LMNA_HUMAN
ID LMNA_HUMAN Reviewed; 664 AA.
AC P02545; B4DI32; D3DVB0; D6RAQ3; E7EUI9; P02546; Q5I6Y4; Q5I6Y6; Q5TCJ2;
AC Q5TCJ3; Q6UYC3; Q969I8; Q96JA2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 03-AUG-2022, entry version 267.
DE RecName: Full=Prelamin-A/C;
DE Contains:
DE RecName: Full=Lamin-A/C;
DE AltName: Full=70 kDa lamin;
DE AltName: Full=Renal carcinoma antigen NY-REN-32;
DE Flags: Precursor;
GN Name=LMNA; Synonyms=LMN1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C).
RX PubMed=3453101; DOI=10.1038/319463a0;
RA McKeon F.D., Kirschner M.W., Caput D.;
RT "Homologies in both primary and secondary structure between nuclear
RT envelope and intermediate filament proteins.";
RL Nature 319:463-468(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C), AND PROTEIN SEQUENCE OF
RP 583-644.
RX PubMed=3462705; DOI=10.1073/pnas.83.17.6450;
RA Fisher D.Z., Chaudhary N., Blobel G.;
RT "cDNA sequencing of nuclear lamins A and C reveals primary and secondary
RT structural homology to intermediate filament proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:6450-6454(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), SUBCELLULAR LOCATION (ISOFORM C),
RP VARIANTS CMD1A TRP-190; GLY-192 AND SER-541, AND CHARACTERIZATION OF
RP VARIANTS CMD1A GLY-192 AND SER-541.
RX PubMed=16061563; DOI=10.1136/jmg.2004.023283;
RA Sylvius N., Bilinska Z.T., Veinot J.P., Fidzianska A., Bolongo P.M.,
RA Poon S., McKeown P., Davies R.A., Chan K.-L., Tang A.S.L., Dyack S.,
RA Grzybowski J., Ruzyllo W., McBride H., Tesson F.;
RT "In vivo and in vitro examination of the functional significances of novel
RT lamin gene mutations in heart failure patients.";
RL J. Med. Genet. 42:639-647(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
RA Csoka A.B.;
RT "The progerin allele of lamin A disrupts chromatin organization.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Corpus callosum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C).
RC TISSUE=Kidney, Lung, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 12-25; 29-90; 102-117; 120-166; 172-189; 197-216;
RP 226-233; 241-260; 281-316; 320-329; 352-386; 440-453; 456-482; 472-482;
RP 516-542; 585-624 AND 628-644, PHOSPHORYLATION AT SER-22, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.,
RA Norman J.C.;
RL Submitted (OCT-2009) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 375-664 (ISOFORM ADELTA10).
RC TISSUE=Colon;
RX PubMed=8621584; DOI=10.1074/jbc.271.16.9249;
RA Machiels B.M., Zorenc A.H., Endert J.M., Kuijpers H.J., van Eys G.J.,
RA Ramaekers F.C., Broers J.L.;
RT "An alternative splicing product of the lamin A/C gene lacks exon 10.";
RL J. Biol. Chem. 271:9249-9253(1996).
RN [11]
RP PROTEOLYTIC CLEAVAGE, ISOPRENYLATION AT CYS-661, AND METHYLATION AT
RP CYS-661.
RX PubMed=8175923; DOI=10.1242/jcs.107.1.61;
RA Sinensky M., Fantle K., Trujillo M., McLain T., Kupfer A., Dalton M.;
RT "The processing pathway of prelamin A.";
RL J. Cell Sci. 107:61-67(1994).
RN [12]
RP PROTEOLYTIC CLEAVAGE, ISOPRENYLATION AT CYS-661, AND METHYLATION AT
RP CYS-661.
RX PubMed=9030603; DOI=10.1074/jbc.272.8.5298;
RA Kilic F., Dalton M.B., Burrell S.K., Mayer J.P., Patterson S.D.,
RA Sinensky M.;
RT "In vitro assay and characterization of the farnesylation-dependent
RT prelamin A endoprotease.";
RL J. Biol. Chem. 272:5298-5304(1997).
RN [13]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-cell
RT carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [14]
RP INTERACTION WITH NARF, AND MUTAGENESIS OF CYS-661.
RX PubMed=10514485; DOI=10.1074/jbc.274.42.30008;
RA Barton R.M., Worman H.J.;
RT "Prenylated prelamin A interacts with Narf, a novel nuclear protein.";
RL J. Biol. Chem. 274:30008-30018(1999).
RN [15]
RP INTERACTION WITH TMPO-ALPHA AND RB1.
RX PubMed=12475961; DOI=10.1091/mbc.e02-07-0450;
RA Markiewicz E., Dechat T., Foisner R., Quinlan R.A., Hutchison C.J.;
RT "Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of
RT retinoblastoma protein.";
RL Mol. Biol. Cell 13:4401-4413(2002).
RN [16]
RP ALTERNATIVE SPLICING, INVOLVEMENT IN HGPS (ISOFORM 6), AND VARIANTS HGPS
RP LYS-145 AND SER-608.
RX PubMed=12714972; DOI=10.1038/nature01629;
RA Eriksson M., Brown W.T., Gordon L.B., Glynn M.W., Singer J., Scott L.,
RA Erdos M.R., Robbins C.M., Moses T.Y., Berglund P., Dutra A., Pak E.,
RA Durkin S., Csoka A.B., Boehnke M., Glover T.W., Collins F.S.;
RT "Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford
RT progeria syndrome.";
RL Nature 423:293-298(2003).
RN [17]
RP INTERACTION WITH LEMD2 (ISOFORM C).
RX PubMed=16339967; DOI=10.1242/jcs.02701;
RA Brachner A., Reipert S., Foisner R., Gotzmann J.;
RT "LEM2 is a novel MAN1-related inner nuclear membrane protein associated
RT with A-type lamins.";
RL J. Cell Sci. 118:5797-5810(2005).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-22; SER-390; SER-392;
RP SER-395; SER-628; SER-632 AND SER-636, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-628, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [21]
RP SUBCELLULAR LOCATION, SUMOYLATION AT LYS-201, MUTAGENESIS OF LYS-201, AND
RP CHARACTERIZATION OF VARIANTS CMD1A GLY-203 AND LYS-203.
RX PubMed=18606848; DOI=10.1083/jcb.200712124;
RA Zhang Y.Q., Sarge K.D.;
RT "Sumoylation regulates lamin A function and is lost in lamin A mutants
RT associated with familial cardiomyopathies.";
RL J. Cell Biol. 182:35-39(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-628, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-18; THR-19; SER-22;
RP SER-301; SER-390; SER-392; SER-395; SER-458; SER-628; SER-632; SER-636 AND
RP SER-652, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [26]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH EMD.
RX PubMed=19323649; DOI=10.1042/bc20080175;
RA Capanni C., Del Coco R., Mattioli E., Camozzi D., Columbaro M., Schena E.,
RA Merlini L., Squarzoni S., Maraldi N.M., Lattanzi G.;
RT "Emerin-prelamin A interplay in human fibroblasts.";
RL Biol. Cell 101:541-554(2009).
RN [27]
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS FPLD2 CYS-439 AND
RP TRP-482.
RX PubMed=19220582; DOI=10.1111/j.1582-4934.2009.00690.x;
RA Verstraeten V.L., Caputo S., van Steensel M.A., Duband-Goulet I.,
RA Zinn-Justin S., Kamps M., Kuijpers H.J., Ostlund C., Worman H.J.,
RA Briede J.J., Le Dour C., Marcelis C.L., van Geel M., Steijlen P.M.,
RA van den Wijngaard A., Ramaekers F.C., Broers J.L.;
RT "The R439C mutation in LMNA causes lamin oligomerization and susceptibility
RT to oxidative stress.";
RL J. Cell. Mol. Med. 13:959-971(2009).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-108; LYS-270; LYS-311 AND
RP LYS-450, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [29]
RP FUNCTION.
RX PubMed=20079404; DOI=10.1016/j.bbagen.2010.01.002;
RA De Vos W.H., Houben F., Hoebe R.A., Hennekam R., van Engelen B.,
RA Manders E.M., Ramaekers F.C., Broers J.L., Van Oostveldt P.;
RT "Increased plasticity of the nuclear envelope and hypermobility of
RT telomeres due to the loss of A-type lamins.";
RL Biochim. Biophys. Acta 1800:448-458(2010).
RN [30]
RP SUBCELLULAR LOCATION, AND VARIANTS CMD1A LEU-89; PRO-101; PRO-166; GLN-190;
RP LYS-203; SER-210; PRO-215; THR-318; HIS-388; CYS-399 AND HIS-471.
RX PubMed=20160190; DOI=10.1161/circgenetics.109.905422;
RA Cowan J., Li D., Gonzalez-Quintana J., Morales A., Hershberger R.E.;
RT "Morphological analysis of 13 LMNA variants identified in a cohort of 324
RT unrelated patients with idiopathic or familial dilated cardiomyopathy.";
RL Circ. Cardiovasc. Genet. 3:6-14(2010).
RN [31]
RP FUNCTION, PROTEOLYTIC PROCESSING, AND TISSUE SPECIFICITY.
RX PubMed=20458013; DOI=10.1161/circulationaha.109.902056;
RA Ragnauth C.D., Warren D.T., Liu Y., McNair R., Tajsic T., Figg N.,
RA Shroff R., Skepper J., Shanahan C.M.;
RT "Prelamin A acts to accelerate smooth muscle cell senescence and is a novel
RT biomarker of human vascular aging.";
RL Circulation 121:2200-2210(2010).
RN [32]
RP INTERACTION WITH SUN1, CHARACTERIZATION OF VARIANTS EDMD2 PRO-527 AND
RP PRO-530, AND CHARACTERIZATION OF VARIANT HGPS SER-608.
RX PubMed=19933576; DOI=10.1074/jbc.m109.071910;
RA Haque F., Mazzeo D., Patel J.T., Smallwood D.T., Ellis J.A., Shanahan C.M.,
RA Shackleton S.;
RT "Mammalian SUN protein interaction networks at the inner nuclear membrane
RT and their role in laminopathy disease processes.";
RL J. Biol. Chem. 285:3487-3498(2010).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT THR-3; SER-12; THR-19; SER-22; SER-212; SER-277; SER-301;
RP SER-390; SER-392; SER-395; SER-404; SER-414; SER-431; SER-458; SER-463;
RP THR-505; SER-628; SER-632; SER-636 AND SER-652, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [35]
RP INTERACTION WITH MLIP.
RX PubMed=21498514; DOI=10.1074/jbc.m110.165548;
RA Ahmady E., Deeke S.A., Rabaa S., Kouri L., Kenney L., Stewart A.F.,
RA Burgon P.G.;
RT "Identification of a novel muscle enriched A-type Lamin interacting protein
RT (MLIP).";
RL J. Biol. Chem. 286:19702-19713(2011).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-390; SER-392; SER-404;
RP SER-414; SER-458 AND SER-636, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [37]
RP MUTAGENESIS OF ARG-644; LEU-647; LEU-648; ASN-650 AND CYS-661, AND
RP CHARACTERIZATION OF VARIANT HGPS CYS-644.
RX PubMed=22355414; DOI=10.1371/journal.pone.0032120;
RA Barrowman J., Hamblet C., Kane M.S., Michaelis S.;
RT "Requirements for efficient proteolytic cleavage of prelamin A by
RT ZMPSTE24.";
RL PLoS ONE 7:E32120-E32120(2012).
RN [38]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN HGPS, VARIANT HGPS GLY-300,
RP AND CHARACTERIZATION OF VARIANT HGPS GLY-300.
RX PubMed=23666920; DOI=10.1002/ajmg.a.35971;
RA Kane M.S., Lindsay M.E., Judge D.P., Barrowman J., Ap Rhys C., Simonson L.,
RA Dietz H.C., Michaelis S.;
RT "LMNA-associated cardiocutaneous progeria: An inherited autosomal dominant
RT premature aging syndrome with late onset.";
RL Am. J. Med. Genet. A 161:1599-1611(2013).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; THR-19; SER-22; SER-51;
RP SER-66; SER-71; SER-107; SER-212; SER-301; SER-390; SER-392; SER-398;
RP SER-429; SER-458; SER-463; SER-533; SER-613; SER-619; SER-628; SER-632 AND
RP SER-636, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [40]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SUV39H1.
RX PubMed=23695662; DOI=10.1038/ncomms2885;
RA Liu B., Wang Z., Zhang L., Ghosh S., Zheng H., Zhou Z.;
RT "Depleting the methyltransferase Suv39h1 improves DNA repair and extends
RT lifespan in a progeria mouse model.";
RL Nat. Commun. 4:1868-1868(2013).
RN [41]
RP INTERACTION WITH DMPK.
RX PubMed=21949239; DOI=10.1074/jbc.m111.241455;
RA Harmon E.B., Harmon M.L., Larsen T.D., Yang J., Glasford J.W.,
RA Perryman M.B.;
RT "Myotonic dystrophy protein kinase is critical for nuclear envelope
RT integrity.";
RL J. Biol. Chem. 286:40296-40306(2011).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; THR-19; SER-22; SER-212;
RP SER-301; SER-307; SER-390; SER-395; SER-403; SER-404; SER-414; SER-458;
RP SER-463; SER-612 AND SER-636, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [43]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-97; LYS-208; LYS-233; LYS-311;
RP LYS-378; LYS-417 AND LYS-420, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [44]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-233 AND LYS-597, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [45]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-97; LYS-311; LYS-378 AND LYS-420,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [46]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-233; LYS-260; LYS-270; LYS-378;
RP LYS-417 AND LYS-420, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [47]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [48]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-97; LYS-171; LYS-201;
RP LYS-208; LYS-219; LYS-233; LYS-260; LYS-270; LYS-311; LYS-366; LYS-378;
RP LYS-417; LYS-420; LYS-450; LYS-470; LYS-486 AND LYS-597, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [49]
RP INTERACTION WITH ITSN1 ISOFORM 2, AND SUBCELLULAR LOCATION.
RX PubMed=29599122; DOI=10.1042/bcj20170897;
RA Alvisi G., Paolini L., Contarini A., Zambarda C., Di Antonio V.,
RA Colosini A., Mercandelli N., Timmoneri M., Palu G., Caimi L., Ricotta D.,
RA Radeghieri A.;
RT "Intersectin goes nuclear: secret life of an endocytic protein.";
RL Biochem. J. 475:1455-1472(2018).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 435-552.
RX PubMed=11901143; DOI=10.1074/jbc.c200038200;
RA Dhe-Paganon S., Werner E.D., Chi Y.I., Shoelson S.E.;
RT "Structure of the globular tail of nuclear lamin.";
RL J. Biol. Chem. 277:17381-17384(2002).
RN [51]
RP STRUCTURE BY NMR OF 428-549.
RX PubMed=12057196; DOI=10.1016/s0969-2126(02)00777-3;
RA Krimm I., Ostlund C., Gilquin B., Couprie J., Hossenlopp P., Mornon J.-P.,
RA Bonne G., Courvalin J.-C., Worman H.J., Zinn-Justin S.;
RT "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in
RT muscular dystrophies, cardiomyopathy, and partial lipodystrophy.";
RL Structure 10:811-823(2002).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 305-387.
RX PubMed=15476822; DOI=10.1016/j.jmb.2004.08.093;
RA Strelkov S.V., Schumacher J., Burkhard P., Aebi U., Herrmann H.;
RT "Crystal structure of the human lamin A coil 2B dimer: implications for the
RT head-to-tail association of nuclear lamins.";
RL J. Mol. Biol. 343:1067-1080(2004).
RN [53]
RP VARIANTS EDMD2 TRP-453; PRO-527 AND PRO-530, AND FUNCTION.
RX PubMed=10080180; DOI=10.1038/6799;
RA Bonne G., Di Barletta M.R., Varnous S., Becane H.-M., Hammouda E.-H.,
RA Merlini L., Muntoni F., Greenberg C.R., Gary F., Urtizberea J.-A.,
RA Duboc D., Fardeau M., Toniolo D., Schwartz K.;
RT "Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-
RT Dreifuss muscular dystrophy.";
RL Nat. Genet. 21:285-288(1999).
RN [54]
RP VARIANTS CMD1A GLY-60; ARG-85; LYS-195 AND GLY-203, AND FUNCTION.
RX PubMed=10580070; DOI=10.1056/nejm199912023412302;
RA Fatkin D., MacRae C., Sasaki T., Wolff M.R., Porcu M., Frenneaux M.,
RA Atherton J., Vidaillet H.J. Jr., Spudich S., De Girolami U., Seidman J.G.,
RA Seidman C.E.;
RT "Missense mutations in the rod domain of the lamin A/C gene as causes of
RT dilated cardiomyopathy and conduction-system disease.";
RL N. Engl. J. Med. 341:1715-1724(1999).
