LEM domain-containing protein 3 (LEMD3), also known as MAN1, is an integral
protein in the inner nuclear membrane (INM) of the
nuclear envelope
The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material.
The nuclear envelope consists of two lipid bilayer membran ...
. It is encoded by the ''LEMD3'' gene
and was first identified after it was isolated from the
serum of a patient with a collagen vascular disease.
Structure
The protein is 82.3 kDa and has a 40 amino acid long
LEM domain located at its amino-terminal region. In its carboxyl end it has a
RNA recognition motif (RRM). The LEM domain is also common to two other integral proteins of the INM:
lamina-associated polypeptide 2 (LAP2) and
emerin
Emerin is a protein that in humans is encoded by the ''EMD'' gene, also known as the ''STA'' gene. Emerin, together with LEMD3, is a LEM domain-containing integral protein of the inner nuclear membrane in vertebrates. Emerin is highly express ...
.
The LEM segment enables LEMD3 to attach to the
barrier-to-autointegration factor (BAF), and therefore, indirectly interact with the
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
. LEMD3 also has several implications in regulating the
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
family such as the
transforming growth factor beta
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other ...
(TGF-β) and
bone morphogenic protein (BMPs). The RRM domain in its carboxylic region attaches to the
SMAD (protein)
Smads (or SMADs) comprise a family of structurally similar proteins that are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily, which are critically important for regulating cell development and gr ...
proteins, which is involved in mediating TGF-β
cellular signalling
In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
. Consequently, LEMD3 indirectly regulates downstream genes.
LEMD3 seems to play an important role in regulating the expression of several fundamental genes.
LEMD3 and disease
LEMD3 has been associated with
laminopathies as well as
osteopoikilosis.
Mutations in the ''LEMD3'' gene have been linked to several genetic diseases such as
osteopoikilosis,
melorheostosis and
Buschke–Ollendorff syndrome.
See also
Inner nuclear membrane proteins
Inner nuclear membrane proteins (INM proteins) are membrane proteins that are embedded in or associated with the inner membrane of the nuclear envelope. There are about 60 INM proteins, most of which are poorly characterized with respect to str ...
References
External links
* {{MeshName, LEMD3+protein,+human