LMNA_MOUSE
ID LMNA_MOUSE Reviewed; 665 AA.
AC P48678; B3RH23; B3RH24; P11516; P97859; Q3TIH0; Q3TTS8; Q3U733; Q3U7I5;
AC Q3UCA0; Q3UCJ8; Q3UCU3; Q91WF2; Q9DC21;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Prelamin-A/C;
DE Contains:
DE RecName: Full=Lamin-A/C;
DE Flags: Precursor;
GN Name=Lmna; Synonyms=Lmn1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7781761; DOI=10.1016/0014-5793(95)00453-g;
RA Nakajima N., Abe K.;
RT "Genomic structure of the mouse A-type lamin gene locus encoding somatic
RT and germ cell-specific lamins.";
RL FEBS Lett. 365:108-114(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
RX PubMed=2719959; DOI=10.1016/0167-4781(89)90179-6;
RA Riedel W., Werner D.;
RT "Nucleotide sequence of the full-length mouse lamin C cDNA and its deduced
RT amino-acid sequence.";
RL Biochim. Biophys. Acta 1008:119-122(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C2).
RC STRAIN=ddY; TISSUE=Testis;
RX PubMed=8187835; DOI=10.1006/excr.1994.1164;
RA Furukawa K., Inagaki H., Hotta Y.;
RT "Identification and cloning of an mRNA coding for a germ cell-specific A-
RT type lamin in mice.";
RL Exp. Cell Res. 212:426-430(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C).
RA Fujita T.;
RT "Lamin A binds to Runx2.";
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C).
RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Amnion, Bone marrow, Head, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Salivary gland;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 235-665 (ISOFORM A).
RX PubMed=7916626; DOI=10.1016/0167-4781(93)90072-l;
RA Nakajima N., Sado T.;
RT "Nucleotide sequence of a mouse lamin A cDNA and its deduced amino acid
RT sequence.";
RL Biochim. Biophys. Acta 1171:311-314(1993).
RN [9]
RP PROTEIN SEQUENCE OF 521-574, AND C-TERMINAL PROCESSING OF ISOFORM A.
RX PubMed=2583287; DOI=10.1016/0014-5793(89)81584-4;
RA Weber K., Plessmann U., Traub P.;
RT "Maturation of nuclear lamin A involves a specific carboxy-terminal
RT trimming, which removes the polyisoprenylation site from the precursor;
RT implications for the structure of the nuclear lamina.";
RL FEBS Lett. 257:411-414(1989).
RN [10]
RP PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT SER-392; SER-407 AND
RP SER-409 (ISOFORM C).
RX PubMed=1959608; DOI=10.1016/0014-5793(91)80868-4;
RA Eggert M., Radomski N., Tripier D., Traub P., Jost E.;
RT "Identification of phosphorylation sites on murine nuclear lamin C by RP-
RT HPLC and microsequencing.";
RL FEBS Lett. 292:205-209(1991).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=10579712; DOI=10.1083/jcb.147.5.913;
RA Sullivan T., Escalante-Alcalde D., Bhatt H., Anver M., Bhat N.,
RA Nagashima K., Stewart C.L., Burke B.;
RT "Loss of A-type lamin expression compromises nuclear envelope integrity
RT leading to muscular dystrophy.";
RL J. Cell Biol. 147:913-920(1999).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [13]
RP INTERACTION WITH SREBF1 AND SREBF2.
RX PubMed=11929849; DOI=10.1093/hmg/11.7.769;
RA Lloyd D.J., Trembath R.C., Shackleton S.;
RT "A novel interaction between lamin A and SREBP1: implications for partial
RT lipodystrophy and other laminopathies.";
RL Hum. Mol. Genet. 11:769-777(2002).
RN [14]
RP INTERACTION WITH SUN1.
