The LEM (LAP2, emerin, MAN1) domain is a globular module of approximately 40 amino acids, which is mostly found in the nucleoplasmic portions of metazoan inner nuclear membrane proteins. The LEM domain has been shown to mediate binding to BAF (barrier-to-autointegration factor) and BAF-DNA complexes. BAF dimers bind to double-stranded DNA non-specifically and thereby bridge DNA molecules to form a large, discrete nucleoprotein complex [ (PUBMED:10671519) (PUBMED:11500367) ].
The resolution of the solution structure of the LEM domain reveals that it is composed of a three-residue N-terminal helical turn and two large parallel alpha helices interacting through a set of conserved hydrophobic amino acids. The two helices, which are connected by a long loop are oriented at an angle of ~45 degree [ (PUBMED:11500367) (PUBMED:11435115) ].
Proteins known to contain a LEM domain include:
Vertebrate inner nuclear membrane protein MAN1.
Vertebrate lamina-associated polypeptide 2 (LAP2) or thymopoietin.
Mammalian emerin (EMD). In human, defects in EMD are a cause of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD), an X-linked disorder, characterised by early contractures, muscle wasting and weakness and cardiomyopathy.
MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin.
J Biol Chem. 2000; 275: 4840-7
Display abstract
The "MAN antigens" are polypeptides recognized by autoantibodies from a patient with a collagen vascular disease and localized to the nuclear envelope. We now show that one of the human MAN antigens termed MAN1 is a 82.3-kDa protein with an amino-terminal domain followed by two hydrophobic segments and a carboxyl-terminal tail. The MAN1 gene contains seven protein-coding exons and is assigned to human chromosome 12q14. Its mRNA is approximately 5.5 kilobases and is detected in several different cell types that were examined. Cell extraction experiments show that MAN1 is an integral membrane protein. When expressed in transfected cells, MAN1 is exclusively targeted to the nuclear envelope, consistent with an inner nuclear membrane localization. Protein sequence analysis reveals that MAN1 shares a conserved globular domain of approximately 40 amino acids, which we term the LEM module, with inner nuclear membrane proteins lamina-associated polypeptide 2 and emerin. The LEM module is also present in two proteins of Caenorhabditis elegans. These results show that MAN1 is an integral protein of the inner nuclear membrane that shares the LEM module with other proteins of this subcellular localization.
Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy.
Nat Genet. 1994; 8: 323-7
Display abstract
Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive disorder characterized by slowly progressing contractures, wasting of skeletal muscle and cardiomyopathy. Heart block is a frequent cause of death. The disease gene has been mapped to distal Xq28. Among many genes in this region, we selected eight transcripts expressed at high levels in skeletal muscle, heart and/or brain as the best candidates for the disease. We now report, in all five patients studied, unique mutations in one of the genes, STA: these mutations result in the loss of all or part of the protein. The EDMD gene encodes a novel serine-rich protein termed emerin, which contains a 20 amino acid hydrophobic domain at the C terminus, similar to that described for many membrane proteins of the secretory pathway involved in vesicular transport.
