UniProtKB/Swiss-Prot P05067: Variant p.Glu665Asp

Amyloid beta A4 protein
Gene: APP
Chromosomal location: 21q21.2
Variant information

Variant position:  665
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  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:  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:  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:  In a patient with late onset Alzheimer disease.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  665
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  770
The length of the canonical sequence.

Location on the sequence:   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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         AADRGLTTRPGSGLTNIK-------------TEEISEVKMDAEFRHD----------------SGYEVHH

Chimpanzee                    AADRGLTTRPGSGLTNIK-------------TEEISEVKMD

Mouse                         AADRGLTTRPGSGLTNIK-------------TEEISEVKMD

Rat                           AADRGLTTRPGSGLTNIK-------------TEEISEVKMD

Pig                           AADRGLTTRPGSGLTNIK-------------TEEISEVKMD

Caenorhabditis elegans        QTDDEDDDEDSSSSTSSE--------SDEDEDKNIKELRVD

Drosophila                    EKDLSDTEYGEATVSSTKVQTVLPTVDDDAVQRAVEDVAAA

Sequence annotation in neighborhood:  
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 A4 protein
Chain 18 – 687 Soluble APP-alpha
Chain 18 – 671 Soluble APP-beta
Topological domain 18 – 699 Extracellular
Metal binding 677 – 677 Copper or zinc 2
Metal binding 681 – 681 Copper or zinc 2
Metal binding 684 – 684 Copper or zinc 2
Metal binding 685 – 685 Copper or zinc 2
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 beta-APP (28) peptide aggregation.
Mutagenesis 681 – 681 Y -> F. 60-70% zinc-induced beta-APP (28) peptide aggregation.
Mutagenesis 684 – 684 H -> R. Only 23% zinc-induced beta-APP (28) peptide 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.