RX PubMed=16380439; DOI=10.1083/jcb.200509124;
RA Crisp M., Liu Q., Roux K., Rattner J.B., Shanahan C., Burke B., Stahl P.D.,
RA Hodzic D.;
RT "Coupling of the nucleus and cytoplasm: role of the LINC complex.";
RL J. Cell Biol. 172:41-53(2006).
RN [15]
RP INTERACTION WITH SUN1.
RX PubMed=16648470; DOI=10.1128/mcb.26.10.3738-3751.2006;
RA Haque F., Lloyd D.J., Smallwood D.T., Dent C.L., Shanahan C.M., Fry A.M.,
RA Trembath R.C., Shackleton S.;
RT "SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a
RT physical connection between the nuclear lamina and the cytoskeleton.";
RL Mol. Cell. Biol. 26:3738-3751(2006).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-22 AND SER-653, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [18]
RP SUBCELLULAR LOCATION, SUMOYLATION AT LYS-201, AND MUTAGENESIS OF LYS-201
RP AND GLU-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 [19]
RP INTERACTION WITH TMEM43.
RX PubMed=18230648; DOI=10.1242/jcs.019281;
RA Bengtsson L., Otto H.;
RT "LUMA interacts with emerin and influences its distribution at the inner
RT nuclear membrane.";
RL J. Cell Sci. 121:536-548(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22 AND SER-546, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [21]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19124654; DOI=10.1083/jcb.200811035;
RA Mejat A., Decostre V., Li J., Renou L., Kesari A., Hantai D., Stewart C.L.,
RA Xiao X., Hoffman E., Bonne G., Misteli T.;
RT "Lamin A/C-mediated neuromuscular junction defects in Emery-Dreifuss
RT muscular dystrophy.";
RL J. Cell Biol. 184:31-44(2009).
RN [22]
RP INTERACTION WITH SUN1 AND SUN2.
RX PubMed=19843581; DOI=10.1242/jcs.057075;
RA Ostlund C., Folker E.S., Choi J.C., Gomes E.R., Gundersen G.G.,
RA Worman H.J.;
RT "Dynamics and molecular interactions of linker of nucleoskeleton and
RT cytoskeleton (LINC) complex proteins.";
RL J. Cell Sci. 122:4099-4108(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-390 AND SER-392, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; THR-19; SER-22; SER-301;
RP SER-390; SER-392; SER-458; THR-548; SER-570; SER-573; SER-617; SER-620;
RP SER-629; SER-633; SER-637 AND SER-653, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-572 (ISOFORM C), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-460 (ISOFORM C2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [25]
RP INTERACTION WITH SUN2.
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 [26]
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 [27]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21982926; DOI=10.1016/j.mad.2011.09.004;
RA Tong J., Li W., Vidal C., Yeo L.S., Fatkin D., Duque G.;
RT "Lamin A/C deficiency is associated with fat infiltration of muscle and
RT bone.";
RL Mech. Ageing Dev. 132:552-559(2011).
RN [28]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21547077; DOI=10.1371/journal.pone.0019313;
RA Li W., Yeo L.S., Vidal C., McCorquodale T., Herrmann M., Fatkin D.,
RA Duque G.;
RT "Decreased bone formation and osteopenia in lamin a/c-deficient mice.";
RL PLoS ONE 6:E19313-E19313(2011).
RN [29]
RP INTERACTION WITH TMEM201.
RX PubMed=22349700; DOI=10.1242/jcs.087049;
RA Borrego-Pinto J., Jegou T., Osorio D.S., Aurade F., Gorjanacz M., Koch B.,
RA Mattaj I.W., Gomes E.R.;
RT "Samp1 is a component of TAN lines and is required for nuclear movement.";
RL J. Cell Sci. 125:1099-1105(2012).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-123; LYS-135; LYS-155;
RP LYS-171; LYS-201; LYS-260; LYS-270; LYS-311; LYS-450 AND LYS-457,
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-32 AND LYS-171, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [31]
RP 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 [32]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23535822; DOI=10.1093/hmg/ddt135;
RA Cohen T.V., Gnocchi V.F., Cohen J.E., Phadke A., Liu H., Ellis J.A.,
RA Foisner R., Stewart C.L., Zammit P.S., Partridge T.A.;
RT "Defective skeletal muscle growth in lamin A/C-deficient mice is rescued by
RT loss of Lap2alpha.";
RL Hum. Mol. Genet. 22:2852-2869(2013).
