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 RSASSVFQPYVLASAMFITAI CIIAFAITNARRRRAM--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;
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.