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UniProtKB/Swiss-Prot P10636: Variant p.Gly706Arg

Microtubule-associated protein tau
Gene: MAPT
Variant information

Variant position:  706
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 Glycine (G) to Arginine (R) at position 706 (G706R, p.Gly706Arg).
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 glycine (G) to large size and basic (R)
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. {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; in vitro the mutation reduces the ability of tau to promote microtubule assembly by 25 to 30%.
Any additional useful information about the variant.

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



Sequence information

Variant position:  706
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:   KKIETHKLTFRENAKAKTDH  G AEIVYKSPVVSGDTSPRHLS
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                         KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

Gorilla                       KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

Rhesus macaque                KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

Chimpanzee                    KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

Mouse                         KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

Rat                           KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

Bovine                        KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

Goat                          KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLS

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
Site 712 – 712 Not glycated
Modified residue 686 – 686 N6-acetyllysine; alternate
Modified residue 702 – 702 N6-acetyllysine; alternate
Modified residue 711 – 711 Phosphotyrosine
Modified residue 713 – 713 Phosphoserine; by CK1 and PDPK1
Modified residue 717 – 717 Phosphoserine; alternate
Modified residue 720 – 720 Phosphothreonine
Modified residue 721 – 721 Phosphoserine; by CK1 and PDPK1
Modified residue 726 – 726 Phosphoserine
Glycosylation 686 – 686 N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
Glycosylation 717 – 717 O-linked (GlcNAc) serine; alternate
Cross 686 – 686 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 692 – 692 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 702 – 702 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Mutagenesis 713 – 713 S -> E. No association with plasma membrane.
Mutagenesis 721 – 721 S -> E. No association with plasma membrane.
Mutagenesis 726 – 726 S -> E. No association with plasma membrane.


Literature citations

Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits.
Murrell J.R.; Spillantini M.G.; Zolo P.; Guazzelli M.; Smith M.J.; Hasegawa M.; Redi F.; Crowther R.A.; Pietrini P.; Ghetti B.; Goedert M.;
J. Neuropathol. Exp. Neurol. 58:1207-1226(1999)
Cited for: VARIANT PIDB ARG-706;

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)
Cited for: VARIANTS PIDB THR-574 AND ARG-706; CHARACTERIZATION OF VARIANTS PIDB THR-574 AND ARG-706;

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.