UniProtKB/Swiss-Prot P10636: Variant p.Pro618Ser

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

Variant position:  618
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 Proline (P) to Serine (S) at position 618 (P618S, p.Pro618Ser).
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 medium size and hydrophobic (P) to small size and polar (S)
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

Variant description:  In FTD and CBD; reduction in the ability to promote microtubule assembly.
Any additional useful information about the variant.



Sequence information

Variant position:  618
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:   KLDLSNVQSKCGSKDNIKHV  P GGGSVQIVYKPVDLSKVTSK
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                         KLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSK

Gorilla                       KLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSK

Rhesus macaque                KLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSK

Chimpanzee                    KLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSK

Mouse                         KLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSK

Rat                           KLDLSNVQSKCGSKDNIKHVPGGGSVHIVYKPVDLSKVTSK

Bovine                        KLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSK

Goat                          KLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSK

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 592 – 622 Tau/MAP 2
Site 607 – 607 Not glycated
Site 611 – 611 Not glycated
Site 615 – 615 Not glycated
Site 628 – 628 Not glycated
Site 634 – 634 Not glycated
Site 638 – 638 Not glycated
Modified residue 602 – 602 Phosphoserine; by PHK
Modified residue 606 – 606 Phosphoserine; by PHK
Modified residue 610 – 610 Phosphoserine; by MARK1; in PHF-tau
Modified residue 622 – 622 Phosphoserine; by MARK1; in PHF-tau
Glycosylation 598 – 598 N-linked (Glc) (glycation); in PHF-tau; in vitro
Disulfide bond 608 – 639
Cross 628 – 628 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau
Alternative sequence 592 – 622 Missing. In isoform Tau-A, isoform Tau-B, isoform Tau-C and isoform Fetal-tau.


Literature citations

FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation.
Sperfeld A.D.; Collatz M.B.; Baier H.; Palmbach M.; Storch A.; Schwarz J.; Tatsch K.; Reske S.; Joosse M.; Heutink P.; Ludolph A.C.;
Ann. Neurol. 46:708-715(1999)
Cited for: VARIANT FTD SER-618;

Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau.
Bugiani O.; Murrell J.R.; Giaccone G.; Hasegawa M.; Ghigo G.; Tabaton M.; Morbin M.; Primavera A.; Carella F.; Solaro C.; Grisoli M.; Savoiardo M.; Spillantini M.G.; Tagliavini F.; Goedert M.; Ghetti B.;
J. Neuropathol. Exp. Neurol. 58:667-677(1999)
Cited for: VARIANT FTD/CBD SER-618;

A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation.
Yasuda M.; Yokoyama K.; Nakayasu T.; Nishimura Y.; Matsui M.; Yokoyama T.; Miyoshi K.; Tanaka C.;
Neurology 55:1224-1227(2000)
Cited for: VARIANT FTD SER-618;

Phenotypic heterogeneity within a new family with the MAPT P301S mutation.
Yasuda M.; Nakamura Y.; Kawamata T.; Kaneyuki H.; Maeda K.; Komure O.;
Ann. Neurol. 58:920-928(2005)
Cited for: VARIANT FTD SER-618;

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.