RN [55]
RP VARIANTS FPLD2 ASP-465; GLN-482; TRP-482 AND HIS-582.
RX PubMed=10739751; DOI=10.1086/302836;
RA Speckman R.A., Garg A., Du F., Bennett L., Veile R., Arioglu E.,
RA Taylor S.I., Lovett M., Bowcock A.M.;
RT "Mutational and haplotype analyses of families with familial partial
RT lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the
RT globular C-terminal domain of lamin A/C.";
RL Am. J. Hum. Genet. 66:1192-1198(2000).
RN [56]
RP ERRATUM OF PUBMED:10739751.
RA Speckman R.A., Garg A., Du F., Bennett L., Veile R., Arioglu E.,
RA Taylor S.I., Lovett M., Bowcock A.M.;
RL Am. J. Hum. Genet. 67:775-775(2000).
RN [57]
RP VARIANTS EDMD2 TYR-222; GLN-249; GLN-336; TRP-453; THR-469; PRO-527 AND
RP LYS-528.
RX PubMed=10739764; DOI=10.1086/302869;
RA Raffaele di Barletta M., Ricci E., Galluzzi G., Tonali P., Mora M.,
RA Morandi L., Romorini A., Voit T., Orstavik K.H., Merlini L., Trevisan C.,
RA Biancalana V., Housmanowa-Petrusewicz I., Bione S., Ricotti R.,
RA Schwartz K., Bonne G., Toniolo D.;
RT "Different mutations in the LMNA gene cause autosomal dominant and
RT autosomal recessive Emery-Dreifuss muscular dystrophy.";
RL Am. J. Hum. Genet. 66:1407-1412(2000).
RN [58]
RP VARIANTS EDMD2 CYS-45; PRO-50; SER-63; GLU-112 DEL; PRO-222; GLU-232;
RP GLN-249; LYS-261 DEL; PRO-294; LYS-358; LYS-371; LYS-386; TRP-453; LYS-456;
RP SER-520; PRO-527 AND LYS-528.
RX PubMed=10939567;
RX DOI=10.1002/1531-8249(200008)48:2<170::aid-ana6>3.0.co;2-j;
RA Bonne G., Mercuri E., Muchir A., Urtizberea A., Becane H.M., Recan D.,
RA Merlini L., Wehnert M., Boor R., Reuner U., Vorgerd M., Wicklein E.M.,
RA Eymard B., Duboc D., Penisson-Besnier I., Cuisset J.M., Ferrer X.,
RA Desguerre I., Lacombe D., Bushby K., Pollitt C., Toniolo D., Fardeau M.,
RA Schwartz K., Muntoni F.;
RT "Clinical and molecular genetic spectrum of autosomal dominant Emery-
RT Dreifuss muscular dystrophy due to mutations of the lamin A/C gene.";
RL Ann. Neurol. 48:170-180(2000).
RN [59]
RP VARIANT FPLD2 GLN-482.
RX PubMed=10587585; DOI=10.1093/hmg/9.1.109;
RA Cao H., Hegele R.A.;
RT "Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type
RT familial partial lipodystrophy.";
RL Hum. Mol. Genet. 9:109-112(2000).
RN [60]
RP VARIANTS EDMD2 LYS-208 DEL AND HIS-377, AND FUNCTION.
RX PubMed=10814726; DOI=10.1093/hmg/9.9.1453;
RA Muchir A., Bonne G., van der Kooi A.J., van Meegen M., Baas F.,
RA Bolhuis P.A., de Visser M., Schwartz K.;
RT "Identification of mutations in the gene encoding lamins A/C in autosomal
RT dominant limb girdle muscular dystrophy with atrioventricular conduction
RT disturbances (LGMD1B).";
RL Hum. Mol. Genet. 9:1453-1459(2000).
RN [61]
RP VARIANTS FPLD2 LEU-482 AND TRP-482.
RX PubMed=10655060; DOI=10.1038/72807;
RA Shackleton S., Lloyd D.J., Jackson S.N.J., Evans R., Niermeijer M.F.,
RA Singh B.M., Schmidt H., Brabant G., Kumar S., Durrington P.N., Gregory S.,
RA O'Rahilly S., Trembath R.C.;
RT "LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.";
RL Nat. Genet. 24:153-156(2000).
RN [62]
RP VARIANTS EDMD2 PRO-150 AND LYS-261 DEL.
RX PubMed=10908904; DOI=10.1212/wnl.55.2.275;
RA Felice K.J., Schwartz R.C., Brown C.A., Leicher C.R., Grunnet M.L.;
RT "Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain
RT of the lamin A/C gene.";
RL Neurology 55:275-280(2000).
RN [63]
RP VARIANTS EDMD2 PRO-25; THR-43; SER-50; PRO-133; 196-ARG--THR-199 DELINS
RP SER; GLN-249; LYS-261 DEL; LYS-358; TRP-453; ILE-456; PRO-527 AND HIS-624.
RX PubMed=11503164; DOI=10.1002/ajmg.1463;
RA Brown C.A., Lanning R.W., McKinney K.Q., Salvino A.R., Cherniske E.,
RA Crowe C.A., Darras B.T., Gominak S., Greenberg C.R., Grosmann C.,
RA Heydemann P., Mendell J.R., Pober B.R., Sasaki T., Shapiro F.,
RA Simpson D.A., Suchowersky O., Spence J.E.;
RT "Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss
RT muscular dystrophy.";
RL Am. J. Med. Genet. 102:359-367(2001).
RN [64]
RP VARIANT CMD1A LYS-203.
RX PubMed=11561226; DOI=10.1054/jcaf.2001.26339;
RA Jakobs P.M., Hanson E.L., Crispell K.A., Toy W., Keegan H., Schilling K.,
RA Icenogle T.B., Litt M., Hershberger R.E.;
RT "Novel lamin A/C mutations in two families with dilated cardiomyopathy and
RT conduction system disease.";
RL J. Card. Fail. 7:249-256(2001).
RN [65]
RP CHARACTERIZATION OF VARIANTS CMD1A GLY-60; ARG-85; LYS-195 AND GLY-203,
RP CHARACTERIZATION OF VARIANTS EDMD2 LYS-358; LYS-371; LYS-386; TRP-453;
RP SER-520; PRO-527; LYS-528 AND PRO-530, AND CHARACTERIZATION OF VARIANTS
RP FPLD2 GLN-482; TRP-482 AND ASN-486.
RX PubMed=11792809; DOI=10.1242/jcs.114.24.4435;
RA Oestlund C., Bonne G., Schwartz K., Worman H.J.;
RT "Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy,
RT cardiomyopathy and Dunnigan-type partial lipodystrophy.";
RL J. Cell Sci. 114:4435-4445(2001).
RN [66]
RP VARIANT EDMD2 HIS-481.
RX PubMed=11525883; DOI=10.1016/s0960-8966(01)00207-3;
RA Kitaguchi T., Matsubara S., Sato M., Miyamoto K., Hirai S., Schwartz K.,
RA Bonne G.;
RT "A missense mutation in the exon 8 of lamin A/C gene in a Japanese case of
RT autosomal dominant limb-girdle muscular dystrophy and cardiac conduction
RT block.";
RL Neuromuscul. Disord. 11:542-546(2001).
RN [67]
RP VARIANT CMD1A PRO-215.
RX PubMed=12486434; DOI=10.1067/mhj.2002.126737;
RA Hershberger R.E., Hanson E.L., Jakobs P.M., Keegan H., Coates K.,
RA Bousman S., Litt M.;
RT "A novel lamin A/C mutation in a family with dilated cardiomyopathy,
RT prominent conduction system disease, and need for permanent pacemaker
RT implantation.";
RL Am. Heart J. 144:1081-1086(2002).
RN [68]
RP VARIANT CMT2B1 CYS-298, AND FUNCTION.
RX PubMed=11799477; DOI=10.1086/339274;
RA De Sandre-Giovannoli A., Chaouch M., Kozlov S., Vallat J.-M., Tazir M.,
RA Kassouri N., Szepetowski P., Hammadouche T., Vandenberghe A., Stewart C.L.,
RA Grid D., Levy N.;
RT "Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins,
RT cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth
RT disorder type 2) and mouse.";
RL Am. J. Hum. Genet. 70:726-736(2002).
RN [69]
RP ERRATUM OF PUBMED:11799477.
RA De Sandre-Giovannoli A., Chaouch M., Kozlov S., Vallat J.-M., Tazir M.,
RA Kassouri N., Szepetowski P., Hammadouche T., Vandenberghe A., Stewart C.L.,
RA Grid D., Levy N.;
RL Am. J. Hum. Genet. 70:1075-1075(2002).
RN [70]
RP VARIANT MADA HIS-527, AND FUNCTION.
RX PubMed=12075506; DOI=10.1086/341908;
RA Novelli G., Muchir A., Sangiuolo F., Helbling-Leclerc A., D'Apice M.R.,
RA Massart C., Capon F., Sbraccia P., Federici M., Lauro R., Tudisco C.,
RA Pallotta R., Scarano G., Dallapiccola B., Merlini L., Bonne G.;
RT "Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin
RT A/C.";
RL Am. J. Hum. Genet. 71:426-431(2002).
RN [71]
RP VARIANTS FPLD2 TRP-28 AND GLY-62.
RX PubMed=12015247; DOI=10.1016/s0002-9343(02)01070-7;
RA Garg A., Speckman R.A., Bowcock A.M.;
RT "Multisystem dystrophy syndrome due to novel missense mutations in the
RT amino-terminal head and alpha-helical rod domains of the lamin A/C gene.";
RL Am. J. Med. 112:549-555(2002).
RN [72]
RP VARIANTS CMD1A GLU-97; TRP-190 AND LYS-317.
RX PubMed=11897440; DOI=10.1016/s0735-1097(02)01724-2;
RA Arbustini E., Pilotto A., Repetto A., Grasso M., Negri A., Diegoli M.,
RA Campana C., Scelsi L., Baldini E., Gavazzi A., Tavazzi L.;
RT "Autosomal dominant dilated cardiomyopathy with atrioventricular block: a
RT lamin A/C defect-related disease.";
RL J. Am. Coll. Cardiol. 39:981-990(2002).
RN [73]
RP VARIANT EDMD2 GLN-249, AND VARIANT EDMD2 LEU-377.
RX PubMed=12032588; DOI=10.1007/s100380200029;
RA Ki C.-S., Hong J.S., Jeong G.-Y., Ahn K.J., Choi K.-M., Kim D.-K.,
RA Kim J.-W.;
RT "Identification of lamin A/C (LMNA) gene mutations in Korean patients with
RT autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle
RT muscular dystrophy 1B.";
RL J. Hum. Genet. 47:225-228(2002).
RN [74]
RP VARIANTS FPLD2 GLY-60 AND PRO-527.
RX PubMed=12196663; DOI=10.1212/wnl.59.4.620;
RA van der Kooi A.J., Bonne G., Eymard B., Duboc D., Talim B.,
RA Van der Valk M., Reiss P., Richard P., Demay L., Merlini L., Schwartz K.,
RA Busch H.F.M., de Visser M.;
RT "Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and
RT muscular dystrophy.";
RL Neurology 59:620-623(2002).
RN [75]
RP VARIANTS EDMD2 LYS-32 DEL; ASN-63; GLN-336; GLN-343 AND CYS-401.
RX PubMed=12467752; DOI=10.1016/s0960-8966(02)00178-5;
RA Vytopil M., Ricci E., Dello Russo A., Hanisch F., Neudecker S., Zierz S.,
RA Ricotti R., Demay L., Richard P., Wehnert M., Bonne G., Merlini L.,
RA Toniolo D.;
RT "Frequent low penetrance mutations in the Lamin A/C gene, causing Emery
RT Dreifuss muscular dystrophy.";
RL Neuromuscul. Disord. 12:958-963(2002).
RN [76]
RP VARIANT CMD1A CYS-541.
RX PubMed=14675861; DOI=10.1016/s1388-9842(03)00149-1;
RA Forissier J.-F., Bonne G., Bouchier C., Duboscq-Bidot L., Richard P.,
RA Wisnewski C., Briault S., Moraine C., Dubourg O., Schwartz K., Komajda M.;
RT "Apical left ventricular aneurysm without atrio-ventricular block due to a
RT lamin A/C gene mutation.";
RL Eur. J. Heart Fail. 5:821-825(2003).
RN [77]
RP VARIANT EDMD2 HIS-377.
RX PubMed=12673789; DOI=10.1002/humu.10170;
RA Charniot J.-C., Pascal C., Bouchier C., Sebillon P., Salama J.,
RA Duboscq-Bidot L., Peuchmaurd M., Desnos M., Artigou J.-Y., Komajda M.;
RT "Functional consequences of an LMNA mutation associated with a new cardiac
RT and non-cardiac phenotype.";
RL Hum. Mutat. 21:473-481(2003).
RN [78]
RP VARIANTS CMD1A LEU-89; HIS-377 AND LEU-573.
RX PubMed=12628721; DOI=10.1016/s0735-1097(02)02954-6;
RG Familial dilated cardiomyopathy registry research group;
RA Taylor M.R.G., Fain P.R., Sinagra G., Robinson M.L., Robertson A.D.,
RA Carniel E., Di Lenarda A., Bohlmeyer T.J., Ferguson D.A., Brodsky G.L.,
RA Boucek M.M., Lascor J., Moss A.C., Li W.-L.P., Stetler G.L., Muntoni F.,
RA Bristow M.R., Mestroni L.;
RT "Natural history of dilated cardiomyopathy due to lamin A/C gene
RT mutations.";
RL J. Am. Coll. Cardiol. 41:771-780(2003).
RN [79]
RP ERRATUM OF PUBMED:12628721.
RG Familial dilated cardiomyopathy registry research group;
RA Taylor M.R.G., Fain P.R., Sinagra G., Robinson M.L., Robertson A.D.,
RA Carniel E., Di Lenarda A., Bohlmeyer T.J., Ferguson D.A., Brodsky G.L.,
RA Boucek M.M., Lascor J., Moss A.C., Li W.-L.P., Stetler G.L., Muntoni F.,
RA Bristow M.R., Mestroni L.;
RL J. Am. Coll. Cardiol. 42:590-590(2003).
RN [80]
RP VARIANT FPLD2 LEU-133.
RX PubMed=12629077; DOI=10.1210/jc.2002-021506;
RA Caux F., Dubosclard E., Lascols O., Buendia B., Chazouilleres O., Cohen A.,
RA Courvalin J.-C., Laroche L., Capeau J., Vigouroux C., Christin-Maitre S.;
RT "A new clinical condition linked to a novel mutation in lamins A and C with
RT generalized lipoatrophy, insulin-resistant diabetes, disseminated
RT leukomelanodermic papules, liver steatosis, and cardiomyopathy.";
RL J. Clin. Endocrinol. Metab. 88:1006-1013(2003).
RN [81]
RP VARIANTS HGPS CYS-471; CYS-527 AND SER-608.
RX PubMed=12768443; DOI=10.1007/s10038-003-0025-3;
RA Cao H., Hegele R.A.;
RT "LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in
RT Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).";
RL J. Hum. Genet. 48:271-274(2003).
RN [82]
RP VARIANT CMD1A LYS-161.
RX PubMed=12920062; DOI=10.1136/jmg.40.8.560;
RA Sebillon P., Bouchier C., Bidot L.D., Bonne G., Ahamed K., Charron P.,
RA Drouin-Garraud V., Millaire A., Desrumeaux G., Benaiche A., Charniot J.-C.,
RA Schwartz K., Villard E., Komajda M.;
RT "Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and
RT functional consequences of these mutations.";
RL J. Med. Genet. 40:560-567(2003).
RN [83]
RP VARIANTS EDMD2 GLY-25; LYS-32 DEL; VAL-35; GLY-65; GLU-112 DEL; PRO-248;
RP GLN-249; CYS-267; VAL-446; TRP-453; ARG-528 AND HIS-541, AND VARIANT CMD1A
RP CYS-435.
RX PubMed=14684700; DOI=10.1136/jmg.40.12.e132;
RA Vytopil M., Benedetti S., Ricci E., Galluzzi G., Dello Russo A.,
RA Merlini L., Boriani G., Gallina M., Morandi L., Politano L., Moggio M.,
RA Chiveri L., Hausmanova-Petrusewicz I., Ricotti R., Vohanka S., Toman J.,
RA Toniolo D.;
RT "Mutation analysis of the lamin A/C gene (LMNA) among patients with
RT different cardiomuscular phenotypes.";
RL J. Med. Genet. 40:E132-E132(2003).
