LEM domain-containing protein 3

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; ; trabecular 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.

External links[edit]

LEMD3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000174106 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000048661 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Worman-5] 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.

[PL-6] 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-7] 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-8] 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.

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Structure[edit]

LEMD3 and disease[edit]

See also[edit]

References[edit]

External links[edit]