RN [33]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH MLIP, AND SUBCELLULAR
RP LOCATION.
RX PubMed=26436652; DOI=10.1172/jci82423;
RA Huang Z.P., Kataoka M., Chen J., Wu G., Ding J., Nie M., Lin Z., Liu J.,
RA Hu X., Ma L., Zhou B., Wakimoto H., Zeng C., Kyselovic J., Deng Z.L.,
RA Seidman C.E., Seidman J.G., Pu W.T., Wang D.Z.;
RT "Cardiomyocyte-enriched protein CIP protects against pathophysiological
RT stresses and regulates cardiac homeostasis.";
RL J. Clin. Invest. 125:4122-4134(2015).
RN [34]
RP STRUCTURE BY NMR OF 406-546.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of immunoglobulin-like domain of mouse nuclear lamin.";
RL Submitted (JUN-2004) to the PDB data bank.
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 (By similarity). Plays an
CC 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. Required for osteoblastogenesis and bone formation.
CC Also prevents fat infiltration of muscle and bone marrow, helping to
CC maintain the volume and strength of skeletal muscle and bone. Required
CC for cardiac homeostasis (PubMed:26436652). Isoform C2 may have a role
CC in determining the organization of nuclear and chromosomal structures
CC during spermatogenesis. {ECO:0000250|UniProtKB:P02545,
CC ECO:0000269|PubMed:10579712, ECO:0000269|PubMed:11799477,
CC ECO:0000269|PubMed:19124654, ECO:0000269|PubMed:21547077,
CC ECO:0000269|PubMed:21982926, ECO:0000269|PubMed:23535822,
CC ECO:0000269|PubMed:26436652}.
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 (By similarity). {ECO:0000250}.
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 Proteolytically processed isoform A interacts with NARF (By
CC similarity). Interacts with SREBF1, SREBF2, SUN1, SUN2 and TMEM43.
CC Interacts with TMEM201. Prelamin-A/C interacts with EMD. Interacts with
CC DMPK; may regulate nuclear envelope stability (By similarity).
CC Interacts with MLIP (PubMed:26436652, PubMed:21498514). Interacts with
CC SUV39H1; the interaction increases stability of SUV39H1. Interacts with
CC ITSN1 isoform 2 (By similarity). Interacts with IFFO1; the interaction
CC forms an interior nucleoskeleton and the recruitment to DNA double-
CC strand breaks (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P02545, ECO:0000269|PubMed:11929849,
CC ECO:0000269|PubMed:16380439, ECO:0000269|PubMed:16648470,
CC ECO:0000269|PubMed:18230648, ECO:0000269|PubMed:19843581,
CC ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:21498514,
CC ECO:0000269|PubMed:22349700, ECO:0000269|PubMed:23695662,
CC ECO:0000269|PubMed:26436652}.
CC -!- SUBUNIT: [Isoform C]: Interacts (via C-terminus) with LEMD2 (via N-
CC terminus) (in vitro). {ECO:0000250|UniProtKB:P02545}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26436652}. Nucleus
CC envelope {ECO:0000250|UniProtKB:P02545}. Nucleus lamina {ECO:0000250}.