RN [84]
RP VARIANT CMDHH PRO-57, VARIANT HGPS ARG-140, AND FUNCTION.
RX PubMed=12927431; DOI=10.1016/s0140-6736(03)14069-x;
RA Chen L., Lee L., Kudlow B.A., Dos Santos H.G., Sletvold O., Shafeghati Y.,
RA Botha E.G., Garg A., Hanson N.B., Martin G.M., Mian I.S., Kennedy B.K.,
RA Oshima J.;
RT "LMNA mutations in atypical Werner's syndrome.";
RL Lancet 362:440-445(2003).
RN [85]
RP VARIANTS EDMD2 ASN-63; PRO-140; GLN-249; LEU-377; LYS-386 AND PRO-527.
RX PubMed=12649505; DOI=10.1161/01.str.0000064322.47667.49;
RA Boriani G., Gallina M., Merlini L., Bonne G., Toniolo D., Amati S.,
RA Biffi M., Martignani C., Frabetti L., Bonvicini M., Rapezzi C., Branzi A.;
RT "Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker
RT implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-
RT term longitudinal study.";
RL Stroke 34:901-908(2003).
RN [86]
RP VARIANTS CMD1A TRP-190 AND LEU-349.
RX PubMed=15219508; DOI=10.1016/j.amjcard.2004.03.029;
RA Hermida-Prieto M., Monserrat L., Castro-Beiras A., Laredo R., Soler R.,
RA Peteiro J., Rodriguez E., Bouzas B., Alvarez N., Muniz J., Crespo-Leiro M.;
RT "Familial dilated cardiomyopathy and isolated left ventricular
RT noncompaction associated with lamin A/C gene mutations.";
RL Am. J. Cardiol. 94:50-54(2004).
RN [87]
RP VARIANT CMD1A PRO-143.
RX PubMed=15140538; DOI=10.1016/j.ehj.2004.01.020;
RA Kaerkkaeinen S., Helioe T., Miettinen R., Tuomainen P., Peltola P.,
RA Rummukainen J., Ylitalo K., Kaartinen M., Kuusisto J., Toivonen L.,
RA Nieminen M.S., Laakso M., Peuhkurinen K.;
RT "A novel mutation, Ser143Pro, in the lamin A/C gene is common in Finnish
RT patients with familial dilated cardiomyopathy.";
RL Eur. Heart J. 25:885-893(2004).
RN [88]
RP INVOLVEMENT IN RSDM2, AND FUNCTION.
RX PubMed=15317753; DOI=10.1093/hmg/ddh265;
RA Navarro C.L., De Sandre-Giovannoli A., Bernard R., Boccaccio I., Boyer A.,
RA Genevieve D., Hadj-Rabia S., Gaudy-Marqueste C., Smitt H.S., Vabres P.,
RA Faivre L., Verloes A., Van Essen T., Flori E., Hennekam R., Beemer F.A.,
RA Laurent N., Le Merrer M., Cau P., Levy N.;
RT "Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and
RT identify restrictive dermopathy as a lethal neonatal laminopathy.";
RL Hum. Mol. Genet. 13:2493-2503(2004).
RN [89]
RP VARIANT HGPS CYS-644, AND VARIANTS ILE-10 AND VAL-578.
RX PubMed=15060110; DOI=10.1136/jmg.2003.015651;
RA Csoka A.B., Cao H., Sammak P.J., Constantinescu D., Schatten G.P.,
RA Hegele R.A.;
RT "Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes.";
RL J. Med. Genet. 41:304-308(2004).
RN [90]
RP VARIANT HGPS ASN-542.
RX PubMed=15286156; DOI=10.1136/jmg.2004.019661;
RA Plasilova M., Chattopadhyay C., Pal P., Schaub N.A., Buechner S.A.,
RA Mueller H., Miny P., Ghosh A., Heinimann K.;
RT "Homozygous missense mutation in the lamin A/C gene causes autosomal
RT recessive Hutchinson-Gilford progeria syndrome.";
RL J. Med. Genet. 41:609-614(2004).
RN [91]
RP VARIANT CMT2 ASP-33, AND VARIANT EDMD2 GLY-33.
RX PubMed=14985400; DOI=10.1136/jmg.2003.013383;
RA Goizet C., Yaou R.B., Demay L., Richard P., Bouillot S., Rouanet M.,
RA Hermosilla E., Le Masson G., Lagueny A., Bonne G., Ferrer X.;
RT "A new mutation of the lamin A/C gene leading to autosomal dominant axonal
RT neuropathy, muscular dystrophy, cardiac disease, and leuconychia.";
RL J. Med. Genet. 41:E29-E29(2004).
RN [92]
RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL;
RP SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF
RP VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2
RP LEU-482, AND CHARACTERIZATION OF VARIANT CMD1A CYS-541.
RX PubMed=15372542; DOI=10.1002/mus.20122;
RA Muchir A., Medioni J., Laluc M., Massart C., Arimura T., van der Kooi A.J.,
RA Desguerre I., Mayer M., Ferrer X., Briault S., Hirano M., Worman H.J.,
RA Mallet A., Wehnert M., Schwartz K., Bonne G.;
RT "Nuclear envelope alterations in fibroblasts from patients with muscular
RT dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C
RT gene mutations.";
RL Muscle Nerve 30:444-450(2004).
RN [93]
RP VARIANT HGPS PHE-143.
RX PubMed=15622532; DOI=10.1002/ana.20359;
RA Kirschner J., Brune T., Wehnert M., Denecke J., Wasner C., Feuer A.,
RA Marquardt T., Ketelsen U.-P., Wieacker P., Boennemann C.G.,
RA Korinthenberg R.;
RT "p.S143F mutation in lamin A/C: a new phenotype combining myopathy and
RT progeria.";
RL Ann. Neurol. 57:148-151(2005).
RN [94]
RP VARIANT CMDA1 ASN-260.
RX PubMed=16156025;
RA Arbustini Eloisa A.E., Pilotto A., Pasotti M., Grasso M., Diegoli M.,
RA Campana C., Gavazzi A., Alessandra R., Tavazzi L.;
RT "Gene symbol: LMNA. Disease: cardiomyopathy, dilated, with conduction
RT defect 1.";
RL Hum. Genet. 117:298-298(2005).
RN [95]
RP VARIANT MADA VAL-529.
RX PubMed=15998779; DOI=10.1210/jc.2004-2560;
RA Garg A., Cogulu O., Ozkinay F., Onay H., Agarwal A.K.;
RT "A novel homozygous Ala529Val LMNA mutation in Turkish patients with
RT mandibuloacral dysplasia.";
RL J. Clin. Endocrinol. Metab. 90:5259-5264(2005).
RN [96]
RP VARIANT EDMD2 HIS-377, AND VARIANTS EDMD2 ASN-63; PRO-140; GLN-190; GLN-249
RP AND PRO-527.
RX PubMed=15744034; DOI=10.1136/jmg.2004.026112;
RA Cenni V., Sabatelli P., Mattioli E., Marmiroli S., Capanni C., Ognibene A.,
RA Squarzoni S., Maraldi N.M., Bonne G., Columbaro M., Merlini L.,
RA Lattanzi G.;
RT "Lamin A N-terminal phosphorylation is associated with myoblast activation:
RT impairment in Emery-Dreifuss muscular dystrophy.";
RL J. Med. Genet. 42:214-220(2005).
RN [97]
RP VARIANT MADA LEU-573.
RX PubMed=16278265; DOI=10.1210/jc.2005-1297;
RA Van Esch H., Agarwal A.K., Debeer P., Fryns J.-P., Garg A.;
RT "A homozygous mutation in the lamin A/C gene associated with a novel
RT syndrome of arthropathy, tendinous calcinosis, and progeroid features.";
RL J. Clin. Endocrinol. Metab. 91:517-521(2006).
RN [98]
RP VARIANT CMDHH ARG-59.
RX PubMed=17150192; DOI=10.1016/j.bbrc.2006.11.070;
RA Nguyen D., Leistritz D.F., Turner L., MacGregor D., Ohson K., Dancey P.,
RA Martin G.M., Oshima J.;
RT "Collagen expression in fibroblasts with a novel LMNA mutation.";
RL Biochem. Biophys. Res. Commun. 352:603-608(2007).
RN [99]
RP VARIANTS FPLD2 ASN-230; CYS-399 AND LEU-573.
RX PubMed=17250669; DOI=10.1111/j.1399-0004.2007.00740.x;
RA Lanktree M., Cao H., Rabkin S.W., Hanna A., Hegele R.A.;
RT "Novel LMNA mutations seen in patients with familial partial lipodystrophy
RT subtype 2 (FPLD2; MIM 151660).";
RL Clin. Genet. 71:183-186(2007).
RN [100]
RP VARIANT EDMD2 HIS-377.
RX PubMed=17136397; DOI=10.1007/s10048-006-0070-0;
RA Rudnik-Schoeneborn S., Botzenhart E., Eggermann T., Senderek J.,
RA Schoser B.G.H., Schroeder R., Wehnert M., Wirth B., Zerres K.;
RT "Mutations of the LMNA gene can mimic autosomal dominant proximal spinal
RT muscular atrophy.";
RL Neurogenetics 8:137-142(2007).
RN [101]
RP VARIANT PRO-421.
RX PubMed=17711925; DOI=10.1210/jc.2007-0654;
RA Decaudain A., Vantyghem M.C., Guerci B., Hecart A.C., Auclair M.,
RA Reznik Y., Narbonne H., Ducluzeau P.H., Donadille B., Lebbe C.,
RA Bereziat V., Capeau J., Lascols O., Vigouroux C.;
RT "New metabolic phenotypes in laminopathies: LMNA mutations in patients with
RT severe metabolic syndrome.";
RL J. Clin. Endocrinol. Metab. 92:4835-4844(2007).
RN [102]
RP VARIANTS MDCL SER-39; PRO-50; TRP-249; PRO-302; LYS-358; SER-380; PRO-453;
RP PRO-455 AND ASP-456.
RX PubMed=18551513; DOI=10.1002/ana.21417;
RA Quijano-Roy S., Mbieleu B., Bonnemann C.G., Jeannet P.Y., Colomer J.,
RA Clarke N.F., Cuisset J.M., Roper H., De Meirleir L., D'Amico A.,
RA Ben Yaou R., Nascimento A., Barois A., Demay L., Bertini E., Ferreiro A.,
RA Sewry C.A., Romero N.B., Ryan M., Muntoni F., Guicheney P., Richard P.,
RA Bonne G., Estournet B.;
RT "De novo LMNA mutations cause a new form of congenital muscular
RT dystrophy.";
RL Ann. Neurol. 64:177-186(2008).
RN [103]
RP INVOLVEMENT IN HHS-SLOVENIAN, AND FUNCTION.
RX PubMed=18611980; DOI=10.1136/jmg.2008.060020;
RA Renou L., Stora S., Yaou R.B., Volk M., Sinkovec M., Demay L., Richard P.,
RA Peterlin B., Bonne G.;
RT "Heart-hand syndrome of Slovenian type: a new kind of laminopathy.";
RL J. Med. Genet. 45:666-671(2008).
RN [104]
RP FUNCTION, INTERACTION WITH IFFO1, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP SER-22; GLU-358 AND ARG-386, AND REGION.
RX PubMed=31548606; DOI=10.1038/s41556-019-0388-0;
RA Li W., Bai X., Li J., Zhao Y., Liu J., Zhao H., Liu L., Ding M., Wang Q.,
RA Shi F.Y., Hou M., Ji J., Gao G., Guo R., Sun Y., Liu Y., Xu D.;
RT "The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses
RT chromosome translocation during tumorigenesis.";
RL Nat. Cell Biol. 21:1273-1285(2019).
RN [105]
RP VARIANT CMDHH ARG-59.
RX PubMed=19283854; DOI=10.1002/ajmg.a.32627;
RA McPherson E., Turner L., Zador I., Reynolds K., Macgregor D.,
RA Giampietro P.F.;
RT "Ovarian failure and dilated cardiomyopathy due to a novel lamin
RT mutation.";
RL Am. J. Med. Genet. A 149:567-572(2009).
RN [106]
RP VARIANTS SER-125; ILE-415 AND PRO-488.
RX PubMed=19427440; DOI=10.1016/j.amjcard.2009.01.354;
RA Brauch K.M., Chen L.Y., Olson T.M.;
RT "Comprehensive mutation scanning of LMNA in 268 patients with lone atrial
RT fibrillation.";
RL Am. J. Cardiol. 103:1426-1428(2009).
RN [107]
RP VARIANT CMD1A CYS-541.
RX PubMed=19167105; DOI=10.1016/j.ijcard.2008.12.083;
RA Saj M., Jankowska A., Lewandowski M., Szwed H., Szperl M., Ploski R.,
RA Bilinska Z.T.;
RT "Dilated cardiomyopathy with profound segmental wall motion abnormalities
RT and ventricular arrhythmia caused by the R541C mutation in the LMNA gene.";
RL Int. J. Cardiol. 144:E51-E53(2010).
RN [108]
RP VARIANTS CMD1A PHE-92; LYS-161; LYS-317 AND ARG-523.
RX PubMed=21846512; DOI=10.1016/j.ejmg.2011.07.005;
RA Millat G., Bouvagnet P., Chevalier P., Sebbag L., Dulac A., Dauphin C.,
RA Jouk P.S., Delrue M.A., Thambo J.B., Le Metayer P., Seronde M.F.,
RA Faivre L., Eicher J.C., Rousson R.;
RT "Clinical and mutational spectrum in a cohort of 105 unrelated patients
RT with dilated cardiomyopathy.";
RL Eur. J. Med. Genet. 54:E570-E575(2011).
RN [109]
RP VARIANT HGPS LYS-138.
RX PubMed=21791255; DOI=10.1016/j.ejmg.2011.06.012;
RA Gonzalez-Quereda L., Delgadillo V., Juan-Mateu J., Verdura E.,
RA Rodriguez M.J., Baiget M., Pineda M., Gallano P.;
RT "LMNA mutation in progeroid syndrome in association with strokes.";
RL Eur. J. Med. Genet. 54:E576-E579(2011).
RN [110]
RP VARIANTS EDMD2 SER-39; CYS-45; PRO-150; PRO-189; ARG-190 INS; LEU-206;
RP TRP-249; GLN-249; PRO-268; PRO-271; PRO-294; PRO-295; PRO-303; GLN-355 DEL;
RP LYS-358; LYS-361; LYS-386; ASP-449; TRP-453; PRO-454; TYR-461; ARG-467;
RP PRO-527; LYS-528; ARG-528; SER-541; PRO-541; SER-602 AND CYS-644, AND
RP CHARACTERIZATION OF VARIANTS EDMD2 PRO-25; TRP-249; ILE-456 AND PRO-541.
RX PubMed=20848652; DOI=10.1002/humu.21361;
RA Scharner J., Brown C.A., Bower M., Iannaccone S.T., Khatri I.A.,
RA Escolar D., Gordon E., Felice K., Crowe C.A., Grosmann C., Meriggioli M.N.,
RA Asamoah A., Gordon O., Gnocchi V.F., Ellis J.A., Mendell J.R., Zammit P.S.;
RT "Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy
RT and functional characterization of four LMNA mutations.";
RL Hum. Mutat. 32:152-167(2011).
RN [111]
RP VARIANTS ASP-411 AND ASP-631.
RX PubMed=21724554; DOI=10.1093/hmg/ddr294;
RA Dutour A., Roll P., Gaborit B., Courrier S., Alessi M.C., Tregouet D.A.,
RA Angelis F., Robaglia-Schlupp A., Lesavre N., Cau P., Levy N., Badens C.,
RA Morange P.E.;
RT "High prevalence of laminopathies among patients with metabolic syndrome.";
RL Hum. Mol. Genet. 20:3779-3786(2011).
RN [112]
RP VARIANT EDMD3 GLN-225, AND FUNCTION.
RX PubMed=22431096; DOI=10.1002/mus.22324;
RA Jimenez-Escrig A., Gobernado I., Garcia-Villanueva M., Sanchez-Herranz A.;
RT "Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel
RT mutation (R225Q) in the lamin A/C gene identified by exome sequencing.";
RL Muscle Nerve 45:605-610(2012).
RN [113]
RP CHARACTERIZATION OF VARIANTS CYS-401; ASP-411; CYS-413; ILE-415; CYS-419;
RP PRO-421 AND GLY-427, AND INTERACTION WITH SYNE2.
