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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13496: Variant p.Ser376Asn

Myotubularin
Gene: MTM1
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Variant information Variant position: help 376 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 Serine (S) to Asparagine (N) at position 376 (S376N, p.Ser376Asn). 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 small size and polar (S) to medium size and polar (N) 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 CNMX; dramatic decrease in phosphatase activity. Any additional useful information about the variant.


Sequence information Variant position: help 376 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 GAIQVADKVSSGKSSVLVHC S DGWDRTAQLTSLAMLMLDSF 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                         GAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSF

Mouse                         GAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSF

Rat                           GAIRVADKVASGLSSVLVHCSDGWDRTAQLTTLAMLMLDGF

Bovine                        GAIQVADRVSSGKSSVVVHCSDGWDRTAQLTSLAMLMLDSF

Xenopus laevis                GAIQVADKVASGKSSVVVHCSDGWDRTAQLTSLAMLMLDSY

Xenopus tropicalis            GAIQVADKVASGKSSVVVHCSDGWDRTAQLTSLAMLMLDSY

Baker's yeast                 GCI-------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
Binding site 376 – 376
Binding site 376 – 376
Binding site 377 – 377
Binding site 377 – 377
Binding site 378 – 378
Binding site 378 – 378
Binding site 379 – 379
Binding site 379 – 379
Binding site 380 – 380
Binding site 380 – 380
Binding site 381 – 381
Binding site 381 – 381
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;
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.