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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P02545: Variant p.Arg401Cys

Prelamin-A/C
Gene: LMNA
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Variant information Variant position: help 401 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 Arginine (R) to Cysteine (C) at position 401 (R401C, p.Arg401Cys). 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 large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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 EDMD2; abnormal nuclear localization in a honeycomb expression pattern in about 22% of cultured skin fibroblasts from heterozygous patients; enhances the interaction with SYNE2; no effect on nuclear localization; no effect on protein level. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 401 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 EGEEERLRLSPSPTSQRSRG R ASSHSSQTQGGGSVTKKRKL 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                         EGEEERLRLSPSPTSQRSRGRASSHSSQTQGGGSVTKKRKL

Mouse                         EGEEERLRLSPSPTSQRSRGRASSHSSQSQGGGSVTKKRKL

Rat                           EGEEERLRLSPSPTSQRSRGRASSHSSQSQGGGSVTKKRKL

Pig                           EGEEERLRLSPSPTSQRSRGRASSHSSQTQSGGSVTKKRKL

Chicken                       EGEEERLRLSPSPSSQRG---ARSSGLQHSGAGS-AKKRRL

Xenopus laevis                EGEEERLRLSPSPNTQKRSARTIASHSGAHISSSASKRRRL
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
Region 384 – 664 Tail
Region 384 – 442 Disordered
Compositional bias 391 – 417 Polar residues
Modified residue 390 – 390 Phosphoserine
Modified residue 392 – 392 Phosphoserine; by CDK1
Modified residue 395 – 395 Phosphoserine; by ATR
Modified residue 398 – 398 Phosphoserine
Modified residue 403 – 403 Phosphoserine
Modified residue 404 – 404 Phosphoserine
Modified residue 406 – 406 Phosphoserine
Modified residue 407 – 407 Phosphoserine
Modified residue 414 – 414 Phosphoserine
Modified residue 416 – 416 Phosphothreonine
Modified residue 417 – 417 N6-acetyllysine
Cross 417 – 417 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross 420 – 420 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 381 – 381 E -> K. Impaired lamin assembly.
Mutagenesis 384 – 384 E -> K. Impaired lamin assembly.
Mutagenesis 386 – 386 R -> M. Loss of interaction with IFFO1.
Mutagenesis 386 – 386 R -> VLP. Impaired lamin assembly.
Mutagenesis 390 – 390 S -> A. Decreased localization to the nucleoplasm during interphase.
Mutagenesis 392 – 392 S -> A. Impaired disassembly of the nuclear envelope during mitosis. Strongly decreased disassembly of the nuclear envelope during mitosis; when associates with A-22. Decreased localization to the nucleoplasm during interphase. Impaired disassembly of the micronuclear envelope in response to genome instability.
Mutagenesis 392 – 392 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-22 and D-628.
Mutagenesis 395 – 395 S -> A. Impaired phosphorylation by ATR in response to genome instability leading ro decreased phosphorylation by CDK1.
Mutagenesis 395 – 395 S -> D. Mimics phosphorylation; disassembly of the micronuclear envelope in response to genome instability.



Literature citations
Frequent low penetrance mutations in the Lamin A/C gene, causing Emery Dreifuss muscular dystrophy.
Vytopil M.; Ricci E.; Dello Russo A.; Hanisch F.; Neudecker S.; Zierz S.; Ricotti R.; Demay L.; Richard P.; Wehnert M.; Bonne G.; Merlini L.; Toniolo D.;
Neuromuscul. Disord. 12:958-963(2002)
Cited for: VARIANTS EDMD2 LYS-32 DEL; ASN-63; GLN-336; GLN-343 AND CYS-401; Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations.
Muchir A.; Medioni J.; Laluc M.; Massart C.; Arimura T.; van der Kooi A.J.; Desguerre I.; Mayer M.; Ferrer X.; Briault S.; Hirano M.; Worman H.J.; Mallet A.; Wehnert M.; Schwartz K.; Bonne G.;
Muscle Nerve 30:444-450(2004)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527; CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377; CHARACTERIZATION OF VARIANT FPLD2 LEU-482; CHARACTERIZATION OF VARIANT CMD1A CYS-541; Mutations in LMNA modulate the lamin A--Nesprin-2 interaction and cause LINC complex alterations.
Yang L.; Munck M.; Swamvdinathan K.; Kapinos L.E.; Noegel A.A.; Neumann S.;
PLoS ONE 8:E71850-E71850(2013)
Cited for: CHARACTERIZATION OF VARIANTS CYS-401; ASP-411; CYS-413; ILE-415; CYS-419; PRO-421 AND GLY-427; INTERACTION WITH SYNE2;
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.