UniProtKB/Swiss-Prot P04156: Variant p.Thr188Arg

Major prion protein
Gene: PRNP
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Variant information Variant position:

188 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 Threonine (T) to Arginine (R) at position 188 (T188R, p.Thr188Arg). 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 polar (T) to large size and basic (R) 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.
Other resources:

Links to websites of interest for the variant.

Variant rs372878791 [ dbSNP | Ensembl ]

Sequence information Variant position:

188 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:

EYSNQNNFVHDCVNITIKQH T VTTTTKGENFTETDVKMMER 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                         EYSNQNNFVHDCVNITIKQHTVTTTTK--------GENFTETDV--KMMER

Gorilla                       QYSNQNNFVHDCVNITIKQHTVTTTTK--------GENFTE

                              QYNNQSTFVHDCVNITVKQHTV-TTTK--------GENFTE

Rhesus macaque                QYSNQNNFVHDCVNITIKQHTVTTTTK--------GENFTE

Chimpanzee                    QYSSQNNFVHDCVNITIKQHTVTTTTK--------GENFTE

Mouse                         QYSNQNNFVHDCVNITIKQHTVTTTTK--------GENFTE

Rat                           QYSNQNNFVHDCVNITIKQHTVTTTTK--------GENFTE

Pig                           QYSNQNSFVHDCVNITVKQHTVTTTTK--------GENFTE

Bovine                        QYSNQNNFVHDCVNITVKEHTVTTTTK--------GENFTE

Rabbit                        QYSNQNSFVHDCVNITVKQHTVTTTTK--------GENFTE

Goat                          QYSNQNNFVHDCVNITVKQHTVTTTTK--------GENFTE

Sheep                         RYSNQNNFVHDCVNITVKQHTVTTTTK--------GENFTE

Cat                           QYSNQNNFVHDCVNITVKQHTVTTTTK--------GENFTE

Chicken                       SPVPQDVFVADCFNITVTEYSIGPAAKKNTSEAVAAANQTE

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
Glycosylation	181 – 181	N-linked (GlcNAc...) asparagine
Glycosylation	197 – 197	N-linked (GlcNAc...) asparagine
Disulfide bond	179 – 214

Literature citations
Molecular genetics of human prion diseases in Germany.
Windl O.; Giese A.; Schulz-Schaeffer W.; Zerr I.; Skworc K.; Arendt S.; Oberdieck C.; Bodemer M.; Poser S.; Kretzschmar H.A.;
Hum. Genet. 105:244-252(1999)
Cited for: VARIANTS ARG-188 AND SER-238;

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.