RX PubMed=23977161; DOI=10.1371/journal.pone.0071850;
RA Yang L., Munck M., Swamvdinathan K., Kapinos L.E., Noegel A.A., Neumann S.;
RT "Mutations in LMNA modulate the lamin A--Nesprin-2 interaction and cause
RT LINC complex alterations.";
RL PLoS ONE 8:E71850-E71850(2013).
RN [114]
RP VARIANT FPLD2 GLU-515.
RX PubMed=24485160; DOI=10.1016/j.diabet.2013.12.008;
RA Chirico V., Ferrau V., Loddo I., Briuglia S., Amorini M., Salpietro V.,
RA Lacquaniti A., Salpietro C., Arrigo T.;
RT "LMNA gene mutation as a model of cardiometabolic dysfunction: from genetic
RT analysis to treatment response.";
RL Diabetes Metab. 40:224-228(2014).
RN [115]
RP VARIANT EDMD3 SER-24, AND VARIANT EDMD2 CYS-259.
RX PubMed=27234031; DOI=10.1111/cge.12810;
RA Fattahi Z., Kalhor Z., Fadaee M., Vazehan R., Parsimehr E., Abolhassani A.,
RA Beheshtian M., Zamani G., Nafissi S., Nilipour Y., Akbari M.R., Kahrizi K.,
RA Kariminejad A., Najmabadi H.;
RT "Improved diagnostic yield of neuromuscular disorders applying clinical
RT exome sequencing in patients arising from a consanguineous population.";
RL Clin. Genet. 91:386-402(2017).
CC -!- FUNCTION: Lamins are components of the nuclear lamina, a fibrous layer
CC on the nucleoplasmic side of the inner nuclear membrane, which is
CC thought to provide a framework for the nuclear envelope and may also
CC interact with chromatin. Lamin A and C are present in equal amounts in
CC the lamina of mammals. Recruited by DNA repair proteins XRCC4 and IFFO1
CC to the DNA double-strand breaks (DSBs) to prevent chromosome
CC translocation by immobilizing broken DNA ends (PubMed:31548606). Plays
CC an important role in nuclear assembly, chromatin organization, nuclear
CC membrane and telomere dynamics. Required for normal development of
CC peripheral nervous system and skeletal muscle and for muscle satellite
CC cell proliferation (PubMed:10080180, PubMed:22431096, PubMed:10814726,
CC PubMed:11799477, PubMed:18551513). Required for osteoblastogenesis and
CC bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980).
CC Also prevents fat infiltration of muscle and bone marrow, helping to
CC maintain the volume and strength of skeletal muscle and bone
CC (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070,
CC PubMed:12927431, PubMed:18611980, PubMed:23666920).
CC {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070,
CC ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726,
CC ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506,
CC ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753,
CC ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980,
CC ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:23666920,
CC ECO:0000269|PubMed:31548606}.
CC -!- FUNCTION: Prelamin-A/C can accelerate smooth muscle cell senescence. It
CC acts to disrupt mitosis and induce DNA damage in vascular smooth muscle
CC cells (VSMCs), leading to mitotic failure, genomic instability, and
CC premature senescence.
CC -!- SUBUNIT: Homodimer of lamin A and lamin C. Interacts with lamin-
CC associated polypeptides IA, IB and TMPO-alpha, RB1 and with emerin.
CC Interacts with SREBF1, SREBF2, SUN2 and TMEM43. Interacts with TMEM201
CC (By similarity). Proteolytically processed isoform A interacts with
CC NARF. Interacts with SUN1. Prelamin-A/C interacts with EMD. Interacts
CC with MLIP. Interacts with DMPK; may regulate nuclear envelope
CC stability. Interacts with SUV39H1; the interaction increases stability
CC of SUV39H1. Interacts with SYNE2. Interacts with ITSN1 isoform 2
CC (PubMed:29599122). Interacts with IFFO1; enables the formation of an
CC interior nucleoskeleton that is recruited to DNA double-strand breaks
CC (PubMed:31548606). {ECO:0000250, ECO:0000269|PubMed:10514485,
CC ECO:0000269|PubMed:12475961, ECO:0000269|PubMed:19323649,
CC ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:21498514,
CC ECO:0000269|PubMed:21949239, ECO:0000269|PubMed:23695662,
CC ECO:0000269|PubMed:23977161, ECO:0000269|PubMed:29599122,
CC ECO:0000269|PubMed:31548606}.
CC -!- SUBUNIT: [Isoform C]: Interacts (via C-terminus) with LEMD2 (via N-
CC terminus) (in vitro). {ECO:0000269|PubMed:16339967}.
CC -!- INTERACTION:
CC P02545; Q6H8Q1-8: ABLIM2; NbExp=3; IntAct=EBI-351935, EBI-16436655;
CC P02545; P18054: ALOX12; NbExp=4; IntAct=EBI-351935, EBI-1633210;
CC P02545; Q96DX5: ASB9; NbExp=3; IntAct=EBI-351935, EBI-745641;
CC P02545; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-351935, EBI-2410266;
CC P02545; P46379-2: BAG6; NbExp=3; IntAct=EBI-351935, EBI-10988864;
CC P02545; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-351935, EBI-742750;
CC P02545; Q9ULD4-2: BRPF3; NbExp=3; IntAct=EBI-351935, EBI-23662416;
CC P02545; Q96GN5-2: CDCA7L; NbExp=3; IntAct=EBI-351935, EBI-9091443;
CC P02545; Q9UII6: DUSP13; NbExp=7; IntAct=EBI-351935, EBI-749800;
CC P02545; P50402: EMD; NbExp=7; IntAct=EBI-351935, EBI-489887;
CC P02545; Q3B820: FAM161A; NbExp=3; IntAct=EBI-351935, EBI-719941;
CC P02545; A6H8Z2-3: FAM221B; NbExp=3; IntAct=EBI-351935, EBI-25843965;
CC P02545; P58499: FAM3B; NbExp=3; IntAct=EBI-351935, EBI-12955347;
CC P02545; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-351935, EBI-8468186;
CC P02545; Q8NEA9: GMCL2; NbExp=3; IntAct=EBI-351935, EBI-745707;
CC P02545; P16104: H2AX; NbExp=3; IntAct=EBI-351935, EBI-494830;
CC P02545; Q71DI3: H3C15; NbExp=6; IntAct=EBI-351935, EBI-750650;
CC P02545; Q0D2I5-5: IFFO1; NbExp=4; IntAct=EBI-351935, EBI-21251044;
CC P02545; Q13123: IK; NbExp=3; IntAct=EBI-351935, EBI-713456;
CC P02545; Q14005-2: IL16; NbExp=3; IntAct=EBI-351935, EBI-17178971;
CC P02545; Q96EL1: INKA1; NbExp=3; IntAct=EBI-351935, EBI-10285157;
CC P02545; Q8NA54: IQUB; NbExp=3; IntAct=EBI-351935, EBI-10220600;
CC P02545; Q99612: KLF6; NbExp=3; IntAct=EBI-351935, EBI-714994;
CC P02545; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-351935, EBI-10172290;
CC P02545; P20700: LMNB1; NbExp=10; IntAct=EBI-351935, EBI-968218;
CC P02545; Q03252: LMNB2; NbExp=6; IntAct=EBI-351935, EBI-2830427;
CC P02545; O76041: NEBL; NbExp=3; IntAct=EBI-351935, EBI-2880203;
CC P02545; Q12986: NFX1; NbExp=3; IntAct=EBI-351935, EBI-2130062;
CC P02545; Q9Y239: NOD1; NbExp=3; IntAct=EBI-351935, EBI-1051262;
CC P02545; Q13133-3: NR1H3; NbExp=3; IntAct=EBI-351935, EBI-11952806;
CC P02545; Q9BZ95-3: NSD3; NbExp=3; IntAct=EBI-351935, EBI-22002759;
CC P02545; Q6X4W1-6: NSMF; NbExp=3; IntAct=EBI-351935, EBI-25842707;
CC P02545; O75694: NUP155; NbExp=6; IntAct=EBI-351935, EBI-1050769;
CC P02545; Q3SX64: ODF3L2; NbExp=3; IntAct=EBI-351935, EBI-6660184;
CC P02545; Q96RG2: PASK; NbExp=2; IntAct=EBI-351935, EBI-1042651;
CC P02545; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-351935, EBI-11022007;
CC P02545; Q96FA3: PELI1; NbExp=3; IntAct=EBI-351935, EBI-448369;
CC P02545; O75925: PIAS1; NbExp=3; IntAct=EBI-351935, EBI-629434;
CC P02545; Q03181-2: PPARD; NbExp=3; IntAct=EBI-351935, EBI-10223258;
CC P02545; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-351935, EBI-12123390;
CC P02545; Q8TCX5: RHPN1; NbExp=3; IntAct=EBI-351935, EBI-746325;
CC P02545; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-351935, EBI-749039;
CC P02545; P62701: RPS4X; NbExp=3; IntAct=EBI-351935, EBI-354303;
CC P02545; Q6ZNE9: RUFY4; NbExp=3; IntAct=EBI-351935, EBI-10181525;
CC P02545; Q8N488: RYBP; NbExp=3; IntAct=EBI-351935, EBI-752324;
CC P02545; Q8IYM2: SLFN12; NbExp=3; IntAct=EBI-351935, EBI-2822550;
CC P02545; Q13573: SNW1; NbExp=4; IntAct=EBI-351935, EBI-632715;
CC P02545; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-351935, EBI-5235340;
CC P02545; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-351935, EBI-7082156;
CC P02545; O75886: STAM2; NbExp=3; IntAct=EBI-351935, EBI-373258;
CC P02545; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-351935, EBI-357085;
CC P02545; Q9UH99: SUN2; NbExp=4; IntAct=EBI-351935, EBI-1044964;
CC P02545; Q8WXH0-1: SYNE2; NbExp=3; IntAct=EBI-351935, EBI-6170976;
CC P02545; P54274-2: TERF1; NbExp=3; IntAct=EBI-351935, EBI-711018;
CC P02545; P42166: TMPO; NbExp=4; IntAct=EBI-351935, EBI-395393;
CC P02545; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-351935, EBI-2509913;
CC P02545; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-351935, EBI-11525489;
CC P02545; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-351935, EBI-9088812;
CC P02545; Q04323-2: UBXN1; NbExp=3; IntAct=EBI-351935, EBI-11530712;
CC P02545; Q9Y4E8-2: USP15; NbExp=3; IntAct=EBI-351935, EBI-12041225;
CC P02545; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-351935, EBI-11975223;
CC P02545; Q93009: USP7; NbExp=4; IntAct=EBI-351935, EBI-302474;
CC P02545; P63104: YWHAZ; NbExp=2; IntAct=EBI-351935, EBI-347088;
CC P02545; P10074: ZBTB48; NbExp=3; IntAct=EBI-351935, EBI-744864;
CC P02545; Q6ZN57: ZFP2; NbExp=3; IntAct=EBI-351935, EBI-7236323;
CC P02545; Q8WW38: ZFPM2; NbExp=3; IntAct=EBI-351935, EBI-947213;
CC P02545; Q15776: ZKSCAN8; NbExp=3; IntAct=EBI-351935, EBI-2602314;
CC P02545; P17024: ZNF20; NbExp=3; IntAct=EBI-351935, EBI-717634;
CC P02545; Q14585: ZNF345; NbExp=3; IntAct=EBI-351935, EBI-2818408;
CC P02545; Q9C0F3: ZNF436; NbExp=3; IntAct=EBI-351935, EBI-8489702;
CC P02545; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-351935, EBI-12010736;
CC P02545; Q96MN9-2: ZNF488; NbExp=3; IntAct=EBI-351935, EBI-25831733;
CC P02545; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-351935, EBI-10486136;
CC P02545; Q8TBZ8: ZNF564; NbExp=3; IntAct=EBI-351935, EBI-10273713;
CC P02545; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-351935, EBI-10172590;
CC P02545; Q96LX8: ZNF597; NbExp=3; IntAct=EBI-351935, EBI-9091553;
CC P02545; Q9BS31: ZNF649; NbExp=3; IntAct=EBI-351935, EBI-4395789;
CC P02545; O43309: ZSCAN12; NbExp=3; IntAct=EBI-351935, EBI-1210440;
CC P02545; P10073: ZSCAN22; NbExp=3; IntAct=EBI-351935, EBI-10178224;
CC P02545; P10215: NEC1; Xeno; NbExp=2; IntAct=EBI-351935, EBI-7183650;
CC P02545; P10218: NEC2; Xeno; NbExp=2; IntAct=EBI-351935, EBI-7183680;
CC P02545-1; P50402: EMD; NbExp=4; IntAct=EBI-351949, EBI-489887;
CC P02545-1; P20700: LMNB1; NbExp=5; IntAct=EBI-351949, EBI-968218;
CC P02545-1; PRO_0000314029 [P36956]: SREBF1; NbExp=6; IntAct=EBI-351949, EBI-22057616;
CC P02545-1; O75844: ZMPSTE24; NbExp=2; IntAct=EBI-351949, EBI-1056377;
CC P02545-2; Q9HC96: CAPN10; NbExp=3; IntAct=EBI-351953, EBI-3915761;
CC P02545-2; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-351953, EBI-350590;
CC P02545-2; Q0D2I5: IFFO1; NbExp=2; IntAct=EBI-351953, EBI-742894;
CC P02545-2; P02545-2: LMNA; NbExp=4; IntAct=EBI-351953, EBI-351953;
CC P02545-2; P20700: LMNB1; NbExp=19; IntAct=EBI-351953, EBI-968218;
CC P02545-2; O75925: PIAS1; NbExp=3; IntAct=EBI-351953, EBI-629434;
CC P02545-2; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-351953, EBI-6872807;
CC P02545-2; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-351953, EBI-358545;
CC P02545-6; Q71DI3: H3C15; NbExp=3; IntAct=EBI-9034379, EBI-750650;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15372542,
CC ECO:0000269|PubMed:31548606}. Nucleus envelope
CC {ECO:0000269|PubMed:29599122}. Nucleus lamina. Nucleus, nucleoplasm.
CC Nucleus matrix {ECO:0000269|PubMed:31548606}. Note=Farnesylation of
CC prelamin-A/C facilitates nuclear envelope targeting and subsequent
CC cleavage by ZMPSTE24/FACE1 to remove the farnesyl group produces mature
CC lamin-A/C, which can then be inserted into the nuclear lamina. EMD is
CC required for proper localization of non-farnesylated prelamin-A/C.
CC -!- SUBCELLULAR LOCATION: [Isoform C]: Nucleus speckle
CC {ECO:0000269|PubMed:16061563}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=A; Synonyms=Lamin A;
CC IsoId=P02545-1; Sequence=Displayed;
CC Name=C; Synonyms=Lamin C;
CC IsoId=P02545-2; Sequence=VSP_002469, VSP_002470;
CC Name=ADelta10; Synonyms=Lamin ADelta10;
CC IsoId=P02545-3; Sequence=VSP_002468;
CC Name=4;
CC IsoId=P02545-4; Sequence=VSP_045977, VSP_045978, VSP_045979;
CC Name=5;
CC IsoId=P02545-5; Sequence=VSP_053503, VSP_053504;
CC Name=6; Synonyms=Progerin;
CC IsoId=P02545-6; Sequence=VSP_053505;
CC -!- TISSUE SPECIFICITY: In the arteries, prelamin-A/C accumulation is not
CC observed in young healthy vessels but is prevalent in medial vascular
CC smooth muscle cells (VSMCs) from aged individuals and in
CC atherosclerotic lesions, where it often colocalizes with senescent and
CC degenerate VSMCs. Prelamin-A/C expression increases with age and
CC disease. In normal aging, the accumulation of prelamin-A/C is caused in
CC part by the down-regulation of ZMPSTE24/FACE1 in response to oxidative
CC stress. {ECO:0000269|PubMed:20458013}.
CC -!- PTM: Increased phosphorylation of the lamins occurs before envelope
CC disintegration and probably plays a role in regulating lamin
CC associations. Phosphorylation status of S-22 determines its
CC localization between double-strand break (DSB) sites and the nuclear
CC matrix (PubMed:31548606). {ECO:0000269|PubMed:31548606,
CC ECO:0000269|Ref.9}.
CC -!- PTM: Proteolytic cleavage of the C-terminal of 18 residues of prelamin-
CC A/C results in the production of lamin-A/C. The prelamin-A/C maturation
CC pathway includes farnesylation of CAAX motif, ZMPSTE24/FACE1 mediated
CC cleavage of the last three amino acids, methylation of the C-terminal
CC cysteine and endoproteolytic removal of the last 15 C-terminal amino
CC acids. Proteolytic cleavage requires prior farnesylation and
CC methylation, and absence of these blocks cleavage.
CC {ECO:0000269|PubMed:20458013, ECO:0000269|PubMed:8175923,
CC ECO:0000269|PubMed:9030603}.
CC -!- PTM: Sumoylation is necessary for the localization to the nuclear
CC envelope. {ECO:0000269|PubMed:18606848}.
CC -!- PTM: Farnesylation of prelamin-A/C facilitates nuclear envelope
CC targeting.
CC -!- DISEASE: Emery-Dreifuss muscular dystrophy 2, autosomal dominant
CC (EDMD2) [MIM:181350]: A form of Emery-Dreifuss muscular dystrophy, a
CC degenerative myopathy characterized by weakness and atrophy of muscle
CC without involvement of the nervous system, early contractures of the
CC elbows, Achilles tendons and spine, and cardiomyopathy associated with
CC cardiac conduction defects. {ECO:0000269|PubMed:10080180,
CC ECO:0000269|PubMed:10739764, ECO:0000269|PubMed:10814726,
CC ECO:0000269|PubMed:10908904, ECO:0000269|PubMed:10939567,
CC ECO:0000269|PubMed:11503164, ECO:0000269|PubMed:11525883,
CC ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:12032588,
CC ECO:0000269|PubMed:12467752, ECO:0000269|PubMed:12649505,
CC ECO:0000269|PubMed:12673789, ECO:0000269|PubMed:14684700,
CC ECO:0000269|PubMed:14985400, ECO:0000269|PubMed:15372542,
CC ECO:0000269|PubMed:15744034, ECO:0000269|PubMed:17136397,
CC ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:20848652,
CC ECO:0000269|PubMed:27234031}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Emery-Dreifuss muscular dystrophy 3, autosomal recessive
CC (EDMD3) [MIM:616516]: A form of Emery-Dreifuss muscular dystrophy, a
CC degenerative myopathy characterized by weakness and atrophy of muscle
CC without involvement of the nervous system, early contractures of the
CC elbows, Achilles tendons and spine, and cardiomyopathy associated with
CC cardiac conduction defects. {ECO:0000269|PubMed:22431096,
CC ECO:0000269|PubMed:27234031}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cardiomyopathy, dilated 1A (CMD1A) [MIM:115200]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:10580070,
CC ECO:0000269|PubMed:11561226, ECO:0000269|PubMed:11792809,
CC ECO:0000269|PubMed:11897440, ECO:0000269|PubMed:12486434,
CC ECO:0000269|PubMed:12628721, ECO:0000269|PubMed:12920062,
CC ECO:0000269|PubMed:14675861, ECO:0000269|PubMed:14684700,
CC ECO:0000269|PubMed:15140538, ECO:0000269|PubMed:15219508,
CC ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:16061563,
CC ECO:0000269|PubMed:18606848, ECO:0000269|PubMed:19167105,
CC ECO:0000269|PubMed:20160190, ECO:0000269|PubMed:21846512}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Lipodystrophy, familial partial, 2 (FPLD2) [MIM:151660]: A
CC disorder characterized by the loss of subcutaneous adipose tissue in
CC the lower parts of the body (limbs, buttocks, trunk). It is accompanied
CC by an accumulation of adipose tissue in the face and neck causing a
CC double chin, fat neck, or cushingoid appearance. Adipose tissue may
CC also accumulate in the axillae, back, labia majora, and intraabdominal
CC region. Affected patients are insulin-resistant and may develop glucose
CC intolerance and diabetes mellitus after age 20 years,
CC hypertriglyceridemia, and low levels of high density lipoprotein
CC cholesterol. {ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10655060,
CC ECO:0000269|PubMed:10739751, ECO:0000269|PubMed:11792809,
CC ECO:0000269|PubMed:12015247, ECO:0000269|PubMed:12196663,
CC ECO:0000269|PubMed:12629077, ECO:0000269|PubMed:15372542,
CC ECO:0000269|PubMed:17250669, ECO:0000269|PubMed:19220582,
CC ECO:0000269|PubMed:24485160}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2B1 (CMT2B1) [MIM:605588]: A
CC recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the
CC peripheral nervous system, characterized by progressive weakness and
CC atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two
CC main groups on the basis of electrophysiologic properties and
CC histopathology: primary peripheral demyelinating neuropathies
CC (designated CMT1 when they are dominantly inherited) and primary
CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group
CC are characterized by signs of axonal degeneration in the absence of
CC obvious myelin alterations, normal or slightly reduced nerve conduction
CC velocities, and progressive distal muscle weakness and atrophy.
CC {ECO:0000269|PubMed:11799477}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670]: Rare
CC genetic disorder characterized by features reminiscent of marked
CC premature aging. {ECO:0000269|PubMed:12714972,
CC ECO:0000269|PubMed:12768443, ECO:0000269|PubMed:12927431,
CC ECO:0000269|PubMed:15060110, ECO:0000269|PubMed:15286156,
CC ECO:0000269|PubMed:15622532, ECO:0000269|PubMed:19933576,
CC ECO:0000269|PubMed:21791255, ECO:0000269|PubMed:22355414,
CC ECO:0000269|PubMed:23666920}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. HGPS is caused by the
CC toxic accumulation of a truncated form of lamin-A/C. This mutant
CC protein, called progerin (isoform 6), acts to deregulate mitosis and
CC DNA damage signaling, leading to premature cell death and senescence.
CC The mutant form is mainly generated by a silent or missense mutation at
CC codon 608 of prelamin A that causes activation of a cryptic splice
CC donor site, resulting in production of isoform 6 with a deletion of 50
CC amino acids near the C terminus. Progerin lacks the conserved
CC ZMPSTE24/FACE1 cleavage site and therefore remains permanently
CC farnesylated. Thus, although it can enter the nucleus and associate
CC with the nuclear envelope, it cannot incorporate normally into the
CC nuclear lamina (PubMed:12714972). {ECO:0000269|PubMed:12714972}.
CC -!- DISEASE: Cardiomyopathy, dilated, with hypergonadotropic hypogonadism
CC (CMDHH) [MIM:212112]: A disorder characterized by the association of
CC genital anomalies, hypergonadotropic hypogonadism and dilated
CC cardiomyopathy. Patients can present other variable clinical
CC manifestations including intellectual disability, skeletal anomalies,
CC scleroderma-like skin, graying and thinning of hair, osteoporosis.
CC Dilated cardiomyopathy is characterized by ventricular dilation and
CC impaired systolic function, resulting in congestive heart failure and
CC arrhythmia. {ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:17150192,
CC ECO:0000269|PubMed:19283854}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Mandibuloacral dysplasia with type A lipodystrophy (MADA)
CC [MIM:248370]: A form of mandibuloacral dysplasia, a rare progeroid
CC disorder with clinical and genetic heterogeneity, characterized by
CC growth retardation, craniofacial dysmorphic features due to distal bone
CC resorption, musculoskeletal and skin abnormalities associated with
CC lipodystrophy. MADA is an autosomal recessive disease characterized by
CC mandibular and clavicular hypoplasia, acroosteolysis, delayed closure
CC of the cranial suture, progeroid appearance, partial alopecia, soft
CC tissue calcinosis, joint contractures, and partial lipodystrophy with
CC loss of subcutaneous fat from the extremities. Adipose tissue in the
CC face, neck and trunk is normal or increased.
CC {ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:15998779,
CC ECO:0000269|PubMed:16278265}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Restrictive dermopathy 2 (RSDM2) [MIM:619793]: An autosomal
CC dominant form of restrictive dermopathy, a genodermatosis mainly
CC characterized by intrauterine growth retardation, tight and rigid skin
CC with erosions, prominent superficial vasculature and epidermal
CC hyperkeratosis, facial dysmorphism, sparse/absent eyelashes and
CC eyebrows, mineralization defects of the skull, thin dysplastic
CC clavicles, pulmonary hypoplasia, multiple joint contractures and an
CC early neonatal lethal course. Liveborn children usually die within the
CC first week of life. {ECO:0000269|PubMed:15317753}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Heart-hand syndrome Slovenian type (HHS-Slovenian)
CC [MIM:610140]: Heart-hand syndrome (HHS) is a clinically and genetically
CC heterogeneous disorder characterized by the co-occurrence of a
CC congenital cardiac disease and limb malformations.
CC {ECO:0000269|PubMed:18611980}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Muscular dystrophy congenital LMNA-related (MDCL)
CC [MIM:613205]: A form of congenital muscular dystrophy. Patients present
CC at birth, or within the first few months of life, with hypotonia,
CC muscle weakness and often with joint contractures.
CC {ECO:0000269|PubMed:18551513}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in LMNA may cause a late-onset cardiocutaneous
CC progeria syndrome characterized by cutaneous manifestations of aging
CC appearing in the third decade of life, cardiac valve calcification and
CC dysfunction, prominent atherosclerosis, and cardiomyopathy, leading to
CC death on average in the fourth decade. {ECO:0000269|PubMed:23666920}.
CC -!- MISCELLANEOUS: There are three types of lamins in human cells: A, B,
CC and C.
CC -!- MISCELLANEOUS: The structural integrity of the lamina is strictly
CC controlled by the cell cycle, as seen by the disintegration and
CC formation of the nuclear envelope in prophase and telophase,
CC respectively.
CC -!- MISCELLANEOUS: [Isoform 6]: Disease-associated isoform. Polymorphism at
CC codon 608 results in activation of a cryptic splice donor site within
CC exon 11, resulting in a truncated protein product that lacks the site
CC for endoproteolytic cleavage. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA27173.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
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DR EMBL; X03444; CAA27173.1; ALT_FRAME; mRNA.
DR EMBL; X03445; CAA27174.1; -; mRNA.
DR EMBL; M13451; AAA36164.1; -; mRNA.
DR EMBL; M13452; AAA36160.1; -; mRNA.
DR EMBL; AY847597; AAW32540.1; -; mRNA.
DR EMBL; AY847595; AAW32538.1; -; mRNA.
DR EMBL; AY357727; AAR29466.1; -; mRNA.
DR EMBL; AK295390; BAG58344.1; -; mRNA.
DR EMBL; AL135927; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356734; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52997.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52999.1; -; Genomic_DNA.
DR EMBL; BC000511; AAH00511.1; -; mRNA.
DR EMBL; BC003162; AAH03162.1; -; mRNA.
DR EMBL; BC014507; AAH14507.1; -; mRNA.
DR EMBL; AF381029; AAK59326.1; -; mRNA.
DR CCDS; CCDS1129.1; -. [P02545-1]
DR CCDS; CCDS1131.1; -. [P02545-2]
DR CCDS; CCDS58038.1; -. [P02545-4]
DR CCDS; CCDS72941.1; -. [P02545-6]
DR PIR; A02961; VEHULA.
DR PIR; A02962; VEHULC.
DR RefSeq; NP_001244303.1; NM_001257374.2. [P02545-4]
DR RefSeq; NP_001269553.1; NM_001282624.1.
DR RefSeq; NP_001269554.1; NM_001282625.1. [P02545-2]
DR RefSeq; NP_001269555.1; NM_001282626.1. [P02545-6]
DR RefSeq; NP_005563.1; NM_005572.3. [P02545-2]
DR RefSeq; NP_733821.1; NM_170707.3. [P02545-1]
DR RefSeq; NP_733822.1; NM_170708.3. [P02545-3]
DR PDB; 1IFR; X-ray; 1.40 A; A=436-552.
DR PDB; 1IVT; NMR; -; A=428-549.
DR PDB; 1X8Y; X-ray; 2.20 A; A=305-387.
DR PDB; 2XV5; X-ray; 2.40 A; A/B=328-398.
DR PDB; 2YPT; X-ray; 3.80 A; F/G/H/I=661-664.
DR PDB; 3GEF; X-ray; 1.50 A; A/B/C/D=436-552.
DR PDB; 3V4Q; X-ray; 3.06 A; A=313-386.
DR PDB; 3V4W; X-ray; 3.70 A; A=313-386.
DR PDB; 3V5B; X-ray; 3.00 A; A=313-386.
DR PDB; 6GHD; X-ray; 2.10 A; B/F=428-546.
DR PDB; 6JLB; X-ray; 3.21 A; A/B/C/D=1-300.
DR PDB; 6RPR; X-ray; 2.26 A; B=430-545.
DR PDB; 6SNZ; X-ray; 2.60 A; A/B/C/D=65-222.
DR PDB; 6YF5; X-ray; 1.83 A; A/B/C/D=17-70.
DR PDB; 6YJD; X-ray; 2.90 A; A=329-403.
DR PDB; 7CRG; X-ray; 1.80 A; A/B/C=406-553.
DR PDB; 7D9N; X-ray; 3.70 A; A/B=27-229.
DR PDBsum; 1IFR; -.
DR PDBsum; 1IVT; -.
DR PDBsum; 1X8Y; -.
DR PDBsum; 2XV5; -.
DR PDBsum; 2YPT; -.
DR PDBsum; 3GEF; -.
DR PDBsum; 3V4Q; -.
DR PDBsum; 3V4W; -.
DR PDBsum; 3V5B; -.
DR PDBsum; 6GHD; -.
DR PDBsum; 6JLB; -.
DR PDBsum; 6RPR; -.
DR PDBsum; 6SNZ; -.
DR PDBsum; 6YF5; -.
DR PDBsum; 6YJD; -.
DR PDBsum; 7CRG; -.
DR PDBsum; 7D9N; -.
DR AlphaFoldDB; P02545; -.
DR BMRB; P02545; -.
DR SMR; P02545; -.
DR BioGRID; 110186; 1026.
DR CORUM; P02545; -.
DR DIP; DIP-32948N; -.
DR DIP; DIP-58162N; -.
DR IntAct; P02545; 365.
DR MINT; P02545; -.
DR STRING; 9606.ENSP00000357283; -.
DR ChEMBL; CHEMBL1293235; -.
DR GlyConnect; 2876; 1 O-Linked glycan (2 sites). [P02545-3]
DR GlyGen; P02545; 12 sites, 2 O-linked glycans (12 sites).
DR iPTMnet; P02545; -.
DR MetOSite; P02545; -.
DR PhosphoSitePlus; P02545; -.
DR SwissPalm; P02545; -.
DR BioMuta; LMNA; -.
DR DMDM; 125962; -.
DR REPRODUCTION-2DPAGE; IPI00021405; -.
DR REPRODUCTION-2DPAGE; IPI00216952; -.
DR REPRODUCTION-2DPAGE; P02545; -.
DR SWISS-2DPAGE; P02545; -.
DR CPTAC; CPTAC-399; -.
DR CPTAC; CPTAC-400; -.
DR CPTAC; CPTAC-973; -.
DR CPTAC; CPTAC-974; -.
DR EPD; P02545; -.
DR jPOST; P02545; -.
DR MassIVE; P02545; -.
DR MaxQB; P02545; -.
DR PaxDb; P02545; -.
DR PeptideAtlas; P02545; -.
DR PRIDE; P02545; -.
DR ProteomicsDB; 13394; -.
DR ProteomicsDB; 18441; -.
DR ProteomicsDB; 51530; -. [P02545-1]
DR ProteomicsDB; 51531; -. [P02545-2]
DR ProteomicsDB; 51532; -. [P02545-3]
DR ProteomicsDB; 67698; -.
DR TopDownProteomics; P02545-1; -. [P02545-1]
DR TopDownProteomics; P02545-2; -. [P02545-2]
DR TopDownProteomics; P02545-4; -. [P02545-4]
DR Antibodypedia; 1676; 1671 antibodies from 49 providers.
DR DNASU; 4000; -.
DR Ensembl; ENST00000361308.9; ENSP00000355292.6; ENSG00000160789.24. [P02545-1]
DR Ensembl; ENST00000368299.7; ENSP00000357282.3; ENSG00000160789.24. [P02545-6]
DR Ensembl; ENST00000368300.9; ENSP00000357283.4; ENSG00000160789.24. [P02545-1]
DR Ensembl; ENST00000368301.6; ENSP00000357284.2; ENSG00000160789.24. [P02545-2]
DR Ensembl; ENST00000448611.6; ENSP00000395597.2; ENSG00000160789.24. [P02545-4]
DR Ensembl; ENST00000473598.6; ENSP00000421821.1; ENSG00000160789.24. [P02545-5]
DR Ensembl; ENST00000675939.1; ENSP00000502256.1; ENSG00000160789.24. [P02545-1]
DR Ensembl; ENST00000676385.2; ENSP00000502091.1; ENSG00000160789.24. [P02545-3]
DR Ensembl; ENST00000677389.1; ENSP00000503633.1; ENSG00000160789.24. [P02545-2]
DR Ensembl; ENST00000682650.1; ENSP00000506904.1; ENSG00000160789.24. [P02545-3]
DR Ensembl; ENST00000683032.1; ENSP00000506771.1; ENSG00000160789.24. [P02545-1]
DR GeneID; 4000; -.
DR KEGG; hsa:4000; -.
DR MANE-Select; ENST00000368300.9; ENSP00000357283.4; NM_170707.4; NP_733821.1.
DR UCSC; uc001fnf.3; human. [P02545-1]
DR CTD; 4000; -.
DR DisGeNET; 4000; -.
DR GeneCards; LMNA; -.
DR GeneReviews; LMNA; -.
DR HGNC; HGNC:6636; LMNA.
DR HPA; ENSG00000160789; Low tissue specificity.
DR MalaCards; LMNA; -.
DR MIM; 115200; phenotype.
DR MIM; 150330; gene.
DR MIM; 151660; phenotype.
DR MIM; 176670; phenotype.
DR MIM; 181350; phenotype.
DR MIM; 212112; phenotype.
DR MIM; 248370; phenotype.
DR MIM; 605588; phenotype.
DR MIM; 610140; phenotype.
DR MIM; 613205; phenotype.
DR MIM; 616516; phenotype.
DR MIM; 619793; phenotype.
DR neXtProt; NX_P02545; -.
DR OpenTargets; ENSG00000160789; -.
DR Orphanet; 79474; Atypical Werner syndrome.
DR Orphanet; 98853; Autosomal dominant Emery-Dreifuss muscular dystrophy.
DR Orphanet; 98855; Autosomal recessive Emery-Dreifuss muscular dystrophy.
DR Orphanet; 280365; Autosomal semi-dominant severe lipodystrophic laminopathy.
DR Orphanet; 98856; Charcot-Marie-Tooth disease type 2B1.
DR Orphanet; 157973; Congenital muscular dystrophy due to LMNA mutation.
DR Orphanet; 2229; Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome.
DR Orphanet; 300751; Familial dilated cardiomyopathy with conduction defect due to LMNA mutation.
DR Orphanet; 293899; Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
DR Orphanet; 293888; Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
DR Orphanet; 293910; Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 2348; Familial partial lipodystrophy, Dunnigan type.
DR Orphanet; 79084; Familial partial lipodystrophy, Koebberling type.
DR Orphanet; 168796; Heart-hand syndrome, Slovenian type.
DR Orphanet; 740; Hutchinson-Gilford progeria syndrome.
DR Orphanet; 54260; Left ventricular noncompaction.
DR Orphanet; 363618; LMNA-related cardiocutaneous progeria syndrome.
DR Orphanet; 90153; Mandibuloacral dysplasia with type A lipodystrophy.
DR Orphanet; 1662; Restrictive dermopathy.
DR PharmGKB; PA231; -.
DR VEuPathDB; HostDB:ENSG00000160789; -.
DR eggNOG; KOG0977; Eukaryota.
DR GeneTree; ENSGT00940000157244; -.
DR HOGENOM; CLU_012560_9_1_1; -.
DR InParanoid; P02545; -.
DR OMA; MSIHHRH; -.
DR OrthoDB; 701388at2759; -.
DR PhylomeDB; P02545; -.
DR TreeFam; TF101181; -.
DR PathwayCommons; P02545; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis. [P02545-2]
DR Reactome; R-HSA-2980766; Nuclear Envelope Breakdown.
DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-HSA-352238; Breakdown of the nuclear lamina. [P02545-1]
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR Reactome; R-HSA-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models. [P02545-1]
DR SABIO-RK; P02545; -.
DR SignaLink; P02545; -.
DR SIGNOR; P02545; -.
DR BioGRID-ORCS; 4000; 85 hits in 1082 CRISPR screens.
DR ChiTaRS; LMNA; human.
DR EvolutionaryTrace; P02545; -.
DR GeneWiki; LMNA; -.
DR GenomeRNAi; 4000; -.
DR Pharos; P02545; Tbio.
DR PRO; PR:P02545; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P02545; protein.
DR Bgee; ENSG00000160789; Expressed in nipple and 206 other tissues.
DR ExpressionAtlas; P02545; baseline and differential.
DR Genevisible; P02545; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005882; C:intermediate filament; TAS:UniProtKB.
DR GO; GO:0005638; C:lamin filament; TAS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005652; C:nuclear lamina; IBA:GO_Central.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; HDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:CAFA.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central.
DR GO; GO:0005198; F:structural molecule activity; TAS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
DR GO; GO:0090398; P:cellular senescence; IDA:GO_Central.
DR GO; GO:1990683; P:DNA double-strand break attachment to nuclear envelope; IDA:UniProtKB.
DR GO; GO:0030951; P:establishment or maintenance of microtubule cytoskeleton polarity; ISS:BHF-UCL.
DR GO; GO:0031507; P:heterochromatin assembly; IBA:GO_Central.
DR GO; GO:0007517; P:muscle organ development; IMP:UniProtKB.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:CAFA.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0072201; P:negative regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:0006998; P:nuclear envelope organization; IMP:CAFA.
DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central.
DR GO; GO:0051664; P:nuclear pore localization; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1900114; P:positive regulation of histone H3-K9 trimethylation; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0008104; P:protein localization; IMP:CAFA.
DR GO; GO:0090435; P:protein localization to nuclear envelope; IBA:GO_Central.
DR GO; GO:0034504; P:protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISS:BHF-UCL.
DR GO; GO:1900180; P:regulation of protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0032204; P:regulation of telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IEA:Ensembl.
DR DisProt; DP00716; -.
DR Gene3D; 2.60.40.1260; -; 1.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR001322; Lamin_tail_dom.
DR InterPro; IPR036415; Lamin_tail_dom_sf.
DR Pfam; PF00038; Filament; 1.
DR Pfam; PF00932; LTD; 1.
DR SMART; SM01391; Filament; 1.
DR SUPFAM; SSF74853; SSF74853; 1.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
DR PROSITE; PS51841; LTD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cardiomyopathy;
KW Charcot-Marie-Tooth disease; Coiled coil; Congenital muscular dystrophy;
KW Direct protein sequencing; Disease variant;
KW Emery-Dreifuss muscular dystrophy; Intermediate filament; Isopeptide bond;
KW Limb-girdle muscular dystrophy; Lipoprotein; Methylation;
KW Neurodegeneration; Neuropathy; Nucleus; Phosphoprotein; Prenylation;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..661
FT /note="Prelamin-A/C"
FT /id="PRO_0000398835"
FT CHAIN 1..646
FT /note="Lamin-A/C"
FT /id="PRO_0000063810"
FT PROPEP 647..661
FT /note="Removed in Lamin-A/C form"
FT /id="PRO_0000398836"
FT PROPEP 662..664
FT /note="Removed in Prelamin-A/C form and in Lamin-A/C form"
FT /id="PRO_0000403442"
FT DOMAIN 31..387
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT DOMAIN 428..545
FT /note="LTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01187"
FT REGION 1..130
FT /note="Interaction with MLIP"
FT /evidence="ECO:0000269|PubMed:21498514"
FT REGION 1..33
FT /note="Head"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 34..70
FT /note="Coil 1A"
FT REGION 71..80
FT /note="Linker 1"
FT REGION 81..218
FT /note="Coil 1B"
FT REGION 219..242
FT /note="Linker 2"
FT REGION 243..383
FT /note="Coil 2"
FT REGION 259..331
FT /note="Necessary and sufficient for the interaction with
FT IFFO1"
FT /evidence="ECO:0000269|PubMed:31548606"
FT REGION 384..664
FT /note="Tail"
FT REGION 384..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 552..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 417..422
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 391..417
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 266
FT /note="Heptad change of phase"
FT SITE 325
FT /note="Stutter"
FT /evidence="ECO:0000250"
FT SITE 330
FT /note="Heptad change of phase"
FT SITE 646..647
FT /note="Cleavage; by endoprotease"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 19
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 32
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 32
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 108
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 123
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 135
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 155
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 171
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 171
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 201
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 260
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 270
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 311
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 450
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 457
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 496
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48679"
FT MOD_RES 505
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 510
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48679"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 548
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 616
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48678"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 628
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 636
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 652
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 661
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000269|PubMed:8175923,
FT ECO:0000269|PubMed:9030603"
FT LIPID 661
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:8175923,
FT ECO:0000269|PubMed:9030603"
FT CROSSLNK 32
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 97
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 171
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 201
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 201
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 208
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 219
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 233
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 260
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 311
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 366
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 378
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 417
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 420
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 450
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 470
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 486
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 597
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 597
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..99
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_053503"
FT VAR_SEQ 1..7
FT /note="METPSQR -> MGNSEGC (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045977"
FT VAR_SEQ 8..119
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045978"
FT VAR_SEQ 100..119
FT /note="ARLQLELSKVREEFKELKAR -> MDLEAWDPHLEPDAEAMVDG (in
FT isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_053504"
FT VAR_SEQ 537..566
FT /note="Missing (in isoform ADelta10)"
FT /evidence="ECO:0000303|PubMed:8621584"
FT /id="VSP_002468"
FT VAR_SEQ 567..572
FT /note="GSHCSS -> VSGSRR (in isoform C)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:3453101, ECO:0000303|PubMed:3462705"
FT /id="VSP_002469"
FT VAR_SEQ 573..664
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:3453101, ECO:0000303|PubMed:3462705"
FT /id="VSP_002470"
FT VAR_SEQ 607..656
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053505"
FT VAR_SEQ 664
FT /note="M -> IQEMGMRWEVEEGRRKVSLSCLP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045979"
FT VARIANT 10
FT /note="T -> I (in an atypical progeroid patient; diagnosed
FT as Seip syndrome; unknown pathological significance;
FT dbSNP:rs57077886)"
FT /evidence="ECO:0000269|PubMed:15060110"
FT /id="VAR_039745"
FT VARIANT 24
FT /note="T -> S (in EDMD3)"
FT /evidence="ECO:0000269|PubMed:27234031"
FT /id="VAR_076562"
FT VARIANT 25
FT /note="R -> G (in EDMD2; dbSNP:rs58327533)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039746"
FT VARIANT 25
FT /note="R -> P (in EDMD2; mis-localized in the nucleus;
FT causes nuclear deformations and LMNB1 redistribution;
FT dbSNP:rs61578124)"
FT /evidence="ECO:0000269|PubMed:11503164,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_039747"
FT VARIANT 28
FT /note="R -> W (in FPLD2; dbSNP:rs59914820)"
FT /evidence="ECO:0000269|PubMed:12015247"
FT /id="VAR_039748"
FT VARIANT 32
FT /note="Missing (in EDMD2; abnormal nuclear localization in
FT a honeycomb expression pattern in about 11% of cultured
FT skin fibroblasts from heterozygous patients; no effect on
FT protein level)"
FT /evidence="ECO:0000269|PubMed:12467752,
FT ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:15372542"
FT /id="VAR_039749"
FT VARIANT 33
FT /note="E -> D (in CMT2; autosomal dominant form;
FT dbSNP:rs57966821)"
FT /evidence="ECO:0000269|PubMed:14985400"
FT /id="VAR_039750"
FT VARIANT 33
FT /note="E -> G (in EDMD2; dbSNP:rs267607614)"
FT /evidence="ECO:0000269|PubMed:14985400"
FT /id="VAR_039751"
FT VARIANT 35
FT /note="L -> V (in EDMD2; dbSNP:rs56694480)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039752"
FT VARIANT 39
FT /note="N -> S (in MDCL and EDMD2; dbSNP:rs57983345)"
FT /evidence="ECO:0000269|PubMed:18551513,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_063588"
FT VARIANT 43
FT /note="A -> T (in EDMD2; dbSNP:rs60446065)"
FT /evidence="ECO:0000269|PubMed:11503164"
FT /id="VAR_039753"
FT VARIANT 45
FT /note="Y -> C (in EDMD2; dbSNP:rs58436778)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_009971"
FT VARIANT 50
FT /note="R -> P (in EDMD2 and MDCL; dbSNP:rs60695352)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:18551513"
FT /id="VAR_009972"
FT VARIANT 50
FT /note="R -> S (in EDMD2; dbSNP:rs59931416)"
FT /evidence="ECO:0000269|PubMed:11503164"
FT /id="VAR_039754"
FT VARIANT 57
FT /note="A -> P (in CMDHH; phenotype originally designated as
FT atypical Werner syndrome; dbSNP:rs28928903)"
FT /evidence="ECO:0000269|PubMed:12927431"
FT /id="VAR_017656"
FT VARIANT 59
FT /note="L -> R (in CMDHH; dbSNP:rs58922911)"
FT /evidence="ECO:0000269|PubMed:17150192,
FT ECO:0000269|PubMed:19283854"
FT /id="VAR_064055"
FT VARIANT 60
FT /note="R -> G (in CMD1A and FPLD2; interacts with itself
FT and with wild-type LMNA and LMNB1; no decrease in the
FT stability compared with wild-type; dbSNP:rs28928900)"
FT /evidence="ECO:0000269|PubMed:10580070,
FT ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:12196663"
FT /id="VAR_034706"
FT VARIANT 62
FT /note="R -> G (in FPLD2; dbSNP:rs56793579)"
FT /evidence="ECO:0000269|PubMed:12015247"
FT /id="VAR_039755"
FT VARIANT 63
FT /note="I -> N (in EDMD2; dbSNP:rs57793737)"
FT /evidence="ECO:0000269|PubMed:12467752,
FT ECO:0000269|PubMed:12649505, ECO:0000269|PubMed:15744034"
FT /id="VAR_039756"
FT VARIANT 63
FT /note="I -> S (in EDMD2; no effect on protein level; no
FT obvious effect on nuclear morphology in cultured skin
FT fibroblasts from heterozygous patients; dbSNP:rs57793737)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:15372542"
FT /id="VAR_009974"
FT VARIANT 65
FT /note="E -> G (in EDMD2)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039757"
FT VARIANT 85
FT /note="L -> R (in CMD1A; interacts with itself and with
FT wild-type LMNA and LMNB1; no decrease in the stability
FT compared with wild-type; dbSNP:rs28933090)"
FT /evidence="ECO:0000269|PubMed:10580070,
FT ECO:0000269|PubMed:11792809"
FT /id="VAR_009975"
FT VARIANT 89
FT /note="R -> L (in CMD1A; dramatically aberrant localization
FT with almost no nuclear rim staining and formation of
FT intranuclear foci; dbSNP:rs59040894)"
FT /evidence="ECO:0000269|PubMed:12628721,
FT ECO:0000269|PubMed:20160190"
FT /id="VAR_039758"
FT VARIANT 92
FT /note="L -> F (in CMD1A; dbSNP:rs267607560)"
FT /evidence="ECO:0000269|PubMed:21846512"
FT /id="VAR_067257"
FT VARIANT 97
FT /note="K -> E (in CMD1A; dbSNP:rs59065411)"
FT /evidence="ECO:0000269|PubMed:11897440"
FT /id="VAR_039759"
FT VARIANT 101
FT /note="R -> P (in CMD1A; dramatically aberrant localization
FT with almost no nuclear rim staining and formation of
FT intranuclear foci; dbSNP:rs267607568)"
FT /evidence="ECO:0000269|PubMed:20160190"
FT /id="VAR_070174"
FT VARIANT 112
FT /note="Missing (in EDMD2)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:14684700"
FT /id="VAR_009976"
FT VARIANT 125
FT /note="G -> S (found in patients with atrial fibrillation;
FT unknown pathological significance; dbSNP:rs267607605)"
FT /evidence="ECO:0000269|PubMed:19427440"
FT /id="VAR_072817"
FT VARIANT 133
FT /note="R -> L (in FPLD2; dbSNP:rs60864230)"
FT /evidence="ECO:0000269|PubMed:12629077"
FT /id="VAR_016913"
FT VARIANT 133
FT /note="R -> P (in EDMD2; dbSNP:rs60864230)"
FT /evidence="ECO:0000269|PubMed:11503164"
FT /id="VAR_017657"
FT VARIANT 138
FT /note="E -> K (in HGPS; might be associated with early and
FT severe strokes; dbSNP:rs267607649)"
FT /evidence="ECO:0000269|PubMed:21791255"
FT /id="VAR_070175"
FT VARIANT 140
FT /note="L -> P (in EDMD2; dbSNP:rs60652225)"
FT /evidence="ECO:0000269|PubMed:12649505,
FT ECO:0000269|PubMed:15744034"
FT /id="VAR_039760"
FT VARIANT 140
FT /note="L -> R (in HGPS; phenotype originally designated as
FT atypical Werner syndrome; dbSNP:rs60652225)"
FT /evidence="ECO:0000269|PubMed:12927431"
FT /id="VAR_017658"
FT VARIANT 143
FT /note="S -> F (in HGPS; dbSNP:rs58912633)"
FT /evidence="ECO:0000269|PubMed:15622532"
FT /id="VAR_034707"
FT VARIANT 143
FT /note="S -> P (in CMD1A; dbSNP:rs61661343)"
FT /evidence="ECO:0000269|PubMed:15140538"
FT /id="VAR_039761"
FT VARIANT 145
FT /note="E -> K (in HGPS; atypical; dbSNP:rs60310264)"
FT /evidence="ECO:0000269|PubMed:12714972"
FT /id="VAR_017659"
FT VARIANT 150
FT /note="T -> P (in EDMD2; dbSNP:rs58917027)"
FT /evidence="ECO:0000269|PubMed:10908904,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_039762"
FT VARIANT 161
FT /note="E -> K (in CMD1A; dbSNP:rs28933093)"
FT /evidence="ECO:0000269|PubMed:12920062,
FT ECO:0000269|PubMed:21846512"
FT /id="VAR_017660"
FT VARIANT 166
FT /note="R -> P (in CMD1A; dramatically aberrant localization
FT with almost no nuclear rim staining and formation of
FT intranuclear foci; dbSNP:rs267607570)"
FT /evidence="ECO:0000269|PubMed:20160190"
FT /id="VAR_070176"
FT VARIANT 189
FT /note="R -> P (in EDMD2; found also in a patient with limb-
FT girdle muscular dystrophy; sporadic; dbSNP:rs267607643)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064962"
FT VARIANT 190
FT /note="R -> Q (in EDMD2 and CMD1A; aberrant localization
FT with decreased nuclear rim staining and increased formation
FT of intranuclear foci; dbSNP:rs267607571)"
FT /evidence="ECO:0000269|PubMed:15744034,
FT ECO:0000269|PubMed:20160190"
FT /id="VAR_039763"
FT VARIANT 190
FT /note="R -> RR (in EDMD2)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064963"
FT VARIANT 190
FT /note="R -> W (in CMD1A; dbSNP:rs59026483)"
FT /evidence="ECO:0000269|PubMed:11897440,
FT ECO:0000269|PubMed:15219508, ECO:0000269|PubMed:16061563"
FT /id="VAR_039764"
FT VARIANT 192
FT /note="D -> G (in CMD1A; dramatically increases the size of
FT intranuclear speckles and reduces their number; this
FT phenotype is only partially reversed by coexpression of the
FT G-192 mutation and wild-type lamin-C; precludes insertion
FT of lamin-C into the nuclear envelope when co-transfected
FT with the G-192 LMNA; G-192 lamin-C expression totally
FT disrupts the SUMO1 pattern; dbSNP:rs57045855)"
FT /evidence="ECO:0000269|PubMed:16061563"
FT /id="VAR_039765"
FT VARIANT 195
FT /note="N -> K (in CMD1A; dramatically aberrant localization
FT with decreased nuclear rim staining and formation of
FT intranuclear foci; distribution of endogenous LMNA, LMNB1
FT and LMNB2 are altered in cells expressing this mutant;
FT causes an increased loss of endogenous EMD from the nuclear
FT envelope; interacts with itself and with wild-type LMNA and
FT LMNB1; no decrease in the stability compared with wild-
FT type; dbSNP:rs28933091)"
FT /evidence="ECO:0000269|PubMed:10580070,
FT ECO:0000269|PubMed:11792809"
FT /id="VAR_009977"
FT VARIANT 196..199
FT /note="RLQT -> S (in EDMD2)"
FT /evidence="ECO:0000269|PubMed:11503164"
FT /id="VAR_039766"
FT VARIANT 203
FT /note="E -> G (in CMD1A; interacts with itself and with
FT wild-type LMNA and LMNB1; no decrease in the stability
FT compared with wild-type; decreased sumoylation; aberrant
FT localization with decreased nuclear rim staining and
FT formation of intranuclear foci; associated with increased
FT cell death; dbSNP:rs28933092)"
FT /evidence="ECO:0000269|PubMed:10580070,
FT ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:18606848"
FT /id="VAR_009978"
FT VARIANT 203
FT /note="E -> K (in CMD1A; decreased sumoylation; aberrant
FT localization with decreased nuclear rim staining and
FT formation of intranuclear foci; associated with increased
FT cell death; dbSNP:rs61195471)"
FT /evidence="ECO:0000269|PubMed:11561226,
FT ECO:0000269|PubMed:18606848, ECO:0000269|PubMed:20160190"
FT /id="VAR_039767"
FT VARIANT 206
FT /note="F -> L (in EDMD2; dbSNP:rs267607629)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064964"
FT VARIANT 208
FT /note="Missing (in EDMD2; no obvious effect on nuclear
FT morphology in cultured skin fibroblasts from heterozygous
FT patients; no effect on protein level)"
FT /evidence="ECO:0000269|PubMed:10814726,
FT ECO:0000269|PubMed:15372542"
FT /id="VAR_034708"
FT VARIANT 210
FT /note="I -> S (in CMD1A; dramatically aberrant localization
FT with almost no nuclear rim staining and increased formation
FT of intranuclear foci; dbSNP:rs267607572)"
FT /evidence="ECO:0000269|PubMed:20160190"
FT /id="VAR_070177"
FT VARIANT 215
FT /note="L -> P (in CMD1A; aberrant localization with
FT decreased nuclear rim staining and formation of
FT intranuclear foci; dbSNP:rs61295588)"
FT /evidence="ECO:0000269|PubMed:12486434,
FT ECO:0000269|PubMed:20160190"
FT /id="VAR_039768"
FT VARIANT 222
FT /note="H -> P (in EDMD2; dbSNP:rs58034145)"
FT /evidence="ECO:0000269|PubMed:10939567"
FT /id="VAR_039769"
FT VARIANT 222
FT /note="H -> Y (in EDMD2; dbSNP:rs28928901)"
FT /evidence="ECO:0000269|PubMed:10739764"
FT /id="VAR_009979"
FT VARIANT 225
FT /note="R -> Q (in EDMD3; dbSNP:rs199474724)"
FT /evidence="ECO:0000269|PubMed:22431096"
FT /id="VAR_067697"
FT VARIANT 230
FT /note="D -> N (in FPLD2; dbSNP:rs61214927)"
FT /evidence="ECO:0000269|PubMed:17250669"
FT /id="VAR_039770"
FT VARIANT 232
FT /note="G -> E (in EDMD2; dbSNP:rs57207746)"
FT /evidence="ECO:0000269|PubMed:10939567"
FT /id="VAR_039771"
FT VARIANT 248
FT /note="L -> P (in EDMD2; dbSNP:rs58850446)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039772"
FT VARIANT 249
FT /note="R -> Q (in EDMD2; no obvious effect on nuclear
FT morphology in cultured skin fibroblasts from heterozygous
FT patients; no effect on protein level; dbSNP:rs59332535)"
FT /evidence="ECO:0000269|PubMed:10739764,
FT ECO:0000269|PubMed:10939567, ECO:0000269|PubMed:11503164,
FT ECO:0000269|PubMed:12032588, ECO:0000269|PubMed:12649505,
FT ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:15372542,
FT ECO:0000269|PubMed:15744034, ECO:0000269|PubMed:20848652"
FT /id="VAR_009980"
FT VARIANT 249
FT /note="R -> W (in MDCL and EDMD2; mislocalized in the
FT nucleus; causes nuclear deformations and LMNB1
FT redistribution; dbSNP:rs121912496)"
FT /evidence="ECO:0000269|PubMed:18551513,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_063589"
FT VARIANT 259
FT /note="Y -> C (in EDMD2)"
FT /evidence="ECO:0000269|PubMed:27234031"
FT /id="VAR_076563"
FT VARIANT 260
FT /note="K -> N (in CMDA1)"
FT /evidence="ECO:0000269|PubMed:16156025"
FT /id="VAR_039773"
FT VARIANT 261
FT /note="Missing (in EDMD2)"
FT /evidence="ECO:0000269|PubMed:10908904,
FT ECO:0000269|PubMed:10939567, ECO:0000269|PubMed:11503164"
FT /id="VAR_009981"
FT VARIANT 267
FT /note="Y -> C (in EDMD2; dbSNP:rs57048196)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039774"
FT VARIANT 268
FT /note="S -> P (in EDMD2; dbSNP:rs267607630)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064965"
FT VARIANT 271
FT /note="L -> P (in EDMD2; dbSNP:rs267607641)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064966"
FT VARIANT 294
FT /note="Q -> P (in EDMD2; dbSNP:rs61616775)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_009982"
FT VARIANT 295
FT /note="S -> P (in EDMD2; dbSNP:rs267607633)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064967"
FT VARIANT 298
FT /note="R -> C (in CMT2B1; dbSNP:rs59885338)"
FT /evidence="ECO:0000269|PubMed:11799477"
FT /id="VAR_017661"
FT VARIANT 300
FT /note="D -> G (in HGPS; atypical form with late onset;
FT abnormal nuclear morphology with single or multple blebs,
FT lobulation and occasional ringed or donut shaped nuclei;
FT dbSNP:rs79907212)"
FT /evidence="ECO:0000269|PubMed:23666920"
FT /id="VAR_070178"
FT VARIANT 302
FT /note="L -> P (in MDCL; dbSNP:rs267607596)"
FT /evidence="ECO:0000269|PubMed:18551513"
FT /id="VAR_063590"
FT VARIANT 303
FT /note="S -> P (in EDMD2; dbSNP:rs61527854)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064968"
FT VARIANT 317
FT /note="E -> K (in CMD1A; dbSNP:rs56816490)"
FT /evidence="ECO:0000269|PubMed:11897440,
FT ECO:0000269|PubMed:21846512"
FT /id="VAR_039775"
FT VARIANT 318
FT /note="A -> T (in CMD1A; no effect on nuclear morphology
FT and lamin A localization; dbSNP:rs267607574)"
FT /evidence="ECO:0000269|PubMed:20160190"
FT /id="VAR_070179"
FT VARIANT 336
FT /note="R -> Q (in EDMD2; dbSNP:rs58105277)"
FT /evidence="ECO:0000269|PubMed:10739764,
FT ECO:0000269|PubMed:12467752"
FT /id="VAR_009983"
FT VARIANT 343
FT /note="R -> Q (in EDMD2; dbSNP:rs61177390)"
FT /evidence="ECO:0000269|PubMed:12467752"
FT /id="VAR_009984"
FT VARIANT 349
FT /note="R -> L (in CMD1A; dbSNP:rs58789393)"
FT /evidence="ECO:0000269|PubMed:15219508"
FT /id="VAR_039776"
FT VARIANT 355
FT /note="Missing (in EDMD2)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064969"
FT VARIANT 358
FT /note="E -> K (in EDMD2 and MDCL; aberrant localization
FT with decreased nuclear rim staining and formation of
FT intranuclear foci when transfected in C2C12 myoblasts; no
FT obvious effect on nuclear morphology in cultured skin
FT fibroblasts from heterozygous patients; distribution of
FT endogenous LMNA, LMNB1 and LMNB2 are altered in cells
FT expressing this mutant; interacts with itself and with
FT wild-type LMNA and LMNB1; no effect on protein level;
FT dbSNP:rs60458016)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:11503164, ECO:0000269|PubMed:11792809,
FT ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:18551513,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_009985"
FT VARIANT 361
FT /note="E -> K (in EDMD2; dbSNP:rs267607634)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064970"
FT VARIANT 371
FT /note="M -> K (in EDMD2; dramatically aberrant localization
FT with decreased nuclear rim staining and formation of
FT intranuclear foci; distribution of endogenous LMNA, LMNB1
FT and LMNB2 are altered in cells expressing this mutant;
FT causes an increased loss of endogenous EMD from the nuclear
FT envelope; interacts with itself and with wild-type LMNA and
FT LMNB1; no decrease in the stability compared with wild-
FT type; dbSNP:rs59653062)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:11792809"
FT /id="VAR_009986"
FT VARIANT 377
FT /note="R -> H (in EDMD2; no obvious effect on nuclear
FT morphology in cultured skin fibroblasts from heterozygous
FT patients; no effect on protein level; dbSNP:rs61672878)"
FT /evidence="ECO:0000269|PubMed:10814726,
FT ECO:0000269|PubMed:12628721, ECO:0000269|PubMed:12673789,
FT ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:15744034,
FT ECO:0000269|PubMed:17136397"
FT /id="VAR_016205"
FT VARIANT 377
FT /note="R -> L (in EDMD2; dbSNP:rs61672878)"
FT /evidence="ECO:0000269|PubMed:12032588,
FT ECO:0000269|PubMed:12649505"
FT /id="VAR_039777"
FT VARIANT 380
FT /note="L -> S (in MDCL; dbSNP:rs121912495)"
FT /evidence="ECO:0000269|PubMed:18551513"
FT /id="VAR_063591"
FT VARIANT 386
FT /note="R -> K (in EDMD2; dramatically aberrant localization
FT with decreased nuclear rim staining and formation of
FT intranuclear foci; distribution of endogenous LMNA, LMNB1
FT and LMNB2 are altered in cells expressing this mutant;
FT causes an increased loss of endogenous EMD from the nuclear
FT envelope; interacts with itself and with wild-type LMNA and
FT LMNB1; no decrease in the stability compared with wild-
FT type; dbSNP:rs267607545)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:12649505,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_009987"
FT VARIANT 388
FT /note="R -> H (in CMD1A; no effect on nuclear morphology
FT but restricts lamin A to the cytoplasm; dbSNP:rs267607576)"
FT /evidence="ECO:0000269|PubMed:20160190"
FT /id="VAR_070180"
FT VARIANT 399
FT /note="R -> C (in FPLD2 and CMD1A; no effect on nuclear
FT morphology and lamin A localization; dbSNP:rs58672172)"
FT /evidence="ECO:0000269|PubMed:17250669,
FT ECO:0000269|PubMed:20160190"
FT /id="VAR_039778"
FT VARIANT 401
FT /note="R -> C (in EDMD2; abnormal nuclear localization in a
FT honeycomb expression pattern in about 22% of cultured skin
FT fibroblasts from heterozygous patients; enhances the
FT interaction with SYNE2; no effect on nuclear localization;
FT no effect on protein level; dbSNP:rs61094188)"
FT /evidence="ECO:0000269|PubMed:12467752,
FT ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:23977161"
FT /id="VAR_072818"
FT VARIANT 411
FT /note="G -> D (probable disease-associated variant found in
FT patients with metabolic syndromes; no effect on nuclear
FT lamin A localization; no effect on the interaction with
FT SYNE2; dbSNP:rs267607647)"
FT /evidence="ECO:0000269|PubMed:21724554,
FT ECO:0000269|PubMed:23977161"
