LEM domain-containing protein 3 (LEMD3), also known as MAN1, is an integral
protein in the inner nuclear membrane (INM) of the
nuclear envelope. 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
RNA recognition motif, RNP-1 is a putative RNA-binding domain of about 90 amino acids that are known to bind single-stranded RNAs. It was found in many eukaryotic proteins.
The largest group of single strand RNA-binding protein is the eukaryot ...
(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 Transmembrane protein, integral protein of the Inner nuclear membrane proteins, inner Cell ...
.
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 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 roles in 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 peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
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
Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pi ...
(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. 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
Laminopathies ('' lamino-'' + '' -opathy'') are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. They are included in the more generic term ''nuclear envelopathies'' that was coined in 2000 fo ...
as well as
osteopoikilosis
Osteopoikilosis is a benign, autosomal dominant sclerosing dysplasia of bone characterized by the presence of numerous bone islands in the skeleton.
Presentation
The radiographic appearance of osteopoikilosis on an X-ray is characterized by a patt ...
.
Mutations in the ''LEMD3'' gene have been linked to several genetic diseases such as
osteopoikilosis
Osteopoikilosis is a benign, autosomal dominant sclerosing dysplasia of bone characterized by the presence of numerous bone islands in the skeleton.
Presentation
The radiographic appearance of osteopoikilosis on an X-ray is characterized by a patt ...
,
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 stru ...
References
External links
* {{MeshName, LEMD3+protein,+human