LMNA

Lamin A/C also known as LMNA is a is_associated_with::protein that in humans is encoded by the LMNA is_associated_with::gene. Lamin A/C belongs to the is_associated_with::lamin family of proteins.

Function


The is_associated_with::nuclear lamina consist of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The is_associated_with::lamin family of proteins make up the matrix and are highly conserved in evolution. During is_associated_with::mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, is_associated_with::chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Through is_associated_with::alternate splicing, this gene encodes three type A lamin isoforms.

Early in mitosis, is_associated_with::Maturation promoting factor (abbreviated MPF, also called mitosis-promoting factor or M-Phase-promoting factor) phosphorylates specific serine residues in all three nuclear lamins, causing depolymerization of the lamin intermediate filaments. The phosphorylated lamin B dimers remain associated with the nuclear membrane via their isoprenyl anchor. Lamin A is targeted to the nuclear membrane by an isoprenyl group but it is cleaved shortly after arriving at the membrane. It stays associated with the membrane through protein-protein interactions of itself and other membrane associated proteins, such as LAP1. Depolymerization of the nuclear lamins leads to disintegration of the nuclear envelope. Transfection experiments demonstrate that phosphorylation of human lamin A is required for lamin depolymerization, and thus for disassembly of the nuclear envelope, which normally occurs early in mitosis.

Clinical significance


Mutations in the LMNA gene are associated with several diseases, including is_associated_with::Emery-Dreifuss muscular dystrophy, is_associated_with::familial partial lipodystrophy, is_associated_with::limb girdle muscular dystrophy, is_associated_with::dilated cardiomyopathy, is_associated_with::Charcot-Marie-Tooth disease, is_associated_with::Restrictive dermopathy and is_associated_with::Hutchinson-Gilford progeria syndrome. A truncated version of lamin A, commonly known as is_associated_with::progerin, causes Hutchinson-Gilford progeria syndrome. To date over 1,400 SNPs are known. They can manifest in changes on mRNA, splicing or protein (e.g. Arg471Cys, Arg482Gln, Arg527Leu, Arg527Cys, Ala529Val ) level.

Interactions
LMNA has been shown to interact with:


 * is_associated_with::ALOX12
 * EMD
 * NARF
 * is_associated_with::SREBF1
 * TMPO
 * is_associated_with::ZNF239
 * is_associated_with::SIRT1