Home  |  Contact

UniProtKB/Swiss-Prot P17661: Variant p.Thr453Ile

Desmin
Gene: DES
Variant information

Variant position:  453
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 Threonine (T) to Isoleucine (I) at position 453 (T453I, p.Thr453Ile).
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 polar (T) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In MFM1; exhibits significantly delayed filament assembly kinetics when bound to NEB and NEBL; enhanced binding affinity towards NEB and NEBL.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  453
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  470
The length of the canonical sequence.

Location on the sequence:   PEQRGSEVHTKKTVMIKTIE  T RDGEVVSEATQQQHEVL
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                         PEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Mouse                         PEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Rat                           PEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Pig                           PEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Bovine                        PEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Chicken                       PDQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Xenopus laevis                PEQRASEVHTKKTVMIKTIETRDGEVLSEASQQHQEIL

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 2 – 470 Desmin
Region 413 – 470 Tail
Region 438 – 453 Interaction with CRYAB


Literature citations

Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects.
Arbustini E.; Pasotti M.; Pilotto A.; Pellegrini C.; Grasso M.; Previtali S.; Repetto A.; Bellini O.; Azan G.; Scaffino M.; Campana C.; Piccolo G.; Vigano M.; Tavazzi L.;
Eur. J. Heart Fail. 8:477-483(2006)
Cited for: VARIANTS MFM1 CYS-16; TRP-406 AND ILE-453;

Nebulin binding impedes mutant desmin filament assembly.
Baker L.K.; Gillis D.C.; Sharma S.; Ambrus A.; Herrmann H.; Conover G.M.;
Mol. Biol. Cell 24:1918-1932(2013)
Cited for: CHARACTERIZATION OF VARIANTS MFM1 PHE-46; ASP-245 AND ILE-453; INTERACTION WITH NEB;

Nebulette is a powerful cytolinker organizing desmin and actin in mouse hearts.
Hernandez D.A.; Bennett C.M.; Dunina-Barkovskaya L.; Wedig T.; Capetanaki Y.; Herrmann H.; Conover G.M.;
Mol. Biol. Cell 27:3869-3882(2016)
Cited for: CHARACTERIZATION OF VARIANTS MFM1 ASP-245 AND ILE-453; INTERACTION WITH NEBL;

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.