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UniProtKB/Swiss-Prot P02545: Variant p.Ile63Ser

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  63
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 Isoleucine (I) to Serine (S) at position 63 (I63S, p.Ile63Ser).
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 medium size and hydrophobic (I) to small size and polar (S)
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

Involvement in disease:  Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2) [MIM:181350]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10739764, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:10908904, ECO:0000269|PubMed:10939567, ECO:0000269|PubMed:11503164, ECO:0000269|PubMed:11525883, ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:12032588, ECO:0000269|PubMed:12467752, ECO:0000269|PubMed:12649505, ECO:0000269|PubMed:12673789, ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:14985400, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:15744034, ECO:0000269|PubMed:17136397, ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:20848652, ECO:0000269|PubMed:27234031}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In EDMD2; no effect on protein level; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients.
Any additional useful information about the variant.

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



Sequence information

Variant position:  63
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:   AVYIDRVRSLETENAGLRLR  I TESEEVVSREVSGIKAAYEA
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                         AVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAAYEA

Mouse                         AVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAAYEA

Rat                           AVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAAYEA

Pig                           AVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKSAYEA

Chicken                       AVYIDKVRSLELENAGLRLRITESEEVVSREVSGIKAAYEA

Xenopus laevis                AVYIDKVRSLELENARLRLRITESEDVISREVTGIKSAYET

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 31 – 387 IF rod
Region 1 – 130 Interaction with MLIP
Region 34 – 70 Coil 1A
Modified residue 51 – 51 Phosphoserine
Modified residue 66 – 66 Phosphoserine
Modified residue 71 – 71 Phosphoserine
Alternative sequence 1 – 99 Missing. In isoform 5.
Alternative sequence 8 – 119 Missing. In isoform 4.


Literature citations

A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
Beausoleil S.A.; Villen J.; Gerber S.A.; Rush J.; Gygi S.P.;
Nat. Biotechnol. 24:1285-1292(2006)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-22; SER-390; SER-392; SER-395; SER-628; SER-632 AND SER-636; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
Daub H.; Olsen J.V.; Bairlein M.; Gnad F.; Oppermann F.S.; Korner R.; Greff Z.; Keri G.; Stemmann O.; Mann M.;
Mol. Cell 31:438-448(2008)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

A quantitative atlas of mitotic phosphorylation.
Dephoure N.; Zhou C.; Villen J.; Beausoleil S.A.; Bakalarski C.E.; Elledge S.J.; Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-18; THR-19; SER-22; SER-301; SER-390; SER-392; SER-395; SER-458; SER-628; SER-632; SER-636 AND SER-652; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
Olsen J.V.; Vermeulen M.; Santamaria A.; Kumar C.; Miller M.L.; Jensen L.J.; Gnad F.; Cox J.; Jensen T.S.; Nigg E.A.; Brunak S.; Mann M.;
Sci. Signal. 3:RA3-RA3(2010)
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; SER-12; THR-19; SER-22; SER-212; SER-277; SER-301; SER-390; SER-392; SER-395; SER-404; SER-414; SER-431; SER-458; SER-463; THR-505; SER-628; SER-632; SER-636 AND SER-652; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
Rigbolt K.T.; Prokhorova T.A.; Akimov V.; Henningsen J.; Johansen P.T.; Kratchmarova I.; Kassem M.; Mann M.; Olsen J.V.; Blagoev B.;
Sci. Signal. 4:RS3-RS3(2011)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-390; SER-392; SER-404; SER-414; SER-458 AND SER-636; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

Toward a comprehensive characterization of a human cancer cell phosphoproteome.
Zhou H.; Di Palma S.; Preisinger C.; Peng M.; Polat A.N.; Heck A.J.; Mohammed S.;
J. Proteome Res. 12:260-271(2013)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; THR-19; SER-22; SER-51; SER-66; SER-71; SER-107; SER-212; SER-301; SER-390; SER-392; SER-398; SER-429; SER-458; SER-463; SER-533; SER-613; SER-619; SER-628; SER-632 AND SER-636; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
Bian Y.; Song C.; Cheng K.; Dong M.; Wang F.; Huang J.; Sun D.; Wang L.; Ye M.; Zou H.;
J. Proteomics 96:253-262(2014)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; THR-19; SER-22; SER-212; SER-301; SER-307; SER-390; SER-395; SER-403; SER-404; SER-414; SER-458; SER-463; SER-612 AND SER-636; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

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;

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;

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.