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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P02545: Variant p.Arg386Lys

Prelamin-A/C
Gene: LMNA
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Variant information Variant position: help 386 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 Lysine (K) at position 386 (R386K, p.Arg386Lys). 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 Similar physico-chemical property. Both residues are large size and basic. 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 EDMD2; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 386 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 KLALDMEIHAYRKLLEGEEE R LRLSPSPTSQRSRGRASSHS 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                         KLALDMEIHAYRKLLEGEEERLRLSPSPTSQRSRGRASSHS

Mouse                         KLALDMEIHAYRKLLEGEEERLRLSPSPTSQRSRGRASSHS

Rat                           KLALDMEIHAYRKLLEGEEERLRLSPSPTSQRSRGRASSHS

Pig                           KLALDMEIHAYRKLLEGEEERLRLSPSPTSQRSRGRASSHS

Chicken                       KLALDMEINAYRKLLEGEEERLRLSPSPSSQRG---ARSSG

Xenopus laevis                KLALDMEINAYRKLLEGEEERLRLSPSPNTQKRSARTIASH
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 384 – 664 Tail
Region 384 – 442 Disordered
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
Cross 366 – 366 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross 378 – 378 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 373 – 373 I -> E. Impaired lamin assembly.
Mutagenesis 375 – 375 A -> D. Impaired lamin assembly.
Mutagenesis 377 – 377 R -> HP. Impaired lamin assembly.
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
Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene.
Bonne G.; Mercuri E.; Muchir A.; Urtizberea A.; Becane H.M.; Recan D.; Merlini L.; Wehnert M.; Boor R.; Reuner U.; Vorgerd M.; Wicklein E.M.; Eymard B.; Duboc D.; Penisson-Besnier I.; Cuisset J.M.; Ferrer X.; Desguerre I.; Lacombe D.; Bushby K.; Pollitt C.; Toniolo D.; Fardeau M.; Schwartz K.; Muntoni F.;
Ann. Neurol. 48:170-180(2000)
Cited for: VARIANTS EDMD2 CYS-45; PRO-50; SER-63; GLU-112 DEL; PRO-222; GLU-232; GLN-249; LYS-261 DEL; PRO-294; LYS-358; LYS-371; LYS-386; TRP-453; LYS-456; SER-520; PRO-527 AND LYS-528; 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; Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study.
Boriani G.; Gallina M.; Merlini L.; Bonne G.; Toniolo D.; Amati S.; Biffi M.; Martignani C.; Frabetti L.; Bonvicini M.; Rapezzi C.; Branzi A.;
Stroke 34:901-908(2003)
Cited for: VARIANTS EDMD2 ASN-63; PRO-140; GLN-249; LEU-377; LYS-386 AND PRO-527; Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.
Scharner J.; Brown C.A.; Bower M.; Iannaccone S.T.; Khatri I.A.; Escolar D.; Gordon E.; Felice K.; Crowe C.A.; Grosmann C.; Meriggioli M.N.; Asamoah A.; Gordon O.; Gnocchi V.F.; Ellis J.A.; Mendell J.R.; Zammit P.S.;
Hum. Mutat. 32:152-167(2011)
Cited for: VARIANTS EDMD2 SER-39; CYS-45; PRO-150; PRO-189; ARG-190 INS; LEU-206; TRP-249; GLN-249; PRO-268; PRO-271; PRO-294; PRO-295; PRO-303; GLN-355 DEL; LYS-358; LYS-361; LYS-386; ASP-449; TRP-453; PRO-454; TYR-461; ARG-467; PRO-527; LYS-528; ARG-528; SER-541; PRO-541; SER-602 AND CYS-644; CHARACTERIZATION OF VARIANTS EDMD2 PRO-25; TRP-249; ILE-456 AND PRO-541;
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.