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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49768: Variant p.Ile213Thr

Presenilin-1
Gene: PSEN1
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Variant information Variant position: help 213 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Isoleucine (I) to Threonine (T) at position 213 (I213T, p.Ile213Thr). 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: help Change from medium size and hydrophobic (I) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 213 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 467 The length of the canonical sequence.
Location on the sequence: help VDYITVALLIWNFGVVGMIS I HWKGPLRLQQAYLIMISALM 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.
Sequence annotation in neighborhood: help 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 1 – 298 Presenilin-1 NTF subunit
Transmembrane 195 – 216 Helical
Alternative sequence 185 – 467 Missing. In isoform 4.
Mutagenesis 202 – 202 I -> F. Nearly abolishes protease activity with APP.
Mutagenesis 212 – 212 S -> Y. Nearly abolishes protease activity with APP.
Mutagenesis 214 – 214 H -> D. Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 219 – 219 L -> F. Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 223 – 223 Q -> R. Abolishes protease activity with APP.
Mutagenesis 226 – 226 L -> F. Increases protease activity with APP.
Mutagenesis 230 – 230 S -> I. Abolishes protease activity with APP.
Helix 195 – 214



Literature citations
Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families.
Kamino K.; Sato S.; Sakaki Y.; Yoshiiwa A.; Nishiwaki Y.; Takeda H.; Tanabe H.; Nishimura T.; Li K.; St George-Hyslop P.H.; Miki T.; Ogihara T.;
Neurosci. Lett. 208:195-198(1996)
Cited for: VARIANTS AD3 PHE-96; ARG-163 AND THR-213; Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta.
Shimojo M.; Sahara N.; Mizoroki T.; Funamoto S.; Morishima-Kawashima M.; Kudo T.; Takeda M.; Ihara Y.; Ichinose H.; Takashima A.;
J. Biol. Chem. 283:16488-16496(2008)
Cited for: CHARACTERIZATION OF VARIANT AD3 THR-213;
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.