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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95278: Variant p.Gln293Leu

Laforin
Gene: EPM2A
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Variant information Variant position: help 293 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Glutamine (Q) to Leucine (L) at position 293 (Q293L, p.Gln293Leu). 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: help Change from medium size and polar (Q) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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: help In MELF1; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 293 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 331 The length of the canonical sequence.
Location on the sequence: help STAAVCGWLQYVMGWNLRKV Q YFLMAKRPAVYIDEEALARA 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         STAAVCGWLQYVMGWNLRKVQYFLMAKRPAVYIDEEALARA

                              STAAVCGWLQYVMGWNLRKVQYFLMAKRPAVYIDEDALARA

Mouse                         STAAVCGWLHYVIGWNLRKVQYFIMAKRPAVYIDEDALAQA

Rat                           STAAVCGWLHYVIGWSLRKVQYFIMAKRPAVYIDEEALAQA
Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 331 Laforin
Domain 156 – 323 Tyrosine-protein phosphatase
Binding site 304 – 304
Alternative sequence 160 – 293 Missing. In isoform 5.
Alternative sequence 200 – 331 Missing. In isoform 4.
Helix 289 – 296



Literature citations
Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy.
Minassian B.A.; Lee J.R.; Herbrick J.-A.; Huizenga J.; Soder S.; Mungall A.J.; Dunham I.; Gardner R.; Fong C.G.; Carpenter S.; Jardim L.; Satishchandra P.; Andermann E.; Snead O.C. III; Lopes-Cendes I.; Tsui L.-C.; Delgado-Escueta A.V.; Rouleau G.A.; Scherer S.W.;
Nat. Genet. 20:171-174(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2); ALTERNATIVE SPLICING; TISSUE SPECIFICITY; VARIANTS MELF1 CYS-108; SER-279 AND LEU-293; VARIANT ASP-114; Laforin, defective in the progressive myoclonus epilepsy of Lafora type, is a dual-specificity phosphatase associated with polyribosomes.
Ganesh S.; Agarwala K.L.; Ueda K.; Akagi T.; Shoda K.; Usui T.; Hashikawa T.; Osada H.; Delgado-Escueta A.V.; Yamakawa K.;
Hum. Mol. Genet. 9:2251-2261(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTIONAL CHARACTERIZATION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS MELF1 HIS-171 AND LEU-293; Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation.
Fernandez-Sanchez M.E.; Criado-Garcia O.; Heath K.E.; Garcia-Fojeda B.; Medrano-Fernandez I.; Gomez-Garre P.; Sanz P.; Serratosa J.M.; Rodriguez de Cordoba S.;
Hum. Mol. Genet. 12:3161-3171(2003)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SELF-INTERACTION; SUBCELLULAR LOCATION; GLYCOGEN-BINDING; INTERACTION WITH PPP1R3C; TISSUE SPECIFICITY; MUTAGENESIS OF ASP-235 AND CYS-266; ACTIVE SITE; CHARACTERIZATION OF VARIANTS MELF1 GLY-32; LEU-84; CYS-108; ILE-194; SER-240; SER-279; LEU-293; ASN-294 AND LEU-301; Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype.
Ganesh S.; Delgado-Escueta A.V.; Suzuki T.; Francheschetti S.; Riggio C.; Avanzini G.; Rabinowicz A.; Bohlega S.; Bailey J.; Alonso M.E.; Rasmussen A.; Thomson A.E.; Ochoa A.; Prado A.J.; Medina M.T.; Yamakawa K.;
Hum. Mol. Genet. 11:1263-1271(2002)
Cited for: VARIANTS MELF1 PRO-25; CYS-108; HIS-171 AND LEU-293; CHARACTERIZATION OF VARIANTS MELF1 GLY-32; CYS-108; ILE-194; SER-279 AND ASN-294;
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.