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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13496: Variant p.Gly378Arg

Myotubularin
Gene: MTM1
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Variant information Variant position: help 378 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 Glycine (G) to Arginine (R) at position 378 (G378R, p.Gly378Arg). 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 glycine (G) to large size and basic (R) 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 CNMX; severe; dramatic decrease in phosphatase activity; does not affect EGFR degradation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 378 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 603 The length of the canonical sequence.
Location on the sequence: help IQVADKVSSGKSSVLVHCSD G WDRTAQLTSLAMLMLDSFYR 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                         IQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYR

Mouse                         IQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYR

Rat                           IRVADKVASGLSSVLVHCSDGWDRTAQLTTLAMLMLDGFYR

Bovine                        IQVADRVSSGKSSVVVHCSDGWDRTAQLTSLAMLMLDSFYR

Xenopus laevis                IQVADKVASGKSSVVVHCSDGWDRTAQLTSLAMLMLDSYYR

Xenopus tropicalis            IQVADKVASGKSSVVVHCSDGWDRTAQLTSLAMLMLDSYYR

Baker's yeast                 I-------SGMIAAI--CTHPFDVGKTRWQISMM-------
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 – 603 Myotubularin
Domain 163 – 538 Myotubularin phosphatase
Active site 375 – 375 Phosphocysteine intermediate
Mutagenesis 375 – 375 C -> A. No effect on subcellular location.
Mutagenesis 375 – 375 C -> S. Lacks activity toward PI3P. Does not affect interaction with DES or MTMR12.
Mutagenesis 377 – 377 D -> A. No effect on subcellular location.
Mutagenesis 380 – 380 D -> A. Does not affect interaction with DES.
Mutagenesis 394 – 394 D -> A. Produces an unstable protein.



Literature citations
Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate.
Taylor G.S.; Maehama T.; Dixon J.E.;
Proc. Natl. Acad. Sci. U.S.A. 97:8910-8915(2000)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS LEU-205; LEU-241; ASN-376; ARG-378 AND CYS-397; MUTAGENESIS OF CYS-375; Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.
Laporte J.; Guiraud-Chaumeil C.; Vincent M.-C.; Mandel J.-L.; Tanner S.M.; Liechti-Gallati S.; Wallgren-Pettersson C.; Dahl N.; Kress W.; Bolhuis P.A.; Fardeau M.; Samson F.; Bertini E.;
Hum. Mol. Genet. 6:1505-1511(1997)
Cited for: VARIANTS CNMX CYS-69; PHE-70; PRO-87; SER-189; LEU-205; PRO-229; CYS-241; ASN-376; ARG-378; CYS-397; ALA-402; GLN-421; ASN-431; ASN-433 AND PRO-469; Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy.
Buj-Bello A.; Biancalana V.; Moutou C.; Laporte J.; Mandel J.-L.;
Hum. Mutat. 14:320-325(1999)
Cited for: VARIANTS CNMX SER-179; THR-225; CYS-241; SER-264; GLY-294 DEL; ARG-378 AND ASN-510; Characterization of mutations in fifty North American patients with X-linked myotubular myopathy.
Herman G.E.; Kopacz K.; Zhao W.; Mills P.L.; Metzenberg A.; Das S.;
Hum. Mutat. 19:114-121(2002)
Cited for: VARIANTS CNMX PHE-49; CYS-69; SER-179; ILE-186; LEU-205; MET-227; PRO-228; CYS-241; GLY-279; ARG-378; PRO-391; CYS-397; ARG-402 AND GLN-421; Rapid scanning of myotubularin (MTM1) gene by denaturing high-performance liquid chromatography (DHPLC).
Flex E.; De Luca A.; D'Apice M.R.; Buccino A.; Dallapiccola B.; Novelli G.;
Neuromuscul. Disord. 12:501-505(2002)
Cited for: VARIANTS CNMX ILE-197; SER-199; ARG-378 AND ARG-402;
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.