UniProtKB/Swiss-Prot P10636: Variant p.Lys686Ile

Microtubule-associated protein tau
Gene: MAPT
Chromosomal location: 17q21.1
Variant information

Variant position:  686
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Lysine (K) to Isoleucine (I) at position 686 (K686I, p.Lys686Ile).
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:  Change from large size and basic (K) to medium size and hydrophobic (I)
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 PIDB; 90% reduction in the rate of microtubule assembly.
Any additional useful information about the variant.



Sequence information

Variant position:  686
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  758
The length of the canonical sequence.

Location on the sequence:   RVQSKIGSLDNITHVPGGGN  K KIETHKLTFRENAKAKTDHG
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                         RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

Gorilla                       RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

Rhesus macaque                RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

Chimpanzee                    RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

Mouse                         RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

Rat                           RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

Bovine                        RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

Goat                          RVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHG

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 2 – 758 Microtubule-associated protein tau
Site 687 – 687 Not glycated
Site 692 – 692 Not glycated
Site 700 – 700 Not glycated
Site 702 – 702 Not glycated
Modified residue 669 – 669 Phosphoserine; by PHK
Modified residue 673 – 673 Phosphoserine; by MARK1; in PHF-tau
Glycosylation 670 – 670 N-linked (Glc) (glycation); in PHF-tau; in vitro
Glycosylation 686 – 686 N-linked (Glc) (glycation); in PHF-tau; in vitro
Cross 670 – 670 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau


Literature citations

Pick's disease associated with the novel Tau gene mutation K369I.
Neumann M.; Schulz-Schaeffer W.; Crowther R.A.; Smith M.J.; Spillantini M.G.; Goedert M.; Kretzschmar H.A.;
Ann. Neurol. 50:503-513(2001)
Cited for: VARIANT PIDB ILE-686; CHARACTERIZATION OF VARIANT PIDB ILE-686;

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.