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UniProtKB/Swiss-Prot P10636: Variant p.Arg5Leu

Microtubule-associated protein tau
Gene: MAPT
Variant information

Variant position:  5
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 Arginine (R) to Leucine (L) at position 5 (R5L, p.Arg5Leu).
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 (R) to medium size and hydrophobic (L)
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:  Progressive supranuclear palsy 1 (PSNP1) [MIM:601104]: Characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613. {ECO:0000269|PubMed:10534245, ECO:0000269|PubMed:11220749, ECO:0000269|PubMed:12325083, ECO:0000269|PubMed:14991828, ECO:0000269|PubMed:14991829, ECO:0000269|PubMed:16157753}. 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 PSNP1; delays assembly initiation and lowers the mass of microtubules formed; but the assembly rate is increased compared to normal tau.
Any additional useful information about the variant.

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

Sequence information

Variant position:  5
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:   MAEP  R QEFEVMEDHAGTYGLGDRKD
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                         MAEPRQEFEVMEDHAGTYGLGDRKD

Gorilla                       MAEPRQEFEVMEDHAGTYGLGDRKD

Rhesus macaque                MAEPRQEFDVMEDHAGTYGLGDRKD

Chimpanzee                    MAEPRQEFEVMEDHAGTYGLGDRKD

Mouse                         MADPRQEFDTMEDHA----------

Rat                           MAEPRQEFDTMEDQA----------

Bovine                        MAEPRQEFDVMEDHA----------

Goat                          MAEPRQEFDVMEDHA----------

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.

Initiator methionine 1 – 1 Removed
Chain 2 – 758 Microtubule-associated protein tau
Site 24 – 24 Not glycated
Modified residue 2 – 2 N-acetylalanine
Modified residue 18 – 18 Phosphotyrosine; by FYN

Literature citations

An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype.
Poorkaj P.; Muma N.A.; Zhukareva V.; Cochran E.J.; Shannon K.M.; Hurtig H.; Koller W.C.; Bird T.D.; Trojanowski J.Q.; Lee V.M.-Y.; Schellenberg G.D.;
Ann. Neurol. 52:511-516(2002)

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.