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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P05067: Variant p.Glu665Asp

Amyloid-beta precursor protein
Gene: APP
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Variant information Variant position: help 665 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LB/B The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Glutamate (E) to Aspartate (D) at position 665 (E665D, p.Glu665Asp). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Similar physico-chemical property. Both residues are medium size and acidic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In a patient with late onset Alzheimer disease. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 665 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 770 The length of the canonical sequence.
Location on the sequence: help AADRGLTTRPGSGLTNIKTE E ISEVKMDAEFRHDSGYEVHH The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         AA---------------DRGL-----------TTRPGSGLTNIKTEEISEV-----------KMDAEFRHDSGYEVHH

Chimpanzee                    AA---------------DRGL-----------TTRPGSGLT

Mouse                         AA---------------DRGL-----------TTRPGSGLT

Rat                           AA---------------DRGL-----------TTRPGSGLT

Pig                           AA---------------DRGL-----------TTRPGSGLT

Caenorhabditis elegans        KEIKVTIEEEKKAPKLVETSVQTDDEDDDEDSSSSTSSESD

Drosophila                    DAALVTAANPNLETTKSEKDLSDTEYGEATVSSTKVQTVLP
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 18 – 770 Amyloid-beta precursor protein
Chain 18 – 687 Soluble APP-alpha
Chain 18 – 671 Soluble APP-beta
Topological domain 18 – 701 Extracellular
Binding site 677 – 677
Binding site 677 – 677
Binding site 681 – 681
Binding site 681 – 681
Binding site 684 – 684
Binding site 684 – 684
Binding site 685 – 685
Binding site 685 – 685
Glycosylation 651 – 651 O-linked (GalNAc...) threonine; partial
Glycosylation 652 – 652 O-linked (GalNAc...) threonine; partial
Glycosylation 656 – 656 O-linked (Xyl...) (chondroitin sulfate) serine; in L-APP isoforms
Glycosylation 659 – 659 O-linked (HexNAc...) threonine; partial
Glycosylation 663 – 663 O-linked (GalNAc...) threonine; partial
Glycosylation 667 – 667 O-linked (GalNAc...) serine; partial
Glycosylation 681 – 681 O-linked (HexNAc...) tyrosine; partial
Alternative sequence 306 – 770 Missing. In isoform APP305.
Mutagenesis 656 – 656 S -> A. Abolishes chondroitin sulfate binding in L-APP733 isoform.
Mutagenesis 676 – 676 R -> G. 60-70% zinc-induced amyloid-beta protein 28 aggregation.
Mutagenesis 681 – 681 Y -> F. 60-70% zinc-induced amyloid-beta protein 28 aggregation.
Mutagenesis 684 – 684 H -> R. Only 23% zinc-induced amyloid-beta protein 28 aggregation.



Literature citations
Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late-onset Alzheimer's disease.
Peacock M.L.; Murman D.L.; Sima A.A.F.; Warren J.T. Jr.; Roses A.D.; Fink J.K.;
Ann. Neurol. 35:432-438(1994)
Cited for: VARIANT ASP-665;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.