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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95278: Variant p.Thr194Ile

Laforin
Gene: EPM2A
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Variant information Variant position: help 194 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 Threonine (T) to Isoleucine (I) at position 194 (T194I, p.Thr194Ile). 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 (T) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In MELF1; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 194 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 EHVTIKLKHELGITAVMNFQ T EWDIVQNSSGCNRYPEPMTP 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                         EHVTIKLKHELGITAVMNFQTEWDIVQNSSGCNRYPEPMTP

                              EHITIKLKHELGITAVMNFQTEWDIVQNSSGCNRYPEPMTP

Mouse                         EHVTIKLKHELGVTAVMNFQTEWDIIQNSSGCNRYPEPMTP

Rat                           EHVTIKLKHELGITAVMNFQTEWDIIQNSSGCNRYPEPMTP
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 197 – 197
Alternative sequence 1 – 243 Missing. In isoform 6.
Alternative sequence 102 – 199 NGPHHDRCCTYNENNLVDGVYCLPIGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSRILPNIWLGSCPRQVEHVTIKLKHELGITAVMNFQTEWDIV -> IASRRLPPAQSGSSGPHPQPGPRPRAGPAGPGGARPGLFARVPAHSPGDLG. In isoform 4.
Alternative sequence 160 – 293 Missing. In isoform 5.
Mutagenesis 187 – 187 T -> D. Abolishes interaction with NHLRC1.
Mutagenesis 194 – 194 T -> D. Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2.
Mutagenesis 197 – 197 D -> A. Strongly decreased phosphatase activity. No effect on glycogen binding.
Mutagenesis 205 – 205 C -> S. No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity.



Literature citations
A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2).
Serratosa J.M.; Gomez-Garre P.; Gallardo M.E.; Anta B.; de Bernabe D.B.; Lindhout D.; Augustijn P.B.; Tassinari C.A.; Malafosse R.M.; Topcu M.; Grid D.; Dravet C.; Berkovic S.F.; de Cordoba S.R.;
Hum. Mol. Genet. 8:345-352(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 82-331 (ISOFORMS 1 AND 2); VARIANTS MELF1 HIS-171; ILE-194; SER-279 AND ASN-294; 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.