UniProtKB/Swiss-Prot P10636: Variant p.Ser669Leu

Microtubule-associated protein tau
Gene: MAPT
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Variant information Variant position:

669 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Serine (S) to Leucine (L) at position 669 (S669L, p.Ser669Leu). 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 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
Variant description:

In fatal respiratory hypoventilation; unusual apparent autosomal recessive inheritance; reduced binding to microtubules as well as increased fibrillization and aggregation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs63750425 [ dbSNP | Ensembl ]

Sequence information Variant position:

669 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:

PGGGQVEVKSEKLDFKDRVQ S KIGSLDNITHVPGGGNKKIE 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                         PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

Gorilla                       PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

Rhesus macaque                PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

Chimpanzee                    PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

Mouse                         PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

Rat                           PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

Bovine                        PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

Goat                          PGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIE

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.

Type	Positions	Description
Chain	2 – 758	Microtubule-associated protein tau
Repeat	654 – 685	Tau/MAP 4
Region	561 – 685	Microtubule-binding domain
Site	657 – 657	Not glycated
Site	660 – 660	Not glycated
Site	687 – 687	Not glycated
Modified residue	660 – 660	N6-acetyllysine; alternate
Modified residue	664 – 664	N6-acetyllysine; alternate
Modified residue	666 – 666	Omega-N-methylarginine
Modified residue	669 – 669	Phosphoserine; by PHK
Modified residue	673 – 673	Phosphoserine
Modified residue	686 – 686	N6-acetyllysine; alternate
Glycosylation	664 – 664	N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
Glycosylation	670 – 670	N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
Glycosylation	686 – 686	N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
Cross	660 – 660	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross	664 – 664	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross	670 – 670	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau
Cross	686 – 686	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Beta strand	667 – 671

Literature citations
An English kindred with a novel recessive tauopathy and respiratory failure.
Nicholl D.J.; Greenstone M.A.; Clarke C.E.; Rizzu P.; Crooks D.; Crowe A.; Trojanowski J.Q.; Lee V.M.-Y.; Heutink P.;
Ann. Neurol. 54:682-686(2003)
Cited for: VARIANT FATAL RESPIRATORY HYPOVENTILATION LEU-669; CHARACTERIZATION OF VARIANT FATAL RESPIRATORY HYPOVENTILATION LEU-669;

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.