LEM_domain-containing_protein_3 Knowpia

LEMD3
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2CH0
Identifiers
Aliases	LEMD3, MAN1, LEM domain containing 3, LEM domain-containing protein 3
External IDs	OMIM: 607844 MGI: 3580376 HomoloGene: 8633 GeneCards: LEMD3
Gene location (Human)
Chr.	Chromosome 12 (human)
End	65,248,355 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	120,815,237 bp
RNA expression pattern
	Top expressed in
	endothelial cell; ; cerebellar vermis; ; germinal epithelium; ; visceral pleura; ; superficial temporal artery; ; spongy bone; ; Brodmann area 23; ; tibia; ; parietal pleura; ; middle temporal gyrus;
	Top expressed in
	hand; ; cerebellar vermis; ; ventromedial nucleus; ; piriform cortex; ; suprachiasmatic nucleus; ; superior cervical ganglion; ; habenula; ; cumulus cell; ; mammillary body; ; primary motor cortex;
	More reference expression data
	n/a
Gene ontology
Molecular function	DNA binding; protein binding; nucleic acid binding; chromatin DNA binding;
Cellular component	integral component of membrane; nuclear inner membrane; membrane; nucleus; nuclear membrane; integral component of nuclear inner membrane;
Biological process	negative regulation of activin receptor signaling pathway; negative regulation of transforming growth factor beta receptor signaling pathway; negative regulation of BMP signaling pathway; nuclear envelope organization; meiotic attachment of telomere to nuclear envelope; angiogenesis; nucleus organization; regulation of intracellular signal transduction;
	Sources:Amigo / QuickGO
Orthologs
	23592
	380664
	ENSG00000174106
	ENSMUSG00000048661
	Q9Y2U8
	Q9WU40
	NM_014319; NM_001167614
	NM_001081193
	NP_001161086; NP_055134; NP_055134.2
	NP_001074662
	Wikidata
View/Edit Human	View/Edit Mouse

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 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.^[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 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^[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.

References edit

^ ^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.