CC Nucleus, nucleoplasm {ECO:0000250}. Nucleus matrix
CC {ECO:0000250|UniProtKB:P02545}. Note=Farnesylation of prelamin-A/C
CC facilitates nuclear envelope targeting and subsequent cleavage by
CC ZMPSTE24/FACE1 to remove the farnesyl group produces mature lamin-A/C,
CC which can then be inserted into the nuclear lamina. EMD is required for
CC proper localization of non-farnesylated prelamin-A/C (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Isoform A and isoform C are present in equal amounts in the
CC lamina of mammals.;
CC Name=A;
CC IsoId=P48678-1; Sequence=Displayed;
CC Name=C;
CC IsoId=P48678-2, P11516-1;
CC Sequence=VSP_017064, VSP_017065;
CC Name=C2;
CC IsoId=P48678-3, P11516-2;
CC Sequence=VSP_002471, VSP_002472, VSP_017064, VSP_017065;
CC -!- TISSUE SPECIFICITY: Expressed in liver and in bone marrow (at protein
CC level). Isoform C2 is specifically expressed in germ cells. Expressed
CC in cardiomyocytes (PubMed:26436652). {ECO:0000269|PubMed:10579712,
CC ECO:0000269|PubMed:21547077, ECO:0000269|PubMed:26436652}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Sumoylation is necessary for the localization to the nuclear
CC envelope. {ECO:0000250}.
CC -!- PTM: Farnesylation of prelamin-A/C facilitates nuclear envelope
CC targeting. {ECO:0000250}.
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 (By similarity). {ECO:0000250|UniProtKB:P02545}.
CC -!- PTM: Isoform C is phosphorylated on Ser-392, Ser-407 and Ser-409 at
CC interphase. {ECO:0000269|PubMed:1959608}.
CC -!- PTM: The N-terminus is blocked.
CC -!- DISRUPTION PHENOTYPE: Mutant mice survive postnatally for 6-8 weeks and
CC show skeletal and cardiac myopathy, sarcopenia, osteopenia, decreased
CC bone formation, neuropathy, abnormal neuromuscular junctions, decreased
CC skeletal muscle growth and decreased muscle satellite cell
CC proliferation. They develop ventricular dilation and cardiac
CC dysfunction. Within 2-3 weeks they show a reduction in their growth
CC rate and by week 4 their growth ceases with their mean body weight
CC being half of that of the wild-type or the heterozygous littermates.
CC Simultaneous knockout of LMNA and LAP2 results in partial rescue of the
CC phenotype, with a 30% increase in survival rate and a 25-50% increase
CC in body weight. Double knockouts for MLIP and LMNA die sooner than
CC single LMNA knockout. They develop much more severe ventricular
CC dilation and cardiac dysfunction (PubMed:26436652).
CC {ECO:0000269|PubMed:10579712, ECO:0000269|PubMed:11799477,
CC ECO:0000269|PubMed:19124654, ECO:0000269|PubMed:21547077,
CC ECO:0000269|PubMed:21982926, ECO:0000269|PubMed:23535822,
CC ECO:0000269|PubMed:26436652}.
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 -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE31539.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D49733; BAA08569.1; -; Genomic_DNA.
DR EMBL; D49733; BAA08570.1; -; Genomic_DNA.
DR EMBL; D49733; BAA08571.1; -; Genomic_DNA.
DR EMBL; X14170; CAA32372.1; -; mRNA.
DR EMBL; D14850; BAA03578.1; -; mRNA.
DR EMBL; DQ832702; ABI16251.1; -; mRNA.
DR EMBL; DQ832703; ABI16252.1; -; mRNA.
DR EMBL; AK004619; BAB23415.1; -; mRNA.
DR EMBL; AK147150; BAE27717.1; -; mRNA.
DR EMBL; AK149998; BAE29226.1; -; mRNA.
DR EMBL; AK150391; BAE29519.1; -; mRNA.
DR EMBL; AK150501; BAE29614.1; -; mRNA.
DR EMBL; AK150624; BAE29714.1; -; mRNA.
DR EMBL; AK152539; BAE31294.1; -; mRNA.
DR EMBL; AK152646; BAE31384.1; -; mRNA.
DR EMBL; AK152846; BAE31539.1; ALT_INIT; mRNA.
