UniProtKB/Swiss-Prot P04156: Variant p.Glu219Lys

Major prion protein
Gene: PRNP
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Variant information Variant position:

219 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 Glutamate (E) to Lysine (K) at position 219 (E219K, p.Glu219Lys). 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 acidic (E) to large size and basic (K) 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
Polymorphism:

The five tandem octapeptide repeats region is highly unstable. Insertions or deletions of octapeptide repeat units are associated to prion disease.A number of polymorphisms confer resistance to prion diseases (PubMed:1439789, PubMed:19923577, PubMed:26061765, PubMed:9482303). Val-127 has been selected for in response to the Kuru epidemic and confers resistance to prion disease by acting as a 'dominant negative' inhibitor of prion conversion (PubMed:26061765). Val-127 is not only itself resistant to conformational conversion, but also inhibits conversion of wild-type proteins. Confers protection against classical Creutzfeldt-Jakob disease (CJD) and Kuru in the heterozygous state, but can be infected with variant CJD prions, resulting from exposure to bovine spongiform encephalopathy prions. Confers complete resistance to all prion strains when homozygous (PubMed:26061765). Always associated with M-129 variant (PubMed:26061765). Val-129 confers relative protection against acquired, sporadic and some inherited prion diseases in the heterozygous state, possibly by preventing homodimerization (PubMed:1439789). Lys-219 confers relative protection against sporadic Creutzfeldt-Jakob disease (CJD) in the heterozygous state (PubMed:9482303). - Additional information on the polymorphism described.
Variant description:

Confers relative protection against sporadic Creutzfeldt-Jakob disease (CJD) in the heterozygous state. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1800014 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

TETDVKMMERVVEQMCITQY E RESQAYYQRGSSMVLFSSPP 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                         TETDV--KMMERVVEQMCITQYERESQAYYQ--RGSSMVLFSSPP--

Gorilla                       TETDV--KMMERVVEQMCITQYERESQAYYQ--RGSSMVLF

                              TETDI--KMMERVVEQMCITQYQRESEAYYQ--RGASVILF

Rhesus macaque                TETDV--KMMERVVEQMCITQYEKESQAYYQ--RGSSMVLF

Chimpanzee                    TETDV--KMMERVVEQMCITQYERESQAYYQ--RGSSMVLF

Mouse                         TETDV--KMMERVVEQMCVTQYQKESQAYYDGRRSSSTVLF

Rat                           TETDV--KMMERVVEQMCVTQYQKESQAYYDG-RRSSAVLF

Pig                           TETDV--KMIERVVEQMCITQYQKEYEAYAQ--RGASVILF

Bovine                        TETDI--KMMERVVEQMCITQYQRESQAYYQ--RGASVILF

Rabbit                        TETDI--KIMERVVEQMCITQYQQESQAAYQ--RAAGVLLF

Goat                          TETDI--KIMERVVEQMCITQYQRESQAYYQ--RGASVILF

Sheep                         TETDI--KIMERVVEQMCITQYQRESQAYYQ--RGASVILF

Cat                           TETDM--KIMERVVEQMCVTQYQKESEAYYQ--RRASAILF

Chicken                       TEVEMENKVVTKVIREMCVQQYRE-----YR--LASGIQLH

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	23 – 230	Major prion protein
Region	23 – 230	Interaction with GRB2, ERI3 and SYN1
Lipidation	230 – 230	GPI-anchor amidated serine

Literature citations
Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Straussler-Scheinker disease (PrP-P102L mutation).
Barbanti P.; Fabbrini G.; Salvatore M.; Petraroli R.; Cardone F.; Maras B.; Equestre M.; Macchi G.; Lenzi G.L.; Pocchiari M.;
Neurology 47:734-741(1996)
Cited for: VARIANT GSD LEU-102; VARIANT LYS-219; Protective prion protein polymorphisms against sporadic Creutzfeldt-Jakob disease.
Shibuya S.; Higuchi J.; Shin R.W.; Tateishi J.; Kitamoto T.;
Lancet 351:419-419(1998)
Cited for: VARIANT LYS-219; CHARACTERIZATION OF VARIANT LYS-219; POLYMORPHISM;

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.