroitin sulfate E in the repeating disaccharide region and 4-O-sulfated galactose in the linkage region.”  Tsuchida K.et.al.   11479316
Structure:
1NMJ   1OQN   1M7E   2LI9     

External Searches:

  • Search: DB with
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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MLPSLALLLL AAWTVRALEV PTDGNAGLLA EPQIAMFCGK LNMHMNVQNG KWESDPSGTK 
61:	TCIGTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHTH IVIPYRCLVG 
121:	EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR 
181:	GVEFVCCPLA EESDSIDSAD AEEDDSDVWW GGADTDYADG GEDKVVEVAE EEEVADVEEE 
241:	EAEDDEDVED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC 
301:	RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSVSSQSLL KTTSEPLPQD 
361:	PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA 
421:	KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL 
481:	QAVPPRPHHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER 
541:	MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET 
601:	KTTVELLPVN GEFSLDDLQP WHPFGVDSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN 
661:	IKTEEISEVK MDAEFGHDSG FEVRHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL 
721:	VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN