UniProtKB/Swiss-Prot P02545: Variant p.Asn39Ser

Prelamin-A/C
Gene: LMNA
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Variant information Variant position:

39 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Asparagine (N) to Serine (S) at position 39 (N39S, p.Asn39Ser). 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 polar (N) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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 MDCL and EDMD2. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs57983345 [ dbSNP | Ensembl ]

Sequence information Variant position:

39 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:

TPLSPTRITRLQEKEDLQEL N DRLAVYIDRVRSLETENAGL 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                         TPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLETENAGL

Mouse                         TPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLETENAGL

Rat                           TPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLETENAGL

Pig                           TPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLETENAGL

Chicken                       TPLSPTRITRLQEKEDLQELNDRLAVYIDKVRSLELENAGL

Xenopus laevis                TPLSPTRITRLQEKEDLQGLNDRLAVYIDKVRSLELENARL

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.

Type	Positions	Description
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	19 – 19	Phosphothreonine
Modified residue	22 – 22	Phosphoserine; by CDK1
Modified residue	32 – 32	N6-acetyllysine; alternate
Modified residue	32 – 32	N6-succinyllysine; alternate
Modified residue	51 – 51	Phosphoserine
Cross	32 – 32	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Alternative sequence	1 – 99	Missing. In isoform 5.
Alternative sequence	8 – 119	Missing. In isoform 4.
Mutagenesis	22 – 22	S -> A. Impaired disassembly of the nuclear envelope during mitosis. Strongly decreased disassembly of the nuclear envelope during mitosis; when associates with A-392. Decreased accumulation to the double-strand break (DSB) sites.
Mutagenesis	22 – 22	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-392 and D-628. Decreased nuclear mechanical properties. Increased accumulation to the double-strand break (DSB) sites.
Mutagenesis	28 – 28	R -> T. Impaired lamin assembly.
Mutagenesis	32 – 32	K -> Q. Impaired lamin assembly.
Mutagenesis	41 – 41	R -> H. Impaired lamin assembly.
Helix	28 – 70

Literature citations
Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis.
Heald R.; McKeon F.;
Cell 61:579-589(1990)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-22 AND SER-392; MUTAGENESIS OF 20-PRO--PRO-23; SER-22; ARG-28; LYS-32; ARG-41; ILE-373; ALA-375; ARG-377; GLU-381; GLU-384; ARG-386; 391-PRO--PRO-393 AND SER-392; Identification of cell cycle-regulated phosphorylation sites on nuclear lamin C.
Ward G.E.; Kirschner M.W.;
Cell 61:561-577(1990)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-22; SER-392 AND SER-404; 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]; 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]; Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin.
Buxboim A.; Swift J.; Irianto J.; Spinler K.R.; Dingal P.C.; Athirasala A.; Kao Y.R.; Cho S.; Harada T.; Shin J.W.; Discher D.E.;
Curr. Biol. 24:1909-1917(2014)
Cited for: FUNCTION; PHOSPHORYLATION AT SER-22; SER-390 AND SER-392; MUTAGENESIS OF SER-22; Interphase phosphorylation of lamin A.
Kochin V.; Shimi T.; Torvaldson E.; Adam S.A.; Goldman A.; Pack C.G.; Melo-Cardenas J.; Imanishi S.Y.; Goldman R.D.; Eriksson J.E.;
J. Cell Sci. 127:2683-2696(2014)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION AT THR-3; SER-5; THR-10; SER-12; SER-18; THR-19; SER-22; SER-390; SER-392; SER-403; SER-404; SER-406; SER-407; THR-416; SER-423; SER-426; SER-458; SER-628; SER-636 AND SER-652; MUTAGENESIS OF SER-22; SER-390; SER-392; 404-SER--SER-407 AND SER-628; 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]; ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei.
Joo Y.K.; Black E.M.; Trier I.; Haakma W.; Zou L.; Kabeche L.;
Mol. Cell 83:3642-3658(2023)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-392 AND SER-395; MUTAGENESIS OF SER-392 AND SER-395; De novo LMNA mutations cause a new form of congenital muscular dystrophy.
Quijano-Roy S.; Mbieleu B.; Bonnemann C.G.; Jeannet P.Y.; Colomer J.; Clarke N.F.; Cuisset J.M.; Roper H.; De Meirleir L.; D'Amico A.; Ben Yaou R.; Nascimento A.; Barois A.; Demay L.; Bertini E.; Ferreiro A.; Sewry C.A.; Romero N.B.; Ryan M.; Muntoni F.; Guicheney P.; Richard P.; Bonne G.; Estournet B.;
Ann. Neurol. 64:177-186(2008)
Cited for: VARIANTS MDCL SER-39; PRO-50; TRP-249; PRO-302; LYS-358; SER-380; PRO-453; PRO-455 AND ASP-456; 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.