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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P02545: Variant p.Glu203Gly

Prelamin-A/C
Gene: LMNA
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Variant information Variant position: help 203 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 Glutamate (E) to Glycine (G) at position 203 (E203G, p.Glu203Gly). 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 medium size and acidic (E) to glycine (G) 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 CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; results in increased cell death. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 203 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 664 The length of the canonical sequence.
Location on the sequence: help LQDEMLRRVDAENRLQTMKE E LDFQKNIYSEELRETKRRHE 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                         LQDEMLRRVDAENRLQTMKEELDFQKNIYSEELRETKRRHE

Mouse                         LQDEMLRRVDAENRLQTLKEELDFQKNIYSEELRETKRRHE

Rat                           LQDEMLRRVDAENRLQTLKEELDFQKNIYSEELRETKRRHE

Pig                           LQDEMLRRVDAENRLQTLKEELDFQKNIYSEELRETKRRHE

Chicken                       LQDEMLRRVDAENRLQTLKEELEFQKNIYSEELRETKRRHE

Xenopus laevis                LQDEMLRRVDTENRNQTLKEELEFQKSIYNEEMRETKRRHE
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 – 661 Prelamin-A/C
Chain 1 – 646 Lamin-A/C
Domain 31 – 387 IF rod
Region 81 – 218 Coil 1B
Modified residue 201 – 201 N6-acetyllysine
Modified residue 208 – 208 N6-acetyllysine
Modified residue 212 – 212 Phosphoserine
Cross 201 – 201 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross 201 – 201 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Cross 208 – 208 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross 219 – 219 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 201 – 201 K -> L. Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death.



Literature citations
Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies.
Zhang Y.Q.; Sarge K.D.;
J. Cell Biol. 182:35-39(2008)
Cited for: SUBCELLULAR LOCATION; SUMOYLATION AT LYS-201; MUTAGENESIS OF LYS-201; CHARACTERIZATION OF VARIANTS CMD1A GLY-203 AND LYS-203; Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.
Fatkin D.; MacRae C.; Sasaki T.; Wolff M.R.; Porcu M.; Frenneaux M.; Atherton J.; Vidaillet H.J. Jr.; Spudich S.; De Girolami U.; Seidman J.G.; Seidman C.E.;
N. Engl. J. Med. 341:1715-1724(1999)
Cited for: VARIANTS CMD1A GLY-60; ARG-85; LYS-195 AND GLY-203; FUNCTION; Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy.
Oestlund C.; Bonne G.; Schwartz K.; Worman H.J.;
J. Cell Sci. 114:4435-4445(2001)
Cited for: CHARACTERIZATION OF VARIANTS CMD1A GLY-60; ARG-85; LYS-195 AND GLY-203; CHARACTERIZATION OF VARIANTS EDMD2 LYS-358; LYS-371; LYS-386; TRP-453; SER-520; PRO-527; LYS-528 AND PRO-530; CHARACTERIZATION OF VARIANTS FPLD2 GLN-482; TRP-482 AND ASN-486;
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.