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]

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; OMA:LEMD3 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q14.3 Start 65,169,583 bp[1] End 65,248,355 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 D2 Start 120,759,318 bp[2] End 120,815,237 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell cerebellar vermis germinal epithelium visceral pleura superficial temporal artery trabecular bone Brodmann area 23 tibia Epithelium of choroid plexus parietal pleura Top expressed in hand lobe of cerebellum cerebellar vermis ventromedial nucleus piriform cortex suprachiasmatic nucleus superior cervical ganglion lateral septal nucleus habenula cumulus cell More reference expression data BioGPS 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 Species Human Mouse Entrez 23592 380664 Ensembl ENSG00000174106 ENSMUSG00000048661 UniProt Q9Y2U8 Q9WU40 RefSeq (mRNA) NM_014319 NM_001167614 NM_001081193 RefSeq (protein) NP_001161086 NP_055134 NP_055134.2 NP_001074662 Location (UCSC) Chr 12: 65.17 – 65.25 Mb Chr 10: 120.76 – 120.82 Mb PubMed search [3] [4]
Wikidata
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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.^[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

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

1. GRCh38: Ensembl release 89: ENSG00000174106 – Ensembl, May 2017
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.
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.
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.
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.
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.

External links

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