UniProtKB/SwissProt variant VAR

Variant information

Variant position:

200

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Glutamate (E) to Lysine (K) at position 200 (E200K, p.Glu200Lys).

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

Involvement in disease:

Creutzfeldt-Jakob disease (CJD) [MIM:123400]: Occurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected animal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness. {ECO:0000269|PubMed:10790216, ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:1671440, ECO:0000269|PubMed:1975028, ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:7902693, ECO:0000269|PubMed:7906019, ECO:0000269|PubMed:7913755, ECO:0000269|PubMed:8461023, ECO:0000269|PubMed:8909447}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In CJD.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28933385 [ dbSNP | Ensembl ]

Sequence information

Variant position:

200

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:

VNITIKQHTVTTTTKGENFT E TDVKMMERVVEQMCITQYER

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                         VNITIKQHTVTTTTK--------GENFTETDV--KMMERVVEQMCITQYER

Gorilla                       VNITIKQHTVTTTTK--------GENFTETDV--KMMERVV

                              VNITVKQHTVTTT-K--------GENFTETDI--KMMERVV

Rhesus macaque                VNITIKQHTVTTTTK--------GENFTETDV--KMMERVV

Chimpanzee                    VNITIKQHTVTTTTK--------GENFTETDV--KMMERVV

Mouse                         VNITIKQHTVTTTTK--------GENFTETDV--KMMERVV

Rat                           VNITIKQHTVTTTTK--------GENFTETDV--KMMERVV

Pig                           VNITVKQHTVTTTTK--------GENFTETDV--KMIERVV

Bovine                        VNITVKEHTVTTTTK--------GENFTETDI--KMMERVV

Rabbit                        VNITVKQHTVTTTTK--------GENFTETDI--KIMERVV

Goat                          VNITVKQHTVTTTTK--------GENFTETDI--KIMERVV

Sheep                         VNITVKQHTVTTTTK--------GENFTETDI--KIMERVV

Cat                           VNITVKQHTVTTTTK--------GENFTETDM--KIMERVV

Chicken                       FNITVTEYSIGPAAKKNTSEAVAAANQTEVEMENKVVTKVI

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

Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases.
Zhang Y.; Swietnicki W.; Zagorski M.G.; Surewicz W.K.; Soennichsen F.D.;
J. Biol. Chem. 275:33650-33654(2000)
Cited for: STRUCTURE BY NMR OF 90-231 OF MUTANT LYS-200;

Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt-Jakob disease in Slovakia.
Goldfarb L.; Mitrova E.; Brown P.; Toh B.K.; Gajdusek D.C.;
Lancet 336:514-515(1990)
Cited for: VARIANT CJD LYS-200;

Japanese family with Creutzfeldt-Jakob disease with codon 200 point mutation of the prion protein gene.
Inoue I.; Kitamoto T.; Doh-Ura K.; Shii H.; Goto I.; Tateishi J.;
Neurology 44:299-301(1994)
Cited for: VARIANT CJD LYS-200;

Mutation in codon 200 and polymorphism in codon 129 of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease.
Gabizon R.; Rosenman H.; Meiner Z.; Kahana I.; Kahana E.; Shugart Y.; Ott J.; Prusiner S.B.;
Philos. Trans. R. Soc. Lond., B, Biol. Sci. 343:385-390(1994)
Cited for: VARIANT CJD LYS-200;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04156: Variant p.Glu200Lys