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

domain A domain is a geographic area controlled by a single person or organization. Domain may also refer to: Law and human geography * Demesne, in English common law and other Medieval European contexts, lands directly managed by their holder rather ...

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

(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 Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Professor Marshall Urist and Professor Hari Reddi discovered their ability to induce the formation of bone and cartilage, BMPs are now ...

(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 Laminopathies ('' lamino-'' + '' -pathy'') are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. Since the first reports of laminopathies in the late 1990s, increased research efforts have sta ...

as well as

osteopoikilosis Osteopoikilosis is a benign, autosomal dominant, sclerosing (hardening) 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 charact ...

. Mutations in the ''LEMD3'' gene have been linked to several genetic diseases such as

, melorheostosis and

Buschke–Ollendorff syndrome Buschke–Ollendorff syndrome (BOS) is a rare genodermatosis, genetic skin disorder associated with LEMD3 that typically presents with widespread painless papules. It is inherited in an autosome, autosomal Dominance relationship#Dominant allele, ...

References

External links

* {{MeshName, LEMD3+protein,+human

Structure

LEMD3 and disease

See also

References

External links