Nebulette: Difference between revisions
Structure and Function |
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''NEBL'' encodes the protein '''Nebulette''', a cardiac-specific [[isoform]] belonging to the [[nebulin]] family of |
The ''NEBL'' [[gene]] encodes the [[protein]] '''Nebulette''', a [[cardiac]]-specific [[isoform]] belonging to the [[nebulin]] family of [[protein]]s. This family is comprised of 5 members: nebulette, [[NEB|nebulin]], [[NRAP|N-RAP]], [[LASP1|LASP-1]] and LASP-2. Nebulette localizes to [[sarcomere|Z-discs]] of [[cardiac muscle]] and appears to regulate the length of [[ACTC1|actin]] thin filaments. |
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==Structure== |
==Structure== |
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Nebulette is a 116.4 kDa protein comprised of 1014 amino acids ([http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O76041 See human NEBL sequence features here]). As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved |
Nebulette is a 116.4 kDa protein comprised of 1014 amino acids ([http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O76041 See human NEBL sequence features here]). As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved [[serine|S]][[aspartate|D]]xx[[tyrosine|Y]][[lysine|K]] motif (PMID 2037050). Like nebulin, nebulette has an acidic region with unknown structure at its N-terminus, and a serine-rich region adjacent to an SH3 domain at its C-terminus (PMID 20951588). Though nebulette shares structural features with nebulin, nebulin is expressed preferentially in [[skeletal muscle]] and has an enormous size (600-900 kDa), while nebulette is expressed in [[cardiac muscle]] at [[sarcomere|Z-disc]] regions and is significantly smaller (roughly 1/6 of the size) (PMID 8581976). Nebulette interacts with [[ACTC1|actin]], [[TPM1|tropomyosin]] and [[ACTN2|alpha-actinin]] (PMID 10470015). |
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==Function== |
==Function== |
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Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic [[cardiomyocyte]]s by [[immunoprecipitation]]s with certain anti-nebulin [[monoclonal antibodies]].<ref name="moncman">{{cite journal |author=Moncman & Wang |title=Nebulette: a 107 kD nebulin-like protein in cardiac muscle |journal=[[Cell Motil Cytoskeleton]] |volume=32 |issue=3 |pages=205–25 |year=1995 |pmid=8581976 |doi=10.1002/cm.970320305 |last2=Wang |first2=K }}</ref> Normal expression of nebulette is essential for the assembly and [[muscle contraction|contractile function]] of [[myofibril]]s.<ref name="moncman2">{{cite journal |author=Moncman & Wang |title=Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function |journal=Exp Cell Res |volume=273 |issue=2 |pages=204–18 |year=2002 |pmid=11822876 |doi=10.1006/excr.2001.5423 |last2=Wang |first2=K }}</ref> |
Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic [[cardiomyocyte]]s by [[immunoprecipitation]]s with certain anti-nebulin [[monoclonal antibodies]].<ref name="moncman">{{cite journal |author=Moncman & Wang |title=Nebulette: a 107 kD nebulin-like protein in cardiac muscle |journal=[[Cell Motil Cytoskeleton]] |volume=32 |issue=3 |pages=205–25 |year=1995 |pmid=8581976 |doi=10.1002/cm.970320305 |last2=Wang |first2=K }}</ref> Normal expression of nebulette is essential for the assembly and [[muscle contraction|contractile function]] of [[myofibril]]s.<ref name="moncman2">{{cite journal |author=Moncman & Wang |title=Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function |journal=Exp Cell Res |volume=273 |issue=2 |pages=204–18 |year=2002 |pmid=11822876 |doi=10.1006/excr.2001.5423 |last2=Wang |first2=K }}</ref> Specifically, nebulette appears to regulate the stability and length of actin thin filaments, as well as beating frequencies of cardiomyocytes; reduction of full-length nebulette protein in cardiomyocytes resulted in reduced thin filament lengths, depressed beating frequencies and loss of thin filament regulatory proteins [[TNNI3|troponin I]] and [[TPM1|tropomyosin]] (PMID 18823973)<ref name="moncman2">. |
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==Clinical Significance== |
==Clinical Significance== |
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Revision as of 20:13, 20 March 2015
The NEBL gene encodes the protein Nebulette, a cardiac-specific isoform belonging to the nebulin family of proteins. This family is comprised of 5 members: nebulette, nebulin, N-RAP, LASP-1 and LASP-2. Nebulette localizes to Z-discs of cardiac muscle and appears to regulate the length of actin thin filaments.
Structure
Nebulette is a 116.4 kDa protein comprised of 1014 amino acids (See human NEBL sequence features here). As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved SDxxYK motif (PMID 2037050). Like nebulin, nebulette has an acidic region with unknown structure at its N-terminus, and a serine-rich region adjacent to an SH3 domain at its C-terminus (PMID 20951588). Though nebulette shares structural features with nebulin, nebulin is expressed preferentially in skeletal muscle and has an enormous size (600-900 kDa), while nebulette is expressed in cardiac muscle at Z-disc regions and is significantly smaller (roughly 1/6 of the size) (PMID 8581976). Nebulette interacts with actin, tropomyosin and alpha-actinin (PMID 10470015).
Function
Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic cardiomyocytes by immunoprecipitations with certain anti-nebulin monoclonal antibodies.[1] Normal expression of nebulette is essential for the assembly and contractile function of myofibrils.[2] Specifically, nebulette appears to regulate the stability and length of actin thin filaments, as well as beating frequencies of cardiomyocytes; reduction of full-length nebulette protein in cardiomyocytes resulted in reduced thin filament lengths, depressed beating frequencies and loss of thin filament regulatory proteins troponin I and tropomyosin (PMID 18823973)<ref name="moncman2">.
Clinical Significance
References
- ^ Moncman & Wang; Wang, K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motil Cytoskeleton. 32 (3): 205–25. doi:10.1002/cm.970320305. PMID 8581976.
- ^ Moncman & Wang; Wang, K (2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Exp Cell Res. 273 (2): 204–18. doi:10.1006/excr.2001.5423. PMID 11822876.
External links
- nebulette at the U.S. National Library of Medicine Medical Subject Headings (MeSH)