LEM domain-containing protein 3

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LEM domain containing protein 3
Identifiers
Symbol LEMD3
Alt. symbols MAN1
Entrez 23592
HUGO 28887
OMIM 607844
RefSeq NM_014319
UniProt Q9Y2U8
Other data
Locus Chr. 12 q14

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[1] and was first identified after it was isolated from the serum of a patient with a collagen vascular disease.[2]

Structure[edit]

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.[3]

The LEM segment enables LEMD3 to attach to the barrier-to-autointegration factor (BAF), and therefore, indirectly interact with the chromatin. LEMD3 also has several implications in regulating the cytokine family such as the transforming growth factor beta (TGF-β) and bone morphogenic protein (BMPs). The RRM domain in its carboxylic region attaches to the SMAD (protein) 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[edit]

LEMD3 has been associated with laminopathies[1] as well as osteopoikilosis.[4] Mutations in the LEMD3 gene have been linked to several genetic diseases such as osteopoikilosis, melorheostosis and Buschke-Ollendorff syndrome.

See also[edit]

Inner nuclear membrane proteins


References[edit]

  1. ^ a b Worman, H. J.; Fong, L. G.; Muchir, A.; Young, S. G. (2009). "Laminopathies and the long strange trip from basic cell biology to therapy". Journal of Clinical Investigation 119 (7): 1825–1836. doi:10.1172/JCI37679. PMC 2701866. PMID 19587457.  edit
  2. ^ Paulin-Levasseur, M.; Blake, D. L.; Julien, M.; Rouleau, L. (1996). "The MAN antigens are non-lamin constituents of the nuclear lamina in vertebrate cells". Chromosoma 104 (5): 367–379. doi:10.1007/BF00337226. PMID 8575249.  edit
  3. ^ Lin, F.; Blake, D. L.; Callebaut, I.; Skerjanc, I. S.; Holmer, L.; McBurney, M. W.; Paulin-Levasseur, M.; Worman, H. J. (2000). "MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin". The Journal of biological chemistry 275 (7): 4840–4847. doi:10.1074/jbc.275.7.4840. PMID 10671519.  edit
  4. ^ Mumm, S.; Wenkert, D.; Zhang, X.; McAlister, W. H.; Mier, R. J.; Whyte, M. P. (2006). "Deactivating Germline Mutations in LEMD3 Cause Osteopoikilosis and Buschke-Ollendorff Syndrome, but Not Sporadic Melorheostosis". Journal of Bone and Mineral Research 22 (2): 243–250. doi:10.1359/jbmr.061102. PMID 17087626.  edit

External links[edit]