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 membrane ...

. 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 Lem may refer to: Places * 3836 Lem, an asteroid named after Stanisław Lem * , a municipality in Jutland People Given name or nickname (Alphabetical by surname) * Lemuel Lem Barney (born 1945), American football player * Lem Billings (1916– ...

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

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 eukaryoti ...

(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 In molecular biology, barrier-to-autointegration factor (BAF) is a family of essential proteins that is highly conserved in metazoan evolution, and which may act as DNA-bridging proteins. BAF binds directly to double-stranded DNA, to transcriptio ...

(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 sign ...

(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 p ...

(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) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

. 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

melorheostosis Melorheostosis is a medical developmental disorder and mesenchymal dysplasia in which the bony cortex widens and becomes hyperdense in a sclerotomal distribution. The condition begins in childhood and is characterized by thickening of the bones. P ...

and Buschke-Ollendorff syndrome.

References

External links

* {{MeshName, LEMD3+protein,+human

Structure

LEMD3 and disease

See also

References

External links