DR EMBL; AK161221; BAE36246.1; -; mRNA.
DR EMBL; AK167858; BAE39876.1; -; mRNA.
DR EMBL; CH466547; EDL15275.1; -; Genomic_DNA.
DR EMBL; BC015302; AAH15302.1; -; mRNA.
DR EMBL; BC094020; AAH94020.1; -; mRNA.
DR EMBL; D13181; BAA02476.1; -; mRNA.
DR CCDS; CCDS38482.1; -. [P48678-1]
DR CCDS; CCDS38483.1; -. [P48678-3]
DR CCDS; CCDS50951.1; -. [P48678-2]
DR PIR; I53414; I53414.
DR PIR; S04333; S04333.
DR PIR; S18324; S18324.
DR PIR; S28182; S28182.
DR RefSeq; NP_001002011.2; NM_001002011.3. [P48678-1]
DR RefSeq; NP_001104572.1; NM_001111102.2. [P48678-2]
DR RefSeq; NP_062263.1; NM_019390.3. [P48678-3]
DR RefSeq; XP_006501136.1; XM_006501073.1. [P48678-1]
DR PDB; 1UFG; NMR; -; A=408-545.
DR PDBsum; 1UFG; -.
DR AlphaFoldDB; P48678; -.
DR BMRB; P48678; -.
DR SMR; P48678; -.
DR BioGRID; 201176; 79.
DR DIP; DIP-31384N; -.
DR IntAct; P48678; 25.
DR MINT; P48678; -.
DR STRING; 10090.ENSMUSP00000029699; -.
DR iPTMnet; P48678; -.
DR PhosphoSitePlus; P48678; -.
DR SwissPalm; P48678; -.
DR REPRODUCTION-2DPAGE; IPI00400300; -.
DR REPRODUCTION-2DPAGE; IPI00620256; -.
DR CPTAC; non-CPTAC-3719; -.
DR CPTAC; non-CPTAC-3925; -.
DR EPD; P48678; -.
DR jPOST; P48678; -.
DR MaxQB; P48678; -.
DR PaxDb; P48678; -.
DR PeptideAtlas; P48678; -.
DR PRIDE; P48678; -.
DR ProteomicsDB; 286217; -. [P48678-1]
DR ProteomicsDB; 286218; -. [P48678-2]
DR ProteomicsDB; 286219; -. [P48678-3]
DR TopDownProteomics; P48678-2; -. [P48678-2]
DR Antibodypedia; 1676; 1671 antibodies from 49 providers.
DR DNASU; 16905; -.
DR Ensembl; ENSMUST00000029699; ENSMUSP00000029699; ENSMUSG00000028063. [P48678-1]
DR Ensembl; ENSMUST00000036252; ENSMUSP00000040265; ENSMUSG00000028063. [P48678-3]
DR Ensembl; ENSMUST00000120377; ENSMUSP00000113093; ENSMUSG00000028063. [P48678-2]
DR GeneID; 16905; -.
DR KEGG; mmu:16905; -.
DR UCSC; uc008pvj.3; mouse. [P48678-1]
DR UCSC; uc008pvk.3; mouse. [P48678-3]
DR UCSC; uc008pvl.3; mouse. [P48678-2]
DR CTD; 4000; -.
DR MGI; MGI:96794; Lmna.
DR VEuPathDB; HostDB:ENSMUSG00000028063; -.
DR eggNOG; KOG0977; Eukaryota.
DR GeneTree; ENSGT00940000157244; -.
DR HOGENOM; CLU_012560_9_1_1; -.
DR InParanoid; P48678; -.
DR OMA; MSIHHRH; -.
DR OrthoDB; 701388at2759; -.
DR PhylomeDB; P48678; -.
DR TreeFam; TF101181; -.
DR Reactome; R-MMU-352238; Breakdown of the nuclear lamina. [P48678-1]
DR Reactome; R-MMU-4419969; Depolymerisation of the Nuclear Lamina. [P48678-1]
DR BioGRID-ORCS; 16905; 8 hits in 76 CRISPR screens.
