UniProtKB/Swiss-Prot P10636: Variant p.Ser637Phe

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

Variant position:  637
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 Serine (S) to Phenylalanine (F) at position 637 (S637F, p.Ser637Phe).
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 small size and polar (S) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Involvement in disease:  Pick disease of the brain (PIDB) [MIM:172700]: A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PIDB; markedly reduced ability of tau to promote microtubule assembly.
Any additional useful information about the variant.



Sequence information

Variant position:  637
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:   VPGGGSVQIVYKPVDLSKVT  S KCGSLGNIHHKPGGGQVEVK
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                         VPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

Gorilla                       VPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

Rhesus macaque                VPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

Chimpanzee                    VPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

Mouse                         VPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

Rat                           VPGGGSVHIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

Bovine                        VPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

Goat                          VPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVK

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
Repeat 623 – 653 Tau/MAP 3
Site 628 – 628 Not glycated
Site 634 – 634 Not glycated
Site 638 – 638 Not glycated
Site 648 – 648 Not glycated
Site 657 – 657 Not glycated
Modified residue 622 – 622 Phosphoserine; by MARK1; in PHF-tau
Modified residue 641 – 641 Phosphoserine; by MARK1; in PHF-tau
Disulfide bond 608 – 639
Cross 628 – 628 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau


Literature citations

A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease.
Rosso S.M.; Van Herpen E.; Deelen W.; Kamphorst W.; Severijnen L.-A.; Willemsen R.; Ravid R.; Niermeijer M.F.; Dooijes D.; Smith M.J.; Goedert M.; Heutink P.; Van Swieten J.C.;
Ann. Neurol. 51:373-376(2002)
Cited for: VARIANT PIDB PHE-637; CHARACTERIZATION OF VARIANT PIDB PHE-637;

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.