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UniProtKB/Swiss-Prot P05067: Variant p.Leu705Val

Amyloid-beta precursor protein
Gene: APP
Variant information

Variant position:  705
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 Leucine (L) to Valine (V) at position 705 (L705V, p.Leu705Val).
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:  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:  In CAA-APP; Italian type.
Any additional useful information about the variant.

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



Sequence information

Variant position:  705
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:   HQKLVFFAEDVGSNKGAIIG  L MVGGVVIATVIVITLVMLKK
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                         HQKLVFFAEDVGSNKGAIIGLMVGGVVIATVI-VITLVMLKK

Chimpanzee                    HQKLVFFAEDVGSNKGAIIGLMVGGVVIATVI-VITLVMLK

Mouse                         HQKLVFFAEDVGSNKGAIIGLMVGGVVIATVI-VITLVMLK

Rat                           HQKLVFFAEDVGSNKGAIIGLMVGGVVIATVI-VITLVMLK

Pig                           HQKLVFFAEDVGSNKGAIIGLMVGGVVIATVI-VITLVMLK

Caenorhabditis elegans        HDKLIQSPEVERSASSVFQPYVLASAMFITAICIIAFAITN

Drosophila                    RREFAQHAHAAKEGRNVYFTLSFAGIALMAAV-FVGVAVAK

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 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
Transmembrane 702 – 722 Helical
Region 695 – 722 Interaction with PSEN1
Metal binding 685 – 685 Cu(2+) 2
Metal binding 685 – 685 Zn(2+)
Site 704 – 704 Implicated in free radical propagation
Site 706 – 706 Susceptible to oxidation
Alternative sequence 306 – 770 Missing. In isoform APP305.
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.
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.


Literature citations

A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy.
Obici L.; Demarchi A.; de Rosa G.; Bellotti V.; Marciano S.; Donadei S.; Arbustini E.; Palladini G.; Diegoli M.; Genovese E.; Ferrari G.; Coverlizza S.; Merlini G.;
Ann. Neurol. 58:639-644(2005)
Cited for: VARIANT CAA-APP VAL-705;

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.