FT /id="VAR_072819"
FT VARIANT 413
FT /note="G -> C (found in patients with skeletal and cardiac
FT muscular dystrophies; no effect on nuclear lamin A
FT localization; no effect on the interaction with SYNE2;
FT dbSNP:rs766811975)"
FT /evidence="ECO:0000269|PubMed:23977161"
FT /id="VAR_072820"
FT VARIANT 415
FT /note="V -> I (rare variant; found in patients with atrial
FT fibrillation; unknown pathological significance; no effect
FT on nuclear lamin A localization; enhances the interaction
FT with SYNE2; causes nuclear deformations in heat shock
FT experiments; dbSNP:rs267607606)"
FT /evidence="ECO:0000269|PubMed:19427440,
FT ECO:0000269|PubMed:23977161"
FT /id="VAR_072821"
FT VARIANT 419
FT /note="R -> C (found in patients with lipodystrophy; no
FT effect on nuclear lamin A localization; no effect on the
FT interaction with SYNE2; dbSNP:rs755686359)"
FT /evidence="ECO:0000269|PubMed:23977161"
FT /id="VAR_072822"
FT VARIANT 421
FT /note="L -> P (probable disease-associated variant found in
FT patient with severe metabolic syndrome; no effect on
FT nuclear lamin A localization; no effect on the interaction
FT with SYNE2; dbSNP:rs267607564)"
FT /evidence="ECO:0000269|PubMed:17711925,
FT ECO:0000269|PubMed:23977161"
FT /id="VAR_072823"
FT VARIANT 427
FT /note="R -> G (found in patients with skeletal and cardiac
FT muscular dystrophies; unknown pathological significance; no
FT effect on nuclear lamin A localization; no effect on the
FT interaction with SYNE2)"
FT /evidence="ECO:0000269|PubMed:23977161"
FT /id="VAR_072824"
FT VARIANT 435
FT /note="R -> C (in CMD1A; dbSNP:rs150840924)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039779"
FT VARIANT 439
FT /note="R -> C (in FPLD2; increase in nuclear blebbing and
FT formation of honeycomb-like structures in the nuclei with
FT no accumulation of prelamin A in skin fibroblasts; causes
FT oligomerization of the C-terminal globular domain of lamins
FT A and C under no-reducing conditions and increases binding
FT affinity for DNA; increases sensitivity to oxidative
FT stress; no significant differences in stability and
FT structure compared with the wild-type; dbSNP:rs62636506)"
FT /evidence="ECO:0000269|PubMed:19220582"
FT /id="VAR_070181"
FT VARIANT 446
FT /note="D -> V (in EDMD2; dbSNP:rs58541611)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039780"
FT VARIANT 449
FT /note="G -> D (in EDMD2; dbSNP:rs267607637)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064971"
FT VARIANT 453
FT /note="R -> P (in MDCL; dbSNP:rs267607598)"
FT /evidence="ECO:0000269|PubMed:18551513"
FT /id="VAR_063592"
FT VARIANT 453
FT /note="R -> W (in EDMD2; abnormal nuclear localization;
FT forms nuclear foci in about 8% of cultured skin fibroblasts
FT from heterozygous patients; interacts with itself and with
FT wild-type LMNA and LMNB1; no effect on protein level;
FT dbSNP:rs58932704)"
FT /evidence="ECO:0000269|PubMed:10080180,
FT ECO:0000269|PubMed:10739764, ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:11503164, ECO:0000269|PubMed:11792809,
FT ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:15372542,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_009988"
FT VARIANT 454
FT /note="L -> P (in EDMD2; dbSNP:rs267607638)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064972"
FT VARIANT 455
FT /note="R -> P (in MDCL; dbSNP:rs267607597)"
FT /evidence="ECO:0000269|PubMed:18551513"
FT /id="VAR_063593"
FT VARIANT 456
FT /note="N -> D (in MDCL; dbSNP:rs267607599)"
FT /evidence="ECO:0000269|PubMed:18551513"
FT /id="VAR_063594"
FT VARIANT 456
FT /note="N -> I (in EDMD2; mislocalized in the nucleus; does
FT not alter nuclear size or shape; dbSNP:rs60992550)"
FT /evidence="ECO:0000269|PubMed:11503164,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_039781"
FT VARIANT 456
FT /note="N -> K (in EDMD2; dbSNP:rs61235244)"
FT /evidence="ECO:0000269|PubMed:10939567"
FT /id="VAR_039782"
FT VARIANT 461
FT /note="D -> Y (in EDMD2; dbSNP:rs267607642)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064973"
FT VARIANT 465
FT /note="G -> D (in FPLD2; dbSNP:rs61282106)"
FT /evidence="ECO:0000269|PubMed:10739751"
FT /id="VAR_009989"
FT VARIANT 467
FT /note="W -> R (in EDMD2; dbSNP:rs267607639)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064974"
FT VARIANT 469
FT /note="I -> T (in EDMD2; dbSNP:rs57394692)"
FT /evidence="ECO:0000269|PubMed:10739764"
FT /id="VAR_009990"
FT VARIANT 471
FT /note="R -> C (in HGPS; dbSNP:rs28928902)"
FT /evidence="ECO:0000269|PubMed:12768443"
FT /id="VAR_017662"
FT VARIANT 471
FT /note="R -> H (in CMD1A; no effect on nuclear morphology
FT and lamin A localization; dbSNP:rs267607578)"
FT /evidence="ECO:0000269|PubMed:20160190"
FT /id="VAR_070182"
FT VARIANT 481
FT /note="Y -> H (in EDMD2; dbSNP:rs57747780)"
FT /evidence="ECO:0000269|PubMed:11525883"
FT /id="VAR_039783"
FT VARIANT 482
FT /note="R -> L (in FPLD2; abnormal nuclear localization in a
FT honeycomb expression pattern in about 10% of cultured skin
FT fibroblasts from heterozygous patients; no effect on
FT protein level; dbSNP:rs11575937)"
FT /evidence="ECO:0000269|PubMed:10655060,
FT ECO:0000269|PubMed:15372542"
FT /id="VAR_009991"
FT VARIANT 482
FT /note="R -> Q (in FPLD2; interacts with itself and with
FT wild-type LMNA and LMNB1; no decrease in the stability
FT compared with wild-type; dbSNP:rs11575937)"
FT /evidence="ECO:0000269|PubMed:10587585,
FT ECO:0000269|PubMed:10739751, ECO:0000269|PubMed:11792809"
FT /id="VAR_009992"
FT VARIANT 482
FT /note="R -> W (in FPLD2; interacts with itself and with
FT wild-type LMNA and LMNB1; no decrease in the stability
FT compared with wild-type; decreases binding affinity for
FT DNA; increases sensitivity to oxidative stress;
FT dbSNP:rs57920071)"
FT /evidence="ECO:0000269|PubMed:10655060,
FT ECO:0000269|PubMed:10739751, ECO:0000269|PubMed:11792809,
FT ECO:0000269|PubMed:19220582"
FT /id="VAR_009993"
FT VARIANT 486
FT /note="K -> N (in FPLD2; interacts with itself and with
FT wild-type LMNA and LMNB1; no decrease in the stability
FT compared with wild-type; dbSNP:rs59981161)"
FT /evidence="ECO:0000269|PubMed:11792809"
FT /id="VAR_009994"
FT VARIANT 488
FT /note="T -> P (found in patient with atrial fibrillation;
FT dbSNP:rs267607607)"
FT /evidence="ECO:0000269|PubMed:19427440"
FT /id="VAR_072825"
FT VARIANT 515
FT /note="K -> E (in FPLD2)"
FT /evidence="ECO:0000269|PubMed:24485160"
FT /id="VAR_071968"
FT VARIANT 520
FT /note="W -> S (in EDMD2; interacts with itself and with
FT wild-type LMNA and LMNB1; no decrease in the stability
FT compared with wild-type; dbSNP:rs58362413)"
FT /evidence="ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:11792809"
FT /id="VAR_039784"
FT VARIANT 523
FT /note="G -> R (in CMD1A; unknown pathological significance;
FT dbSNP:rs201583907)"
FT /evidence="ECO:0000269|PubMed:21846512"
FT /id="VAR_067258"
FT VARIANT 527
FT /note="R -> C (in HGPS; dbSNP:rs57318642)"
FT /evidence="ECO:0000269|PubMed:12768443"
FT /id="VAR_017663"
FT VARIANT 527
FT /note="R -> H (in MADA; dbSNP:rs57520892)"
FT /evidence="ECO:0000269|PubMed:12075506"
FT /id="VAR_018727"
FT VARIANT 527
FT /note="R -> P (in EDMD2 and FPLD2; interacts with itself
FT and with wild-type LMNA and LMNB1; reduced binding to SUN1;
FT abnormal nuclear localization; forms nuclear foci in about
FT 13% of cultured skin fibroblasts from heterozygous
FT patients; no effect on protein level; dbSNP:rs57520892)"
FT /evidence="ECO:0000269|PubMed:10080180,
FT ECO:0000269|PubMed:10739764, ECO:0000269|PubMed:10939567,
FT ECO:0000269|PubMed:11503164, ECO:0000269|PubMed:11792809,
FT ECO:0000269|PubMed:12196663, ECO:0000269|PubMed:12649505,
FT ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:15744034,
FT ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:20848652"
FT /id="VAR_009995"
FT VARIANT 528
FT /note="T -> K (in EDMD2; interacts with itself and with
FT wild-type LMNA and LMNB1; no decrease in the stability
FT compared with wild-type; dbSNP:rs57629361)"
FT /evidence="ECO:0000269|PubMed:10739764,
FT ECO:0000269|PubMed:10939567, ECO:0000269|PubMed:11792809,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_009996"
FT VARIANT 528
FT /note="T -> R (in EDMD2; dbSNP:rs57629361)"
FT /evidence="ECO:0000269|PubMed:14684700,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_039785"
FT VARIANT 529
FT /note="A -> V (in MADA; dbSNP:rs60580541)"
FT /evidence="ECO:0000269|PubMed:15998779"
FT /id="VAR_034709"
FT VARIANT 530
FT /note="L -> P (in EDMD2; interacts with itself and with
FT wild-type LMNA and LMNB1; reduced binding to SUN1; no
FT decrease in the stability compared with wild-type;
FT dbSNP:rs60934003)"
FT /evidence="ECO:0000269|PubMed:10080180,
FT ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:19933576"
FT /id="VAR_009997"
FT VARIANT 541
FT /note="R -> C (in CMD1A; grossly abnormal nuclear shape
FT with the nuclear envelope producing prominent lobules in
FT about 10% of cultured skin fibroblasts from heterozygous
FT patients; dbSNP:rs56984562)"
FT /evidence="ECO:0000269|PubMed:14675861,
FT ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:19167105"
FT /id="VAR_039786"
FT VARIANT 541
FT /note="R -> H (in EDMD2; dbSNP:rs61444459)"
FT /evidence="ECO:0000269|PubMed:14684700"
FT /id="VAR_039787"
FT VARIANT 541
FT /note="R -> P (in EDMD2; mis-localized in the nucleus; does
FT not alter nuclear size or shape; dbSNP:rs61444459)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064975"
FT VARIANT 541
FT /note="R -> S (in EDMD2 and CMD1A; modest and non-specific
FT nuclear membrane alterations; the phenotype is entirely
FT reversed by coexpression of the S-541 mutation and wild-
FT type lamin-C; dbSNP:rs56984562)"
FT /evidence="ECO:0000269|PubMed:16061563,
FT ECO:0000269|PubMed:20848652"
FT /id="VAR_039788"
FT VARIANT 542
FT /note="K -> N (in HGPS; dbSNP:rs56673169)"
FT /evidence="ECO:0000269|PubMed:15286156"
FT /id="VAR_034710"
FT VARIANT 573
FT /note="S -> L (in CMD1A, FPLD2 and MADA; dbSNP:rs60890628)"
FT /evidence="ECO:0000269|PubMed:12628721,
FT ECO:0000269|PubMed:16278265, ECO:0000269|PubMed:17250669"
FT /id="VAR_039789"
FT VARIANT 578
FT /note="E -> V (in an atypical progeroid patient; diagnosed
FT as Werner syndrome; dbSNP:rs61224243)"
FT /evidence="ECO:0000269|PubMed:15060110"
FT /id="VAR_039790"
FT VARIANT 582
FT /note="R -> H (in FPLD2; dbSNP:rs57830985)"
FT /evidence="ECO:0000269|PubMed:10739751"
FT /id="VAR_009998"
FT VARIANT 602
FT /note="G -> S (in EDMD2; dbSNP:rs60662302)"
FT /evidence="ECO:0000269|PubMed:20848652"
FT /id="VAR_064976"
FT VARIANT 608
FT /note="G -> S (in HGPS; reduced binding to SUN1; may affect
FT splicing by activating a cryptic splice donor site;
FT dbSNP:rs61064130)"
FT /evidence="ECO:0000269|PubMed:12714972,
FT ECO:0000269|PubMed:12768443, ECO:0000269|PubMed:19933576"
FT /id="VAR_017664"
FT VARIANT 624
FT /note="R -> H (in EDMD2; dbSNP:rs13768)"
FT /evidence="ECO:0000269|PubMed:11503164"
FT /id="VAR_039791"
FT VARIANT 631
FT /note="G -> D (probable disease-associated variant found in
FT a patient with metabolic syndrome; dbSNP:rs267607648)"
FT /evidence="ECO:0000269|PubMed:21724554"
FT /id="VAR_072826"
FT VARIANT 644
FT /note="R -> C (in HGPS and EDMD2; partially inhibits tail
FT cleavage; dbSNP:rs142000963)"
FT /evidence="ECO:0000269|PubMed:15060110,
FT ECO:0000269|PubMed:20848652, ECO:0000269|PubMed:22355414"
FT /id="VAR_039792"
FT MUTAGEN 22
FT /note="S->A: Decreased accumulation to the double-strand
FT break (DSB) sites."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 22
FT /note="S->D: Increased accumulation to the double-strand
FT break (DSB) sites."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 201
FT /note="K->L: Decreased sumoylation; aberrant localization
FT with decreased nuclear rim staining and formation of
FT intranuclear foci; associated with increased cell death."
FT /evidence="ECO:0000269|PubMed:18606848"
FT MUTAGEN 358
FT /note="E->K: Loss of interaction with IFFO1."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 386
FT /note="R->M: Loss of interaction with IFFO1."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 644
FT /note="R->A: Does not affect tail cleavage."
FT /evidence="ECO:0000269|PubMed:22355414"
FT MUTAGEN 647
FT /note="L->R: Completely inhibits tail cleavage."
FT /evidence="ECO:0000269|PubMed:22355414"
FT MUTAGEN 648
FT /note="L->A: Completely inhibits tail cleavage."
FT /evidence="ECO:0000269|PubMed:22355414"
FT MUTAGEN 650
FT /note="N->A: Partially inhibits tail cleavage."
FT /evidence="ECO:0000269|PubMed:22355414"
FT MUTAGEN 661
FT /note="C->S: Loss of interaction with NARF. Abolishes
FT farnesylation."
FT /evidence="ECO:0000269|PubMed:10514485,
FT ECO:0000269|PubMed:22355414"
FT CONFLICT 340
FT /note="E -> K (in Ref. 5; BAG58344)"
FT /evidence="ECO:0000305"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:6YF5"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:6YF5"
FT HELIX 28..70
FT /evidence="ECO:0007829|PDB:6YF5"
FT HELIX 252..278
FT /evidence="ECO:0007829|PDB:6JLB"
FT HELIX 316..384
FT /evidence="ECO:0007829|PDB:1X8Y"
FT STRAND 424..436
FT /evidence="ECO:0007829|PDB:7CRG"
FT STRAND 438..445
FT /evidence="ECO:0007829|PDB:1IFR"
FT STRAND 449..456
FT /evidence="ECO:0007829|PDB:1IFR"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:1IFR"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:1IVT"
FT STRAND 468..473
FT /evidence="ECO:0007829|PDB:1IFR"
FT STRAND 479..482
FT /evidence="ECO:0007829|PDB:1IFR"
FT STRAND 494..499
FT /evidence="ECO:0007829|PDB:1IFR"
FT HELIX 500..502
FT /evidence="ECO:0007829|PDB:3GEF"
FT TURN 508..510
FT /evidence="ECO:0007829|PDB:1IFR"
FT STRAND 511..514
FT /evidence="ECO:0007829|PDB:1IFR"
FT STRAND 526..531
FT /evidence="ECO:0007829|PDB:1IFR"
FT STRAND 537..543
FT /evidence="ECO:0007829|PDB:1IFR"
FT CONFLICT P02545-4:556
FT /note="G -> R (in Ref. 5; BAG58344)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 664 AA; 74139 MW; E0855F7699F0318B CRC64;
METPSQRRAT RSGAQASSTP LSPTRITRLQ EKEDLQELND RLAVYIDRVR SLETENAGLR
LRITESEEVV SREVSGIKAA YEAELGDARK TLDSVAKERA RLQLELSKVR EEFKELKARN
TKKEGDLIAA QARLKDLEAL LNSKEAALST ALSEKRTLEG ELHDLRGQVA KLEAALGEAK
KQLQDEMLRR VDAENRLQTM KEELDFQKNI YSEELRETKR RHETRLVEID NGKQREFESR
LADALQELRA QHEDQVEQYK KELEKTYSAK LDNARQSAER NSNLVGAAHE ELQQSRIRID
SLSAQLSQLQ KQLAAKEAKL RDLEDSLARE RDTSRRLLAE KEREMAEMRA RMQQQLDEYQ
ELLDIKLALD MEIHAYRKLL EGEEERLRLS PSPTSQRSRG RASSHSSQTQ GGGSVTKKRK
LESTESRSSF SQHARTSGRV AVEEVDEEGK FVRLRNKSNE DQSMGNWQIK RQNGDDPLLT
YRFPPKFTLK AGQVVTIWAA GAGATHSPPT DLVWKAQNTW GCGNSLRTAL INSTGEEVAM
RKLVRSVTVV EDDEDEDGDD LLHHHHGSHC SSSGDPAEYN LRSRTVLCGT CGQPADKASA
SGSGAQVGGP ISSGSSASSV TVTRSYRSVG GSGGGSFGDN LVTRSYLLGN SSPRTQSPQN
CSIM
