UniProtKB/Swiss-Prot O95278 : Variant p.Arg108Cys
Laforin
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Variant information
Variant position:
108
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
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:
108 (R108C, p.Arg108Cys).
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:
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
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).following page
Variant description:
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
108
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:
R CCTYNENNLVDGVYCLPIGH
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 FLKREPGGELSWEGNGPHHDR CCTYNENNLVDGVYCLPIGH
FLKREPGGALSWEGNGPHHDR CCTYNENNLVDGVYCLPIGH
Mouse FLQREPGGELHWEGNGPHHDR CCTYNEDNLVDGVYCLPVGH
Rat FLQREPGGELHWEGNGPHHDR CCTYNENNLVDGVYCLPVGH
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
1 – 331 Laforin
Domain
1 – 124 CBM20
Alternative sequence
1 – 243 Missing. In isoform 6.
Alternative sequence
1 – 159 MRFRFGVVVPPAVAGARPELLVVGSRPELGRWEPRGAVRLRPAGTAAGDGALALQEPGLWLGEVELAAEEAAQDGAEPGRVDTFWYKFLKREPGGELSWEGNGPHHDRCCTYNENNLVDGVYCLPIGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSR -> MIFNK. In isoform 7.
Alternative sequence
1 – 138 Missing. In isoform 8.
Alternative sequence
102 – 199 NGPHHDRCCTYNENNLVDGVYCLPIGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSRILPNIWLGSCPRQVEHVTIKLKHELGITAVMNFQTEWDIV -> IASRRLPPAQSGSSGPHPQPGPRPRAGPAGPGGARPGLFARVPAHSPGDLG. In isoform 4.
Mutagenesis
99 – 99 W -> A. Strongly reduces phosphatase activity. Strongly reduces glycogen binding.
Mutagenesis
123 – 123 C -> S. No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity.
Mutagenesis
126 – 126 I -> T. Strongly decreased phosphatase activity. No effect on glycogen binding.
Beta strand
108 – 110
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, 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.
