UniProtKB/SwissProt variant VAR

Variant information

Variant position:

693

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

Type of variant:

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:

From Glutamate (E) to Glycine (G) at position 693 (E693G, p.Glu693Gly).

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:

Change from medium size and acidic (E) to glycine (G)

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 AD1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs63751039 [ dbSNP | Ensembl ]

Sequence information

Variant position:

693

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:

AEFRHDSGYEVHHQKLVFFA E DVGSNKGAIIGLMVGGVVIA

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                         AEFRHD----------------SGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA

Chimpanzee                    AEFRHD----------------SGYEVHHQKLVFFAEDVGS

Mouse                         AEFGHD----------------SGFEVRHQKLVFFAEDVGS

Rat                           AEFGHD----------------SGFEVRHQKLVFFAEDVGS

Pig                           AEFRHD----------------SGYEVHHQKLVFFAEDVGS

Caenorhabditis elegans        IEPIIDEP--------------ASFY-RHDKLIQSPEVERS

Drosophila                    VAHQEAEPQVQHFMTHDLGHRESSFS-LRREFAQHAHAAKE

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.

Type	Positions	Description
Chain	18 – 770	Amyloid-beta precursor protein
Chain	672 – 770	C99
Chain	672 – 713	Amyloid-beta protein 42
Chain	672 – 711	Amyloid-beta protein 40
Chain	688 – 770	C83
Peptide	688 – 713	P3(42)
Peptide	688 – 711	P3(40)
Chain	691 – 770	C80
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	704 – 704	Implicated in free radical propagation
Site	706 – 706	Susceptible to oxidation
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.
Mutagenesis	704 – 704	G -> V. Reduced protein oxidation. No hippocampal neuron toxicity.
Mutagenesis	706 – 706	M -> L. Reduced lipid peroxidation inhibition.
Mutagenesis	706 – 706	M -> V. No free radical production. No hippocampal neuron toxicity.
Beta strand	692 – 694

Literature citations

Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region.
Kamino K.; Orr H.T.; Payami H.; Wijsman E.M.; Alonso M.E.; Pulst S.M.; Anderson L.; O'Dahl S.; Nemens E.; White J.A.; Sadovnick A.D.; Ball M.J.; Kaye J.; Warren A.; McInnis M.G.; Antonarakis S.E.; Korenberg J.R.; Sharma V.; Kukull W.; Larson E.; Heston L.L.; Martin G.M.; Bird T.D.; Schellenberg G.D.;
Am. J. Hum. Genet. 51:998-1014(1992)
Cited for: VARIANT AD1 GLY-693;

The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation.
Nilsberth C.; Westlind-Danielsson A.; Eckman C.B.; Condron M.M.; Axelman K.; Forsell C.; Stenh C.; Luthman J.; Teplow D.B.; Younkin S.G.; Naeslund J.; Lannfelt L.;
Nat. Neurosci. 4:887-893(2001)
Cited for: VARIANT AD1 GLY-693;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P05067: Variant p.Glu693Gly