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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P05067: Variant p.Asp678Asn

Amyloid-beta precursor protein
Gene: APP
Variant information Variant position: help 678 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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 Aspartate (D) to Asparagine (N) at position 678 (D678N, p.Asp678Asn). 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 Change from medium size and acidic (D) to medium size and polar (N) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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 AD1. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.

Sequence information Variant position: help 678 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 LTNIKTEEISEVKMDAEFRH D SGYEVHHQKLVFFAEDVGSN 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                         LTNIKTEEISEV-----------KMDAEFRHDSGYEVHHQKLVF-----FAEDV-GSN

Chimpanzee                    LTNIKTEEISEV-----------KMDAEFRHDSGYEVHHQK

Mouse                         LTNIKTEEISEV-----------KMDAEFGHDSGFEVRHQK

Rat                           LTNIKTEEISEV-----------KMDAEFGHDSGFEVRHQK

Pig                           LTNIKTEEISEV-----------KMDAEFRHDSGYEVHHQK

Caenorhabditis elegans        SDEDEDKNIKEL---------RVDIEPIIDEPASF-YRHDK


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.
Chain 18 – 770 Amyloid-beta precursor protein
Chain 18 – 687 Soluble APP-alpha
Chain 672 – 770 C99
Chain 672 – 713 Amyloid-beta protein 42
Chain 672 – 711 Amyloid-beta protein 40
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
Site 678 – 679 Cleavage; by ACE
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 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.
Mutagenesis 695 – 695 V -> C. Causes formation of an artifactual disulfide bond with PSEN1.
Turn 677 – 679

Literature citations
Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease.
Wakutani Y.; Watanabe K.; Adachi Y.; Wada-Isoe K.; Urakami K.; Ninomiya H.; Saido T.C.; Hashimoto T.; Iwatsubo T.; Nakashima K.;
J. Neurol. Neurosurg. Psych. 75:1039-1042(2004)
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.