LEM domain-containing protein 3
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[5] and was first identified after it was isolated from the serum of a patient with a collagen vascular disease.[6]
Structure[]
The protein is 82.3 kDa and has a 40 amino acid long 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: (LAP2) and emerin.[7]
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 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[5] as well as osteopoikilosis.[8] 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[]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000174106 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048661 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Worman HJ, Fong LG, Muchir A, Young SG (July 2009). "Laminopathies and the long strange trip from basic cell biology to therapy". The Journal of Clinical Investigation. 119 (7): 1825–36. doi:10.1172/JCI37679. PMC 2701866. PMID 19587457.
- ^ Paulin-Levasseur M, Blake DL, Julien M, Rouleau L (1996). "The MAN antigens are non-lamin constituents of the nuclear lamina in vertebrate cells". Chromosoma. 104 (5): 367–79. doi:10.1007/BF00337226. PMID 8575249. S2CID 13727509.
- ^ Lin F, Blake DL, Callebaut I, Skerjanc IS, Holmer L, McBurney MW, Paulin-Levasseur M, Worman HJ (February 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): 4840–7. doi:10.1074/jbc.275.7.4840. PMID 10671519.
- ^ Mumm S, Wenkert D, Zhang X, McAlister WH, Mier RJ, Whyte MP (February 2007). "Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis". Journal of Bone and Mineral Research. 22 (2): 243–50. doi:10.1359/jbmr.061102. PMID 17087626. S2CID 28338454.
External links[]
- LEMD3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Genes on human chromosome 12