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{{protein
{{Infobox protein
| Name = LEM domain containing protein 3  
| Name = LEM domain containing protein 3  
| caption =  
| caption =  
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
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'''LEM domain-containing protein 3''' is a [[membrane protein]] associated with [[laminopathies]].


It is also associated with [[osteopoikilosis]].<ref name="pmid17087626">{{cite journal |author=Mumm S, Wenkert D, Zhang X, McAlister WH, Mier RJ, Whyte MP |title=Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis |journal=J. Bone Miner. Res. |volume=22 |issue=2 |pages=243–50 |year=2007 |pmid=17087626 |doi=10.1359/jbmr.061102 |url=http://dx.doi.org/10.1359/jbmr.061102}}</ref>
'''LEM domain-containing protein 3''' (LEMD3), also known as '''MAN1''', is an integral [[Inner nuclear membrane proteins|protein in the inner nuclear membrane (INM)]] of the [[nuclear envelope]]. It is encoded by the ''LEMD3'' gene<ref name=Worman>{{Cite journal
| last1 = Worman | first1 = H. J.
| last2 = Fong | first2 = L. G.
| last3 = Muchir | first3 = A.
| last4 = Young | first4 = S. G.
| title = Laminopathies and the long strange trip from basic cell biology to therapy
| doi = 10.1172/JCI37679
| journal = Journal of Clinical Investigation
| volume = 119
| issue = 7
| pages = 1825–1836
| year = 2009
| pmid = 19587457
| pmc =2701866
}}</ref> and was first identified after it was isolated from the [[serum (blood)|serum]] of a patient with a collagen vascular disease.<ref name=PL>{{Cite journal
| last1 = Paulin-Levasseur | first1 = M.
| last2 = Blake | first2 = D. L.
| last3 = Julien | first3 = M.
| last4 = Rouleau | first4 = L.
| title = The MAN antigens are non-lamin constituents of the nuclear lamina in vertebrate cells
| journal = Chromosoma
| volume = 104
| issue = 5
| pages = 367–379
| year = 1996
| pmid = 8575249 | doi=10.1007/BF00337226
}}</ref>
 
==Structure==
The protein is 82.3 kDa and has a 40 amino acid long [[LEM domain|LEM]] [[protein domain|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]].<ref name=Lin>{{Cite journal
| last1 = Lin | first1 = F.
| last2 = Blake | first2 = D. L.
| last3 = Callebaut | first3 = I.
| last4 = Skerjanc | first4 = I. S.
| last5 = Holmer | first5 = L.
| last6 = McBurney | first6 = M. W.
| last7 = Paulin-Levasseur | first7 = M.
| last8 = Worman | first8 = H. J.
| title = MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin
| journal = The Journal of Biological Chemistry
| volume = 275
| issue = 7
| pages = 4840–4847
| year = 2000
| pmid = 10671519 | doi=10.1074/jbc.275.7.4840
}}</ref>
 
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 [[Smads|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]]<ref name=Worman /> as well as [[osteopoikilosis]].<ref name=Mumm>{{Cite journal  
| last1 = Mumm | first1 = S.
| last2 = Wenkert | first2 = D.
| last3 = Zhang | first3 = X.
| last4 = McAlister | first4 = W. H.
| last5 = Mier | first5 = R. J.
| last6 = Whyte | first6 = M. P.
| doi = 10.1359/jbmr.061102
| title = Deactivating Germline Mutations in LEMD3 Cause Osteopoikilosis and Buschke-Ollendorff Syndrome, but Not Sporadic Melorheostosis
| journal = Journal of Bone and Mineral Research
| volume = 22  
| issue = 2  
| pages = 243–250
| year = 2006
| pmid = 17087626  
| pmc =  
}}</ref> Mutations in the ''LEMD3'' gene have been linked to several genetic diseases such as [[osteopoikilosis]], [[melorheostosis]] and [[Buschke-Ollendorff syndrome]].


==See also==
==See also==
* [[Buschke-Ollendorff syndrome]]
[[Inner nuclear membrane proteins]]


==References==
==References==
{{reflist|2}}
{{reflist}}


==External links==
==External links==
* {{MeshName|LEMD3+protein,+human}}
* {{MeshName|LEMD3+protein,+human}}
{{biochemistry-stub}}
{{WikiDoc Sources}}

Revision as of 16:32, 29 June 2016

LEM domain containing protein 3
Identifiers
SymbolLEMD3
Alt. symbolsMAN1
Entrez23592
HUGO28887
OMIM607844
RefSeqNM_014319
UniProtQ9Y2U8
Other data
LocusChr. 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. 1.0 1.1 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 2701866. 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.

External links