DR ChiTaRS; Lmna; mouse.
DR EvolutionaryTrace; P48678; -.
DR PRO; PR:P48678; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P48678; protein.
DR Bgee; ENSMUSG00000028063; Expressed in ascending aorta and 249 other tissues.
DR ExpressionAtlas; P48678; baseline and differential.
DR Genevisible; P48678; MM.
DR GO; GO:0005638; C:lamin filament; IDA:MGI.
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; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008157; F:protein phosphatase 1 binding; ISO:MGI.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:BHF-UCL.
DR GO; GO:0090398; P:cellular senescence; ISS:UniProtKB.
DR GO; GO:1990683; P:DNA double-strand break attachment to nuclear envelope; ISS:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; NAS:BHF-UCL.
DR GO; GO:0030951; P:establishment or maintenance of microtubule cytoskeleton polarity; IMP:BHF-UCL.
DR GO; GO:0031507; P:heterochromatin assembly; IBA:GO_Central.
DR GO; GO:0007517; P:muscle organ development; ISS:BHF-UCL.
DR GO; GO:1904178; P:negative regulation of adipose tissue development; ISO:MGI.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0072201; P:negative regulation of mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IMP:MGI.
DR GO; GO:0006998; P:nuclear envelope organization; IGI:MGI.
DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central.
DR GO; GO:0051664; P:nuclear pore localization; IBA:GO_Central.
DR GO; GO:0006997; P:nucleus organization; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:1900114; P:positive regulation of histone H3-K9 trimethylation; IMP:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0006606; P:protein import into nucleus; IMP:MGI.
DR GO; GO:0008104; P:protein localization; ISO:MGI.
DR GO; GO:0090435; P:protein localization to nuclear envelope; IBA:GO_Central.
DR GO; GO:0034504; P:protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:1900180; P:regulation of protein localization to nucleus; IMP:MGI.
DR GO; GO:0031647; P:regulation of protein stability; IMP:MGI.
DR GO; GO:0032204; P:regulation of telomere maintenance; ISO:MGI.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IMP:MGI.
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; Coiled coil;
KW Direct protein sequencing; Intermediate filament; Isopeptide bond;
KW Lipoprotein; Methylation; Nucleus; Phosphoprotein; Prenylation;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..662
FT /note="Prelamin-A/C"
FT /id="PRO_0000398837"
FT CHAIN 1..647
FT /note="Lamin-A/C"
FT /id="PRO_0000063811"
FT PROPEP 648..662
FT /note="Removed in Lamin-A/C form"
FT /id="PRO_0000398838"
FT PROPEP 663..665
FT /note="Removed in Prelamin-A/C form and in Lamin-A/C form"
FT /id="PRO_0000403443"
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:0000250"
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 384..665
FT /note="Tail"
FT REGION 384..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 553..577
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 647..648
FT /note="Cleavage; by endoprotease"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 19
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 32
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 32
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 108
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 123
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 135
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 155
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 171
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 171
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 201
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 260
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 270
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 311
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 392
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:1959608,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:1959608"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:1959608"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 450
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 457
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 496
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48679"
FT MOD_RES 500
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48679"
FT MOD_RES 505
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 510
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48679"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 548
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT MOD_RES 617
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 620
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 629
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 653
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 662
