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UniProtKB/Swiss-Prot P10636: Variant p.Lys574Thr

Microtubule-associated protein tau
Gene: MAPT
Variant information

Variant position:  574
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Lysine (K) to Threonine (T) at position 574 (K574T, p.Lys574Thr).
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 polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

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. {ECO:0000269|PubMed:10604746, ECO:0000269|PubMed:11089577, ECO:0000269|PubMed:11117542, ECO:0000269|PubMed:11601501, ECO:0000269|PubMed:11891833}. 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; reduces the ability to promote microtubule assembly by 70%.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  574
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  758
The length of the canonical 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.









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.

Chain 2 – 758 Microtubule-associated protein tau
Repeat 561 – 591 Tau/MAP 1
Region 561 – 685 Microtubule-binding domain
Site 557 – 557 Not glycated
Site 571 – 571 Not glycated
Site 574 – 574 Not glycated
Site 584 – 584 Not glycated
Site 591 – 591 Not glycated
Modified residue 554 – 554 Phosphoserine; by PHK
Modified residue 576 – 576 N6-acetyllysine; alternate
Modified residue 576 – 576 N6-methyllysine; alternate
Modified residue 579 – 579 Phosphoserine; by MARK1, MARK2, MARK3, MARK4, BRSK1, BRSK2 and PHK
Glycosylation 555 – 555 O-linked (GlcNAc) serine
Glycosylation 576 – 576 N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
Cross 571 – 571 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau
Cross 576 – 576 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 584 – 584 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis 579 – 579 S -> A. 8% decrease in microtubule-binding after in vitro phosphorylation of mutant protein.

Literature citations

Pick's disease is associated with mutations in the tau gene.
Pickering-Brown S.; Baker M.; Yen S.-H.; Liu W.-K.; Hasegawa M.; Cairns N.; Lantos P.L.; Rossor M.; Iwatsubo T.; Davies Y.; Allsop D.; Furlong R.; Owen F.; Hardy J.; Mann D.; Hutton M.;
Ann. Neurol. 48:859-867(2000)

Tau gene mutation K257T causes a tauopathy similar to Pick's disease.
Rizzini C.; Goedert M.; Hodges J.R.; Smith M.J.; Jakes R.; Hills R.; Xuereb J.H.; Crowther R.A.; Spillantini M.G.;
J. Neuropathol. Exp. Neurol. 59:990-1001(2000)
Cited for: VARIANT PIDB THR-574;

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.