UniProtKB/Swiss-Prot P04156: Variant p.Pro238Ser

Major prion protein
Gene: PRNP
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Variant information Variant position:

238 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 Proline (P) to Serine (S) at position 238 (P238S, p.Pro238Ser). 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
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:9482303, PubMed:19923577, PubMed:26061765). 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.

Sequence information Variant position:

238 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:

YERESQAYYQRGSSMVLFSS P PVILLISFLIFLIVG 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                         YERESQAYYQ--RGSSMVLFSSPP--VILLISFLIFLIVG

Gorilla                       YERESQAYYQ--RGSSMVLFSSPP--VILLISFLIF

                              YQRESEAYYQ--RGASVILFSSPP--VILLVSFLIF

Rhesus macaque                YEKESQAYYQ--RGSSMVLFSSPP--VILLISFLIF

Chimpanzee                    YERESQAYYQ--RGSSMVLFSSPP--VILLISFLIF

Mouse                         YQKESQAYYDGRRSSSTVLFSSPP--VILLISFLIF

Rat                           YQKESQAYYDG-RRSSAVLFSSPP--VILLISFLIF

Pig                           YQKEYEAYAQ--RGASVILFSSPP--VILLISFLLF

Bovine                        YQRESQAYYQ--RGASVILFSSPP--VILLISFLIF

Rabbit                        YQQESQAAYQ--RAAGVLLFSSPP--VILLISFLIF

Goat                          YQRESQAYYQ--RGASVILFSPPP--VILLISFLIF

Sheep                         YQRESQAYYQ--RGASVILFSSPP--VILLISFLIF

Cat                           YQKESEAYYQ--RRASAILFSSPP--VILLISFLIF

Chicken                       YRE-----YR--LASGIQLHPADTWLAVLLLLLTTL

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
Propeptide	231 – 253	Removed in mature form
Lipidation	230 – 230	GPI-anchor amidated serine

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.