10         20         30         40         50         60
         |          |          |          |          |          |
METPSQRRAT RSGAQASSTP LSPTRITRLQ EKEDLQELND RLAVYIDRVR SLETENAGLR - 60
LRITESEEVV SREVSGIKAA YEAELGDARK TLDSVAKERA RLQLELSKVR EEFKELKARN - 120
TKKEGDLIAA QARLKDLEAL LNSKEAALST ALSEKRTLEG ELHDLRGQVA KLEAALGEAK - 180
KQLQDEMLRR VDAENRLQTM KEELDFQKNI YSEELRETKR RHETRLVEID NGKQREFESR - 240
LADALQELRA QHEDQVEQYK KELEKTYSAK LDNARQSAER NSNLVGAAHE ELQQSRIRID - 300
SLSAQLSQLQ KQLAAKEAKL RDLEDSLARE RDTSRRLLAE KEREMAEMRA RMQQQLDEYQ - 360
ELLDIKLALD MEIHAYRKLL EGEEERLRLS PSPTSQRSRG RASSHSSQTQ GGGSVTKKRK - 420
LESTESRSSF SQHARTSGRV AVEEVDEEGK FVRLRNKSNE DQSMGNWQIK RQNGDDPLLT - 480
YRFPPKFTLK AGQVVTIWAA GAGATHSPPT DLVWKAQNTW GCGNSLRTAL INSTGEEVAM - 540
RKLVRSVTVV EDDEDEDGDD LLHHHHGSHC SSSGDPAEYN LRSRTVLCGT CGQPADKASA - 600
SGSGAQVGGP ISSGSSASSV TVTRSYRSVG GSGGGSFGDN LVTRSYLLGN SSPRTQSPQN - 660
CSIM

Function: Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Play an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.
Function: Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.
SUBUNIT: Homodimer of lamin A and lamin C. Interacts with lamin- associated polypeptides IA, IB and TMPO-alpha, RB1 and with emerin. Interacts with SREBF1, SREBF2, SUN2 and TMEM43 (By similarity). Proteolytically processed isoform A interacts with NARF. Interacts with SUN1. Prelamin-A/C interacts with EMD. P18054:ALOX12; NbExp=3; IntAct=EBI-351935, EBI-1633210;


Subcellular Location: Nucleus. Nucleus envelope. Note=Farnesylation of prelamin-A/C facilitates nuclear envelope targeting and subsequent cleaveage by ZMPSTE24/FACE1 to remove the farnesyl group produces mature lamin-A/C, which can then be inserted into the nuclear lamina. EMD is required for proper localization of non-farnesylated prelamin-A/C. Event=Alternative splicing; Named isoforms=3; Name=A; Synonyms=Lamin A; IsoId=P02545-1; Sequence=Displayed; Name=C; Synonyms=Lamin C; IsoId=P02545-2; Sequence=VSP_002469, VSP_002470; Name=ADelta10; Synonyms=Lamin ADelta10; IsoId=P02545-3; Sequence=VSP_002468;
TISSUE SPECIFICITY: In the arteries, prelamin-A/C accumulation is not observed in young healthy vessels but is prevalent in medial vascular smooth muscle celle (VSMCs) from aged individuals and in atherosclerotic lesions, where it often colocalizes with senescent and degenerate VSMCs. Prelamin-A/C expression increases with age and disease. In normal aging, the accumulation of prelamin-A/C is caused in part by the down-regulation of ZMPSTE24/FACE1 in response to oxidative stress.
PTM: Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations.
PTM: Proteolytic cleavage of the C-terminal of 18 residues of prelamin-A/C results in the production of lamin-A/C. The prelamin- A/C maturation pathway includes farnesylation of CAAX motif, ZMPSTE24/FACE1 mediated cleavage of the last three amino acids, methylation of the C-terminal cysteine and endoproteolytic removal of the last 15 C-terminal amino acids. Proteolytic cleavage requires prior farnesylation and methylation, and absence of these blocks cleavage.
PTM: Sumoylation is necessary for the localization to the nuclear envelope.
PTM: Farnesylation of prelamin-A/C facilitates nuclear envelope targeting.
DISEASE: Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2 (EDMD2), cardiomyopathy dilated type 1A (CMD1A), familial partial lipodystrophy type 2 (FPLD2), limb-girdle muscular dystrophy type 1B (LGMD1B), Charcot-Marie-Tooth disease type 2B1 (CMT2B1), Hutchinson-Gilford progeria syndrome (HGPS), cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH), mandibuloacral dysplasia with type A lipodystrophy (MADA), lethal tight skin contracture syndrome (LTSCS) also known as restrictive dermopathy (RD), heart-hand syndrome Slovenian type (HHS-Slovenian), muscular dystrophy congenital LMNA-related (CMD-LMNA),
MISCELLANEOUS: There are three types of lamins in human cells: A, B, and C.
MISCELLANEOUS: The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.
SIMILARITY: Belongs to the intermediate filament family. Sequence=CAA27173.1; Type=Frameshift; Positions=582;
WEB RESOURCE: Name=Human Intermediate Filament Mutation Database; URL='http://www.interfil.org';
WEB RESOURCE: Name=GeneReviews; URL='http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LMNA'.
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