Home  |  Contact

UniProtKB/Swiss-Prot O95278: Variant p.Leu310Trp

Laforin
Gene: EPM2A
Variant information

Variant position:  310
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Leucine (L) to Tryptophan (W) at position 310 (L310W, p.Leu310Trp).
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 (L) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In EPM2; causes location of isoform 1 at cytoplasmic punctae; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2.
Any additional useful information about the variant.



Sequence information

Variant position:  310
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  331
The length of the canonical sequence.

Location on the sequence:   RKVQYFLMAKRPAVYIDEEA  L ARAQEDFFQKFGKVRSSVCS
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                         RKVQYFLMAKRPAVYIDEEALARAQEDFFQKFGKVRSSVCS

                              RKVQYFLMAKRPAVYIDEDALARAEEDFFQKFGKVRSSVCS

Mouse                         RKVQYFIMAKRPAVYIDEDALAQAQQDFSQKFGKVHSSICA

Rat                           RKVQYFIMAKRPAVYIDEEALAQAQQDFFQKFGKVHSSICT

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.

TypePositionsDescription
Chain 1 – 331 Laforin
Domain 156 – 323 Tyrosine-protein phosphatase
Binding site 304 – 304 Substrate
Site 329 – 329 Required for homodimerization
Alternative sequence 200 – 331 Missing. In isoform 4.
Alternative sequence 294 – 331 YFLMAKRPAVYIDEEALARAQEDFFQKFGKVRSSVCSL -> PSTDAAPGGVPAACAAGEGTHRVRALQRWGGPLHRGCLRLAPVCDGLESEEGAVFPHGQEAGCLH. In isoform 5.
Alternative sequence 310 – 320 LARAQEDFFQK -> ASQDTFPL. In isoform 2.
Mutagenesis 321 – 321 F -> S. Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding.
Mutagenesis 329 – 329 C -> S. Fails to homodimerize. Does not affect carbohydrate binding, interaction with NHLRC1, phosphatase activity, or ubiquitination by NHLRC1.
Mutagenesis 329 – 329 C -> S. No effect on homodimerization.
Helix 307 – 321


Literature citations

Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin.
Singh S.; Satishchandra P.; Shankar S.K.; Ganesh S.;
Hum. Mutat. 29:E1-12(2008)
Cited for: VARIANTS EPM2 ASN-140; TYR-148; LYS-210 AND TRP-310; CHARACTERIZATION OF VARIANT EPM2 TRP-310; SUBCELLULAR LOCATION;

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.