UniProtKB/Swiss-Prot P04156 : Variant p.Thr183Ala
Major prion protein
Gene: PRNP
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Variant information
Variant position:
183
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
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 Alanine (A) at position 183 (T183A, p.Thr183Ala).
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 small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
0
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
Variant description:
In SENF and early-onset dementia; induces loss of glycosylation at N-181.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
183
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:
YRPMDEYSNQNNFVHDCVNI
T IKQHTVTTTTKGENFTETDV
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 YRPMDEYSNQNNFVHDCVNIT IKQHTVTTTTK--------GENFTETDV--
Gorilla YRPMDQYSNQNNFVHDCVNIT IKQHTVTTTTK--------G
YRSVDQYNNQSTFVHDCVNIT VKQHTV-TTTK--------G
Rhesus macaque YRPVDQYSNQNNFVHDCVNIT IKQHTVTTTTK--------G
Chimpanzee YRPMDQYSSQNNFVHDCVNIT IKQHTVTTTTK--------G
Mouse YRPVDQYSNQNNFVHDCVNIT IKQHTVTTTTK--------G
Rat YRPVDQYSNQNNFVHDCVNIT IKQHTVTTTTK--------G
Pig YRPVDQYSNQNSFVHDCVNIT VKQHTVTTTTK--------G
Bovine YRPVDQYSNQNNFVHDCVNIT VKEHTVTTTTK--------G
Rabbit YRPVDQYSNQNSFVHDCVNIT VKQHTVTTTTK--------G
Goat YRPVDQYSNQNNFVHDCVNIT VKQHTVTTTTK--------G
Sheep YRPVDRYSNQNNFVHDCVNIT VKQHTVTTTTK--------G
Cat YRPVDQYSNQNNFVHDCVNIT VKQHTVTTTTK--------G
Chicken YRDYSSPVPQDVFVADCFNIT VTEYSIGPAAKKNTSEAVAA
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
Beta strand
182 – 185
Literature citations
The Thr183Ala mutation, not the loss of the first glycosylation site, alters the physical properties of the prion protein.
Capellari S.; Zaidi S.I.; Long A.C.; Kwon E.E.; Petersen R.B.;
J. Alzheimers Dis. 2:27-35(2000)
Cited for: GLYCOSYLATION AT ASN-181; VARIANT SENF ALA-183; CHARACTERIZATION OF VARIANT SENF ALA-183;
Familial spongiform encephalopathy associated with a novel prion protein gene mutation.
Nitrini R.; Rosemberg S.; Passos-Bueno M.R.; da Silva L.S.; Iughetti P.; Papadopoulos M.; Carrilho P.M.; Caramelli P.; Albrecht S.; Zatz M.; Leblanc A.;
Ann. Neurol. 42:138-146(1997)
Cited for: VARIANT SENF ALA-183;
High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.
Finckh U.; Mueller-Thomsen T.; Mann U.; Eggers C.; Marksteiner J.; Meins W.; Binetti G.; Alberici A.; Hock C.; Nitsch R.M.; Gal A.;
Am. J. Hum. Genet. 66:110-117(2000)
Cited for: VARIANTS EARLY-ONSET DEMENTIA LEU-102; ALA-183 AND LYS-188;
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.