Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95278: Variant p.Arg171His

Laforin
Gene: EPM2A
Feedback?
Variant information Variant position: help 171 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 Arginine (R) to Histidine (H) at position 171 (R171H, p.Arg171His). 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 large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In MELF1; results in ubiquitin-positive perinuclear aggregates; no effect on glycogen binding; abolishes phosphatase activity; may affect proper folding. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 171 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 GHQAMHYSRILPNIWLGSCP R QVEHVTIKLKHELGITAVMN 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                         GHQAMHYSRILPNIWLGSCPRQVEHVTIKLKHELGITAVMN

                              GHQAMHYSRILPNIWLGSCPRQVEHITIKLKHELGITAVMN

Mouse                         GHQAMHYSRILPNIWLGSCPRQLEHVTIKLKHELGVTAVMN

Rat                           GHQAMHYSRILPNIWLGSCPRQLEHVTIKLKHELGITAVMN
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
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 168 – 168 S -> AD. Abolishes interaction with NHLRC1.
Mutagenesis 169 – 169 C -> S. No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity.
Mutagenesis 169 – 169 C -> S. No effect on phosphatase activity.
Mutagenesis 171 – 171 R -> A. No effect on phosphatase activity.
Mutagenesis 187 – 187 T -> D. Abolishes interaction with NHLRC1.



Literature citations
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; 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; Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.
Raththagala M.; Brewer M.K.; Parker M.W.; Sherwood A.R.; Wong B.K.; Hsu S.; Bridges T.M.; Paasch B.C.; Hellman L.M.; Husodo S.; Meekins D.A.; Taylor A.O.; Turner B.D.; Auger K.D.; Dukhande V.V.; Chakravarthy S.; Sanz P.; Woods V.L. Jr.; Li S.; Vander Kooi C.W.; Gentry M.S.;
Mol. Cell 57:261-272(2015)
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-329 IN COMPLEX WITH MALTOHEXAOSE AND PHOSPHATE; CATALYTIC ACTIVITY; FUNCTION; SUBUNIT; MUTAGENESIS OF VAL-8; LYS-87; TRP-99; ILE-126; THR-142; ASP-197; MET-236 AND CYS-266; CHARACTERIZATION OF VARIANTS MELF1 GLY-32; HIS-171; SER-240; 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; Loss of function of the cytoplasmic isoform of the protein laforin (EPM2A) causes Lafora progressive myoclonus epilepsy.
Ianzano L.; Young E.J.; Zhao X.C.; Chan E.M.; Rodriguez M.T.; Torrado M.V.; Scherer S.W.; Minassian B.A.;
Hum. Mutat. 23:170-176(2004)
Cited for: VARIANTS MELF1 PRO-91; HIS-171 AND SER-279; CATALYTIC ACTIVITY; 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.