UniProtKB/SwissProt variant VAR

Variant information

Variant position:

716

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 Isoleucine (I) to Valine (V) at position 716 (I716V, p.Ile716Val).

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 hydrophobic.

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

3

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 rs63750399 [ dbSNP | Ensembl ]

Sequence information

Variant position:

716

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:

GSNKGAIIGLMVGGVVIATV I VITLVMLKKKQYTSIHHGVV

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                         GSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH-HGVV

Chimpanzee                    GSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH-HG

Mouse                         GSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH-HG

Rat                           GSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH-HG

Pig                           GSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH-HG

Caenorhabditis elegans        RSASSVFQPYVLASAMFITAICIIAFAITNARRRRAM--RG

Drosophila                    KEGRNVYFTLSFAGIALMAAV-FVGVAVAKWRTSRSPHAQG

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	688 – 770	C83
Chain	691 – 770	C80
Chain	712 – 770	Gamma-secretase C-terminal fragment 59
Chain	714 – 770	Gamma-secretase C-terminal fragment 57
Transmembrane	702 – 722	Helical
Region	695 – 722	Interaction with PSEN1
Site	704 – 704	Implicated in free radical propagation
Site	706 – 706	Susceptible to oxidation
Modified residue	729 – 729	Phosphothreonine
Modified residue	730 – 730	Phosphoserine; by APP-kinase I
Alternative sequence	306 – 770	Missing. In isoform APP305.
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.
Mutagenesis	717 – 717	V -> CS. Unchanged amyloid-beta protein 42/total amyloid-beta ratio.
Mutagenesis	717 – 717	V -> K. Decreased amyloid-beta protein 42/total amyloid-beta ratio.
Mutagenesis	717 – 717	V -> M. Increased amyloid-beta protein 42/40 ratio. No change in apoptosis after caspase cleavage.
Mutagenesis	728 – 728	Y -> A. No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in amyloid-beta protein 42 secretion.

Literature citations

A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43).
Eckman C.B.; Mehta N.D.; Crook R.; Perez-Tur J.; Prihar G.; Pfeiffer E.; Graff-Radford N.; Hinder P.; Yager D.; Zenk B.; Refolo L.M.; Prada C.M.; Younkin S.G.; Hutton M.; Hardy J.;
Hum. Mol. Genet. 6:2087-2089(1997)
Cited for: VARIANT AD1 VAL-716;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P05067: Variant p.Ile716Val