UniProtKB/Swiss-Prot P42858: Variant p.Gly551Glu

Huntingtin
Gene: HTT
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Variant information Variant position:

551 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 Glycine (G) to Glutamate (E) at position 551 (G551E, p.Gly551Glu). 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 medium size and acidic (E) 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
Polymorphism:

The poly-Gln region of HTT is highly polymorphic (10 to 35 repeats) in the normal population and is expanded to about 36-120 repeats in Huntington disease patients. The repeat length usually increases in successive generations, but contracts also on occasion. The adjacent poly-Pro region is also polymorphic and varies between 7-12 residues. Polyglutamine expansion leads to elevated susceptibility to apopain cleavage and likely result in accelerated neuronal apoptosis (PubMed:8696339). Additional information on the polymorphism described.
Variant description:

Inhibits proteolytic cleavage at D-550; abolishes post-translational myristoylation; results in increased cleavage at D-511. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs118005095 [ dbSNP | Ensembl ]

Sequence information Variant position:

551 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

3142 The length of the canonical sequence.
Location on the sequence:

SHSSSQVSAVPSDPAMDLND G TQASSPISDSSQTTTEGPDS 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                         SHSSSQVSAVPSDPAMDLNDGTQASSPISDSSQTTTEGPDS

Mouse                         SHSSSQFSAVPSDPAMDLNDGTQASSPISDSSQTTTEGPDS

Rat                           SHSSSQFSAVPSDPAMDLNDGTQASSPISDSSQTTTEGPDS

Slime mold                    AQSVKFFPKLFNDEFFKHQPSTIDSNTVTSAEDHICRDYLL

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	1 – 3142	Huntingtin
Chain	551 – 584	Huntingtin, myristoylated N-terminal fragment
Region	517 – 583	Disordered
Compositional bias	531 – 583	Polar residues
Site	550 – 551	Cleavage; by caspase-3
Lipidation	551 – 551	N-myristoyl glycine
Mutagenesis	550 – 550	D -> E. Loss of proteolytic cleavage. Loss of myristoylation.
Mutagenesis	551 – 551	G -> A. Loss of myristoylation.
Mutagenesis	551 – 551	G -> S. Loss of myristoylation.

Literature citations
A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease.
Martin D.D.O.; Kay C.; Collins J.A.; Nguyen Y.T.; Slama R.A.; Hayden M.R.;
Sci. Rep. 8:8096-8096(2018)
Cited for: PROTEOLYTIC CLEAVAGE AT ASP-550; MYRISTOYLATION AT GLY-551; MUTAGENESIS OF ASP-550 AND GLY-551; CHARACTERIZATION OF VARIANT GLU-551;

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.