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PROSITE documentation PDOC50954 [for PROSITE entry PS50954]

LEM and LEM-like domain profiles


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 [1,2,3].

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 α helices interacting through a set of conserved hydrophobic amino acids (see <PDB:1H9F>). The two helices, which are connected by a long loop are oriented at an angle of ~45 degree [3,4].

Some proteins known to contain a LEM domain are listed below:

  • 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 characterized by early contractures, muscle wasting and weakness and cardiomyopathy.
  • Xenopus laevis Smad1 antagonistic effector (SANE).
  • Drosophila melanogaster otefin (OTE).
  • Caenorhabditis elegans W01G7.5 protein.

All LAP2 isoforms share an N-terminal segment composed of a LEM domain that is connected to a highly divergent LEM-like domain by a highly flexible 60-residue linker. The LEM-like globular domain has the same size and structural fold (see <PDB:1H9E>) as the LEM domain, but has been shown to bind directly to DNA [1,2,3,4].

The profiles we developed span the entire LEM and LEM-like domains.

Last update:

January 2004 / First entry.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

LEM, PS50954; LEM domain profile  (MATRIX)

LEM_LIKE, PS50955; LEM-like domain profile  (MATRIX)


1AuthorsLin F. Blake D.L. Callebaut I. Skerjanc I.S. Holmer L. McBurney M.W. Paulin-Levasseur M. Worman H.J.
TitleMAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin.
SourceJ. Biol. Chem. 275:4840-4847(2000).
PubMed ID10671519

2AuthorsMattout-Drubezki A. Gruenbaum Y.
SourceCell. Mol. Life Sci. 60:2053-2063(2003).

3AuthorsCai M. Huang Y. Ghirlando R. Wilson K.L. Craigie R. Clore G.M.
TitleSolution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA.
SourceEMBO J. 20:4399-4407(2001).
PubMed ID11500367

4AuthorsLaguri C. Gilquin B. Wolff N. Romi-Lebrun R. Courchay K. Callebaut I. Worman H.J. Zinn-Justin S.
TitleStructural characterization of the LEM motif common to three human inner nuclear membrane proteins.
SourceStructure 9:503-511(2001).
PubMed ID11435115

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