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 662
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250"
FT CROSSLNK 32
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 97
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 171
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 201
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 201
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 208
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 219
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 233
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 260
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 311
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 366
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 378
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 417
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 420
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 450
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 486
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 599
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT CROSSLNK 599
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P02545"
FT VAR_SEQ 1..112
FT /note="Missing (in isoform C2)"
FT /evidence="ECO:0000303|PubMed:8187835"
FT /id="VSP_002471"
FT VAR_SEQ 113..118
FT /note="FKELKA -> MGNAEG (in isoform C2)"
FT /evidence="ECO:0000303|PubMed:8187835"
FT /id="VSP_002472"
FT VAR_SEQ 569..574
FT /note="GSHCSG -> VSGSRR (in isoform C and isoform C2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:2719959, ECO:0000303|PubMed:8187835,
FT ECO:0000303|Ref.4"
FT /id="VSP_017064"
FT VAR_SEQ 575..665
FT /note="Missing (in isoform C and isoform C2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:2719959, ECO:0000303|PubMed:8187835,
FT ECO:0000303|Ref.4"
FT /id="VSP_017065"
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 203
FT /note="E->G,K: 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 CONFLICT 4
FT /note="P -> S (in Ref. 5; BAE31384/BAE29519)"
FT /evidence="ECO:0000305"
FT CONFLICT 118..119
FT /note="AR -> VC (in Ref. 2; CAA32372)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="A -> D (in Ref. 5; BAE39876)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="E -> G (in Ref. 5; BAE29614)"
FT /evidence="ECO:0000305"
FT CONFLICT 401
FT /note="R -> P (in Ref. 2; CAA32372)"
FT /evidence="ECO:0000305"
FT CONFLICT 439..440
FT /note="RV -> WL (in Ref. 2; CAA32372)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="K -> E (in Ref. 5; BAE31384)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="R -> L (in Ref. 5; BAE36246)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="I -> V (in Ref. 5; BAB23415)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="S -> Y (in Ref. 5; BAB23415)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="V -> A (in Ref. 8; BAA02476)"
FT /evidence="ECO:0000305"
FT STRAND 417..420
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 433..436
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 438..445
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 449..456
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 468..473
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 479..482
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 494..503
FT /evidence="ECO:0007829|PDB:1UFG"
FT TURN 508..510
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 511..514
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 516..518
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 523..531
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 533..535
FT /evidence="ECO:0007829|PDB:1UFG"
FT STRAND 537..544
FT /evidence="ECO:0007829|PDB:1UFG"
FT MOD_RES P48678-2:392
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:1959608"
FT MOD_RES P48678-2:407
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:1959608"
FT MOD_RES P48678-2:409
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:1959608"
FT MOD_RES P48678-2:572
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES P48678-3:460
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 665 AA; 74238 MW; 5434F574803FCB15 CRC64;
METPSQRRAT RSGAQASSTP LSPTRITRLQ EKEDLQELND RLAVYIDRVR SLETENAGLR
LRITESEEVV SREVSGIKAA YEAELGDARK TLDSVAKERA RLQLELSKVR EEFKELKARN
TKKEGDLLAA QARLKDLEAL LNSKEAALST ALSEKRTLEG ELHDLRGQVA KLEAALGEAK
KQLQDEMLRR VDAENRLQTL KEELDFQKNI YSEELRETKR RHETRLVEID NGKQREFESR
LADALQELRA QHEDQVEQYK KELEKTYSAK LDNARQSAER NSNLVGAAHE ELQQSRIRID
SLSAQLSQLQ KQLAAKEAKL RDLEDSLARE RDTSRRLLAE KEREMAEMRA RMQQQLDEYQ
ELLDIKLALD MEIHAYRKLL EGEEERLRLS PSPTSQRSRG RASSHSSQSQ GGGSVTKKRK
LESSESRSSF SQHARTSGRV AVEEVDEEGK FVRLRNKSNE DQSMGNWQIR RQNGDDPLMT
YRFPPKFTLK AGQVVTIWAS GAGATHSPPT DLVWKAQNTW GCGSSLRTAL INSTGEEVAM
RKLVRSLTMV EDNEDDDEDG EELLHHHRGS HCSGSGDPAE YNLRSRTVLC GTCGQPADKA
AGGAGAQVGG SISSGSSASS VTVTRSFRSV GGSGGGSFGD NLVTRSYLLG NSSPRSQSSQ
NCSIM
