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UniProtKB/Swiss-Prot P02545: Variant p.Arg527Pro

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  527
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 Arginine (R) to Proline (P) at position 527 (R527P, p.Arg527Pro).
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:  Change from large size and basic (R) to medium size and hydrophobic (P)
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 EDMD2 and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; abnormal nuclear localization; forms nuclear foci in about 13% of cultured skin fibroblasts from heterozygous patients; no effect on protein level.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  527
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:   SPPTDLVWKAQNTWGCGNSL  R TALINSTGEEVAMRKLVRSV
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                         SPPTDLVWKAQNTWGCGNSLRTALINSTGEEVAMRKLVRSV

Mouse                         SPPTDLVWKAQNTWGCGSSLRTALINSTGEEVAMRKLVRSL

Rat                           SPPTDLVWKAQNTWGCGTSLRTALINATGEEVAMRKLVRSL

Pig                           SPPADLVWKSQNTWGCGNSLRTALINSTGEEVAMRKLVRSV

Chicken                       SPPSDVVWKAQSSWGSGDSLRTALINSNGEEVAMRKLVRTV

Xenopus laevis                SPPSDLVWKAQSSWGTGDSIRTALLTSSNEEVAMRKLVRTV

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 – 661 Prelamin-A/C
Chain 1 – 646 Lamin-A/C
Domain 428 – 545 LTD
Region 384 – 664 Tail
Modified residue 510 – 510 Phosphothreonine
Modified residue 533 – 533 Phosphoserine
Modified residue 546 – 546 Phosphoserine
Beta strand 526 – 531


Literature citations

Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes.
Haque F.; Mazzeo D.; Patel J.T.; Smallwood D.T.; Ellis J.A.; Shanahan C.M.; Shackleton S.;
J. Biol. Chem. 285:3487-3498(2010)
Cited for: INTERACTION WITH SUN1; CHARACTERIZATION OF VARIANTS EDMD2 PRO-527 AND PRO-530; CHARACTERIZATION OF VARIANT HGPS SER-608;

Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.
Bonne G.; Di Barletta M.R.; Varnous S.; Becane H.-M.; Hammouda E.-H.; Merlini L.; Muntoni F.; Greenberg C.R.; Gary F.; Urtizberea J.-A.; Duboc D.; Fardeau M.; Toniolo D.; Schwartz K.;
Nat. Genet. 21:285-288(1999)
Cited for: VARIANTS EDMD2 TRP-453; PRO-527 AND PRO-530; FUNCTION;

Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.
Raffaele di Barletta M.; Ricci E.; Galluzzi G.; Tonali P.; Mora M.; Morandi L.; Romorini A.; Voit T.; Orstavik K.H.; Merlini L.; Trevisan C.; Biancalana V.; Housmanowa-Petrusewicz I.; Bione S.; Ricotti R.; Schwartz K.; Bonne G.; Toniolo D.;
Am. J. Hum. Genet. 66:1407-1412(2000)
Cited for: VARIANTS EDMD2 TYR-222; GLN-249; GLN-336; TRP-453; THR-469; PRO-527 AND LYS-528;

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;

Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.
Brown C.A.; Lanning R.W.; McKinney K.Q.; Salvino A.R.; Cherniske E.; Crowe C.A.; Darras B.T.; Gominak S.; Greenberg C.R.; Grosmann C.; Heydemann P.; Mendell J.R.; Pober B.R.; Sasaki T.; Shapiro F.; Simpson D.A.; Suchowersky O.; Spence J.E.;
Am. J. Med. Genet. 102:359-367(2001)
Cited for: VARIANTS EDMD2 PRO-25; THR-43; SER-50; PRO-133; 196-ARG--THR-199 DELINS SER; GLN-249; LYS-261 DEL; LYS-358; TRP-453; ILE-456; PRO-527 AND HIS-624;

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;

Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.
van der Kooi A.J.; Bonne G.; Eymard B.; Duboc D.; Talim B.; Van der Valk M.; Reiss P.; Richard P.; Demay L.; Merlini L.; Schwartz K.; Busch H.F.M.; de Visser M.;
Neurology 59:620-623(2002)
Cited for: VARIANTS FPLD2 GLY-60 AND PRO-527;

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;

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;

Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy.
Cenni V.; Sabatelli P.; Mattioli E.; Marmiroli S.; Capanni C.; Ognibene A.; Squarzoni S.; Maraldi N.M.; Bonne G.; Columbaro M.; Merlini L.; Lattanzi G.;
J. Med. Genet. 42:214-220(2005)
Cited for: VARIANT EDMD2 HIS-377; VARIANTS EDMD2 ASN-63; PRO-140; GLN-190; GLN-249 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.