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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10636: Variant p.Val654Met

Microtubule-associated protein tau
Gene: MAPT
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Variant information Variant position: help 654 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 Valine (V) to Methionine (M) at position 654 (V654M, p.Val654Met). 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 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: 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 FTD; ultrastructural and biochemical characteristics indistinguishable from Alzheimer disease; accelerates aggregation of tau into filaments. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 654 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 758 The length of the canonical sequence.
Location on the sequence: help KVTSKCGSLGNIHHKPGGGQ V EVKSEKLDFKDRVQSKIGSL 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL

Gorilla                       KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL

Rhesus macaque                KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL

Chimpanzee                    KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL

Mouse                         KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL

Rat                           KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL

Bovine                        KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL

Goat                          KVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSL
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 2 – 758 Microtubule-associated protein tau
Repeat 654 – 685 Tau/MAP 4
Region 561 – 685 Microtubule-binding domain
Site 634 – 634 Not glycated
Site 638 – 638 Not glycated
Site 648 – 648 Not glycated
Site 657 – 657 Not glycated
Site 660 – 660 Not glycated
Modified residue 634 – 634 N6-acetyllysine; alternate
Modified residue 638 – 638 N6-acetyllysine; alternate
Modified residue 641 – 641 Phosphoserine
Modified residue 648 – 648 N6-acetyllysine; alternate
Modified residue 660 – 660 N6-acetyllysine; alternate
Modified residue 664 – 664 N6-acetyllysine; alternate
Modified residue 666 – 666 Omega-N-methylarginine
Modified residue 669 – 669 Phosphoserine; by PHK
Modified residue 673 – 673 Phosphoserine
Glycosylation 664 – 664 N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
Glycosylation 670 – 670 N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
Cross 634 – 634 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 638 – 638 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 648 – 648 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 660 – 660 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 664 – 664 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 670 – 670 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau
Beta strand 654 – 660



Literature citations
Tau is a candidate gene for chromosome 17 frontotemporal dementia.
Poorkaj P.; Bird T.D.; Wijsman E.; Nemens E.; Garruto R.M.; Anderson L.; Andreadis A.; Wiederholt W.C.; Raskind M.; Schellenberg G.D.;
Ann. Neurol. 43:815-825(1998)
Cited for: VARIANT FTD MET-654; VARIANTS ASN-285; ALA-289; HIS-441 AND PRO-447; INVOLVEMENT IN FTD; Accelerated filament formation from tau protein with specific FTDP-17 missense mutations.
Nacharaju P.; Lewis J.; Easson C.; Yen S.; Hackett J.; Hutton M.; Yen S.H.;
FEBS Lett. 447:195-199(1999)
Cited for: VARIANTS FTD LEU-618; MET-654 AND TRP-723;
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.