UniProtKB/Swiss-Prot P50402: Variant p.Gln133His

Emerin
Gene: EMD
Chromosomal location: Xq28
Variant information

Variant position:  133
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glutamine (Q) to Histidine (H) at position 133 (Q133H, p.Gln133His).
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:  Similar physico-chemical property. Both residues are medium size and polar.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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

Involvement in disease:  Emery-Dreifuss muscular dystrophy 1, X-linked (EDMD1) [MIM:310300]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. {ECO:0000269|PubMed:10323252, ECO:0000269|PubMed:11587540, ECO:0000269|PubMed:15009215, ECO:0000269|PubMed:15328537}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In EDMD1; loss of binding to F-actin.
Any additional useful information about the variant.



Sequence information

Variant position:  133
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  254
The length of the canonical sequence.

Location on the sequence:   PSRAVRQSVTSFPDADAFHH  Q VHDDDLLSSSEEECKDRERP
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                         PSRAVRQSVTSFPDA-DAFHHQVHDDDLLSSSEEECKDRERP

Mouse                         MSKSFRQPGTSLVDA-DTFHHQVR-DDIFSSLEEEGKDRER

Rat                           MSKSFRRPGTSLVDADDTFHHQVR-DDIFSSSEEEGKDRER

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 1 – 254 Emerin
Region 46 – 222 Interaction with F-actin
Modified residue 141 – 141 Phosphoserine
Modified residue 142 – 142 Phosphoserine
Modified residue 143 – 143 Phosphoserine


Literature citations

Emerin caps the pointed end of actin filaments: evidence for an actin cortical network at the nuclear inner membrane.
Holaska J.M.; Kowalski A.K.; Wilson K.L.;
PLoS Biol. 2:1354-1362(2004)
Cited for: FUNCTION; INTERACTION WITH ACTB; SPTAN1 AND F-ACTIN; MUTAGENESIS OF SER-196 AND SER-197; CHARACTERIZATION OF VARIANTS EDMD1 PHE-54; HIS-133 AND HIS-183;

How does a g993t mutation in the emerin gene cause Emery-Dreifuss muscular dystrophy?
Holt I.; Clements L.; Manilal S.; Morris G.E.;
Biochem. Biophys. Res. Commun. 287:1129-1133(2001)
Cited for: VARIANT EDMD1 HIS-133;

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.