Variant position: 714 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:
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 DVGSNKGAIIGLMVGGVVIA TVI-VITLVMLKKKQYTSIH-HG
Chimpanzee DVGSNKGAIIGLMVGGVVIA TVI-VITLVMLKKKQYTSIH-
Mouse DVGSNKGAIIGLMVGGVVIA TVI-VITLVMLKKKQYTSIH-
Rat DVGSNKGAIIGLMVGGVVIA TVI-VITLVMLKKKQYTSIH-
Pig DVGSNKGAIIGLMVGGVVIA TVI-VITLVMLKKKQYTSIH-
Caenorhabditis elegans VERSASSVFQPYVLASAMFI TAICIIAFAITNARRRRAM--
Drosophila AAKEGRNVYFTLSFAGIALM AAV-FVGVAVAKWRTSRSPHA
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
18 – 770 Amyloid beta A4 protein
672 – 770 C99
688 – 770 C83
691 – 770 C80
712 – 770 Gamma-secretase C-terminal fragment 59
714 – 770 Gamma-secretase C-terminal fragment 57
700 – 723 Helical;
704 – 704 Implicated in free radical propagation
706 – 706 Susceptible to oxidation
713 – 714 Cleavage; by gamma-secretase; site 2
729 – 729 Phosphothreonine
730 – 730 Phosphoserine; by APP-kinase I
697 – 697 O-linked (GalNAc...)
306 – 770 Missing. In isoform APP305.
704 – 704 G -> V. Reduced protein oxidation. No hippocampal neuron toxicity.
706 – 706 M -> L. Reduced lipid peroxidation inhibition.
706 – 706 M -> V. No free radical production. No hippocampal neuron toxicity.
717 – 717 V -> CS. Unchanged beta-APP42/total APP-beta ratio.
717 – 717 V -> FGI. Increased beta-APP42/beta-APP40 ratio.
717 – 717 V -> K. Decreased beta-APP42/total APP-beta ratio.
717 – 717 V -> M. Increased beta-APP42/beta-APP40 ratio. No change in apoptosis after caspase cleavage.
728 – 728 Y -> A. No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in beta-APP42 secretion.
Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site mutation points to an essential role for N-truncated A beta(42) in Alzheimer's disease.
Kumar-Singh S.; De Jonghe C.; Cruts M.; Kleinert R.; Wang R.; Mercken M.; De Strooper B.; Vanderstichele H.; Loefgren A.; Vanderhoeven I.; Backhovens H.; Vanmechelen E.; Kroisel P.M.; Van Broeckhoven C.;
Hum. Mol. Genet. 9:2589-2598(2000)
Cited for: VARIANT AD1 ILE-714; CHARACTERIZATION OF VARIANT AD1 ILE-714; MUTAGENESIS OF VAL-717;
An African American family with early-onset Alzheimer disease and an APP (T714I) mutation.
Edwards-Lee T.; Ringman J.M.; Chung J.; Werner J.; Morgan A.; St George-Hyslop P.H.; Thompson P.; Dutton R.; Mlikotic A.; Rogaeva E.; Hardy J.;
Cited for: VARIANT AD1 ILE-714;
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.