LEM domain-containing protein 3

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

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

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

Inner nuclear membrane proteins

References

  1. 1 2 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 2701866Freely accessible. PMID 19587457.
  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.
  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.
  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.
This article is issued from Wikipedia - version of the 6/29/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.