UniProtKB/Swiss-Prot P02545: Variant p.Glu33Asp

Prelamin-A/C
Gene: LMNA
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Variant information Variant position:

33 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Glutamate (E) to Aspartate (D) at position 33 (E33D, p.Glu33Asp). 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 acidic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

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:

In CMT2; autosomal dominant form. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs57966821 [ dbSNP | Ensembl ]

Sequence information Variant position:

33 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

664 The length of the canonical sequence.
Location on the sequence:

GAQASSTPLSPTRITRLQEK E DLQELNDRLAVYIDRVRSLE 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                         GAQASSTPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLE

Mouse                         GAQASSTPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLE

Rat                           GAQASSTPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLE

Pig                           GAQASSTPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLE

Chicken                       GG-PSGTPLSPTRITRLQEKEDLQELNDRLAVYIDKVRSLE

Xenopus laevis                ----THTPLSPTRITRLQEKEDLQGLNDRLAVYIDKVRSLE

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 – 661	Prelamin-A/C
Chain	1 – 646	Lamin-A/C
Domain	31 – 387	IF rod
Region	1 – 130	Interaction with MLIP
Region	1 – 33	Head
Modified residue	18 – 18	Phosphoserine
Modified residue	19 – 19	Phosphothreonine
Modified residue	22 – 22	Phosphoserine; by CDK1
Modified residue	32 – 32	N6-acetyllysine; alternate
Modified residue	32 – 32	N6-succinyllysine; alternate
Modified residue	51 – 51	Phosphoserine
Cross	32 – 32	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Alternative sequence	1 – 99	Missing. In isoform 5.
Alternative sequence	8 – 119	Missing. In isoform 4.
Mutagenesis	22 – 22	S -> A. Impaired disassembly of the nuclear envelope during mitosis. Strongly decreased disassembly of the nuclear envelope during mitosis; when associates with A-392. Decreased accumulation to the double-strand break (DSB) sites.
Mutagenesis	22 – 22	S -> D. Mimics phosphorylation; increased localization to the nucleoplasm during interphase. Causes redistribution between the nucleus and the cytoplasm during interphase; when associated with D-392 and D-628. Decreased nuclear mechanical properties. Increased accumulation to the double-strand break (DSB) sites.
Mutagenesis	28 – 28	R -> T. Impaired lamin assembly.
Mutagenesis	32 – 32	K -> Q. Impaired lamin assembly.
Mutagenesis	41 – 41	R -> H. Impaired lamin assembly.
Helix	28 – 70

Literature citations
A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia.
Goizet C.; Yaou R.B.; Demay L.; Richard P.; Bouillot S.; Rouanet M.; Hermosilla E.; Le Masson G.; Lagueny A.; Bonne G.; Ferrer X.;
J. Med. Genet. 41:E29-E29(2004)
Cited for: VARIANT CMT2 ASP-33; VARIANT EDMD2 GLY-33;

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.